Author: "Gur, Raquel" / Database: OAIster - Searchworks@Jio Institute Digital Library Search Results

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173 results on '"Gur, Raquel"'

1. Source-based morphometry reveals structural brain pattern abnormalities in 22q11.2 deletion syndrome

Author: Psychosociale zorg patientenzorg, Ge, Ruiyang, Ching, Christopher R.K., Bassett, Anne S., Kushan, Leila, Antshel, Kevin M., van Amelsvoort, Therese, Bakker, Geor, Butcher, Nancy J., Campbell, Linda E., Chow, Eva W.C., Craig, Michael, Crossley, Nicolas A., Cunningham, Adam, Daly, Eileen, Doherty, Joanne L., Durdle, Courtney A., Emanuel, Beverly S., Fiksinski, Ania, Forsyth, Jennifer K., Fremont, Wanda, Goodrich-Hunsaker, Naomi J., Gudbrandsen, Maria, Gur, Raquel E., Jalbrzikowski, Maria, Kates, Wendy R., Lin, Amy, Linden, David E.J., McCabe, Kathryn L., McDonald-McGinn, Donna, Moss, Hayley, Murphy, Declan G., Murphy, Kieran C., Owen, Michael J., Villalon-Reina, Julio E., Repetto, Gabriela M., Roalf, David R., Ruparel, Kosha, Schmitt, J. Eric, Schuite-Koops, Sanne, Angkustsiri, Kathleen, Sun, Daqiang, Vajdi, Ariana, van den Bree, Marianne, Vorstman, Jacob, Thompson, Paul M., Vila-Rodriguez, Fidel, Bearden, Carrie E., Psychosociale zorg patientenzorg, Ge, Ruiyang, Ching, Christopher R.K., Bassett, Anne S., Kushan, Leila, Antshel, Kevin M., van Amelsvoort, Therese, Bakker, Geor, Butcher, Nancy J., Campbell, Linda E., Chow, Eva W.C., Craig, Michael, Crossley, Nicolas A., Cunningham, Adam, Daly, Eileen, Doherty, Joanne L., Durdle, Courtney A., Emanuel, Beverly S., Fiksinski, Ania, Forsyth, Jennifer K., Fremont, Wanda, Goodrich-Hunsaker, Naomi J., Gudbrandsen, Maria, Gur, Raquel E., Jalbrzikowski, Maria, Kates, Wendy R., Lin, Amy, Linden, David E.J., McCabe, Kathryn L., McDonald-McGinn, Donna, Moss, Hayley, Murphy, Declan G., Murphy, Kieran C., Owen, Michael J., Villalon-Reina, Julio E., Repetto, Gabriela M., Roalf, David R., Ruparel, Kosha, Schmitt, J. Eric, Schuite-Koops, Sanne, Angkustsiri, Kathleen, Sun, Daqiang, Vajdi, Ariana, van den Bree, Marianne, Vorstman, Jacob, Thompson, Paul M., Vila-Rodriguez, Fidel, and Bearden, Carrie E.
Published: 2024

2. Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis.

Author: Wannan, Cassandra, Wannan, Cassandra, Nelson, Barnaby, Addington, Jean, Allott, Kelly, Anticevic, Alan, Arango, Celso, Baker, Justin, McGorry, Patrick, Mittal, Vijay, Nordentoft, Merete, Nunez, Angela, Pasternak, Ofer, Pearlson, Godfrey, Perez, Jesus, Perkins, Diana, Powers, Albert, Roalf, David, Sabb, Fred, Schiffman, Jason, Shah, Jai, Smesny, Stefan, Spark, Jessica, Stone, William, Strauss, Gregory, Tamayo, Zailyn, Torous, John, Upthegrove, Rachel, Vangel, Mark, Verma, Swapna, Wang, Jijun, Rossum, Inge, Wolf, Daniel, Wolff, Phillip, Wood, Stephen, Yung, Alison, Agurto, Carla, Alvarez-Jimenez, Mario, Amminger, Paul, Armando, Marco, Asgari-Targhi, Ameneh, Cahill, John, Carrión, Ricardo, Castro, Eduardo, Cetin-Karayumak, Suheyla, Mallar Chakravarty, M, Cho, Youngsun, Cotter, David, DAlfonso, Simon, Ennis, Michaela, Fadnavis, Shreyas, Fonteneau, Clara, Gao, Caroline, Gupta, Tina, Gur, Raquel, Gur, Ruben, Hamilton, Holly, Hoftman, Gil, Jacobs, Grace, Jarcho, Johanna, Ji, Jie, Kohler, Christian, Lalousis, Paris, Lavoie, Suzie, Lepage, Martin, Liebenthal, Einat, Mervis, Josh, Murty, Vishnu, Nicholas, Spero, Ning, Lipeng, Penzel, Nora, Poldrack, Russell, Polosecki, Pablo, Pratt, Danielle, Rabin, Rachel, Rahimi Eichi, Habiballah, Rathi, Yogesh, Reichenberg, Avraham, Reinen, Jenna, Rogers, Jack, Ruiz-Yu, Bernalyn, Scott, Isabelle, Seitz-Holland, Johanna, Srihari, Vinod, Srivastava, Agrima, Thompson, Andrew, Turetsky, Bruce, Walsh, Barbara, Whitford, Thomas, Wigman, Johanna, Yao, Beier, Yuen, Hok, Ahmed, Uzair, Byun, Andrew, Chung, Yoonho, Do, Kim, Hendricks, Larry, Huynh, Kevin, Jeffries, Clark, Lane, Erlend, Langholm, Carsten, Wannan, Cassandra, Wannan, Cassandra, Nelson, Barnaby, Addington, Jean, Allott, Kelly, Anticevic, Alan, Arango, Celso, Baker, Justin, McGorry, Patrick, Mittal, Vijay, Nordentoft, Merete, Nunez, Angela, Pasternak, Ofer, Pearlson, Godfrey, Perez, Jesus, Perkins, Diana, Powers, Albert, Roalf, David, Sabb, Fred, Schiffman, Jason, Shah, Jai, Smesny, Stefan, Spark, Jessica, Stone, William, Strauss, Gregory, Tamayo, Zailyn, Torous, John, Upthegrove, Rachel, Vangel, Mark, Verma, Swapna, Wang, Jijun, Rossum, Inge, Wolf, Daniel, Wolff, Phillip, Wood, Stephen, Yung, Alison, Agurto, Carla, Alvarez-Jimenez, Mario, Amminger, Paul, Armando, Marco, Asgari-Targhi, Ameneh, Cahill, John, Carrión, Ricardo, Castro, Eduardo, Cetin-Karayumak, Suheyla, Mallar Chakravarty, M, Cho, Youngsun, Cotter, David, DAlfonso, Simon, Ennis, Michaela, Fadnavis, Shreyas, Fonteneau, Clara, Gao, Caroline, Gupta, Tina, Gur, Raquel, Gur, Ruben, Hamilton, Holly, Hoftman, Gil, Jacobs, Grace, Jarcho, Johanna, Ji, Jie, Kohler, Christian, Lalousis, Paris, Lavoie, Suzie, Lepage, Martin, Liebenthal, Einat, Mervis, Josh, Murty, Vishnu, Nicholas, Spero, Ning, Lipeng, Penzel, Nora, Poldrack, Russell, Polosecki, Pablo, Pratt, Danielle, Rabin, Rachel, Rahimi Eichi, Habiballah, Rathi, Yogesh, Reichenberg, Avraham, Reinen, Jenna, Rogers, Jack, Ruiz-Yu, Bernalyn, Scott, Isabelle, Seitz-Holland, Johanna, Srihari, Vinod, Srivastava, Agrima, Thompson, Andrew, Turetsky, Bruce, Walsh, Barbara, Whitford, Thomas, Wigman, Johanna, Yao, Beier, Yuen, Hok, Ahmed, Uzair, Byun, Andrew, Chung, Yoonho, Do, Kim, Hendricks, Larry, Huynh, Kevin, Jeffries, Clark, Lane, Erlend, and Langholm, Carsten
Abstract: This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.
Published: 2024

3. Brain‐age prediction: Systematic evaluation of site effects, and sample age range and size

Author: Yu, Yuetong, Yu, Yuetong, Cui, Hao‐Qi, Haas, Shalaila S, New, Faye, Sanford, Nicole, Yu, Kevin, Zhan, Denghuang, Yang, Guoyuan, Gao, Jia‐Hong, Wei, Dongtao, Qiu, Jiang, Banaj, Nerisa, Boomsma, Dorret I, Breier, Alan, Brodaty, Henry, Buckner, Randy L, Buitelaar, Jan K, Cannon, Dara M, Caseras, Xavier, Clark, Vincent P, Conrod, Patricia J, Crivello, Fabrice, Crone, Eveline A, Dannlowski, Udo, Davey, Christopher G, de Haan, Lieuwe, de Zubicaray, Greig I, Di Giorgio, Annabella, Fisch, Lukas, Fisher, Simon E, Franke, Barbara, Glahn, David C, Grotegerd, Dominik, Gruber, Oliver, Gur, Raquel E, Gur, Ruben C, Hahn, Tim, Harrison, Ben J, Hatton, Sean, Hickie, Ian B, Pol, Hilleke E Hulshoff, Jamieson, Alec J, Jernigan, Terry L, Jiang, Jiyang, Kalnin, Andrew J, Kang, Sim, Kochan, Nicole A, Kraus, Anna, Lagopoulos, Jim, Lazaro, Luisa, McDonald, Brenna C, McDonald, Colm, McMahon, Katie L, Mwangi, Benson, Piras, Fabrizio, Rodriguez‐Cruces, Raul, Royer, Jessica, Sachdev, Perminder S, Satterthwaite, Theodore D, Saykin, Andrew J, Schumann, Gunter, Sevaggi, Pierluigi, Smoller, Jordan W, Soares, Jair C, Spalletta, Gianfranco, Tamnes, Christian K, Trollor, Julian N, Ent, Dennis Van't, Vecchio, Daniela, Walter, Henrik, Wang, Yang, Weber, Bernd, Wen, Wei, Wierenga, Lara M, Williams, Steven CR, Wu, Mon‐Ju, Zunta‐Soares, Giovana B, Bernhardt, Boris, Thompson, Paul, Frangou, Sophia, Ge, Ruiyang, Group, ENIGMA‐Lifespan Working, Yu, Yuetong, Yu, Yuetong, Cui, Hao‐Qi, Haas, Shalaila S, New, Faye, Sanford, Nicole, Yu, Kevin, Zhan, Denghuang, Yang, Guoyuan, Gao, Jia‐Hong, Wei, Dongtao, Qiu, Jiang, Banaj, Nerisa, Boomsma, Dorret I, Breier, Alan, Brodaty, Henry, Buckner, Randy L, Buitelaar, Jan K, Cannon, Dara M, Caseras, Xavier, Clark, Vincent P, Conrod, Patricia J, Crivello, Fabrice, Crone, Eveline A, Dannlowski, Udo, Davey, Christopher G, de Haan, Lieuwe, de Zubicaray, Greig I, Di Giorgio, Annabella, Fisch, Lukas, Fisher, Simon E, Franke, Barbara, Glahn, David C, Grotegerd, Dominik, Gruber, Oliver, Gur, Raquel E, Gur, Ruben C, Hahn, Tim, Harrison, Ben J, Hatton, Sean, Hickie, Ian B, Pol, Hilleke E Hulshoff, Jamieson, Alec J, Jernigan, Terry L, Jiang, Jiyang, Kalnin, Andrew J, Kang, Sim, Kochan, Nicole A, Kraus, Anna, Lagopoulos, Jim, Lazaro, Luisa, McDonald, Brenna C, McDonald, Colm, McMahon, Katie L, Mwangi, Benson, Piras, Fabrizio, Rodriguez‐Cruces, Raul, Royer, Jessica, Sachdev, Perminder S, Satterthwaite, Theodore D, Saykin, Andrew J, Schumann, Gunter, Sevaggi, Pierluigi, Smoller, Jordan W, Soares, Jair C, Spalletta, Gianfranco, Tamnes, Christian K, Trollor, Julian N, Ent, Dennis Van't, Vecchio, Daniela, Walter, Henrik, Wang, Yang, Weber, Bernd, Wen, Wei, Wierenga, Lara M, Williams, Steven CR, Wu, Mon‐Ju, Zunta‐Soares, Giovana B, Bernhardt, Boris, Thompson, Paul, Frangou, Sophia, Ge, Ruiyang, and Group, ENIGMA‐Lifespan Working
Abstract: Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.
Published: 2024

4. Brain-age prediction:Systematic evaluation of site effects, and sample age range and size

Author: Yu, Yuetong, Cui, Hao‐Qi, Haas, Shalaila S., New, Faye, Sanford, Nicole, Yu, Kevin, Zhan, Denghuang, Yang, Guoyuan, Gao, Jia‐Hong, Wei, Dongtao, Qiu, Jiang, Banaj, Nerisa, Boomsma, Dorret I., Breier, Alan, Brodaty, Henry, Buckner, Randy L., Buitelaar, Jan K., Cannon, Dara M., Caseras, Xavier, Clark, Vincent P., Conrod, Patricia J., Crivello, Fabrice, Crone, Eveline A., Dannlowski, Udo, Davey, Christopher G., de Haan, Lieuwe, de Zubicaray, Greig I., Di Giorgio, Annabella, Fisch, Lukas, Fisher, Simon E., Franke, Barbara, Glahn, David C., Grotegerd, Dominik, Gruber, Oliver, Gur, Raquel E., Gur, Ruben C., Hahn, Tim, Harrison, Ben J., Hatton, Sean, Hickie, Ian B., Hulshoff Pol, Hilleke E., Jamieson, Alec J., Jernigan, Terry L., Jiang, Jiyang, Kalnin, Andrew J., Kang, Sim, Kochan, Nicole A., Kraus, Anna, Lagopoulos, Jim, Lazaro, Luisa, McDonald, Brenna C., McDonald, Colm, McMahon, Katie L., Mwangi, Benson, Piras, Fabrizio, Rodriguez‐Cruces, Raul, Royer, Jessica, Sachdev, Perminder S., Satterthwaite, Theodore D., Saykin, Andrew J., Schumann, Gunter, Sevaggi, Pierluigi, Smoller, Jordan W., Soares, Jair C., Spalletta, Gianfranco, Tamnes, Christian K., Trollor, Julian N., Van't Ent, Dennis, Vecchio, Daniela, Walter, Henrik, Wang, Yang, Weber, Bernd, Wen, Wei, Wierenga, Lara M., Williams, Steven C. R., Wu, Mon‐Ju, Zunta‐Soares, Giovana B., Bernhardt, Boris, Thompson, Paul, Frangou, Sophia, Ge, Ruiyang, Yu, Yuetong, Cui, Hao‐Qi, Haas, Shalaila S., New, Faye, Sanford, Nicole, Yu, Kevin, Zhan, Denghuang, Yang, Guoyuan, Gao, Jia‐Hong, Wei, Dongtao, Qiu, Jiang, Banaj, Nerisa, Boomsma, Dorret I., Breier, Alan, Brodaty, Henry, Buckner, Randy L., Buitelaar, Jan K., Cannon, Dara M., Caseras, Xavier, Clark, Vincent P., Conrod, Patricia J., Crivello, Fabrice, Crone, Eveline A., Dannlowski, Udo, Davey, Christopher G., de Haan, Lieuwe, de Zubicaray, Greig I., Di Giorgio, Annabella, Fisch, Lukas, Fisher, Simon E., Franke, Barbara, Glahn, David C., Grotegerd, Dominik, Gruber, Oliver, Gur, Raquel E., Gur, Ruben C., Hahn, Tim, Harrison, Ben J., Hatton, Sean, Hickie, Ian B., Hulshoff Pol, Hilleke E., Jamieson, Alec J., Jernigan, Terry L., Jiang, Jiyang, Kalnin, Andrew J., Kang, Sim, Kochan, Nicole A., Kraus, Anna, Lagopoulos, Jim, Lazaro, Luisa, McDonald, Brenna C., McDonald, Colm, McMahon, Katie L., Mwangi, Benson, Piras, Fabrizio, Rodriguez‐Cruces, Raul, Royer, Jessica, Sachdev, Perminder S., Satterthwaite, Theodore D., Saykin, Andrew J., Schumann, Gunter, Sevaggi, Pierluigi, Smoller, Jordan W., Soares, Jair C., Spalletta, Gianfranco, Tamnes, Christian K., Trollor, Julian N., Van't Ent, Dennis, Vecchio, Daniela, Walter, Henrik, Wang, Yang, Weber, Bernd, Wen, Wei, Wierenga, Lara M., Williams, Steven C. R., Wu, Mon‐Ju, Zunta‐Soares, Giovana B., Bernhardt, Boris, Thompson, Paul, Frangou, Sophia, and Ge, Ruiyang
Abstract: Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5–90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8–80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9–25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5–40 and 40–90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.
Published: 2024

5. Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ):Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis

Author: Wannan, Cassandra M.J., Nelson, Barnaby, Addington, Jean, Allott, Kelly, Anticevic, Alan, Arango, Celso, Baker, Justin T., Bearden, Carrie E., Billah, Tashrif, Bouix, Sylvain, Broome, Matthew R., Buccilli, Kate, Cadenhead, Kristin S., Calkins, Monica E., Cannon, Tyrone D., Cecci, Guillermo, Chen, Eric Yu Hai, Cho, Kang Ik K., Choi, Jimmy, Clark, Scott R., Coleman, Michael J., Conus, Philippe, Corcoran, Cheryl M., Cornblatt, Barbara A., Diaz-Caneja, Covadonga M., Dwyer, Dominic, Ebdrup, Bjørn H., Ellman, Lauren M., Fusar-Poli, Paolo, Galindo, Liliana, Gaspar, Pablo A., Gerber, Carla, Glenthøj, Louise Birkedal, Glynn, Robert, Harms, Michael P., Horton, Leslie E., Kahn, René S., Kambeitz, Joseph, Kambeitz-Ilankovic, Lana, Kane, John M., Kapur, Tina, Keshavan, Matcheri S., Kim, Sung Wan, Koutsouleris, Nikolaos, Kubicki, Marek, Kwon, Jun Soo, Langbein, Kerstin, Lewandowski, Kathryn E., Light, Gregory A., Mamah, Daniel, Marcy, Patricia J., Mathalon, Daniel H., McGorry, Patrick D., Mittal, Vijay A., Nordentoft, Merete, Nunez, Angela, Pasternak, Ofer, Pearlson, Godfrey D., Perez, Jesus, Perkins, Diana O., Powers, Albert R., Roalf, David R., Sabb, Fred W., Schiffman, Jason, Shah, Jai L., Smesny, Stefan, Spark, Jessica, Stone, William S., Strauss, Gregory P., Tamayo, Zailyn, Torous, John, Upthegrove, Rachel, Vangel, Mark, Verma, Swapna, Wang, Jijun, Rossum, Inge Winter van, Wolf, Daniel H., Wolff, Phillip, Wood, Stephen J., Yung, Alison R., Agurto, Carla, Alvarez-Jimenez, Mario, Amminger, Paul, Armando, Marco, Asgari-Targhi, Ameneh, Cahill, John, Carrión, Ricardo E., Castro, Eduardo, Cetin-Karayumak, Suheyla, Mallar Chakravarty, M., Cho, Youngsun T., Cotter, David, D'Alfonso, Simon, Ennis, Michaela, Fadnavis, Shreyas, Fonteneau, Clara, Gao, Caroline, Gupta, Tina, Gur, Raquel E., Gur, Ruben C., Hamilton, Holly K., Hoftman, Gil D., Jacobs, Grace R., Jarcho, Johanna, Ji, Jie Lisa, Kohler, Christian G., Lalousis, Paris Alexandros, Lavoie, Suzie, Lepage, Martin, Liebenthal, Einat, Mervis, Josh, Murty, Vishnu, Nicholas, Spero C., Ning, Lipeng, Penzel, Nora, Poldrack, Russell, Polosecki, Pablo, Pratt, Danielle N., Rabin, Rachel, Rahimi Eichi, Habiballah, Rathi, Yogesh, Reichenberg, Avraham, Reinen, Jenna, Rogers, Jack, Ruiz-Yu, Bernalyn, Scott, Isabelle, Seitz-Holland, Johanna, Srihari, Vinod H., Srivastava, Agrima, Thompson, Andrew, Turetsky, Bruce I., Walsh, Barbara C., Whitford, Thomas, Wigman, Johanna T.W., Yao, Beier, Yuen, Hok Pan, Ahmed, Uzair, Byun, Andrew Jin Soo, Chung, Yoonho, Do, Kim, Hendricks, Larry, Huynh, Kevin, Jeffries, Clark, Lane, Erlend, Langholm, Carsten, Lin, Eric, Mantua, Valentina, Santorelli, Gennarina, Ruparel, Kosha, Zoupou, Eirini, Adasme, Tatiana, Addamo, Lauren, Adery, Laura, Ali, Munaza, Auther, Andrea, Aversa, Samantha, Baek, Seon Hwa, Bates, Kelly, Bathery, Alyssa, Bayer, Johanna M.M., Beedham, Rebecca, Bilgrami, Zarina, Birch, Sonia, Bonoldi, Ilaria, Borders, Owen, Borgatti, Renato, Brown, Lisa, Bruna, Alejandro, Carrington, Holly, Castillo-Passi, Rolando I., Chen, Justine, Cheng, Nicholas, Ching, Ann Ee, Clifford, Chloe, Colton, Beau Luke, Contreras, Pamela, Corral, Sebastián, Damiani, Stefano, Done, Monica, Estradé, Andrés, Etuka, Brandon Asika, Formica, Melanie, Furlan, Rachel, Geljic, Mia, Germano, Carmela, Getachew, Ruth, Goncalves, Mathias, Haidar, Anastasia, Hartmann, Jessica, Jo, Anna, John, Omar, Kerins, Sarah, Kerr, Melissa, Kesselring, Irena, Kim, Honey, Kim, Nicholas, Kinney, Kyle, Krcmar, Marija, Kotler, Elana, Lafanechere, Melanie, Lee, Clarice, Llerena, Joshua, Markiewicz, Christopher, Matnejl, Priya, Maturana, Alejandro, Mavambu, Aissata, Mayol-Troncoso, Rocío, McDonnell, Amelia, McGowan, Alessia, McLaughlin, Danielle, McIlhenny, Rebecca, McQueen, Brittany, Mebrahtu, Yohannes, Mensi, Martina, Hui, Christy Lai Ming, Suen, Yi Nam, Wong, Stephanie Ming Yin, Morrell, Neal, Omar, Mariam, Partridge, Alice, Phassouliotis, Christina, Pichiecchio, Anna, Politi, Pierluigi, Porter, Christian, Provenzani, Umberto, Prunier, Nicholas, Raj, Jasmine, Ray, Susan, Rayner, Victoria, Reyes, Manuel, Reynolds, Kate, Rush, Sage, Salinas, Cesar, Shetty, Jashmina, Snowball, Callum, Tod, Sophie, Turra-Fariña, Gabriel, Valle, Daniela, Veale, Simone, Whitson, Sarah, Wickham, Alana, Youn, Sarah, Zamorano, Francisco, Zavaglia, Elissa, Zinberg, Jamie, Woods, Scott W., Shenton, Martha E., Wannan, Cassandra M.J., Nelson, Barnaby, Addington, Jean, Allott, Kelly, Anticevic, Alan, Arango, Celso, Baker, Justin T., Bearden, Carrie E., Billah, Tashrif, Bouix, Sylvain, Broome, Matthew R., Buccilli, Kate, Cadenhead, Kristin S., Calkins, Monica E., Cannon, Tyrone D., Cecci, Guillermo, Chen, Eric Yu Hai, Cho, Kang Ik K., Choi, Jimmy, Clark, Scott R., Coleman, Michael J., Conus, Philippe, Corcoran, Cheryl M., Cornblatt, Barbara A., Diaz-Caneja, Covadonga M., Dwyer, Dominic, Ebdrup, Bjørn H., Ellman, Lauren M., Fusar-Poli, Paolo, Galindo, Liliana, Gaspar, Pablo A., Gerber, Carla, Glenthøj, Louise Birkedal, Glynn, Robert, Harms, Michael P., Horton, Leslie E., Kahn, René S., Kambeitz, Joseph, Kambeitz-Ilankovic, Lana, Kane, John M., Kapur, Tina, Keshavan, Matcheri S., Kim, Sung Wan, Koutsouleris, Nikolaos, Kubicki, Marek, Kwon, Jun Soo, Langbein, Kerstin, Lewandowski, Kathryn E., Light, Gregory A., Mamah, Daniel, Marcy, Patricia J., Mathalon, Daniel H., McGorry, Patrick D., Mittal, Vijay A., Nordentoft, Merete, Nunez, Angela, Pasternak, Ofer, Pearlson, Godfrey D., Perez, Jesus, Perkins, Diana O., Powers, Albert R., Roalf, David R., Sabb, Fred W., Schiffman, Jason, Shah, Jai L., Smesny, Stefan, Spark, Jessica, Stone, William S., Strauss, Gregory P., Tamayo, Zailyn, Torous, John, Upthegrove, Rachel, Vangel, Mark, Verma, Swapna, Wang, Jijun, Rossum, Inge Winter van, Wolf, Daniel H., Wolff, Phillip, Wood, Stephen J., Yung, Alison R., Agurto, Carla, Alvarez-Jimenez, Mario, Amminger, Paul, Armando, Marco, Asgari-Targhi, Ameneh, Cahill, John, Carrión, Ricardo E., Castro, Eduardo, Cetin-Karayumak, Suheyla, Mallar Chakravarty, M., Cho, Youngsun T., Cotter, David, D'Alfonso, Simon, Ennis, Michaela, Fadnavis, Shreyas, Fonteneau, Clara, Gao, Caroline, Gupta, Tina, Gur, Raquel E., Gur, Ruben C., Hamilton, Holly K., Hoftman, Gil D., Jacobs, Grace R., Jarcho, Johanna, Ji, Jie Lisa, Kohler, Christian G., Lalousis, Paris Alexandros, Lavoie, Suzie, Lepage, Martin, Liebenthal, Einat, Mervis, Josh, Murty, Vishnu, Nicholas, Spero C., Ning, Lipeng, Penzel, Nora, Poldrack, Russell, Polosecki, Pablo, Pratt, Danielle N., Rabin, Rachel, Rahimi Eichi, Habiballah, Rathi, Yogesh, Reichenberg, Avraham, Reinen, Jenna, Rogers, Jack, Ruiz-Yu, Bernalyn, Scott, Isabelle, Seitz-Holland, Johanna, Srihari, Vinod H., Srivastava, Agrima, Thompson, Andrew, Turetsky, Bruce I., Walsh, Barbara C., Whitford, Thomas, Wigman, Johanna T.W., Yao, Beier, Yuen, Hok Pan, Ahmed, Uzair, Byun, Andrew Jin Soo, Chung, Yoonho, Do, Kim, Hendricks, Larry, Huynh, Kevin, Jeffries, Clark, Lane, Erlend, Langholm, Carsten, Lin, Eric, Mantua, Valentina, Santorelli, Gennarina, Ruparel, Kosha, Zoupou, Eirini, Adasme, Tatiana, Addamo, Lauren, Adery, Laura, Ali, Munaza, Auther, Andrea, Aversa, Samantha, Baek, Seon Hwa, Bates, Kelly, Bathery, Alyssa, Bayer, Johanna M.M., Beedham, Rebecca, Bilgrami, Zarina, Birch, Sonia, Bonoldi, Ilaria, Borders, Owen, Borgatti, Renato, Brown, Lisa, Bruna, Alejandro, Carrington, Holly, Castillo-Passi, Rolando I., Chen, Justine, Cheng, Nicholas, Ching, Ann Ee, Clifford, Chloe, Colton, Beau Luke, Contreras, Pamela, Corral, Sebastián, Damiani, Stefano, Done, Monica, Estradé, Andrés, Etuka, Brandon Asika, Formica, Melanie, Furlan, Rachel, Geljic, Mia, Germano, Carmela, Getachew, Ruth, Goncalves, Mathias, Haidar, Anastasia, Hartmann, Jessica, Jo, Anna, John, Omar, Kerins, Sarah, Kerr, Melissa, Kesselring, Irena, Kim, Honey, Kim, Nicholas, Kinney, Kyle, Krcmar, Marija, Kotler, Elana, Lafanechere, Melanie, Lee, Clarice, Llerena, Joshua, Markiewicz, Christopher, Matnejl, Priya, Maturana, Alejandro, Mavambu, Aissata, Mayol-Troncoso, Rocío, McDonnell, Amelia, McGowan, Alessia, McLaughlin, Danielle, McIlhenny, Rebecca, McQueen, Brittany, Mebrahtu, Yohannes, Mensi, Martina, Hui, Christy Lai Ming, Suen, Yi Nam, Wong, Stephanie Ming Yin, Morrell, Neal, Omar, Mariam, Partridge, Alice, Phassouliotis, Christina, Pichiecchio, Anna, Politi, Pierluigi, Porter, Christian, Provenzani, Umberto, Prunier, Nicholas, Raj, Jasmine, Ray, Susan, Rayner, Victoria, Reyes, Manuel, Reynolds, Kate, Rush, Sage, Salinas, Cesar, Shetty, Jashmina, Snowball, Callum, Tod, Sophie, Turra-Fariña, Gabriel, Valle, Daniela, Veale, Simone, Whitson, Sarah, Wickham, Alana, Youn, Sarah, Zamorano, Francisco, Zavaglia, Elissa, Zinberg, Jamie, Woods, Scott W., and Shenton, Martha E.
Abstract: This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals., This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.
Published: 2024

6. Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ):Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis

Author: Wannan, Cassandra M.J., Nelson, Barnaby, Addington, Jean, Allott, Kelly, Anticevic, Alan, Arango, Celso, Baker, Justin T., Bearden, Carrie E., Billah, Tashrif, Bouix, Sylvain, Broome, Matthew R., Buccilli, Kate, Cadenhead, Kristin S., Calkins, Monica E., Cannon, Tyrone D., Cecci, Guillermo, Chen, Eric Yu Hai, Cho, Kang Ik K., Choi, Jimmy, Clark, Scott R., Coleman, Michael J., Conus, Philippe, Corcoran, Cheryl M., Cornblatt, Barbara A., Diaz-Caneja, Covadonga M., Dwyer, Dominic, Ebdrup, Bjørn H., Ellman, Lauren M., Fusar-Poli, Paolo, Galindo, Liliana, Gaspar, Pablo A., Gerber, Carla, Glenthøj, Louise Birkedal, Glynn, Robert, Harms, Michael P., Horton, Leslie E., Kahn, René S., Kambeitz, Joseph, Kambeitz-Ilankovic, Lana, Kane, John M., Kapur, Tina, Keshavan, Matcheri S., Kim, Sung Wan, Koutsouleris, Nikolaos, Kubicki, Marek, Kwon, Jun Soo, Langbein, Kerstin, Lewandowski, Kathryn E., Light, Gregory A., Mamah, Daniel, Marcy, Patricia J., Mathalon, Daniel H., McGorry, Patrick D., Mittal, Vijay A., Nordentoft, Merete, Nunez, Angela, Pasternak, Ofer, Pearlson, Godfrey D., Perez, Jesus, Perkins, Diana O., Powers, Albert R., Roalf, David R., Sabb, Fred W., Schiffman, Jason, Shah, Jai L., Smesny, Stefan, Spark, Jessica, Stone, William S., Strauss, Gregory P., Tamayo, Zailyn, Torous, John, Upthegrove, Rachel, Vangel, Mark, Verma, Swapna, Wang, Jijun, Rossum, Inge Winter van, Wolf, Daniel H., Wolff, Phillip, Wood, Stephen J., Yung, Alison R., Agurto, Carla, Alvarez-Jimenez, Mario, Amminger, Paul, Armando, Marco, Asgari-Targhi, Ameneh, Cahill, John, Carrión, Ricardo E., Castro, Eduardo, Cetin-Karayumak, Suheyla, Mallar Chakravarty, M., Cho, Youngsun T., Cotter, David, D'Alfonso, Simon, Ennis, Michaela, Fadnavis, Shreyas, Fonteneau, Clara, Gao, Caroline, Gupta, Tina, Gur, Raquel E., Gur, Ruben C., Hamilton, Holly K., Hoftman, Gil D., Jacobs, Grace R., Jarcho, Johanna, Ji, Jie Lisa, Kohler, Christian G., Lalousis, Paris Alexandros, Lavoie, Suzie, Lepage, Martin, Liebenthal, Einat, Mervis, Josh, Murty, Vishnu, Nicholas, Spero C., Ning, Lipeng, Penzel, Nora, Poldrack, Russell, Polosecki, Pablo, Pratt, Danielle N., Rabin, Rachel, Rahimi Eichi, Habiballah, Rathi, Yogesh, Reichenberg, Avraham, Reinen, Jenna, Rogers, Jack, Ruiz-Yu, Bernalyn, Scott, Isabelle, Seitz-Holland, Johanna, Srihari, Vinod H., Srivastava, Agrima, Thompson, Andrew, Turetsky, Bruce I., Walsh, Barbara C., Whitford, Thomas, Wigman, Johanna T.W., Yao, Beier, Yuen, Hok Pan, Ahmed, Uzair, Byun, Andrew Jin Soo, Chung, Yoonho, Do, Kim, Hendricks, Larry, Huynh, Kevin, Jeffries, Clark, Lane, Erlend, Langholm, Carsten, Lin, Eric, Mantua, Valentina, Santorelli, Gennarina, Ruparel, Kosha, Zoupou, Eirini, Adasme, Tatiana, Addamo, Lauren, Adery, Laura, Ali, Munaza, Auther, Andrea, Aversa, Samantha, Baek, Seon Hwa, Bates, Kelly, Bathery, Alyssa, Bayer, Johanna M.M., Beedham, Rebecca, Bilgrami, Zarina, Birch, Sonia, Bonoldi, Ilaria, Borders, Owen, Borgatti, Renato, Brown, Lisa, Bruna, Alejandro, Carrington, Holly, Castillo-Passi, Rolando I., Chen, Justine, Cheng, Nicholas, Ching, Ann Ee, Clifford, Chloe, Colton, Beau Luke, Contreras, Pamela, Corral, Sebastián, Damiani, Stefano, Done, Monica, Estradé, Andrés, Etuka, Brandon Asika, Formica, Melanie, Furlan, Rachel, Geljic, Mia, Germano, Carmela, Getachew, Ruth, Goncalves, Mathias, Haidar, Anastasia, Hartmann, Jessica, Jo, Anna, John, Omar, Kerins, Sarah, Kerr, Melissa, Kesselring, Irena, Kim, Honey, Kim, Nicholas, Kinney, Kyle, Krcmar, Marija, Kotler, Elana, Lafanechere, Melanie, Lee, Clarice, Llerena, Joshua, Markiewicz, Christopher, Matnejl, Priya, Maturana, Alejandro, Mavambu, Aissata, Mayol-Troncoso, Rocío, McDonnell, Amelia, McGowan, Alessia, McLaughlin, Danielle, McIlhenny, Rebecca, McQueen, Brittany, Mebrahtu, Yohannes, Mensi, Martina, Hui, Christy Lai Ming, Suen, Yi Nam, Wong, Stephanie Ming Yin, Morrell, Neal, Omar, Mariam, Partridge, Alice, Phassouliotis, Christina, Pichiecchio, Anna, Politi, Pierluigi, Porter, Christian, Provenzani, Umberto, Prunier, Nicholas, Raj, Jasmine, Ray, Susan, Rayner, Victoria, Reyes, Manuel, Reynolds, Kate, Rush, Sage, Salinas, Cesar, Shetty, Jashmina, Snowball, Callum, Tod, Sophie, Turra-Fariña, Gabriel, Valle, Daniela, Veale, Simone, Whitson, Sarah, Wickham, Alana, Youn, Sarah, Zamorano, Francisco, Zavaglia, Elissa, Zinberg, Jamie, Woods, Scott W., Shenton, Martha E., Wannan, Cassandra M.J., Nelson, Barnaby, Addington, Jean, Allott, Kelly, Anticevic, Alan, Arango, Celso, Baker, Justin T., Bearden, Carrie E., Billah, Tashrif, Bouix, Sylvain, Broome, Matthew R., Buccilli, Kate, Cadenhead, Kristin S., Calkins, Monica E., Cannon, Tyrone D., Cecci, Guillermo, Chen, Eric Yu Hai, Cho, Kang Ik K., Choi, Jimmy, Clark, Scott R., Coleman, Michael J., Conus, Philippe, Corcoran, Cheryl M., Cornblatt, Barbara A., Diaz-Caneja, Covadonga M., Dwyer, Dominic, Ebdrup, Bjørn H., Ellman, Lauren M., Fusar-Poli, Paolo, Galindo, Liliana, Gaspar, Pablo A., Gerber, Carla, Glenthøj, Louise Birkedal, Glynn, Robert, Harms, Michael P., Horton, Leslie E., Kahn, René S., Kambeitz, Joseph, Kambeitz-Ilankovic, Lana, Kane, John M., Kapur, Tina, Keshavan, Matcheri S., Kim, Sung Wan, Koutsouleris, Nikolaos, Kubicki, Marek, Kwon, Jun Soo, Langbein, Kerstin, Lewandowski, Kathryn E., Light, Gregory A., Mamah, Daniel, Marcy, Patricia J., Mathalon, Daniel H., McGorry, Patrick D., Mittal, Vijay A., Nordentoft, Merete, Nunez, Angela, Pasternak, Ofer, Pearlson, Godfrey D., Perez, Jesus, Perkins, Diana O., Powers, Albert R., Roalf, David R., Sabb, Fred W., Schiffman, Jason, Shah, Jai L., Smesny, Stefan, Spark, Jessica, Stone, William S., Strauss, Gregory P., Tamayo, Zailyn, Torous, John, Upthegrove, Rachel, Vangel, Mark, Verma, Swapna, Wang, Jijun, Rossum, Inge Winter van, Wolf, Daniel H., Wolff, Phillip, Wood, Stephen J., Yung, Alison R., Agurto, Carla, Alvarez-Jimenez, Mario, Amminger, Paul, Armando, Marco, Asgari-Targhi, Ameneh, Cahill, John, Carrión, Ricardo E., Castro, Eduardo, Cetin-Karayumak, Suheyla, Mallar Chakravarty, M., Cho, Youngsun T., Cotter, David, D'Alfonso, Simon, Ennis, Michaela, Fadnavis, Shreyas, Fonteneau, Clara, Gao, Caroline, Gupta, Tina, Gur, Raquel E., Gur, Ruben C., Hamilton, Holly K., Hoftman, Gil D., Jacobs, Grace R., Jarcho, Johanna, Ji, Jie Lisa, Kohler, Christian G., Lalousis, Paris Alexandros, Lavoie, Suzie, Lepage, Martin, Liebenthal, Einat, Mervis, Josh, Murty, Vishnu, Nicholas, Spero C., Ning, Lipeng, Penzel, Nora, Poldrack, Russell, Polosecki, Pablo, Pratt, Danielle N., Rabin, Rachel, Rahimi Eichi, Habiballah, Rathi, Yogesh, Reichenberg, Avraham, Reinen, Jenna, Rogers, Jack, Ruiz-Yu, Bernalyn, Scott, Isabelle, Seitz-Holland, Johanna, Srihari, Vinod H., Srivastava, Agrima, Thompson, Andrew, Turetsky, Bruce I., Walsh, Barbara C., Whitford, Thomas, Wigman, Johanna T.W., Yao, Beier, Yuen, Hok Pan, Ahmed, Uzair, Byun, Andrew Jin Soo, Chung, Yoonho, Do, Kim, Hendricks, Larry, Huynh, Kevin, Jeffries, Clark, Lane, Erlend, Langholm, Carsten, Lin, Eric, Mantua, Valentina, Santorelli, Gennarina, Ruparel, Kosha, Zoupou, Eirini, Adasme, Tatiana, Addamo, Lauren, Adery, Laura, Ali, Munaza, Auther, Andrea, Aversa, Samantha, Baek, Seon Hwa, Bates, Kelly, Bathery, Alyssa, Bayer, Johanna M.M., Beedham, Rebecca, Bilgrami, Zarina, Birch, Sonia, Bonoldi, Ilaria, Borders, Owen, Borgatti, Renato, Brown, Lisa, Bruna, Alejandro, Carrington, Holly, Castillo-Passi, Rolando I., Chen, Justine, Cheng, Nicholas, Ching, Ann Ee, Clifford, Chloe, Colton, Beau Luke, Contreras, Pamela, Corral, Sebastián, Damiani, Stefano, Done, Monica, Estradé, Andrés, Etuka, Brandon Asika, Formica, Melanie, Furlan, Rachel, Geljic, Mia, Germano, Carmela, Getachew, Ruth, Goncalves, Mathias, Haidar, Anastasia, Hartmann, Jessica, Jo, Anna, John, Omar, Kerins, Sarah, Kerr, Melissa, Kesselring, Irena, Kim, Honey, Kim, Nicholas, Kinney, Kyle, Krcmar, Marija, Kotler, Elana, Lafanechere, Melanie, Lee, Clarice, Llerena, Joshua, Markiewicz, Christopher, Matnejl, Priya, Maturana, Alejandro, Mavambu, Aissata, Mayol-Troncoso, Rocío, McDonnell, Amelia, McGowan, Alessia, McLaughlin, Danielle, McIlhenny, Rebecca, McQueen, Brittany, Mebrahtu, Yohannes, Mensi, Martina, Hui, Christy Lai Ming, Suen, Yi Nam, Wong, Stephanie Ming Yin, Morrell, Neal, Omar, Mariam, Partridge, Alice, Phassouliotis, Christina, Pichiecchio, Anna, Politi, Pierluigi, Porter, Christian, Provenzani, Umberto, Prunier, Nicholas, Raj, Jasmine, Ray, Susan, Rayner, Victoria, Reyes, Manuel, Reynolds, Kate, Rush, Sage, Salinas, Cesar, Shetty, Jashmina, Snowball, Callum, Tod, Sophie, Turra-Fariña, Gabriel, Valle, Daniela, Veale, Simone, Whitson, Sarah, Wickham, Alana, Youn, Sarah, Zamorano, Francisco, Zavaglia, Elissa, Zinberg, Jamie, Woods, Scott W., and Shenton, Martha E.
Abstract: This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals., This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.
Published: 2024

7. Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group

Author: UCL - SSH/IPSY - Psychological Sciences Research Institute, UCL - SSS/IONS/NEUR - Clinical Neuroscience, Groenewold, Nynke A., Bas-Hoogendam, Janna Marie, Amod, Alyssa R., Laansma, Max A., Van Velzen, Laura S., Aghajani, Moji, Hilbert, Kevin, Oh, Hyuntaek, Salas, Ramiro, Jackowski, Andrea P., Pan, Pedro M., Salum, Giovanni A., Blair, James R., Blair, Karina S., Hirsch, Joy, Pantazatos, Spiro P., Schneier, Franklin R., Talati, Ardesheer, Roelofs, Karin, Volman, Inge, Blanco-Hinojo, Laura, Cardoner, Narcís, Pujol, Jesus, Beesdo-Baum, Katja, Ching, Christopher R. K., Thomopoulos, Sophia I., Jansen, Andreas, Kircher, Tilo, Krug, Axel, Nenadić, Igor, Stein, Frederike, Dannlowski, Udo, Grotegerd, Dominik, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Erb, Michael, Kreifelts, Benjamin, Gong, Qiyong, Lui, Su, Zhu, Fei, Mwangi, Benson, Soares, Jair C., Wu, Mon-Ju, Bayram, Ali, Canli, Mesut, Tükel, Raşit, Westenberg, P. Michiel, Heeren, Alexandre, Cremers, Henk R., Hofmann, David, Straube, Thomas, Doruyter, Alexander G. G., Lochner, Christine, Peterburs, Jutta, Van Tol, Marie-José, Gur, Raquel E., Kaczkurkin, Antonia N., Larsen, Bart, Satterthwaite, Theodore D., Filippi, Courtney A., Gold, Andrea L., Harrewijn, Anita, Zugman, André, Bülow, Robin, Grabe, Hans J., Völzke, Henry, Wittfeld, Katharina, Böhnlein, Joscha, Dohm, Katharina, Kugel, Harald, Schrammen, Elisabeth, Zwanzger, Peter, Leehr, Elisabeth J., Sindermann, Lisa, Ball, Tali M., Fonzo, Gregory A., Paulus, Martin P., Simmons, Alan, Stein, Murray B., Klumpp, Heide, Phan, K. Luan, Furmark, Tomas, Månsson, Kristoffer N. T., Manzouri, Amirhossein, Avery, Suzanne N., Blackford, Jennifer Urbano, Clauss, Jacqueline A., Feola, Brandee, Harper, Jennifer C., Sylvester, Chad M., Lueken, Ulrike, Veltman, Dick J., Winkler, Anderson M., Jahanshad, Neda, Pine, Daniel S., Thompson, Paul M., Stein, Dan J., Van der Wee, Nic J. A., UCL - SSH/IPSY - Psychological Sciences Research Institute, UCL - SSS/IONS/NEUR - Clinical Neuroscience, Groenewold, Nynke A., Bas-Hoogendam, Janna Marie, Amod, Alyssa R., Laansma, Max A., Van Velzen, Laura S., Aghajani, Moji, Hilbert, Kevin, Oh, Hyuntaek, Salas, Ramiro, Jackowski, Andrea P., Pan, Pedro M., Salum, Giovanni A., Blair, James R., Blair, Karina S., Hirsch, Joy, Pantazatos, Spiro P., Schneier, Franklin R., Talati, Ardesheer, Roelofs, Karin, Volman, Inge, Blanco-Hinojo, Laura, Cardoner, Narcís, Pujol, Jesus, Beesdo-Baum, Katja, Ching, Christopher R. K., Thomopoulos, Sophia I., Jansen, Andreas, Kircher, Tilo, Krug, Axel, Nenadić, Igor, Stein, Frederike, Dannlowski, Udo, Grotegerd, Dominik, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Erb, Michael, Kreifelts, Benjamin, Gong, Qiyong, Lui, Su, Zhu, Fei, Mwangi, Benson, Soares, Jair C., Wu, Mon-Ju, Bayram, Ali, Canli, Mesut, Tükel, Raşit, Westenberg, P. Michiel, Heeren, Alexandre, Cremers, Henk R., Hofmann, David, Straube, Thomas, Doruyter, Alexander G. G., Lochner, Christine, Peterburs, Jutta, Van Tol, Marie-José, Gur, Raquel E., Kaczkurkin, Antonia N., Larsen, Bart, Satterthwaite, Theodore D., Filippi, Courtney A., Gold, Andrea L., Harrewijn, Anita, Zugman, André, Bülow, Robin, Grabe, Hans J., Völzke, Henry, Wittfeld, Katharina, Böhnlein, Joscha, Dohm, Katharina, Kugel, Harald, Schrammen, Elisabeth, Zwanzger, Peter, Leehr, Elisabeth J., Sindermann, Lisa, Ball, Tali M., Fonzo, Gregory A., Paulus, Martin P., Simmons, Alan, Stein, Murray B., Klumpp, Heide, Phan, K. Luan, Furmark, Tomas, Månsson, Kristoffer N. T., Manzouri, Amirhossein, Avery, Suzanne N., Blackford, Jennifer Urbano, Clauss, Jacqueline A., Feola, Brandee, Harper, Jennifer C., Sylvester, Chad M., Lueken, Ulrike, Veltman, Dick J., Winkler, Anderson M., Jahanshad, Neda, Pine, Daniel S., Thompson, Paul M., Stein, Dan J., and Van der Wee, Nic J. A.
Abstract: There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE < 0.001; right: d = −0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.
Published: 2023

8. Volume of subcortical brain regions in social anxiety disorder : mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group

Author: Groenewold, Nynke A., Bas-Hoogendam, Janna Marie, Amod, Alyssa R., Laansma, Max A., Van Velzen, Laura S., Aghajani, Moji, Hilbert, Kevin, Oh, Hyuntaek, Salas, Ramiro, Jackowski, Andrea P., Pan, Pedro M., Salum, Giovanni A., Blair, James R., Blair, Karina S., Hirsch, Joy, Pantazatos, Spiro P., Schneier, Franklin R., Talati, Ardesheer, Roelofs, Karin, Volman, Inge, Blanco-Hinojo, Laura, Cardoner, Narcís, Pujol, Jesus, Beesdo-Baum, Katja, Ching, Christopher R. K., Thomopoulos, Sophia I., Jansen, Andreas, Kircher, Tilo, Krug, Axel, Nenadić, Igor, Stein, Frederike, Dannlowski, Udo, Grotegerd, Dominik, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Erb, Michael, Kreifelts, Benjamin, Gong, Qiyong, Lui, Su, Zhu, Fei, Mwangi, Benson, Soares, Jair C., Wu, Mon-Ju, Bayram, Ali, Canli, Mesut, Tükel, Raşit, Westenberg, P. Michiel, Heeren, Alexandre, Cremers, Henk R., Hofmann, David, Straube, Thomas, Doruyter, Alexander G. G., Lochner, Christine, Peterburs, Jutta, Van Tol, Marie-José, Gur, Raquel E., Kaczkurkin, Antonia N., Larsen, Bart, Satterthwaite, Theodore D., Filippi, Courtney A., Gold, Andrea L., Harrewijn, Anita, Zugman, André, Bülow, Robin, Grabe, Hans J., Völzke, Henry, Wittfeld, Katharina, Böhnlein, Joscha, Dohm, Katharina, Kugel, Harald, Schrammen, Elisabeth, Zwanzger, Peter, Leehr, Elisabeth J., Sindermann, Lisa, Ball, Tali M., Fonzo, Gregory A., Paulus, Martin P., Simmons, Alan, Stein, Murray B., Klumpp, Heide, Phan, K. Luan, Furmark, Tomas, Månsson, Kristoffer N. T., Manzouri, Amirhossein, Avery, Suzanne N., Blackford, Jennifer Urbano, Clauss, Jacqueline A., Feola, Brandee, Harper, Jennifer C., Sylvester, Chad M., Lueken, Ulrike, Veltman, Dick J., Winkler, Anderson M., Jahanshad, Neda, Pine, Daniel S., Thompson, Paul M., Stein, Dan J., Van der Wee, Nic J. A., Groenewold, Nynke A., Bas-Hoogendam, Janna Marie, Amod, Alyssa R., Laansma, Max A., Van Velzen, Laura S., Aghajani, Moji, Hilbert, Kevin, Oh, Hyuntaek, Salas, Ramiro, Jackowski, Andrea P., Pan, Pedro M., Salum, Giovanni A., Blair, James R., Blair, Karina S., Hirsch, Joy, Pantazatos, Spiro P., Schneier, Franklin R., Talati, Ardesheer, Roelofs, Karin, Volman, Inge, Blanco-Hinojo, Laura, Cardoner, Narcís, Pujol, Jesus, Beesdo-Baum, Katja, Ching, Christopher R. K., Thomopoulos, Sophia I., Jansen, Andreas, Kircher, Tilo, Krug, Axel, Nenadić, Igor, Stein, Frederike, Dannlowski, Udo, Grotegerd, Dominik, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Erb, Michael, Kreifelts, Benjamin, Gong, Qiyong, Lui, Su, Zhu, Fei, Mwangi, Benson, Soares, Jair C., Wu, Mon-Ju, Bayram, Ali, Canli, Mesut, Tükel, Raşit, Westenberg, P. Michiel, Heeren, Alexandre, Cremers, Henk R., Hofmann, David, Straube, Thomas, Doruyter, Alexander G. G., Lochner, Christine, Peterburs, Jutta, Van Tol, Marie-José, Gur, Raquel E., Kaczkurkin, Antonia N., Larsen, Bart, Satterthwaite, Theodore D., Filippi, Courtney A., Gold, Andrea L., Harrewijn, Anita, Zugman, André, Bülow, Robin, Grabe, Hans J., Völzke, Henry, Wittfeld, Katharina, Böhnlein, Joscha, Dohm, Katharina, Kugel, Harald, Schrammen, Elisabeth, Zwanzger, Peter, Leehr, Elisabeth J., Sindermann, Lisa, Ball, Tali M., Fonzo, Gregory A., Paulus, Martin P., Simmons, Alan, Stein, Murray B., Klumpp, Heide, Phan, K. Luan, Furmark, Tomas, Månsson, Kristoffer N. T., Manzouri, Amirhossein, Avery, Suzanne N., Blackford, Jennifer Urbano, Clauss, Jacqueline A., Feola, Brandee, Harper, Jennifer C., Sylvester, Chad M., Lueken, Ulrike, Veltman, Dick J., Winkler, Anderson M., Jahanshad, Neda, Pine, Daniel S., Thompson, Paul M., Stein, Dan J., and Van der Wee, Nic J. A.
Abstract: There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE < 0.001; right: d = −0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adul
Published: 2023
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9. Chromatin regulators in the TBX1 network confer risk for conotruncal heart defects in 22q11.2DS.

Author: Zhao, Yingjie, Zhao, Yingjie, Wang, Yujue, Shi, Lijie, McDonald-McGinn, Donna, Crowley, T, McGinn, Daniel, Tran, Oanh, Miller, Daniella, Lin, Jhih-Rong, Zackai, Elaine, Johnston, H, Chow, Eva, Vorstman, Jacob, Vingerhoets, Claudia, van Amelsvoort, Therese, Gothelf, Doron, Swillen, Ann, Breckpot, Jeroen, Vermeesch, Joris, Eliez, Stephan, Schneider, Maude, van den Bree, Marianne, Owen, Michael, Kates, Wendy, Repetto, Gabriela, Shashi, Vandana, Schoch, Kelly, Digilio, M, Unolt, Marta, Putotto, Carolina, Marino, Bruno, Pontillo, Maria, Armando, Marco, Vicari, Stefano, Angkustsiri, Kathleen, Campbell, Linda, Busa, Tiffany, Heine-Suñer, Damian, Murphy, Kieran, Murphy, Declan, García-Miñaúr, Sixto, Fernández, Luis, Zhang, Zhengdong, Goldmuntz, Elizabeth, Gur, Raquel, Emanuel, Beverly, Zheng, Deyou, Marshall, Christian, Bassett, Anne, Wang, Tao, Morrow, Bernice, Bearden, Carrie, Zhao, Yingjie, Zhao, Yingjie, Wang, Yujue, Shi, Lijie, McDonald-McGinn, Donna, Crowley, T, McGinn, Daniel, Tran, Oanh, Miller, Daniella, Lin, Jhih-Rong, Zackai, Elaine, Johnston, H, Chow, Eva, Vorstman, Jacob, Vingerhoets, Claudia, van Amelsvoort, Therese, Gothelf, Doron, Swillen, Ann, Breckpot, Jeroen, Vermeesch, Joris, Eliez, Stephan, Schneider, Maude, van den Bree, Marianne, Owen, Michael, Kates, Wendy, Repetto, Gabriela, Shashi, Vandana, Schoch, Kelly, Digilio, M, Unolt, Marta, Putotto, Carolina, Marino, Bruno, Pontillo, Maria, Armando, Marco, Vicari, Stefano, Angkustsiri, Kathleen, Campbell, Linda, Busa, Tiffany, Heine-Suñer, Damian, Murphy, Kieran, Murphy, Declan, García-Miñaúr, Sixto, Fernández, Luis, Zhang, Zhengdong, Goldmuntz, Elizabeth, Gur, Raquel, Emanuel, Beverly, Zheng, Deyou, Marshall, Christian, Bassett, Anne, Wang, Tao, Morrow, Bernice, and Bearden, Carrie
Abstract: Congenital heart disease (CHD) affecting the conotruncal region of the heart, occurs in 40-50% of patients with 22q11.2 deletion syndrome (22q11.2DS). This syndrome is a rare disorder with relative genetic homogeneity that can facilitate identification of genetic modifiers. Haploinsufficiency of TBX1, encoding a T-box transcription factor, is one of the main genes responsible for the etiology of the syndrome. We suggest that genetic modifiers of conotruncal defects in patients with 22q11.2DS may be in the TBX1 gene network. To identify genetic modifiers, we analyzed rare, predicted damaging variants in whole genome sequence of 456 cases with conotruncal defects and 537 controls, with 22q11.2DS. We then performed gene set approaches and identified chromatin regulatory genes as modifiers. Chromatin genes with recurrent damaging variants include EP400, KAT6A, KMT2C, KMT2D, NSD1, CHD7 and PHF21A. In total, we identified 37 chromatin regulatory genes, that may increase risk for conotruncal heart defects in 8.5% of 22q11.2DS cases. Many of these genes were identified as risk factors for sporadic CHD in the general population. These genes are co-expressed in cardiac progenitor cells with TBX1, suggesting that they may be in the same genetic network. The genes KAT6A, KMT2C, CHD7 and EZH2, have been previously shown to genetically interact with TBX1 in mouse models. Our findings indicate that disturbance of chromatin regulatory genes impact the TBX1 gene network serving as genetic modifiers of 22q11.2DS and sporadic CHD, suggesting that there are some shared mechanisms involving the TBX1 gene network in the etiology of CHD.
Published: 2023

10. Alprazolam modulates persistence energy during emotion processing in first-degree relatives of individuals with schizophrenia: a network control study.

Author: Parkes, Linden, Parkes, Linden, Larsen, Bart, Adebimpe, Azeez, Kahn, Ari, Gur, Ruben, Gur, Raquel, Satterthwaite, Theodore, Wolf, Daniel, Bassett, Dani, Mahadevan, Arun, Cornblath, Eli, Lydon-Staley, David, Zhou, Dale, Parkes, Linden, Parkes, Linden, Larsen, Bart, Adebimpe, Azeez, Kahn, Ari, Gur, Ruben, Gur, Raquel, Satterthwaite, Theodore, Wolf, Daniel, Bassett, Dani, Mahadevan, Arun, Cornblath, Eli, Lydon-Staley, David, and Zhou, Dale
Abstract: Schizophrenia is marked by deficits in facial affect processing associated with abnormalities in GABAergic circuitry, deficits also found in first-degree relatives. Facial affect processing involves a distributed network of brain regions including limbic regions like amygdala and visual processing areas like fusiform cortex. Pharmacological modulation of GABAergic circuitry using benzodiazepines like alprazolam can be useful for studying this facial affect processing network and associated GABAergic abnormalities in schizophrenia. Here, we use pharmacological modulation and computational modeling to study the contribution of GABAergic abnormalities toward emotion processing deficits in schizophrenia. Specifically, we apply principles from network control theory to model persistence energy - the control energy required to maintain brain activation states - during emotion identification and recall tasks, with and without administration of alprazolam, in a sample of first-degree relatives and healthy controls. Here, persistence energy quantifies the magnitude of theoretical external inputs during the task. We find that alprazolam increases persistence energy in relatives but not in controls during threatening face processing, suggesting a compensatory mechanism given the relative absence of behavioral abnormalities in this sample of unaffected relatives. Further, we demonstrate that regions in the fusiform and occipital cortices are important for facilitating state transitions during facial affect processing. Finally, we uncover spatial relationships (i) between regional variation in differential control energy (alprazolam versus placebo) and (ii) both serotonin and dopamine neurotransmitter systems, indicating that alprazolam may exert its effects by altering neuromodulatory systems. Together, these findings provide a new perspective on the distributed emotion processing network and the effect of GABAergic modulation on this network, in addition to identifying an asso
Published: 2023

11. Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium

Author: Onderzoek, Brain, Dwyer, Dominic B, Chand, Ganesh B, Pigoni, Alessandro, Khuntia, Adyasha, Wen, Junhao, Antoniades, Mathilde, Hwang, Gyujoon, Erus, Guray, Doshi, Jimit, Srinivasan, Dhivya, Varol, Erdem, Kahn, Rene S, Schnack, Hugo G, Meisenzahl, Eva, Wood, Stephen J, Zhuo, Chuanjun, Sotiras, Aristeidis, Shinohara, Russell T, Shou, Haochang, Fan, Yong, Schaulfelberger, Maristela, Rosa, Pedro, Lalousis, Paris A, Upthegrove, Rachel, Kaczkurkin, Antonia N, Moore, Tyler M, Nelson, Barnaby, Gur, Raquel E, Gur, Ruben C, Ritchie, Marylyn D, Satterthwaite, Theodore D, Murray, Robin M, Di Forti, Marta, Ciufolini, Simone, Zanetti, Marcus V, Wolf, Daniel H, Pantelis, Christos, Crespo-Facorro, Benedicto, Busatto, Geraldo F, Davatzikos, Christos, Koutsouleris, Nikolaos, Dazzan, Paola, Onderzoek, Brain, Dwyer, Dominic B, Chand, Ganesh B, Pigoni, Alessandro, Khuntia, Adyasha, Wen, Junhao, Antoniades, Mathilde, Hwang, Gyujoon, Erus, Guray, Doshi, Jimit, Srinivasan, Dhivya, Varol, Erdem, Kahn, Rene S, Schnack, Hugo G, Meisenzahl, Eva, Wood, Stephen J, Zhuo, Chuanjun, Sotiras, Aristeidis, Shinohara, Russell T, Shou, Haochang, Fan, Yong, Schaulfelberger, Maristela, Rosa, Pedro, Lalousis, Paris A, Upthegrove, Rachel, Kaczkurkin, Antonia N, Moore, Tyler M, Nelson, Barnaby, Gur, Raquel E, Gur, Ruben C, Ritchie, Marylyn D, Satterthwaite, Theodore D, Murray, Robin M, Di Forti, Marta, Ciufolini, Simone, Zanetti, Marcus V, Wolf, Daniel H, Pantelis, Christos, Crespo-Facorro, Benedicto, Busatto, Geraldo F, Davatzikos, Christos, Koutsouleris, Nikolaos, and Dazzan, Paola
Published: 2023

12. Assessment of Neuroanatomical Endophenotypes of Autism Spectrum Disorder and Association With Characteristics of Individuals With Schizophrenia and the General Population

Author: Onderzoek, Brain, Hwang, Gyujoon, Wen, Junhao, Sotardi, Susan, Brodkin, Edward S, Chand, Ganesh B, Dwyer, Dominic B, Erus, Guray, Doshi, Jimit, Singhal, Pankhuri, Srinivasan, Dhivya, Varol, Erdem, Sotiras, Aristeidis, Dazzan, Paola, Kahn, Rene S, Schnack, Hugo G, Zanetti, Marcus V, Meisenzahl, Eva, Busatto, Geraldo F, Crespo-Facorro, Benedicto, Pantelis, Christos, Wood, Stephen J, Zhuo, Chuanjun, Shinohara, Russell T, Shou, Haochang, Fan, Yong, Di Martino, Adriana, Koutsouleris, Nikolaos, Gur, Raquel E, Gur, Ruben C, Satterthwaite, Theodore D, Wolf, Daniel H, Davatzikos, Christos, Onderzoek, Brain, Hwang, Gyujoon, Wen, Junhao, Sotardi, Susan, Brodkin, Edward S, Chand, Ganesh B, Dwyer, Dominic B, Erus, Guray, Doshi, Jimit, Singhal, Pankhuri, Srinivasan, Dhivya, Varol, Erdem, Sotiras, Aristeidis, Dazzan, Paola, Kahn, Rene S, Schnack, Hugo G, Zanetti, Marcus V, Meisenzahl, Eva, Busatto, Geraldo F, Crespo-Facorro, Benedicto, Pantelis, Christos, Wood, Stephen J, Zhuo, Chuanjun, Shinohara, Russell T, Shou, Haochang, Fan, Yong, Di Martino, Adriana, Koutsouleris, Nikolaos, Gur, Raquel E, Gur, Ruben C, Satterthwaite, Theodore D, Wolf, Daniel H, and Davatzikos, Christos
Published: 2023

13. Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group

Author: Groenewold, Nynke A, Bas-Hoogendam, Janna Marie, Amod, Alyssa R, Laansma, Max A, Van Velzen, Laura S, Aghajani, Moji, Hilbert, Kevin, Oh, Hyuntaek, Salas, Ramiro, Jackowski, Andrea P, Pan, Pedro M, Salum, Giovanni A, Blair, James R, Blair, Karina S, Hirsch, Joy, Pantazatos, Spiro P, Schneier, Franklin R, Talati, Ardesheer, Roelofs, Karin, Volman, Inge, Blanco-Hinojo, Laura, Cardoner, Narcís, Pujol, Jesus, Beesdo-Baum, Katja, Ching, Christopher R K, Thomopoulos, Sophia I, Jansen, Andreas, Kircher, Tilo, Krug, Axel, Nenadić, Igor, Stein, Frederike, Dannlowski, Udo, Grotegerd, Dominik, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Erb, Michael, Kreifelts, Benjamin, Gong, Qiyong, Lui, Su, Zhu, Fei, Mwangi, Benson, Soares, Jair C, Wu, Mon-Ju, Bayram, Ali, Canli, Mesut, Tükel, Raşit, Westenberg, P Michiel, Heeren, Alexandre, Cremers, Henk R, Hofmann, David, Straube, Thomas, Doruyter, Alexander G G, Lochner, Christine, Peterburs, Jutta, Van Tol, Marie-José, Gur, Raquel E, Kaczkurkin, Antonia N, Larsen, Bart, Satterthwaite, Theodore D, Filippi, Courtney A, Gold, Andrea L, Harrewijn, Anita, Zugman, André, Bülow, Robin, Grabe, Hans J, Völzke, Henry, Wittfeld, Katharina, Böhnlein, Joscha, Dohm, Katharina, Kugel, Harald, Schrammen, Elisabeth, Zwanzger, Peter, Leehr, Elisabeth J, Sindermann, Lisa, Ball, Tali M, Fonzo, Gregory A, Paulus, Martin P, Simmons, Alan, Stein, Murray B, Klumpp, Heide, Phan, K Luan, Furmark, Tomas, Månsson, Kristoffer N T, Manzouri, Amirhossein, Avery, Suzanne N, Blackford, Jennifer Urbano, Clauss, Jacqueline A, Feola, Brandee, Harper, Jennifer C, Sylvester, Chad M, Lueken, Ulrike, Veltman, Dick J, Winkler, Anderson M, Jahanshad, Neda, Pine, Daniel S, Thompson, Paul M, Stein, Dan J, Van der Wee, Nic J A, Groenewold, Nynke A, Bas-Hoogendam, Janna Marie, Amod, Alyssa R, Laansma, Max A, Van Velzen, Laura S, Aghajani, Moji, Hilbert, Kevin, Oh, Hyuntaek, Salas, Ramiro, Jackowski, Andrea P, Pan, Pedro M, Salum, Giovanni A, Blair, James R, Blair, Karina S, Hirsch, Joy, Pantazatos, Spiro P, Schneier, Franklin R, Talati, Ardesheer, Roelofs, Karin, Volman, Inge, Blanco-Hinojo, Laura, Cardoner, Narcís, Pujol, Jesus, Beesdo-Baum, Katja, Ching, Christopher R K, Thomopoulos, Sophia I, Jansen, Andreas, Kircher, Tilo, Krug, Axel, Nenadić, Igor, Stein, Frederike, Dannlowski, Udo, Grotegerd, Dominik, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Erb, Michael, Kreifelts, Benjamin, Gong, Qiyong, Lui, Su, Zhu, Fei, Mwangi, Benson, Soares, Jair C, Wu, Mon-Ju, Bayram, Ali, Canli, Mesut, Tükel, Raşit, Westenberg, P Michiel, Heeren, Alexandre, Cremers, Henk R, Hofmann, David, Straube, Thomas, Doruyter, Alexander G G, Lochner, Christine, Peterburs, Jutta, Van Tol, Marie-José, Gur, Raquel E, Kaczkurkin, Antonia N, Larsen, Bart, Satterthwaite, Theodore D, Filippi, Courtney A, Gold, Andrea L, Harrewijn, Anita, Zugman, André, Bülow, Robin, Grabe, Hans J, Völzke, Henry, Wittfeld, Katharina, Böhnlein, Joscha, Dohm, Katharina, Kugel, Harald, Schrammen, Elisabeth, Zwanzger, Peter, Leehr, Elisabeth J, Sindermann, Lisa, Ball, Tali M, Fonzo, Gregory A, Paulus, Martin P, Simmons, Alan, Stein, Murray B, Klumpp, Heide, Phan, K Luan, Furmark, Tomas, Månsson, Kristoffer N T, Manzouri, Amirhossein, Avery, Suzanne N, Blackford, Jennifer Urbano, Clauss, Jacqueline A, Feola, Brandee, Harper, Jennifer C, Sylvester, Chad M, Lueken, Ulrike, Veltman, Dick J, Winkler, Anderson M, Jahanshad, Neda, Pine, Daniel S, Thompson, Paul M, Stein, Dan J, and Van der Wee, Nic J A
Abstract: There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, p FWE = 0.037; right: d = -0.104, p FWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, p FWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, p FWE < 0.001; right: d = -0.158, p FWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, p FWE = 0.006; right: d = 0.099, p FWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adol
Published: 2023

14. Greater male than female variability in regional brain structure across the lifespan

Author: Wierenga, Lara M., Doucet, Gaelle E., Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn, I, Andreassen, Ole A., Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret, I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Calhoun, Vince D., Canales-Rodriguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Clark, Vincent P., Conrod, Patricia J., Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G., Dickie, Erin W., Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco J. C., Di Giorgio, Annabella, Glahn, David C., Gotlib, Ian H., Grabe, Hans J., Gruber, Oliver, Gruner, Patricia, Gur, Raquel E., Gur, Ruben C., Gurholt, Tiril P., de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J., Hartman, Catharina A., Hatton, Sean N., Heslenfeld, Dirk J., van den Heuvel, Odile A., Hickie, Ian B., Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Pol, Hilleke E. Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony C., Jiang, Jiyang, Jonsson, Erik G., Joska, John A., Kalnin, Andrew J., Klein, Marieke, Koenders, Laura, Kolskar, Knut K., Kramer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S., Lee, Phil H., Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martinez-Zalacain, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C., McDonald, Colm, McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, van der Meer, Dennis, Menchon, Jose M., Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Radua, Joaquim, Reif, Andreas, Richard, Genevieve, Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sarro, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Sim, Kang, Simmons, Andrew, Smoller, Jordan W., Sommer, Iris E., Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Szeszko, Philip R., Temmingh, Henk S., Thomopoulos, Sophia, I, Tomyshev, Alexander S., Trollor, Julian N., Uhlmann, Anne, Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Volzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather C., Williams, Steven C. R., Wittfeld, Katharina, Wolf, Daniel H., Wright, Margaret J., Yoncheva, Yuliya N., Zanetti, Marcus, V, Ziegler, Georg C., de Zubicaray, Greig, I, Thompson, Paul M., Crone, Eveline A., Frangou, Sophia, Tamnes, Christian K., Wierenga, Lara M., Doucet, Gaelle E., Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn, I, Andreassen, Ole A., Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret, I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Calhoun, Vince D., Canales-Rodriguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Clark, Vincent P., Conrod, Patricia J., Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G., Dickie, Erin W., Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco J. C., Di Giorgio, Annabella, Glahn, David C., Gotlib, Ian H., Grabe, Hans J., Gruber, Oliver, Gruner, Patricia, Gur, Raquel E., Gur, Ruben C., Gurholt, Tiril P., de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J., Hartman, Catharina A., Hatton, Sean N., Heslenfeld, Dirk J., van den Heuvel, Odile A., Hickie, Ian B., Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Pol, Hilleke E. Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony C., Jiang, Jiyang, Jonsson, Erik G., Joska, John A., Kalnin, Andrew J., Klein, Marieke, Koenders, Laura, Kolskar, Knut K., Kramer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S., Lee, Phil H., Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martinez-Zalacain, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C., McDonald, Colm, McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, van der Meer, Dennis, Menchon, Jose M., Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Radua, Joaquim, Reif, Andreas, Richard, Genevieve, Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sarro, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Sim, Kang, Simmons, Andrew, Smoller, Jordan W., Sommer, Iris E., Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Szeszko, Philip R., Temmingh, Henk S., Thomopoulos, Sophia, I, Tomyshev, Alexander S., Trollor, Julian N., Uhlmann, Anne, Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Volzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather C., Williams, Steven C. R., Wittfeld, Katharina, Wolf, Daniel H., Wright, Margaret J., Yoncheva, Yuliya N., Zanetti, Marcus, V, Ziegler, Georg C., de Zubicaray, Greig, I, Thompson, Paul M., Crone, Eveline A., Frangou, Sophia, and Tamnes, Christian K.
Abstract: For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
Published: 2022
Full Text: View/download PDF

15. Greater male than female variability in regional brain structure across the lifespan

Author: Wierenga, Lara M., Doucet, Gaelle E., Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn, I, Andreassen, Ole A., Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret, I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Calhoun, Vince D., Canales-Rodriguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Clark, Vincent P., Conrod, Patricia J., Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G., Dickie, Erin W., Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco J. C., Di Giorgio, Annabella, Glahn, David C., Gotlib, Ian H., Grabe, Hans J., Gruber, Oliver, Gruner, Patricia, Gur, Raquel E., Gur, Ruben C., Gurholt, Tiril P., de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J., Hartman, Catharina A., Hatton, Sean N., Heslenfeld, Dirk J., van den Heuvel, Odile A., Hickie, Ian B., Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Pol, Hilleke E. Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony C., Jiang, Jiyang, Jonsson, Erik G., Joska, John A., Kalnin, Andrew J., Klein, Marieke, Koenders, Laura, Kolskar, Knut K., Kramer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S., Lee, Phil H., Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martinez-Zalacain, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C., McDonald, Colm, McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, van der Meer, Dennis, Menchon, Jose M., Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Radua, Joaquim, Reif, Andreas, Richard, Genevieve, Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sarro, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Sim, Kang, Simmons, Andrew, Smoller, Jordan W., Sommer, Iris E., Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Szeszko, Philip R., Temmingh, Henk S., Thomopoulos, Sophia, I, Tomyshev, Alexander S., Trollor, Julian N., Uhlmann, Anne, Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Volzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather C., Williams, Steven C. R., Wittfeld, Katharina, Wolf, Daniel H., Wright, Margaret J., Yoncheva, Yuliya N., Zanetti, Marcus, V, Ziegler, Georg C., de Zubicaray, Greig, I, Thompson, Paul M., Crone, Eveline A., Frangou, Sophia, Tamnes, Christian K., Wierenga, Lara M., Doucet, Gaelle E., Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn, I, Andreassen, Ole A., Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret, I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Calhoun, Vince D., Canales-Rodriguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Clark, Vincent P., Conrod, Patricia J., Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G., Dickie, Erin W., Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco J. C., Di Giorgio, Annabella, Glahn, David C., Gotlib, Ian H., Grabe, Hans J., Gruber, Oliver, Gruner, Patricia, Gur, Raquel E., Gur, Ruben C., Gurholt, Tiril P., de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J., Hartman, Catharina A., Hatton, Sean N., Heslenfeld, Dirk J., van den Heuvel, Odile A., Hickie, Ian B., Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Pol, Hilleke E. Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony C., Jiang, Jiyang, Jonsson, Erik G., Joska, John A., Kalnin, Andrew J., Klein, Marieke, Koenders, Laura, Kolskar, Knut K., Kramer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S., Lee, Phil H., Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martinez-Zalacain, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C., McDonald, Colm, McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, van der Meer, Dennis, Menchon, Jose M., Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Radua, Joaquim, Reif, Andreas, Richard, Genevieve, Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sarro, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Sim, Kang, Simmons, Andrew, Smoller, Jordan W., Sommer, Iris E., Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Szeszko, Philip R., Temmingh, Henk S., Thomopoulos, Sophia, I, Tomyshev, Alexander S., Trollor, Julian N., Uhlmann, Anne, Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Volzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather C., Williams, Steven C. R., Wittfeld, Katharina, Wolf, Daniel H., Wright, Margaret J., Yoncheva, Yuliya N., Zanetti, Marcus, V, Ziegler, Georg C., de Zubicaray, Greig, I, Thompson, Paul M., Crone, Eveline A., Frangou, Sophia, and Tamnes, Christian K.
Abstract: For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
Published: 2022
Full Text: View/download PDF

16. Greater male than female variability in regional brain structure across the lifespan

Author: Wierenga, Lara M, Doucet, Gaelle E, Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N, Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn I, Andreassen, Ole A, Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M, Buitelaar, Jan K, Busatto, Geraldo F, Calhoun, Vince D, Canales-Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Castellanos, Francisco X, Chaim-Avancini, Tiffany M, Ching, Christopher Rk, Clark, Vincent P, Conrod, Patricia J, Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G, Dickie, Erin W, Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E, Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco Jc, Giorgio, Annabella Di, Glahn, David C, Gotlib, Ian H, Grabe, Hans J, Gruber, Oliver, Gruner, Patricia, Gur, Raquel E, Gur, Ruben C, Gurholt, Tiril P, de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J, Hartman, Catharina A, Hatton, Sean N, Heslenfeld, Dirk J, van den Heuvel, Odile A, Hickie, Ian B, Hoekstra, Pieter J, Hohmann, Sarah, Holmes, Avram J, Hoogman, Martine, Hosten, Norbert, Howells, Fleur M, Hulshoff Pol, Hilleke E, Huyser, Chaim, Jahanshad, Neda, James, Anthony C, Jiang, Jiyang, Jönsson, Erik G, Joska, John A, Kalnin, Andrew J, Klein, Marieke, Koenders, Laura, Kolskår, Knut K, Krämer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S, Lee, Phil H, Lochner, Christine, Machielsen, Marise Wj, Maingault, Sophie, Martin, Nicholas G, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C, McDonald, Colm, McIntosh, Andrew M, McMahon, Katie L, McPhilemy, Genevieve, van der Meer, Dennis, Menchón, José M, Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J, Radua, Joaquim, Reif, Andreas, Richard, Geneviève, Roffman, Joshua L, Rosa, Pedro Gp, Sacchet, Matthew D, Sachdev, Perminder S, Salvador, Raymond, Sarró, Salvador, Satterthwaite, Theodore D, Saykin, Andrew J, Serpa, Mauricio H, Sim, Kang, Simmons, Andrew, Smoller, Jordan W, Sommer, Iris E, Soriano-Mas, Carles, Stein, Dan J, Strike, Lachlan T, Szeszko, Philip R, Temmingh, Henk S, Thomopoulos, Sophia I, Tomyshev, Alexander S, Trollor, Julian N, Uhlmann, Anne, Veer, Ilya M, Veltman, Dick J, Voineskos, Aristotle, Völzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D, Westlye, Lars T, Whalley, Heather C, Williams, Steven Cr, Wittfeld, Katharina, Wolf, Daniel H, Wright, Margaret J, Yoncheva, Yuliya N, Zanetti, Marcus V, Ziegler, Georg C, de Zubicaray, Greig I, Thompson, Paul M., Crone, Eveline A, Frangou, Sophia, Tamnes, Christian K, Wierenga, Lara M, Doucet, Gaelle E, Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N, Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn I, Andreassen, Ole A, Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M, Buitelaar, Jan K, Busatto, Geraldo F, Calhoun, Vince D, Canales-Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Castellanos, Francisco X, Chaim-Avancini, Tiffany M, Ching, Christopher Rk, Clark, Vincent P, Conrod, Patricia J, Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G, Dickie, Erin W, Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E, Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco Jc, Giorgio, Annabella Di, Glahn, David C, Gotlib, Ian H, Grabe, Hans J, Gruber, Oliver, Gruner, Patricia, Gur, Raquel E, Gur, Ruben C, Gurholt, Tiril P, de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J, Hartman, Catharina A, Hatton, Sean N, Heslenfeld, Dirk J, van den Heuvel, Odile A, Hickie, Ian B, Hoekstra, Pieter J, Hohmann, Sarah, Holmes, Avram J, Hoogman, Martine, Hosten, Norbert, Howells, Fleur M, Hulshoff Pol, Hilleke E, Huyser, Chaim, Jahanshad, Neda, James, Anthony C, Jiang, Jiyang, Jönsson, Erik G, Joska, John A, Kalnin, Andrew J, Klein, Marieke, Koenders, Laura, Kolskår, Knut K, Krämer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S, Lee, Phil H, Lochner, Christine, Machielsen, Marise Wj, Maingault, Sophie, Martin, Nicholas G, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C, McDonald, Colm, McIntosh, Andrew M, McMahon, Katie L, McPhilemy, Genevieve, van der Meer, Dennis, Menchón, José M, Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J, Radua, Joaquim, Reif, Andreas, Richard, Geneviève, Roffman, Joshua L, Rosa, Pedro Gp, Sacchet, Matthew D, Sachdev, Perminder S, Salvador, Raymond, Sarró, Salvador, Satterthwaite, Theodore D, Saykin, Andrew J, Serpa, Mauricio H, Sim, Kang, Simmons, Andrew, Smoller, Jordan W, Sommer, Iris E, Soriano-Mas, Carles, Stein, Dan J, Strike, Lachlan T, Szeszko, Philip R, Temmingh, Henk S, Thomopoulos, Sophia I, Tomyshev, Alexander S, Trollor, Julian N, Uhlmann, Anne, Veer, Ilya M, Veltman, Dick J, Voineskos, Aristotle, Völzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D, Westlye, Lars T, Whalley, Heather C, Williams, Steven Cr, Wittfeld, Katharina, Wolf, Daniel H, Wright, Margaret J, Yoncheva, Yuliya N, Zanetti, Marcus V, Ziegler, Georg C, de Zubicaray, Greig I, Thompson, Paul M., Crone, Eveline A, Frangou, Sophia, and Tamnes, Christian K
Abstract: For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
Published: 2022

17. Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs

Author: Sønderby, Ida E., Ching, Christopher R.K., Thomopoulos, Sophia I., van der Meer, Dennis, Sun, Daqiang, Villalon-Reina, Julio E., Agartz, Ingrid, Amunts, Katrin, Arango, Celso, Armstrong, Nicola J., Ayesa-Arriola, Rosa, Bakker, Geor, Bassett, Anne S., Boomsma, Dorret I., Bülow, Robin, Butcher, Nancy J., Calhoun, Vince D., Caspers, Svenja, Chow, Eva W.C., Cichon, Sven, Ciufolini, Simone, Craig, Michael C., Crespo-Facorro, Benedicto, Cunningham, Adam C., Dale, Anders M., Dazzan, Paola, de Zubicaray, Greig I., Djurovic, Srdjan, Doherty, Joanne L., Donohoe, Gary, Draganski, Bogdan, Durdle, Courtney A., Ehrlich, Stefan, Emanuel, Beverly S., Espeseth, Thomas, Fisher, Simon E., Ge, Tian, Glahn, David C., Grabe, Hans J., Gur, Raquel E., Gutman, Boris A., Haavik, Jan, Håberg, Asta K., Hansen, Laura A., Hashimoto, Ryota, Hibar, Derrek P., Holmes, Avram J., Hottenga, Jouke Jan, Hulshoff Pol, Hilleke E., Jalbrzikowski, Maria, Knowles, Emma E.M., Kushan, Leila, Linden, David E.J., Liu, Jingyu, Lundervold, Astri J., Martin-Brevet, Sandra, Martínez, Kenia, Mather, Karen A., Mathias, Samuel R., McDonald-McGinn, Donna M., McRae, Allan F., Medland, Sarah E., Moberget, Torgeir, Modenato, Claudia, Monereo Sánchez, Jennifer, Moreau, Clara A., Mühleisen, Thomas W., Paus, Tomas, Pausova, Zdenka, Prieto, Carlos, Ragothaman, Anjanibhargavi, Reinbold, Céline S., Reis Marques, Tiago, Repetto, Gabriela M., Reymond, Alexandre, Roalf, David R., Rodriguez-Herreros, Borja, Rucker, James J., Sachdev, Perminder S., Schmitt, James E., Schofield, Peter R., Silva, Ana I., Stefansson, Hreinn, Stein, Dan J., Tamnes, Christian K., Tordesillas-Gutiérrez, Diana, Ulfarsson, Magnus O., Vajdi, Ariana, van 't Ent, Dennis, van den Bree, Marianne B.M., Vassos, Evangelos, Vázquez-Bourgon, Javier, Vila-Rodriguez, Fidel, Walters, G. Bragi, Wen, Wei, Westlye, Lars T., Wittfeld, Katharina, Zackai, Elaine H., Stefánsson, Kári, Jacquemont, Sebastien, Thompson, Paul M., Bearden, Carrie E., Andreassen, Ole A., other, and, Sønderby, Ida E., Ching, Christopher R.K., Thomopoulos, Sophia I., van der Meer, Dennis, Sun, Daqiang, Villalon-Reina, Julio E., Agartz, Ingrid, Amunts, Katrin, Arango, Celso, Armstrong, Nicola J., Ayesa-Arriola, Rosa, Bakker, Geor, Bassett, Anne S., Boomsma, Dorret I., Bülow, Robin, Butcher, Nancy J., Calhoun, Vince D., Caspers, Svenja, Chow, Eva W.C., Cichon, Sven, Ciufolini, Simone, Craig, Michael C., Crespo-Facorro, Benedicto, Cunningham, Adam C., Dale, Anders M., Dazzan, Paola, de Zubicaray, Greig I., Djurovic, Srdjan, Doherty, Joanne L., Donohoe, Gary, Draganski, Bogdan, Durdle, Courtney A., Ehrlich, Stefan, Emanuel, Beverly S., Espeseth, Thomas, Fisher, Simon E., Ge, Tian, Glahn, David C., Grabe, Hans J., Gur, Raquel E., Gutman, Boris A., Haavik, Jan, Håberg, Asta K., Hansen, Laura A., Hashimoto, Ryota, Hibar, Derrek P., Holmes, Avram J., Hottenga, Jouke Jan, Hulshoff Pol, Hilleke E., Jalbrzikowski, Maria, Knowles, Emma E.M., Kushan, Leila, Linden, David E.J., Liu, Jingyu, Lundervold, Astri J., Martin-Brevet, Sandra, Martínez, Kenia, Mather, Karen A., Mathias, Samuel R., McDonald-McGinn, Donna M., McRae, Allan F., Medland, Sarah E., Moberget, Torgeir, Modenato, Claudia, Monereo Sánchez, Jennifer, Moreau, Clara A., Mühleisen, Thomas W., Paus, Tomas, Pausova, Zdenka, Prieto, Carlos, Ragothaman, Anjanibhargavi, Reinbold, Céline S., Reis Marques, Tiago, Repetto, Gabriela M., Reymond, Alexandre, Roalf, David R., Rodriguez-Herreros, Borja, Rucker, James J., Sachdev, Perminder S., Schmitt, James E., Schofield, Peter R., Silva, Ana I., Stefansson, Hreinn, Stein, Dan J., Tamnes, Christian K., Tordesillas-Gutiérrez, Diana, Ulfarsson, Magnus O., Vajdi, Ariana, van 't Ent, Dennis, van den Bree, Marianne B.M., Vassos, Evangelos, Vázquez-Bourgon, Javier, Vila-Rodriguez, Fidel, Walters, G. Bragi, Wen, Wei, Westlye, Lars T., Wittfeld, Katharina, Zackai, Elaine H., Stefánsson, Kári, Jacquemont, Sebastien, Thompson, Paul M., Bearden, Carrie E., Andreassen, Ole A., and other, and
Abstract: The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype–phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This “genotype-first” approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.
Published: 2022

18. Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs.

Author: Sønderby, Ida E, Sønderby, Ida E, Ching, Christopher RK, Thomopoulos, Sophia I, van der Meer, Dennis, Sun, Daqiang, Villalon-Reina, Julio E, Agartz, Ingrid, Amunts, Katrin, Arango, Celso, Armstrong, Nicola J, Ayesa-Arriola, Rosa, Bakker, Geor, Bassett, Anne S, Boomsma, Dorret I, Bülow, Robin, Butcher, Nancy J, Calhoun, Vince D, Caspers, Svenja, Chow, Eva WC, Cichon, Sven, Ciufolini, Simone, Craig, Michael C, Crespo-Facorro, Benedicto, Cunningham, Adam C, Dale, Anders M, Dazzan, Paola, de Zubicaray, Greig I, Djurovic, Srdjan, Doherty, Joanne L, Donohoe, Gary, Draganski, Bogdan, Durdle, Courtney A, Ehrlich, Stefan, Emanuel, Beverly S, Espeseth, Thomas, Fisher, Simon E, Ge, Tian, Glahn, David C, Grabe, Hans J, Gur, Raquel E, Gutman, Boris A, Haavik, Jan, Håberg, Asta K, Hansen, Laura A, Hashimoto, Ryota, Hibar, Derrek P, Holmes, Avram J, Hottenga, Jouke-Jan, Hulshoff Pol, Hilleke E, Jalbrzikowski, Maria, Knowles, Emma EM, Kushan, Leila, Linden, David EJ, Liu, Jingyu, Lundervold, Astri J, Martin-Brevet, Sandra, Martínez, Kenia, Mather, Karen A, Mathias, Samuel R, McDonald-McGinn, Donna M, McRae, Allan F, Medland, Sarah E, Moberget, Torgeir, Modenato, Claudia, Monereo Sánchez, Jennifer, Moreau, Clara A, Mühleisen, Thomas W, Paus, Tomas, Pausova, Zdenka, Prieto, Carlos, Ragothaman, Anjanibhargavi, Reinbold, Céline S, Reis Marques, Tiago, Repetto, Gabriela M, Reymond, Alexandre, Roalf, David R, Rodriguez-Herreros, Borja, Rucker, James J, Sachdev, Perminder S, Schmitt, James E, Schofield, Peter R, Silva, Ana I, Stefansson, Hreinn, Stein, Dan J, Tamnes, Christian K, Tordesillas-Gutiérrez, Diana, Ulfarsson, Magnus O, Vajdi, Ariana, van 't Ent, Dennis, van den Bree, Marianne BM, Vassos, Evangelos, Vázquez-Bourgon, Javier, Vila-Rodriguez, Fidel, Walters, G Bragi, Wen, Wei, Westlye, Lars T, Wittfeld, Katharina, Zackai, Elaine H, Stefánsson, Kári, Jacquemont, Sebastien, Sønderby, Ida E, Sønderby, Ida E, Ching, Christopher RK, Thomopoulos, Sophia I, van der Meer, Dennis, Sun, Daqiang, Villalon-Reina, Julio E, Agartz, Ingrid, Amunts, Katrin, Arango, Celso, Armstrong, Nicola J, Ayesa-Arriola, Rosa, Bakker, Geor, Bassett, Anne S, Boomsma, Dorret I, Bülow, Robin, Butcher, Nancy J, Calhoun, Vince D, Caspers, Svenja, Chow, Eva WC, Cichon, Sven, Ciufolini, Simone, Craig, Michael C, Crespo-Facorro, Benedicto, Cunningham, Adam C, Dale, Anders M, Dazzan, Paola, de Zubicaray, Greig I, Djurovic, Srdjan, Doherty, Joanne L, Donohoe, Gary, Draganski, Bogdan, Durdle, Courtney A, Ehrlich, Stefan, Emanuel, Beverly S, Espeseth, Thomas, Fisher, Simon E, Ge, Tian, Glahn, David C, Grabe, Hans J, Gur, Raquel E, Gutman, Boris A, Haavik, Jan, Håberg, Asta K, Hansen, Laura A, Hashimoto, Ryota, Hibar, Derrek P, Holmes, Avram J, Hottenga, Jouke-Jan, Hulshoff Pol, Hilleke E, Jalbrzikowski, Maria, Knowles, Emma EM, Kushan, Leila, Linden, David EJ, Liu, Jingyu, Lundervold, Astri J, Martin-Brevet, Sandra, Martínez, Kenia, Mather, Karen A, Mathias, Samuel R, McDonald-McGinn, Donna M, McRae, Allan F, Medland, Sarah E, Moberget, Torgeir, Modenato, Claudia, Monereo Sánchez, Jennifer, Moreau, Clara A, Mühleisen, Thomas W, Paus, Tomas, Pausova, Zdenka, Prieto, Carlos, Ragothaman, Anjanibhargavi, Reinbold, Céline S, Reis Marques, Tiago, Repetto, Gabriela M, Reymond, Alexandre, Roalf, David R, Rodriguez-Herreros, Borja, Rucker, James J, Sachdev, Perminder S, Schmitt, James E, Schofield, Peter R, Silva, Ana I, Stefansson, Hreinn, Stein, Dan J, Tamnes, Christian K, Tordesillas-Gutiérrez, Diana, Ulfarsson, Magnus O, Vajdi, Ariana, van 't Ent, Dennis, van den Bree, Marianne BM, Vassos, Evangelos, Vázquez-Bourgon, Javier, Vila-Rodriguez, Fidel, Walters, G Bragi, Wen, Wei, Westlye, Lars T, Wittfeld, Katharina, Zackai, Elaine H, Stefánsson, Kári, and Jacquemont, Sebastien
Abstract: The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.
Published: 2022

19. Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs.

Author: Sønderby, Ida E, Sønderby, Ida E, Ching, Christopher RK, Thomopoulos, Sophia I, van der Meer, Dennis, Sun, Daqiang, Villalon-Reina, Julio E, Agartz, Ingrid, Amunts, Katrin, Arango, Celso, Armstrong, Nicola J, Ayesa-Arriola, Rosa, Bakker, Geor, Bassett, Anne S, Boomsma, Dorret I, Bülow, Robin, Butcher, Nancy J, Calhoun, Vince D, Caspers, Svenja, Chow, Eva WC, Cichon, Sven, Ciufolini, Simone, Craig, Michael C, Crespo-Facorro, Benedicto, Cunningham, Adam C, Dale, Anders M, Dazzan, Paola, de Zubicaray, Greig I, Djurovic, Srdjan, Doherty, Joanne L, Donohoe, Gary, Draganski, Bogdan, Durdle, Courtney A, Ehrlich, Stefan, Emanuel, Beverly S, Espeseth, Thomas, Fisher, Simon E, Ge, Tian, Glahn, David C, Grabe, Hans J, Gur, Raquel E, Gutman, Boris A, Haavik, Jan, Håberg, Asta K, Hansen, Laura A, Hashimoto, Ryota, Hibar, Derrek P, Holmes, Avram J, Hottenga, Jouke-Jan, Hulshoff Pol, Hilleke E, Jalbrzikowski, Maria, Knowles, Emma EM, Kushan, Leila, Linden, David EJ, Liu, Jingyu, Lundervold, Astri J, Martin-Brevet, Sandra, Martínez, Kenia, Mather, Karen A, Mathias, Samuel R, McDonald-McGinn, Donna M, McRae, Allan F, Medland, Sarah E, Moberget, Torgeir, Modenato, Claudia, Monereo Sánchez, Jennifer, Moreau, Clara A, Mühleisen, Thomas W, Paus, Tomas, Pausova, Zdenka, Prieto, Carlos, Ragothaman, Anjanibhargavi, Reinbold, Céline S, Reis Marques, Tiago, Repetto, Gabriela M, Reymond, Alexandre, Roalf, David R, Rodriguez-Herreros, Borja, Rucker, James J, Sachdev, Perminder S, Schmitt, James E, Schofield, Peter R, Silva, Ana I, Stefansson, Hreinn, Stein, Dan J, Tamnes, Christian K, Tordesillas-Gutiérrez, Diana, Ulfarsson, Magnus O, Vajdi, Ariana, van 't Ent, Dennis, van den Bree, Marianne BM, Vassos, Evangelos, Vázquez-Bourgon, Javier, Vila-Rodriguez, Fidel, Walters, G Bragi, Wen, Wei, Westlye, Lars T, Wittfeld, Katharina, Zackai, Elaine H, Stefánsson, Kári, Jacquemont, Sebastien, Sønderby, Ida E, Sønderby, Ida E, Ching, Christopher RK, Thomopoulos, Sophia I, van der Meer, Dennis, Sun, Daqiang, Villalon-Reina, Julio E, Agartz, Ingrid, Amunts, Katrin, Arango, Celso, Armstrong, Nicola J, Ayesa-Arriola, Rosa, Bakker, Geor, Bassett, Anne S, Boomsma, Dorret I, Bülow, Robin, Butcher, Nancy J, Calhoun, Vince D, Caspers, Svenja, Chow, Eva WC, Cichon, Sven, Ciufolini, Simone, Craig, Michael C, Crespo-Facorro, Benedicto, Cunningham, Adam C, Dale, Anders M, Dazzan, Paola, de Zubicaray, Greig I, Djurovic, Srdjan, Doherty, Joanne L, Donohoe, Gary, Draganski, Bogdan, Durdle, Courtney A, Ehrlich, Stefan, Emanuel, Beverly S, Espeseth, Thomas, Fisher, Simon E, Ge, Tian, Glahn, David C, Grabe, Hans J, Gur, Raquel E, Gutman, Boris A, Haavik, Jan, Håberg, Asta K, Hansen, Laura A, Hashimoto, Ryota, Hibar, Derrek P, Holmes, Avram J, Hottenga, Jouke-Jan, Hulshoff Pol, Hilleke E, Jalbrzikowski, Maria, Knowles, Emma EM, Kushan, Leila, Linden, David EJ, Liu, Jingyu, Lundervold, Astri J, Martin-Brevet, Sandra, Martínez, Kenia, Mather, Karen A, Mathias, Samuel R, McDonald-McGinn, Donna M, McRae, Allan F, Medland, Sarah E, Moberget, Torgeir, Modenato, Claudia, Monereo Sánchez, Jennifer, Moreau, Clara A, Mühleisen, Thomas W, Paus, Tomas, Pausova, Zdenka, Prieto, Carlos, Ragothaman, Anjanibhargavi, Reinbold, Céline S, Reis Marques, Tiago, Repetto, Gabriela M, Reymond, Alexandre, Roalf, David R, Rodriguez-Herreros, Borja, Rucker, James J, Sachdev, Perminder S, Schmitt, James E, Schofield, Peter R, Silva, Ana I, Stefansson, Hreinn, Stein, Dan J, Tamnes, Christian K, Tordesillas-Gutiérrez, Diana, Ulfarsson, Magnus O, Vajdi, Ariana, van 't Ent, Dennis, van den Bree, Marianne BM, Vassos, Evangelos, Vázquez-Bourgon, Javier, Vila-Rodriguez, Fidel, Walters, G Bragi, Wen, Wei, Westlye, Lars T, Wittfeld, Katharina, Zackai, Elaine H, Stefánsson, Kári, and Jacquemont, Sebastien
Abstract: The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.
Published: 2022

20. A normative chart for cognitive development in a genetically selected population.

Author: Fiksinski, Ania M, Fiksinski, Ania M, Bearden, Carrie E, Bassett, Anne S, Kahn, René S, Zinkstok, Janneke R, Hooper, Stephen R, Tempelaar, Wanda, McDonald-McGinn, Donna, Swillen, Ann, Emanuel, Beverly, Morrow, Bernice, Gur, Raquel, Chow, Eva, van den Bree, Marianne, Vermeesch, Joris, Warren, Stephen, Owen, Michael, van Amelsvoort, Therese, Eliez, Stephan, Gothelf, Doron, Arango, Celso, Kates, Wendy, Simon, Tony, Murphy, Kieran, Repetto, Gabriela, Suner, Damian Heine, Vicari, Stefano, Cubells, Joseph, Armando, Marco, Philip, Nicole, Campbell, Linda, Garcia-Minaur, Sixto, Schneider, Maude, Shashi, Vandana, 22q11DS International Consortium on Brain and Behavior, Vorstman, Jacob, Breetvelt, Elemi J, Fiksinski, Ania M, Fiksinski, Ania M, Bearden, Carrie E, Bassett, Anne S, Kahn, René S, Zinkstok, Janneke R, Hooper, Stephen R, Tempelaar, Wanda, McDonald-McGinn, Donna, Swillen, Ann, Emanuel, Beverly, Morrow, Bernice, Gur, Raquel, Chow, Eva, van den Bree, Marianne, Vermeesch, Joris, Warren, Stephen, Owen, Michael, van Amelsvoort, Therese, Eliez, Stephan, Gothelf, Doron, Arango, Celso, Kates, Wendy, Simon, Tony, Murphy, Kieran, Repetto, Gabriela, Suner, Damian Heine, Vicari, Stefano, Cubells, Joseph, Armando, Marco, Philip, Nicole, Campbell, Linda, Garcia-Minaur, Sixto, Schneider, Maude, Shashi, Vandana, 22q11DS International Consortium on Brain and Behavior, Vorstman, Jacob, and Breetvelt, Elemi J
Abstract: Certain pathogenic genetic variants impact neurodevelopment and cause deviations from typical cognitive trajectories. Understanding variant-specific cognitive trajectories is clinically important for informed monitoring and identifying patients at risk for comorbid conditions. Here, we demonstrate a variant-specific normative chart for cognitive development for individuals with 22q11.2 deletion syndrome (22q11DS). We used IQ data from 1365 individuals with 22q11DS to construct variant-specific normative charts for cognitive development (Full Scale, Verbal, and Performance IQ). This allowed us to calculate Z-scores for each IQ datapoint. Then, we calculated the change between first and last available IQ assessments (delta Z-IQ-scores) for each individual with longitudinal IQ data (n = 708). We subsequently investigated whether using the variant-specific IQ-Z-scores would decrease required sample size to detect an effect with schizophrenia risk, as compared to standard IQ-scores. The mean Z-IQ-scores for FSIQ, VIQ, and PIQ were close to 0, indicating that participants had IQ-scores as predicted by the normative chart. The mean delta-Z-IQ-scores were equally close to 0, demonstrating a good fit of the normative chart and indicating that, as a group, individuals with 22q11DS show a decline in IQ-scores as they grow into adulthood. Using variant-specific IQ-Z-scores resulted in 30% decrease of required sample size, as compared to the standard IQ-based approach, to detect the association between IQ-decline and schizophrenia (p < 0.01). Our findings suggest that using variant-specific normative IQ data significantly reduces required sample size in a research context, and may facilitate a more clinically informative interpretation of IQ data. This approach allows identification of individuals that deviate from their expected, variant-specific, trajectory. This group may be at increased risk for comorbid conditions, such as schizophrenia in the case of 22q11DS.
Published: 2022

21. Genes To Mental Health (G2MH): A Framework to Map the Combined Effects of Rare and Common Variants on Dimensions of Cognition and Psychopathology.

Author: Jacquemont, Sébastien, Jacquemont, Sébastien, Huguet, Guillaume, Klein, Marieke, Chawner, Samuel JRA, Donald, Kirsten A, van den Bree, Marianne BM, Sebat, Jonathan, Ledbetter, David H, Constantino, John N, Earl, Rachel K, McDonald-McGinn, Donna M, van Amelsvoort, Therese, Swillen, Ann, O'Donnell-Luria, Anne H, Glahn, David C, Almasy, Laura, Eichler, Evan E, Scherer, Stephen W, Robinson, Elise, Bassett, Anne S, Martin, Christa Lese, Finucane, Brenda, Vorstman, Jacob AS, Bearden, Carrie E, Gur, Raquel E, Genes to Mental Health Network, Jacquemont, Sébastien, Jacquemont, Sébastien, Huguet, Guillaume, Klein, Marieke, Chawner, Samuel JRA, Donald, Kirsten A, van den Bree, Marianne BM, Sebat, Jonathan, Ledbetter, David H, Constantino, John N, Earl, Rachel K, McDonald-McGinn, Donna M, van Amelsvoort, Therese, Swillen, Ann, O'Donnell-Luria, Anne H, Glahn, David C, Almasy, Laura, Eichler, Evan E, Scherer, Stephen W, Robinson, Elise, Bassett, Anne S, Martin, Christa Lese, Finucane, Brenda, Vorstman, Jacob AS, Bearden, Carrie E, Gur, Raquel E, and Genes to Mental Health Network
Abstract: Rare genomic disorders (RGDs) confer elevated risk for neurodevelopmental psychiatric disorders. In this era of intense genomics discoveries, the landscape of RGDs is rapidly evolving. However, there has not been comparable progress to date in scalable, harmonized phenotyping methods. As a result, beyond associations with categorical diagnoses, the effects on dimensional traits remain unclear for many RGDs. The nature and specificity of RGD effects on cognitive and behavioral traits is an area of intense investigation: RGDs are frequently associated with more than one psychiatric condition, and those studied to date affect, to varying degrees, a broad range of developmental and cognitive functions. Although many RGDs have large effects, phenotypic expression is typically influenced by additional genomic and environmental factors. There is emerging evidence that using polygenic risk scores in individuals with RGDs offers opportunities to refine prediction, thus allowing for the identification of those at greatest risk of psychiatric illness. However, translation into the clinic is hindered by roadblocks, which include limited genetic testing in clinical psychiatry, and the lack of guidelines for following individuals with RGDs, who are at high risk of developing psychiatric symptoms. The Genes to Mental Health Network (G2MH) is a newly funded National Institute of Mental Health initiative that will collect, share, and analyze large-scale data sets combining genomics and dimensional measures of psychopathology spanning diverse populations and geography. The authors present here the most recent understanding of the effects of RGDs on dimensional behavioral traits and risk for psychiatric conditions and discuss strategies that will be pursued within the G2MH network, as well as how expected results can be translated into clinical practice to improve patient outcomes.
Published: 2022

22. Efficient coding in the economics of human brain connectomics.

Author: Lynn, Christopher, Lynn, Christopher, Cui, Zaixu, Ciric, Rastko, Baum, Graham, Moore, Tyler, Roalf, David, Detre, John, Gur, Ruben, Gur, Raquel, Satterthwaite, Theodore, Bassett, Dani, Zhou, Dale, Lynn, Christopher, Lynn, Christopher, Cui, Zaixu, Ciric, Rastko, Baum, Graham, Moore, Tyler, Roalf, David, Detre, John, Gur, Ruben, Gur, Raquel, Satterthwaite, Theodore, Bassett, Dani, and Zhou, Dale
Abstract: In systems neuroscience, most models posit that brain regions communicate information under constraints of efficiency. Yet, evidence for efficient communication in structural brain networks characterized by hierarchical organization and highly connected hubs remains sparse. The principle of efficient coding proposes that the brain transmits maximal information in a metabolically economical or compressed form to improve future behavior. To determine how structural connectivity supports efficient coding, we develop a theory specifying minimum rates of message transmission between brain regions to achieve an expected fidelity, and we test five predictions from the theory based on random walk communication dynamics. In doing so, we introduce the metric of compression efficiency, which quantifies the trade-off between lossy compression and transmission fidelity in structural networks. In a large sample of youth (n = 1,042; age 8-23 years), we analyze structural networks derived from diffusion-weighted imaging and metabolic expenditure operationalized using cerebral blood flow. We show that structural networks strike compression efficiency trade-offs consistent with theoretical predictions. We find that compression efficiency prioritizes fidelity with development, heightens when metabolic resources and myelination guide communication, explains advantages of hierarchical organization, links higher input fidelity to disproportionate areal expansion, and shows that hubs integrate information by lossy compression. Lastly, compression efficiency is predictive of behavior-beyond the conventional network efficiency metric-for cognitive domains including executive function, memory, complex reasoning, and social cognition. Our findings elucidate how macroscale connectivity supports efficient coding and serve to foreground communication processes that utilize random walk dynamics constrained by network connectivity.
Published: 2022

23. ASLPrep: a platform for processing of arterial spin labeled MRI and quantification of regional brain perfusion.

Author: Butler, Ellyn, Butler, Ellyn, Cook, Phil, Colcombe, Stan, Covitz, Sydney, Davatzikos, Christos, Davila, Diego, Elliott, Mark, Flounders, Matthew, Franco, Alexandre, Gur, Raquel, Gur, Ruben, Jaber, Basma, McMillian, Corey, Milham, Michael, Mutsaerts, Henk, Oathes, Desmond, Olm, Christopher, Phillips, Jeffrey, Tackett, Will, Roalf, David, Adebimpe, Azeez, Bertolero, Maxwell, Dolui, Sudipto, Cieslak, Matthew, Murtha, Kristin, Baller, Erica, Boeve, Bradley, Esteban, Oscar, Poldrack, Russell, Detre, John, Satterthwaite, Theodore, Tapera, Tinashe, Tisdall, M, Boxer, Adam, Rosen, Howard, Zhou, Dale, Butler, Ellyn, Butler, Ellyn, Cook, Phil, Colcombe, Stan, Covitz, Sydney, Davatzikos, Christos, Davila, Diego, Elliott, Mark, Flounders, Matthew, Franco, Alexandre, Gur, Raquel, Gur, Ruben, Jaber, Basma, McMillian, Corey, Milham, Michael, Mutsaerts, Henk, Oathes, Desmond, Olm, Christopher, Phillips, Jeffrey, Tackett, Will, Roalf, David, Adebimpe, Azeez, Bertolero, Maxwell, Dolui, Sudipto, Cieslak, Matthew, Murtha, Kristin, Baller, Erica, Boeve, Bradley, Esteban, Oscar, Poldrack, Russell, Detre, John, Satterthwaite, Theodore, Tapera, Tinashe, Tisdall, M, Boxer, Adam, Rosen, Howard, and Zhou, Dale
Abstract: Arterial spin labeled (ASL) magnetic resonance imaging (MRI) is the primary method for noninvasively measuring regional brain perfusion in humans. We introduce ASLPrep, a suite of software pipelines that ensure the reproducible and generalizable processing of ASL MRI data.
Published: 2022

24. A framework for the investigation of rare genetic disorders in neuropsychiatry

Author: McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Sanders, Stephan J., Sahin, Mustafa, Hostyk, Joseph, Thurm, Audrey, Jacquemont, Sebastien, Avillach, Paul, Douard, Elise, Martin, Christa L., Modi, Meera E., Moreno-De-Luca, Andres, Raznahan, Armin, Anticevic, Alan, Dolmetsch, Ricardo, Feng, Guoping, Geschwind, Daniel H., Glahn, David C., Goldstein, David B., Ledbetter, David H., Mulle, Jennifer G., Pasca, Sergiu P., Samaco, Rodney, Sebat, Jonathan, Pariser, Anne, Lehner, Thomas, Gur, Raquel E., Bearden, Carrie E., McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Sanders, Stephan J., Sahin, Mustafa, Hostyk, Joseph, Thurm, Audrey, Jacquemont, Sebastien, Avillach, Paul, Douard, Elise, Martin, Christa L., Modi, Meera E., Moreno-De-Luca, Andres, Raznahan, Armin, Anticevic, Alan, Dolmetsch, Ricardo, Feng, Guoping, Geschwind, Daniel H., Glahn, David C., Goldstein, David B., Ledbetter, David H., Mulle, Jennifer G., Pasca, Sergiu P., Samaco, Rodney, Sebat, Jonathan, Pariser, Anne, Lehner, Thomas, Gur, Raquel E., and Bearden, Carrie E.
Abstract: De novo and inherited rare genetic disorders (RGDs) are a major cause of human morbidity, frequently involving neuropsychiatric symptoms. Recent advances in genomic technologies and data sharing have revolutionized the identification and diagnosis of RGDs, presenting an opportunity to elucidate the mechanisms underlying neuropsychiatric disorders by investigating the pathophysiology of high-penetrance genetic risk factors. Here we seek out the best path forward for achieving these goals. We think future research will require consistent approaches across multiple RGDs and developmental stages, involving both the characterization of shared neuropsychiatric dimensions in humans and the identification of neurobiological commonalities in model systems. A coordinated and concerted effort across patients, families, researchers, clinicians and institutions, including rapid and broad sharing of data, is now needed to translate these discoveries into urgently needed therapies.
Published: 2022

25. Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions

Author: Sieberts, Solveig K., Perumal, Thanneer M., Carrasquillo, Minerva M., Allen, Mariet, Reddy, Joseph S., Hoffman, Gabriel E., Dang, Kristen K., Calley, John, Ebert, Philip J., Eddy, James, Wang, Xue, Greenwood, Anna K., Mostafavi, Sara, Akbarian, Schahram, Bendl, Jaroslav, Breen, Michael S., Brennand, Kristen, Brown, Leanne, Browne, Andrew, Buxbaum, Joseph D., Charney, Alexander, Chess, Andrew, Couto, Lizette, Crawford, Greg, Devillers, Olivia, Devlin, Bernie, Dobbyn, Amanda, Domenici, Enrico, Filosi, Michele, Flatow, Elie, Francoeur, Nancy, Fullard, John, Gil, Sergio Espeso, Girdhar, Kiran, Gulyás-Kovács, Attila, Gur, Raquel, Hahn, Chang-Gyu, Haroutunian, Vahram, Hauberg, Mads Engel, Huckins, Laura, Jacobov, Rivky, Jiang, Yan, Johnson, Jessica S., Kassim, Bibi, Kim, Yungil, Klei, Lambertus, Kramer, Robin, Lauria, Mario, Lehner, Thomas, Lewis, David A., Lipska, Barbara K., Montgomery, Kelsey, Park, Royce, Rosenbluh, Chaggai, Roussos, Panagiotis, Ruderfer, Douglas M., Senthil, Geetha, Shah, Hardik R., Sloofman, Laura, Song, Lingyun, Stahl, Eli, Sullivan, Patrick, Visintainer, Roberto, Wang, Jiebiao, Wang, Ying-Chih, Wiseman, Jennifer, Xia, Eva, Zhang, Wen, Zharovsky, Elizabeth, Addis, Laura, Addo, Sadiya N., Airey, David Charles, Arnold, Matthias, Bennett, David A., Bi, Yingtao, Biber, Knut, Blach, Colette, Bradhsaw, Elizabeth, Brennan, Paul, Canet-Aviles, Rosa, Cao, Sherry, Cavalla, Anna, Chae, Yooree, Chen, William W., Cheng, Jie, Collier, David Andrew, Dage, Jeffrey L., Dammer, Eric B., Davis, Justin Wade, Davis, John, Drake, Derek, Duong, Duc, Eastwood, Brian J., Ehrlich, Michelle, Ellingson, Benjamin, Engelmann, Brett W., Esmaeelinieh, Sahar, Felsky, Daniel, Funk, Cory, Gaiteri, Chris, Gandy, Samuel, Gao, Fan, Gileadi, Opher, Golde, Todd, Grosskurth, Shaun E., Gupta, Rishi R., Gutteridge, Alex X., Hooli, Basavaraj, Humphryes-Kirilov, Neil, Iijima, Koichi, James, Corey, Jung, Paul M., Kaddurah-Daouk, Rima, Kastenmuller, Gabi, Klein, Hans-Ulrich, Kummer, Markus, Lacor, Pascale N., Lah, James, Laing, Emma, Levey, Allan, Li, Yupeng, Lipsky, Samantha, Liu, Yushi, Liu, Jimmy, Liu, Zhandong, Louie, Gregory, Lu, Tao, Ma, Yiyi, Matsuoka, Yasuji Y., Menon, Vilas, Miller, Bradley, Misko, Thomas P., Mollon, Jennifer E., Mukherjee, Sumit, Noggle, Scott, Pao, Ping-Chieh, Pearce, Tracy Young, Pearson, Neil, Penny, Michelle, Petyuk, Vladislav A., Price, Nathan, Quarless, Danjuma X., Ravikumar, Brinda, Ried, Janina S., Ruble, Cara Lee Ann, Runz, Heiko, Saykin, Andrew J., Schadt, Eric, Scherschel, James E., Seyfried, Nicholas, Shulman, Joshua M., Snyder, Phil, Soares, Holly, Srivastava, Gyan P., Stockmann, Henning, Taga, Mariko, Tasaki, Shinya, Tenenbaum, Jessie, Tsai, Li-Huei, Vasanthakumar, Aparna, Wachter, Astrid, Wang, Yaming, Wang, Hong, Wang, Minghui, Whelan, Christopher D., White, Charles, Woo, Kara H., Wren, Paul, Wu, Jessica W., Xi, Hualin S., Yankner, Bruce A., Younkin, Steven G., Yu, Lei, Zavodszky, Maria, Zhang, Wenling, Zhang, Guoqiang, Zhang, Bin, Zhu, Jun, Omberg, Larsson, Peters, Mette A., Logsdon, Benjamin A., De Jager, Philip L., Ertekin-Taner, Nilüfer, Mangravite, Lara M., Sieberts, Solveig K., Perumal, Thanneer M., Carrasquillo, Minerva M., Allen, Mariet, Reddy, Joseph S., Hoffman, Gabriel E., Dang, Kristen K., Calley, John, Ebert, Philip J., Eddy, James, Wang, Xue, Greenwood, Anna K., Mostafavi, Sara, Akbarian, Schahram, Bendl, Jaroslav, Breen, Michael S., Brennand, Kristen, Brown, Leanne, Browne, Andrew, Buxbaum, Joseph D., Charney, Alexander, Chess, Andrew, Couto, Lizette, Crawford, Greg, Devillers, Olivia, Devlin, Bernie, Dobbyn, Amanda, Domenici, Enrico, Filosi, Michele, Flatow, Elie, Francoeur, Nancy, Fullard, John, Gil, Sergio Espeso, Girdhar, Kiran, Gulyás-Kovács, Attila, Gur, Raquel, Hahn, Chang-Gyu, Haroutunian, Vahram, Hauberg, Mads Engel, Huckins, Laura, Jacobov, Rivky, Jiang, Yan, Johnson, Jessica S., Kassim, Bibi, Kim, Yungil, Klei, Lambertus, Kramer, Robin, Lauria, Mario, Lehner, Thomas, Lewis, David A., Lipska, Barbara K., Montgomery, Kelsey, Park, Royce, Rosenbluh, Chaggai, Roussos, Panagiotis, Ruderfer, Douglas M., Senthil, Geetha, Shah, Hardik R., Sloofman, Laura, Song, Lingyun, Stahl, Eli, Sullivan, Patrick, Visintainer, Roberto, Wang, Jiebiao, Wang, Ying-Chih, Wiseman, Jennifer, Xia, Eva, Zhang, Wen, Zharovsky, Elizabeth, Addis, Laura, Addo, Sadiya N., Airey, David Charles, Arnold, Matthias, Bennett, David A., Bi, Yingtao, Biber, Knut, Blach, Colette, Bradhsaw, Elizabeth, Brennan, Paul, Canet-Aviles, Rosa, Cao, Sherry, Cavalla, Anna, Chae, Yooree, Chen, William W., Cheng, Jie, Collier, David Andrew, Dage, Jeffrey L., Dammer, Eric B., Davis, Justin Wade, Davis, John, Drake, Derek, Duong, Duc, Eastwood, Brian J., Ehrlich, Michelle, Ellingson, Benjamin, Engelmann, Brett W., Esmaeelinieh, Sahar, Felsky, Daniel, Funk, Cory, Gaiteri, Chris, Gandy, Samuel, Gao, Fan, Gileadi, Opher, Golde, Todd, Grosskurth, Shaun E., Gupta, Rishi R., Gutteridge, Alex X., Hooli, Basavaraj, Humphryes-Kirilov, Neil, Iijima, Koichi, James, Corey, Jung, Paul M., Kaddurah-Daouk, Rima, Kastenmuller, Gabi, Klein, Hans-Ulrich, Kummer, Markus, Lacor, Pascale N., Lah, James, Laing, Emma, Levey, Allan, Li, Yupeng, Lipsky, Samantha, Liu, Yushi, Liu, Jimmy, Liu, Zhandong, Louie, Gregory, Lu, Tao, Ma, Yiyi, Matsuoka, Yasuji Y., Menon, Vilas, Miller, Bradley, Misko, Thomas P., Mollon, Jennifer E., Mukherjee, Sumit, Noggle, Scott, Pao, Ping-Chieh, Pearce, Tracy Young, Pearson, Neil, Penny, Michelle, Petyuk, Vladislav A., Price, Nathan, Quarless, Danjuma X., Ravikumar, Brinda, Ried, Janina S., Ruble, Cara Lee Ann, Runz, Heiko, Saykin, Andrew J., Schadt, Eric, Scherschel, James E., Seyfried, Nicholas, Shulman, Joshua M., Snyder, Phil, Soares, Holly, Srivastava, Gyan P., Stockmann, Henning, Taga, Mariko, Tasaki, Shinya, Tenenbaum, Jessie, Tsai, Li-Huei, Vasanthakumar, Aparna, Wachter, Astrid, Wang, Yaming, Wang, Hong, Wang, Minghui, Whelan, Christopher D., White, Charles, Woo, Kara H., Wren, Paul, Wu, Jessica W., Xi, Hualin S., Yankner, Bruce A., Younkin, Steven G., Yu, Lei, Zavodszky, Maria, Zhang, Wenling, Zhang, Guoqiang, Zhang, Bin, Zhu, Jun, Omberg, Larsson, Peters, Mette A., Logsdon, Benjamin A., De Jager, Philip L., Ertekin-Taner, Nilüfer, and Mangravite, Lara M.
Abstract: © 2020, The Author(s). The availability of high-quality RNA-sequencing and genotyping data of post-mortem brain collections from consortia such as CommonMind Consortium (CMC) and the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) Consortium enable the generation of a large-scale brain cis-eQTL meta-analysis. Here we generate cerebral cortical eQTL from 1433 samples available from four cohorts (identifying >4.1 million significant eQTL for >18,000 genes), as well as cerebellar eQTL from 261 samples (identifying 874,836 significant eQTL for >10,000 genes). We find substantially improved power in the meta-analysis over individual cohort analyses, particularly in comparison to the Genotype-Tissue Expression (GTEx) Project eQTL. Additionally, we observed differences in eQTL patterns between cerebral and cerebellar brain regions. We provide these brain eQTL as a resource for use by the research community. As a proof of principle for their utility, we apply a colocalization analysis to identify genes underlying the GWAS association peaks for schizophrenia and identify a potentially novel gene colocalization with lncRNA RP11-677M14.2 (posterior probability of colocalization 0.975).
Published: 2022

26. Greater male than female variability in regional brain structure across the lifespan

Author: Wierenga, Lara M., Doucet, Gaelle E., Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn, I, Andreassen, Ole A., Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret, I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Calhoun, Vince D., Canales-Rodriguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Clark, Vincent P., Conrod, Patricia J., Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G., Dickie, Erin W., Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco J. C., Di Giorgio, Annabella, Glahn, David C., Gotlib, Ian H., Grabe, Hans J., Gruber, Oliver, Gruner, Patricia, Gur, Raquel E., Gur, Ruben C., Gurholt, Tiril P., de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J., Hartman, Catharina A., Hatton, Sean N., Heslenfeld, Dirk J., van den Heuvel, Odile A., Hickie, Ian B., Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Pol, Hilleke E. Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony C., Jiang, Jiyang, Jonsson, Erik G., Joska, John A., Kalnin, Andrew J., Klein, Marieke, Koenders, Laura, Kolskar, Knut K., Kramer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S., Lee, Phil H., Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martinez-Zalacain, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C., McDonald, Colm, McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, van der Meer, Dennis, Menchon, Jose M., Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Radua, Joaquim, Reif, Andreas, Richard, Genevieve, Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sarro, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Sim, Kang, Simmons, Andrew, Smoller, Jordan W., Sommer, Iris E., Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Szeszko, Philip R., Temmingh, Henk S., Thomopoulos, Sophia, I, Tomyshev, Alexander S., Trollor, Julian N., Uhlmann, Anne, Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Volzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather C., Williams, Steven C. R., Wittfeld, Katharina, Wolf, Daniel H., Wright, Margaret J., Yoncheva, Yuliya N., Zanetti, Marcus, V, Ziegler, Georg C., de Zubicaray, Greig, I, Thompson, Paul M., Crone, Eveline A., Frangou, Sophia, Tamnes, Christian K., Wierenga, Lara M., Doucet, Gaelle E., Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn, I, Andreassen, Ole A., Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret, I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Calhoun, Vince D., Canales-Rodriguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Clark, Vincent P., Conrod, Patricia J., Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G., Dickie, Erin W., Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco J. C., Di Giorgio, Annabella, Glahn, David C., Gotlib, Ian H., Grabe, Hans J., Gruber, Oliver, Gruner, Patricia, Gur, Raquel E., Gur, Ruben C., Gurholt, Tiril P., de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J., Hartman, Catharina A., Hatton, Sean N., Heslenfeld, Dirk J., van den Heuvel, Odile A., Hickie, Ian B., Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Pol, Hilleke E. Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony C., Jiang, Jiyang, Jonsson, Erik G., Joska, John A., Kalnin, Andrew J., Klein, Marieke, Koenders, Laura, Kolskar, Knut K., Kramer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S., Lee, Phil H., Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martinez-Zalacain, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C., McDonald, Colm, McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, van der Meer, Dennis, Menchon, Jose M., Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Radua, Joaquim, Reif, Andreas, Richard, Genevieve, Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sarro, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Sim, Kang, Simmons, Andrew, Smoller, Jordan W., Sommer, Iris E., Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Szeszko, Philip R., Temmingh, Henk S., Thomopoulos, Sophia, I, Tomyshev, Alexander S., Trollor, Julian N., Uhlmann, Anne, Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Volzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather C., Williams, Steven C. R., Wittfeld, Katharina, Wolf, Daniel H., Wright, Margaret J., Yoncheva, Yuliya N., Zanetti, Marcus, V, Ziegler, Georg C., de Zubicaray, Greig, I, Thompson, Paul M., Crone, Eveline A., Frangou, Sophia, and Tamnes, Christian K.
Abstract: For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
Published: 2022
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27. Greater male than female variability in regional brain structure across the lifespan

Author: Wierenga, Lara M., Doucet, Gaelle E., Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn, I, Andreassen, Ole A., Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret, I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Calhoun, Vince D., Canales-Rodriguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Clark, Vincent P., Conrod, Patricia J., Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G., Dickie, Erin W., Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco J. C., Di Giorgio, Annabella, Glahn, David C., Gotlib, Ian H., Grabe, Hans J., Gruber, Oliver, Gruner, Patricia, Gur, Raquel E., Gur, Ruben C., Gurholt, Tiril P., de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J., Hartman, Catharina A., Hatton, Sean N., Heslenfeld, Dirk J., van den Heuvel, Odile A., Hickie, Ian B., Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Pol, Hilleke E. Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony C., Jiang, Jiyang, Jonsson, Erik G., Joska, John A., Kalnin, Andrew J., Klein, Marieke, Koenders, Laura, Kolskar, Knut K., Kramer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S., Lee, Phil H., Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martinez-Zalacain, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C., McDonald, Colm, McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, van der Meer, Dennis, Menchon, Jose M., Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Radua, Joaquim, Reif, Andreas, Richard, Genevieve, Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sarro, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Sim, Kang, Simmons, Andrew, Smoller, Jordan W., Sommer, Iris E., Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Szeszko, Philip R., Temmingh, Henk S., Thomopoulos, Sophia, I, Tomyshev, Alexander S., Trollor, Julian N., Uhlmann, Anne, Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Volzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather C., Williams, Steven C. R., Wittfeld, Katharina, Wolf, Daniel H., Wright, Margaret J., Yoncheva, Yuliya N., Zanetti, Marcus, V, Ziegler, Georg C., de Zubicaray, Greig, I, Thompson, Paul M., Crone, Eveline A., Frangou, Sophia, Tamnes, Christian K., Wierenga, Lara M., Doucet, Gaelle E., Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn, I, Andreassen, Ole A., Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret, I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Calhoun, Vince D., Canales-Rodriguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Clark, Vincent P., Conrod, Patricia J., Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G., Dickie, Erin W., Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco J. C., Di Giorgio, Annabella, Glahn, David C., Gotlib, Ian H., Grabe, Hans J., Gruber, Oliver, Gruner, Patricia, Gur, Raquel E., Gur, Ruben C., Gurholt, Tiril P., de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J., Hartman, Catharina A., Hatton, Sean N., Heslenfeld, Dirk J., van den Heuvel, Odile A., Hickie, Ian B., Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Pol, Hilleke E. Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony C., Jiang, Jiyang, Jonsson, Erik G., Joska, John A., Kalnin, Andrew J., Klein, Marieke, Koenders, Laura, Kolskar, Knut K., Kramer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S., Lee, Phil H., Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martinez-Zalacain, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C., McDonald, Colm, McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, van der Meer, Dennis, Menchon, Jose M., Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Radua, Joaquim, Reif, Andreas, Richard, Genevieve, Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sarro, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Sim, Kang, Simmons, Andrew, Smoller, Jordan W., Sommer, Iris E., Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Szeszko, Philip R., Temmingh, Henk S., Thomopoulos, Sophia, I, Tomyshev, Alexander S., Trollor, Julian N., Uhlmann, Anne, Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Volzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather C., Williams, Steven C. R., Wittfeld, Katharina, Wolf, Daniel H., Wright, Margaret J., Yoncheva, Yuliya N., Zanetti, Marcus, V, Ziegler, Georg C., de Zubicaray, Greig, I, Thompson, Paul M., Crone, Eveline A., Frangou, Sophia, and Tamnes, Christian K.
Abstract: For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
Published: 2022
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28. Exposome and Trans-syndromal Developmental Trajectories Toward Psychosis

Author: Hersenen-Medisch 1, Brain, Barzilay, Ran, Pries, Lotta-Katrin, Moore, Tyler M, Gur, Raquel E, van Os, Jim, Rutten, Bart P F, Guloksuz, Sinan, Hersenen-Medisch 1, Brain, Barzilay, Ran, Pries, Lotta-Katrin, Moore, Tyler M, Gur, Raquel E, van Os, Jim, Rutten, Bart P F, and Guloksuz, Sinan
Published: 2022

29. Schizophrenia Imaging Signatures and Their Associations With Cognition, Psychopathology, and Genetics in the General Population

Author: Onderzoeksgroep 11, Brain, Onderzoek, Chand, Ganesh B, Singhal, Pankhuri, Dwyer, Dominic B, Wen, Junhao, Erus, Guray, Doshi, Jimit, Srinivasan, Dhivya, Mamourian, Elizabeth, Varol, Erdem, Sotiras, Aristeidis, Hwang, Gyujoon, Dazzan, Paola, Kahn, Rene S, Schnack, Hugo G, Zanetti, Marcus V, Meisenzahl, Eva, Busatto, Geraldo F, Crespo-Facorro, Benedicto, Pantelis, Christos, Wood, Stephen J, Zhuo, Chuanjun, Shinohara, Russell T, Shou, Haochang, Fan, Yong, Koutsouleris, Nikolaos, Kaczkurkin, Antonia N, Moore, Tyler M, Verma, Anurag, Calkins, Monica E, Gur, Raquel E, Gur, Ruben C, Ritchie, Marylyn D, Satterthwaite, Theodore D, Wolf, Daniel H, Davatzikos, Christos, Onderzoeksgroep 11, Brain, Onderzoek, Chand, Ganesh B, Singhal, Pankhuri, Dwyer, Dominic B, Wen, Junhao, Erus, Guray, Doshi, Jimit, Srinivasan, Dhivya, Mamourian, Elizabeth, Varol, Erdem, Sotiras, Aristeidis, Hwang, Gyujoon, Dazzan, Paola, Kahn, Rene S, Schnack, Hugo G, Zanetti, Marcus V, Meisenzahl, Eva, Busatto, Geraldo F, Crespo-Facorro, Benedicto, Pantelis, Christos, Wood, Stephen J, Zhuo, Chuanjun, Shinohara, Russell T, Shou, Haochang, Fan, Yong, Koutsouleris, Nikolaos, Kaczkurkin, Antonia N, Moore, Tyler M, Verma, Anurag, Calkins, Monica E, Gur, Raquel E, Gur, Ruben C, Ritchie, Marylyn D, Satterthwaite, Theodore D, Wolf, Daniel H, and Davatzikos, Christos
Published: 2022

30. Inter-rater reliability of subthreshold psychotic symptoms in individuals with 22q11.2 deletion syndrome.

Author: Moore, Tyler M, Moore, Tyler M, Salzer, Deby, Bearden, Carrie E, Calkins, Monica E, Kates, Wendy R, Kushan, Leila, Gallagher, Robert Sean, Frumer, Dafna Sofrin, Weinberger, Ronnie, McDonald-McGinn, Donna M, Gur, Raquel E, Gothelf, Doron, Moore, Tyler M, Moore, Tyler M, Salzer, Deby, Bearden, Carrie E, Calkins, Monica E, Kates, Wendy R, Kushan, Leila, Gallagher, Robert Sean, Frumer, Dafna Sofrin, Weinberger, Ronnie, McDonald-McGinn, Donna M, Gur, Raquel E, and Gothelf, Doron
Abstract: BackgroundPathways leading to psychosis in 22q11.2 deletion syndrome (22q11.2DS) have been the focus of intensive research during the last two decades. One of the common clinical risk factors for the evolution of psychosis in 22q11.2DS is the presence of positive and negative subthreshold psychotic symptoms. The gold standard for measuring subthreshold symptoms is the Structured Interview for Prodromal Syndromes (SIPS) and its accompanying Scale of Prodromal Symptoms (SOPS) ratings. Although the scale has been used by many centers studying 22q11.2DS, the inter-site reliability of the scale in this population has never been established.MethodsIn the present study, experienced clinical assessors from three large international centers studying 22q11.2DS independently rated video recordings of 18 adolescents and young adults with 22q11.2DS.ResultsThe intraclass correlations coefficients (ICCs) among three raters for the SOPS total scores, as well as for the positive, negative, and disorganization subscale scores, were good-to-excellent (ICCs range 0.73-0.93). The raters were also able to reliably determine the subjects' subthreshold syndrome status (ICC = 0.71). The reliability of individual items was good-to-excellent for all items, ranging from 0.61 for motor disturbances [G3] to 0.95 for bizarre thinking.ConclusionsOur results show that trained clinicians can reliably screen for subthreshold psychotic symptoms in individuals with 22q11.2DS. To increase assessment reliability, we suggest specific clarifications and simplifications to the standard SIPS interview for future studies.
Published: 2021

31. Genetic and clinical analyses of psychosis spectrum symptoms in a large multiethnic youth cohort reveal significant link with ADHD.

Author: Olde Loohuis, Loes M, Olde Loohuis, Loes M, Mennigen, Eva, Ori, Anil PS, Perkins, Diana, Robinson, Elise, Addington, Jean, Cadenhead, Kristin S, Cornblatt, Barbara A, Mathalon, Daniel H, McGlashan, Thomas H, Seidman, Larry J, Keshavan, Matcheri S, Stone, William S, Tsuang, Ming T, Walker, Elaine F, Woods, Scott W, Cannon, Tyrone D, Gur, Ruben C, Gur, Raquel E, Bearden, Carrie E, Ophoff, Roel A, Olde Loohuis, Loes M, Olde Loohuis, Loes M, Mennigen, Eva, Ori, Anil PS, Perkins, Diana, Robinson, Elise, Addington, Jean, Cadenhead, Kristin S, Cornblatt, Barbara A, Mathalon, Daniel H, McGlashan, Thomas H, Seidman, Larry J, Keshavan, Matcheri S, Stone, William S, Tsuang, Ming T, Walker, Elaine F, Woods, Scott W, Cannon, Tyrone D, Gur, Ruben C, Gur, Raquel E, Bearden, Carrie E, and Ophoff, Roel A
Abstract: Psychotic symptoms are not only an important feature of severe neuropsychiatric disorders, but are also common in the general population, especially in youth. The genetic etiology of psychosis symptoms in youth remains poorly understood. To characterize genetic risk for psychosis spectrum symptoms (PS), we leverage a community-based multiethnic sample of children and adolescents aged 8-22 years, the Philadelphia Neurodevelopmental Cohort (n = 7225, 20% PS). Using an elastic net regression model, we aim to classify PS status using polygenic scores (PGS) based on a range of heritable psychiatric and brain-related traits in a multi-PGS model. We also perform univariate PGS associations and evaluate age-specific effects. The multi-PGS analyses do not improve prediction of PS status over univariate models, but reveal that the attention deficit hyperactivity disorder (ADHD) PGS is robustly and uniquely associated with PS (OR 1.12 (1.05, 1.18) P = 0.0003). This association is driven by subjects of European ancestry (OR = 1.23 (1.14, 1.34), P = 4.15 × 10-7) but is not observed in African American subjects (P = 0.65). We find a significant interaction of ADHD PGS with age (P = 0.01), with a stronger association in younger children. The association is independent of phenotypic overlap between ADHD and PS, not indirectly driven by substance use or childhood trauma, and appears to be specific to PS rather than reflecting general psychopathology in youth. In an independent sample, we replicate an increased ADHD PGS in 328 youth at clinical high risk for psychosis, compared to 216 unaffected controls (OR 1.06, CI(1.01, 1.11), P = 0.02). Our findings suggest that PS in youth may reflect a different genetic etiology than psychotic symptoms in adulthood, one more akin to ADHD, and shed light on how genetic risk can be investigated across early disease trajectories.
Published: 2021

32. Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion.

Author: Cleynen, Isabelle, Cleynen, Isabelle, Engchuan, Worrawat, Hestand, Matthew S, Heung, Tracy, Holleman, Aaron M, Johnston, H Richard, Monfeuga, Thomas, McDonald-McGinn, Donna M, Gur, Raquel E, Morrow, Bernice E, Swillen, Ann, Vorstman, Jacob AS, Bearden, Carrie E, Chow, Eva WC, van den Bree, Marianne, Emanuel, Beverly S, Vermeesch, Joris R, Warren, Stephen T, Owen, Michael J, Chopra, Pankaj, Cutler, David J, Duncan, Richard, Kotlar, Alex V, Mulle, Jennifer G, Voss, Anna J, Zwick, Michael E, Diacou, Alexander, Golden, Aaron, Guo, Tingwei, Lin, Jhih-Rong, Wang, Tao, Zhang, Zhengdong, Zhao, Yingjie, Marshall, Christian, Merico, Daniele, Jin, Andrea, Lilley, Brenna, Salmons, Harold I, Tran, Oanh, Holmans, Peter, Pardinas, Antonio, Walters, James TR, Demaerel, Wolfram, Boot, Erik, Butcher, Nancy J, Costain, Gregory A, Lowther, Chelsea, Evers, Rens, van Amelsvoort, Therese AMJ, van Duin, Esther, Vingerhoets, Claudia, Breckpot, Jeroen, Devriendt, Koen, Vergaelen, Elfi, Vogels, Annick, Crowley, T Blaine, McGinn, Daniel E, Moss, Edward M, Sharkus, Robert J, Unolt, Marta, Zackai, Elaine H, Calkins, Monica E, Gallagher, Robert S, Gur, Ruben C, Tang, Sunny X, Fritsch, Rosemarie, Ornstein, Claudia, Repetto, Gabriela M, Breetvelt, Elemi, Duijff, Sasja N, Fiksinski, Ania, Moss, Hayley, Niarchou, Maria, Murphy, Kieran C, Prasad, Sarah E, Daly, Eileen M, Gudbrandsen, Maria, Murphy, Clodagh M, Murphy, Declan G, Buzzanca, Antonio, Fabio, Fabio Di, Digilio, Maria C, Pontillo, Maria, Marino, Bruno, Vicari, Stefano, Coleman, Karlene, Cubells, Joseph F, Ousley, Opal Y, Carmel, Miri, Gothelf, Doron, Mekori-Domachevsky, Ehud, Michaelovsky, Elena, Weinberger, Ronnie, Weizman, Abraham, Kushan, Leila, Jalbrzikowski, Maria, Armando, Marco, Eliez, Stéphan, Sandini, Corrado, Schneider, Maude, Cleynen, Isabelle, Cleynen, Isabelle, Engchuan, Worrawat, Hestand, Matthew S, Heung, Tracy, Holleman, Aaron M, Johnston, H Richard, Monfeuga, Thomas, McDonald-McGinn, Donna M, Gur, Raquel E, Morrow, Bernice E, Swillen, Ann, Vorstman, Jacob AS, Bearden, Carrie E, Chow, Eva WC, van den Bree, Marianne, Emanuel, Beverly S, Vermeesch, Joris R, Warren, Stephen T, Owen, Michael J, Chopra, Pankaj, Cutler, David J, Duncan, Richard, Kotlar, Alex V, Mulle, Jennifer G, Voss, Anna J, Zwick, Michael E, Diacou, Alexander, Golden, Aaron, Guo, Tingwei, Lin, Jhih-Rong, Wang, Tao, Zhang, Zhengdong, Zhao, Yingjie, Marshall, Christian, Merico, Daniele, Jin, Andrea, Lilley, Brenna, Salmons, Harold I, Tran, Oanh, Holmans, Peter, Pardinas, Antonio, Walters, James TR, Demaerel, Wolfram, Boot, Erik, Butcher, Nancy J, Costain, Gregory A, Lowther, Chelsea, Evers, Rens, van Amelsvoort, Therese AMJ, van Duin, Esther, Vingerhoets, Claudia, Breckpot, Jeroen, Devriendt, Koen, Vergaelen, Elfi, Vogels, Annick, Crowley, T Blaine, McGinn, Daniel E, Moss, Edward M, Sharkus, Robert J, Unolt, Marta, Zackai, Elaine H, Calkins, Monica E, Gallagher, Robert S, Gur, Ruben C, Tang, Sunny X, Fritsch, Rosemarie, Ornstein, Claudia, Repetto, Gabriela M, Breetvelt, Elemi, Duijff, Sasja N, Fiksinski, Ania, Moss, Hayley, Niarchou, Maria, Murphy, Kieran C, Prasad, Sarah E, Daly, Eileen M, Gudbrandsen, Maria, Murphy, Clodagh M, Murphy, Declan G, Buzzanca, Antonio, Fabio, Fabio Di, Digilio, Maria C, Pontillo, Maria, Marino, Bruno, Vicari, Stefano, Coleman, Karlene, Cubells, Joseph F, Ousley, Opal Y, Carmel, Miri, Gothelf, Doron, Mekori-Domachevsky, Ehud, Michaelovsky, Elena, Weinberger, Ronnie, Weizman, Abraham, Kushan, Leila, Jalbrzikowski, Maria, Armando, Marco, Eliez, Stéphan, Sandini, Corrado, and Schneider, Maude
Abstract: Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10-6). Novel reciprocal case-control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present.
Published: 2021

33. Toward Generalizable and Transdiagnostic Tools for Psychosis Prediction: An Independent Validation and Improvement of the NAPLS-2 Risk Calculator in the Multisite PRONIA Cohort

Author: Koutsouleris, Nikolaos, Worthington, Michelle, Dwyer, Dominic B., Kambeitz-Ilankovic, Lana, Sanfelici, Rachele, Fusar-Poli, Paolo, Rosen, Marlene, Ruhrmann, Stephan, Anticevic, Alan, Addington, Jean, Perkins, Diana O., Bearden, Carrie E., Cornblatt, Barbara A., Cadenhead, Kristin S., Mathalon, Daniel H., McGlashan, Thomas, Seidman, Larry, Tsuang, Ming, Walker, Elaine F., Woods, Scott W., Falkai, Peter, Lencer, Rebekka, Bertolino, Alessandro, Kambeitz, Joseph, Schultze-Lutter, Frauke, Meisenzahl, Eva, Salokangas, Raimo K. R., Hietala, Jarmo, Brambilla, Paolo, Upthegrove, Rachel, Borgwardt, Stefan, Wood, Stephen, Gur, Raquel E., McGuire, Philip, Cannon, Tyrone D., Koutsouleris, Nikolaos, Worthington, Michelle, Dwyer, Dominic B., Kambeitz-Ilankovic, Lana, Sanfelici, Rachele, Fusar-Poli, Paolo, Rosen, Marlene, Ruhrmann, Stephan, Anticevic, Alan, Addington, Jean, Perkins, Diana O., Bearden, Carrie E., Cornblatt, Barbara A., Cadenhead, Kristin S., Mathalon, Daniel H., McGlashan, Thomas, Seidman, Larry, Tsuang, Ming, Walker, Elaine F., Woods, Scott W., Falkai, Peter, Lencer, Rebekka, Bertolino, Alessandro, Kambeitz, Joseph, Schultze-Lutter, Frauke, Meisenzahl, Eva, Salokangas, Raimo K. R., Hietala, Jarmo, Brambilla, Paolo, Upthegrove, Rachel, Borgwardt, Stefan, Wood, Stephen, Gur, Raquel E., McGuire, Philip, and Cannon, Tyrone D.
Abstract: BACKGROUND: Transition to psychosis is among the most adverse outcomes of clinical high-risk (CHR) syndromes encompassing ultra-high risk (UHR) and basic symptom states. Clinical risk calculators may facilitate an early and individualized interception of psychosis, but their real-world implementation requires thorough validation across diverse risk populations, including young patients with depressive syndromes. METHODS: We validated the previously described NAPLS-2 (North American Prodrome Longitudinal Study 2) calculator in 334 patients (26 with transition to psychosis) with CHR or recent-onset depression (ROD) drawn from the multisite European PRONIA (Personalised Prognostic Tools for Early Psychosis Management) study. Patients were categorized into three risk enrichment levels, ranging from UHR, over CHR, to a broad-risk population comprising patients with CHR or ROD (CHR|ROD). We assessed how risk enrichment and different predictive algorithms influenced prognostic performance using reciprocal external validation. RESULTS: After calibration, the NAPLS-2 model predicted psychosis with a balanced accuracy (BAC) (sensitivity, specificity) of 68% (73%, 63%) in the PRONIA-UHR cohort, 67% (74%, 60%) in the CHR cohort, and 70% (73%, 66%) in patients with CHR|ROD. Multiple model derivation in PRONIA-CHR|ROD and validation in NAPLS-2-UHR patients confirmed that broader risk definitions produced more accurate risk calculators (CHR|ROD-based vs. UHR-based performance: 67% [68%, 66%] vs. 58% [61%, 56%]). Support vector machines were superior in CHR|ROD (BAC = 71%), while ridge logistic regression and support vector machines performed similarly in CHR (BAC = 67%) and UHR cohorts (BAC = 65%). Attenuated psychotic symptoms predicted psychosis across risk levels, while younger age and reduced processing speed became increasingly relevant for broader risk cohorts. CONCLUSIONS: Clinical-neurocognitive machine learning models operating in young patients with affective and CHR syn
Published: 2021

34. Toward Generalizable and Transdiagnostic Tools for Psychosis Prediction: An Independent Validation and Improvement of the NAPLS-2 Risk Calculator in the Multisite PRONIA Cohort.

Author: Koutsouleris, Nikolaos, Koutsouleris, Nikolaos, Worthington, Michelle, Dwyer, Dominic B, Kambeitz-Ilankovic, Lana, Sanfelici, Rachele, Fusar-Poli, Paolo, Rosen, Marlene, Ruhrmann, Stephan, Anticevic, Alan, Addington, Jean, Perkins, Diana O, Bearden, Carrie E, Cornblatt, Barbara A, Cadenhead, Kristin S, Mathalon, Daniel H, McGlashan, Thomas, Seidman, Larry, Tsuang, Ming, Walker, Elaine F, Woods, Scott W, Falkai, Peter, Lencer, Rebekka, Bertolino, Alessandro, Kambeitz, Joseph, Schultze-Lutter, Frauke, Meisenzahl, Eva, Salokangas, Raimo KR, Hietala, Jarmo, Brambilla, Paolo, Upthegrove, Rachel, Borgwardt, Stefan, Wood, Stephen, Gur, Raquel E, McGuire, Philip, Cannon, Tyrone D, Koutsouleris, Nikolaos, Koutsouleris, Nikolaos, Worthington, Michelle, Dwyer, Dominic B, Kambeitz-Ilankovic, Lana, Sanfelici, Rachele, Fusar-Poli, Paolo, Rosen, Marlene, Ruhrmann, Stephan, Anticevic, Alan, Addington, Jean, Perkins, Diana O, Bearden, Carrie E, Cornblatt, Barbara A, Cadenhead, Kristin S, Mathalon, Daniel H, McGlashan, Thomas, Seidman, Larry, Tsuang, Ming, Walker, Elaine F, Woods, Scott W, Falkai, Peter, Lencer, Rebekka, Bertolino, Alessandro, Kambeitz, Joseph, Schultze-Lutter, Frauke, Meisenzahl, Eva, Salokangas, Raimo KR, Hietala, Jarmo, Brambilla, Paolo, Upthegrove, Rachel, Borgwardt, Stefan, Wood, Stephen, Gur, Raquel E, McGuire, Philip, and Cannon, Tyrone D
Abstract: BackgroundTransition to psychosis is among the most adverse outcomes of clinical high-risk (CHR) syndromes encompassing ultra-high risk (UHR) and basic symptom states. Clinical risk calculators may facilitate an early and individualized interception of psychosis, but their real-world implementation requires thorough validation across diverse risk populations, including young patients with depressive syndromes.MethodsWe validated the previously described NAPLS-2 (North American Prodrome Longitudinal Study 2) calculator in 334 patients (26 with transition to psychosis) with CHR or recent-onset depression (ROD) drawn from the multisite European PRONIA (Personalised Prognostic Tools for Early Psychosis Management) study. Patients were categorized into three risk enrichment levels, ranging from UHR, over CHR, to a broad-risk population comprising patients with CHR or ROD (CHR|ROD). We assessed how risk enrichment and different predictive algorithms influenced prognostic performance using reciprocal external validation.ResultsAfter calibration, the NAPLS-2 model predicted psychosis with a balanced accuracy (BAC) (sensitivity, specificity) of 68% (73%, 63%) in the PRONIA-UHR cohort, 67% (74%, 60%) in the CHR cohort, and 70% (73%, 66%) in patients with CHR|ROD. Multiple model derivation in PRONIA-CHR|ROD and validation in NAPLS-2-UHR patients confirmed that broader risk definitions produced more accurate risk calculators (CHR|ROD-based vs. UHR-based performance: 67% [68%, 66%] vs. 58% [61%, 56%]). Support vector machines were superior in CHR|ROD (BAC = 71%), while ridge logistic regression and support vector machines performed similarly in CHR (BAC = 67%) and UHR cohorts (BAC = 65%). Attenuated psychotic symptoms predicted psychosis across risk levels, while younger age and reduced processing speed became increasingly relevant for broader risk cohorts.ConclusionsClinical-neurocognitive machine learning models operating in young patients with affective and CHR
Published: 2021

35. Genetic and clinical analyses of psychosis spectrum symptoms in a large multiethnic youth cohort reveal significant link with ADHD.

Author: Olde Loohuis, Loes M, Olde Loohuis, Loes M, Mennigen, Eva, Ori, Anil PS, Perkins, Diana, Robinson, Elise, Addington, Jean, Cadenhead, Kristin S, Cornblatt, Barbara A, Mathalon, Daniel H, McGlashan, Thomas H, Seidman, Larry J, Keshavan, Matcheri S, Stone, William S, Tsuang, Ming T, Walker, Elaine F, Woods, Scott W, Cannon, Tyrone D, Gur, Ruben C, Gur, Raquel E, Bearden, Carrie E, Ophoff, Roel A, Olde Loohuis, Loes M, Olde Loohuis, Loes M, Mennigen, Eva, Ori, Anil PS, Perkins, Diana, Robinson, Elise, Addington, Jean, Cadenhead, Kristin S, Cornblatt, Barbara A, Mathalon, Daniel H, McGlashan, Thomas H, Seidman, Larry J, Keshavan, Matcheri S, Stone, William S, Tsuang, Ming T, Walker, Elaine F, Woods, Scott W, Cannon, Tyrone D, Gur, Ruben C, Gur, Raquel E, Bearden, Carrie E, and Ophoff, Roel A
Abstract: Psychotic symptoms are not only an important feature of severe neuropsychiatric disorders, but are also common in the general population, especially in youth. The genetic etiology of psychosis symptoms in youth remains poorly understood. To characterize genetic risk for psychosis spectrum symptoms (PS), we leverage a community-based multiethnic sample of children and adolescents aged 8-22 years, the Philadelphia Neurodevelopmental Cohort (n = 7225, 20% PS). Using an elastic net regression model, we aim to classify PS status using polygenic scores (PGS) based on a range of heritable psychiatric and brain-related traits in a multi-PGS model. We also perform univariate PGS associations and evaluate age-specific effects. The multi-PGS analyses do not improve prediction of PS status over univariate models, but reveal that the attention deficit hyperactivity disorder (ADHD) PGS is robustly and uniquely associated with PS (OR 1.12 (1.05, 1.18) P = 0.0003). This association is driven by subjects of European ancestry (OR = 1.23 (1.14, 1.34), P = 4.15 × 10-7) but is not observed in African American subjects (P = 0.65). We find a significant interaction of ADHD PGS with age (P = 0.01), with a stronger association in younger children. The association is independent of phenotypic overlap between ADHD and PS, not indirectly driven by substance use or childhood trauma, and appears to be specific to PS rather than reflecting general psychopathology in youth. In an independent sample, we replicate an increased ADHD PGS in 328 youth at clinical high risk for psychosis, compared to 216 unaffected controls (OR 1.06, CI(1.01, 1.11), P = 0.02). Our findings suggest that PS in youth may reflect a different genetic etiology than psychotic symptoms in adulthood, one more akin to ADHD, and shed light on how genetic risk can be investigated across early disease trajectories.
Published: 2021

36. Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion.

Author: Cleynen, Isabelle, Cleynen, Isabelle, Engchuan, Worrawat, Hestand, Matthew S, Heung, Tracy, Holleman, Aaron M, Johnston, H Richard, Monfeuga, Thomas, McDonald-McGinn, Donna M, Gur, Raquel E, Morrow, Bernice E, Swillen, Ann, Vorstman, Jacob AS, Bearden, Carrie E, Chow, Eva WC, van den Bree, Marianne, Emanuel, Beverly S, Vermeesch, Joris R, Warren, Stephen T, Owen, Michael J, Chopra, Pankaj, Cutler, David J, Duncan, Richard, Kotlar, Alex V, Mulle, Jennifer G, Voss, Anna J, Zwick, Michael E, Diacou, Alexander, Golden, Aaron, Guo, Tingwei, Lin, Jhih-Rong, Wang, Tao, Zhang, Zhengdong, Zhao, Yingjie, Marshall, Christian, Merico, Daniele, Jin, Andrea, Lilley, Brenna, Salmons, Harold I, Tran, Oanh, Holmans, Peter, Pardinas, Antonio, Walters, James TR, Demaerel, Wolfram, Boot, Erik, Butcher, Nancy J, Costain, Gregory A, Lowther, Chelsea, Evers, Rens, van Amelsvoort, Therese AMJ, van Duin, Esther, Vingerhoets, Claudia, Breckpot, Jeroen, Devriendt, Koen, Vergaelen, Elfi, Vogels, Annick, Crowley, T Blaine, McGinn, Daniel E, Moss, Edward M, Sharkus, Robert J, Unolt, Marta, Zackai, Elaine H, Calkins, Monica E, Gallagher, Robert S, Gur, Ruben C, Tang, Sunny X, Fritsch, Rosemarie, Ornstein, Claudia, Repetto, Gabriela M, Breetvelt, Elemi, Duijff, Sasja N, Fiksinski, Ania, Moss, Hayley, Niarchou, Maria, Murphy, Kieran C, Prasad, Sarah E, Daly, Eileen M, Gudbrandsen, Maria, Murphy, Clodagh M, Murphy, Declan G, Buzzanca, Antonio, Fabio, Fabio Di, Digilio, Maria C, Pontillo, Maria, Marino, Bruno, Vicari, Stefano, Coleman, Karlene, Cubells, Joseph F, Ousley, Opal Y, Carmel, Miri, Gothelf, Doron, Mekori-Domachevsky, Ehud, Michaelovsky, Elena, Weinberger, Ronnie, Weizman, Abraham, Kushan, Leila, Jalbrzikowski, Maria, Armando, Marco, Eliez, Stéphan, Sandini, Corrado, Schneider, Maude, Cleynen, Isabelle, Cleynen, Isabelle, Engchuan, Worrawat, Hestand, Matthew S, Heung, Tracy, Holleman, Aaron M, Johnston, H Richard, Monfeuga, Thomas, McDonald-McGinn, Donna M, Gur, Raquel E, Morrow, Bernice E, Swillen, Ann, Vorstman, Jacob AS, Bearden, Carrie E, Chow, Eva WC, van den Bree, Marianne, Emanuel, Beverly S, Vermeesch, Joris R, Warren, Stephen T, Owen, Michael J, Chopra, Pankaj, Cutler, David J, Duncan, Richard, Kotlar, Alex V, Mulle, Jennifer G, Voss, Anna J, Zwick, Michael E, Diacou, Alexander, Golden, Aaron, Guo, Tingwei, Lin, Jhih-Rong, Wang, Tao, Zhang, Zhengdong, Zhao, Yingjie, Marshall, Christian, Merico, Daniele, Jin, Andrea, Lilley, Brenna, Salmons, Harold I, Tran, Oanh, Holmans, Peter, Pardinas, Antonio, Walters, James TR, Demaerel, Wolfram, Boot, Erik, Butcher, Nancy J, Costain, Gregory A, Lowther, Chelsea, Evers, Rens, van Amelsvoort, Therese AMJ, van Duin, Esther, Vingerhoets, Claudia, Breckpot, Jeroen, Devriendt, Koen, Vergaelen, Elfi, Vogels, Annick, Crowley, T Blaine, McGinn, Daniel E, Moss, Edward M, Sharkus, Robert J, Unolt, Marta, Zackai, Elaine H, Calkins, Monica E, Gallagher, Robert S, Gur, Ruben C, Tang, Sunny X, Fritsch, Rosemarie, Ornstein, Claudia, Repetto, Gabriela M, Breetvelt, Elemi, Duijff, Sasja N, Fiksinski, Ania, Moss, Hayley, Niarchou, Maria, Murphy, Kieran C, Prasad, Sarah E, Daly, Eileen M, Gudbrandsen, Maria, Murphy, Clodagh M, Murphy, Declan G, Buzzanca, Antonio, Fabio, Fabio Di, Digilio, Maria C, Pontillo, Maria, Marino, Bruno, Vicari, Stefano, Coleman, Karlene, Cubells, Joseph F, Ousley, Opal Y, Carmel, Miri, Gothelf, Doron, Mekori-Domachevsky, Ehud, Michaelovsky, Elena, Weinberger, Ronnie, Weizman, Abraham, Kushan, Leila, Jalbrzikowski, Maria, Armando, Marco, Eliez, Stéphan, Sandini, Corrado, and Schneider, Maude
Abstract: Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10-6). Novel reciprocal case-control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present.
Published: 2021

37. Inter-rater reliability of subthreshold psychotic symptoms in individuals with 22q11.2 deletion syndrome.

Author: Moore, Tyler M, Moore, Tyler M, Salzer, Deby, Bearden, Carrie E, Calkins, Monica E, Kates, Wendy R, Kushan, Leila, Gallagher, Robert Sean, Frumer, Dafna Sofrin, Weinberger, Ronnie, McDonald-McGinn, Donna M, Gur, Raquel E, Gothelf, Doron, Moore, Tyler M, Moore, Tyler M, Salzer, Deby, Bearden, Carrie E, Calkins, Monica E, Kates, Wendy R, Kushan, Leila, Gallagher, Robert Sean, Frumer, Dafna Sofrin, Weinberger, Ronnie, McDonald-McGinn, Donna M, Gur, Raquel E, and Gothelf, Doron
Abstract: BackgroundPathways leading to psychosis in 22q11.2 deletion syndrome (22q11.2DS) have been the focus of intensive research during the last two decades. One of the common clinical risk factors for the evolution of psychosis in 22q11.2DS is the presence of positive and negative subthreshold psychotic symptoms. The gold standard for measuring subthreshold symptoms is the Structured Interview for Prodromal Syndromes (SIPS) and its accompanying Scale of Prodromal Symptoms (SOPS) ratings. Although the scale has been used by many centers studying 22q11.2DS, the inter-site reliability of the scale in this population has never been established.MethodsIn the present study, experienced clinical assessors from three large international centers studying 22q11.2DS independently rated video recordings of 18 adolescents and young adults with 22q11.2DS.ResultsThe intraclass correlations coefficients (ICCs) among three raters for the SOPS total scores, as well as for the positive, negative, and disorganization subscale scores, were good-to-excellent (ICCs range 0.73-0.93). The raters were also able to reliably determine the subjects' subthreshold syndrome status (ICC = 0.71). The reliability of individual items was good-to-excellent for all items, ranging from 0.61 for motor disturbances [G3] to 0.95 for bizarre thinking.ConclusionsOur results show that trained clinicians can reliably screen for subthreshold psychotic symptoms in individuals with 22q11.2DS. To increase assessment reliability, we suggest specific clarifications and simplifications to the standard SIPS interview for future studies.
Published: 2021

38. A Genetics-First Approach to Dissecting the Heterogeneity of Autism: Phenotypic Comparison of Autism Risk Copy Number Variants.

Author: Chawner, Samuel JRA, Chawner, Samuel JRA, Doherty, Joanne L, Anney, Richard JL, Antshel, Kevin M, Bearden, Carrie E, Bernier, Raphael, Chung, Wendy K, Clements, Caitlin C, Curran, Sarah R, Cuturilo, Goran, Fiksinski, Ania M, Gallagher, Louise, Goin-Kochel, Robin P, Gur, Raquel E, Hanson, Ellen, Jacquemont, Sebastien, Kates, Wendy R, Kushan, Leila, Maillard, Anne M, McDonald-McGinn, Donna M, Mihaljevic, Marina, Miller, Judith S, Moss, Hayley, Pejovic-Milovancevic, Milica, Schultz, Robert T, Green-Snyder, LeeAnne, Vorstman, Jacob A, Wenger, Tara L, IMAGINE-ID Consortium, Hall, Jeremy, Owen, Michael J, van den Bree, Marianne BM, Chawner, Samuel JRA, Chawner, Samuel JRA, Doherty, Joanne L, Anney, Richard JL, Antshel, Kevin M, Bearden, Carrie E, Bernier, Raphael, Chung, Wendy K, Clements, Caitlin C, Curran, Sarah R, Cuturilo, Goran, Fiksinski, Ania M, Gallagher, Louise, Goin-Kochel, Robin P, Gur, Raquel E, Hanson, Ellen, Jacquemont, Sebastien, Kates, Wendy R, Kushan, Leila, Maillard, Anne M, McDonald-McGinn, Donna M, Mihaljevic, Marina, Miller, Judith S, Moss, Hayley, Pejovic-Milovancevic, Milica, Schultz, Robert T, Green-Snyder, LeeAnne, Vorstman, Jacob A, Wenger, Tara L, IMAGINE-ID Consortium, Hall, Jeremy, Owen, Michael J, and van den Bree, Marianne BM
Abstract: ObjectiveCertain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is underpinned by specific genotype-phenotype relationships.MethodsThis international study included 547 individuals (mean age, 12.3 years [SD=4.2], 54% male) who were ascertained on the basis of having a genetic diagnosis of a rare CNV associated with high risk of autism (82 16p11.2 deletion carriers, 50 16p11.2 duplication carriers, 370 22q11.2 deletion carriers, and 45 22q11.2 duplication carriers), as well as 2,027 individuals (mean age, 9.1 years [SD=4.9], 86% male) with autism of heterogeneous etiology. Assessments included the Autism Diagnostic Interview-Revised and IQ testing.ResultsThe four genetic variant groups differed in autism symptom severity, autism subdomain profile, and IQ profile. However, substantial variability was observed in phenotypic outcome in individual genetic variant groups (74%-97% of the variance, depending on the trait), whereas variability between groups was low (1%-21%, depending on the trait). CNV carriers who met autism criteria were compared with individuals with heterogeneous autism, and a range of profile differences were identified. When clinical cutoff scores were applied, 54% of individuals with one of the four CNVs who did not meet full autism diagnostic criteria had elevated levels of autistic traits.ConclusionsMany CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant.
Published: 2021

39. Anticholinergic Medication Burden-Associated Cognitive Impairment in Schizophrenia.

Author: Joshi, Yash B, Joshi, Yash B, Thomas, Michael L, Braff, David L, Green, Michael F, Gur, Ruben C, Gur, Raquel E, Nuechterlein, Keith H, Stone, William S, Greenwood, Tiffany A, Lazzeroni, Laura C, MacDonald, Laura R, Molina, Juan L, Nungaray, John A, Radant, Allen D, Silverman, Jeremy M, Sprock, Joyce, Sugar, Catherine A, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, Swerdlow, Neal R, Light, Gregory A, Joshi, Yash B, Joshi, Yash B, Thomas, Michael L, Braff, David L, Green, Michael F, Gur, Ruben C, Gur, Raquel E, Nuechterlein, Keith H, Stone, William S, Greenwood, Tiffany A, Lazzeroni, Laura C, MacDonald, Laura R, Molina, Juan L, Nungaray, John A, Radant, Allen D, Silverman, Jeremy M, Sprock, Joyce, Sugar, Catherine A, Tsuang, Debby W, Tsuang, Ming T, Turetsky, Bruce I, Swerdlow, Neal R, and Light, Gregory A
Abstract: ObjectiveMany psychotropic medications used to treat schizophrenia have significant anticholinergic properties, which are linked to cognitive impairment and dementia risk in healthy subjects. Clarifying the impact of cognitive impairment attributable to anticholinergic medication burden may help optimize cognitive outcomes in schizophrenia. The aim of this study was to comprehensively characterize how this burden affects functioning across multiple cognitive domains in schizophrenia outpatients.MethodsCross-sectional data were analyzed using inferential statistics and exploratory structural equation modeling to determine the relationship between anticholinergic medication burden and cognition. Patients with a diagnosis of schizophrenia or schizoaffective disorder (N=1,120) were recruited from the community at five U.S. universities as part of the Consortium on the Genetics of Schizophrenia-2. For each participant, prescribed medications were rated and summed according to a modified Anticholinergic Cognitive Burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB).ResultsACB score was significantly associated with cognitive performance, with higher ACB groups scoring worse than lower ACB groups on all domains tested on the PCNB. Similar effects were seen on other cognitive tests. Effects remained significant after controlling for demographic characteristics and potential proxies of illness severity, including clinical symptoms and chlorpromazine-equivalent antipsychotic dosage.ConclusionsAnticholinergic medication burden in schizophrenia is substantial, common, conferred by multiple medication classes, and associated with cognitive impairments across all cognitive domains. Anticholinergic medication burden from all medication classes-including psychotropics used in usual care-should be considered in treatment decisions and accounted for in studies of cognitive functioning in schizophrenia.
Published: 2021

40. QSIPrep: an integrative platform for preprocessing and reconstructing diffusion MRI data.

Author: Cieslak, Matthew, Cieslak, Matthew, Cook, Philip A, He, Xiaosong, Yeh, Fang-Cheng, Dhollander, Thijs, Adebimpe, Azeez, Aguirre, Geoffrey K, Bassett, Danielle S, Betzel, Richard F, Bourque, Josiane, Cabral, Laura M, Davatzikos, Christos, Detre, John A, Earl, Eric, Elliott, Mark A, Fadnavis, Shreyas, Fair, Damien A, Foran, Will, Fotiadis, Panagiotis, Garyfallidis, Eleftherios, Giesbrecht, Barry, Gur, Ruben C, Gur, Raquel E, Kelz, Max B, Keshavan, Anisha, Larsen, Bart S, Luna, Beatriz, Mackey, Allyson P, Milham, Michael P, Oathes, Desmond J, Perrone, Anders, Pines, Adam R, Roalf, David R, Richie-Halford, Adam, Rokem, Ariel, Sydnor, Valerie J, Tapera, Tinashe M, Tooley, Ursula A, Vettel, Jean M, Yeatman, Jason D, Grafton, Scott T, Satterthwaite, Theodore D, Cieslak, Matthew, Cieslak, Matthew, Cook, Philip A, He, Xiaosong, Yeh, Fang-Cheng, Dhollander, Thijs, Adebimpe, Azeez, Aguirre, Geoffrey K, Bassett, Danielle S, Betzel, Richard F, Bourque, Josiane, Cabral, Laura M, Davatzikos, Christos, Detre, John A, Earl, Eric, Elliott, Mark A, Fadnavis, Shreyas, Fair, Damien A, Foran, Will, Fotiadis, Panagiotis, Garyfallidis, Eleftherios, Giesbrecht, Barry, Gur, Ruben C, Gur, Raquel E, Kelz, Max B, Keshavan, Anisha, Larsen, Bart S, Luna, Beatriz, Mackey, Allyson P, Milham, Michael P, Oathes, Desmond J, Perrone, Anders, Pines, Adam R, Roalf, David R, Richie-Halford, Adam, Rokem, Ariel, Sydnor, Valerie J, Tapera, Tinashe M, Tooley, Ursula A, Vettel, Jean M, Yeatman, Jason D, Grafton, Scott T, and Satterthwaite, Theodore D
Abstract: Diffusion-weighted magnetic resonance imaging (dMRI) is the primary method for noninvasively studying the organization of white matter in the human brain. Here we introduce QSIPrep, an integrative software platform for the processing of diffusion images that is compatible with nearly all dMRI sampling schemes. Drawing on a diverse set of software suites to capitalize on their complementary strengths, QSIPrep facilitates the implementation of best practices for processing of diffusion images.
Published: 2021

41. Counterpoint. Early intervention for psychosis risk syndromes: Minimizing risk and maximizing benefit.

Author: Woods, Scott W, Woods, Scott W, Bearden, Carrie E, Sabb, Fred W, Stone, William S, Torous, John, Cornblatt, Barbara A, Perkins, Diana O, Cadenhead, Kristin S, Addington, Jean, Powers, Albert R, Mathalon, Daniel H, Calkins, Monica E, Wolf, Daniel H, Corcoran, Cheryl M, Horton, Leslie E, Mittal, Vijay A, Schiffman, Jason, Ellman, Lauren M, Strauss, Gregory P, Mamah, Daniel, Choi, Jimmy, Pearlson, Godfrey D, Shah, Jai L, Fusar-Poli, Paolo, Arango, Celso, Perez, Jesus, Koutsouleris, Nikolaos, Wang, Jijun, Kwon, Jun Soo, Walsh, Barbara C, McGlashan, Thomas H, Hyman, Steven E, Gur, Raquel E, Cannon, Tyrone D, Kane, John M, Anticevic, Alan, Woods, Scott W, Woods, Scott W, Bearden, Carrie E, Sabb, Fred W, Stone, William S, Torous, John, Cornblatt, Barbara A, Perkins, Diana O, Cadenhead, Kristin S, Addington, Jean, Powers, Albert R, Mathalon, Daniel H, Calkins, Monica E, Wolf, Daniel H, Corcoran, Cheryl M, Horton, Leslie E, Mittal, Vijay A, Schiffman, Jason, Ellman, Lauren M, Strauss, Gregory P, Mamah, Daniel, Choi, Jimmy, Pearlson, Godfrey D, Shah, Jai L, Fusar-Poli, Paolo, Arango, Celso, Perez, Jesus, Koutsouleris, Nikolaos, Wang, Jijun, Kwon, Jun Soo, Walsh, Barbara C, McGlashan, Thomas H, Hyman, Steven E, Gur, Raquel E, Cannon, Tyrone D, Kane, John M, and Anticevic, Alan
Abstract: BackgroundMalhi et al. in this issue critique the clinical high risk (CHR) syndrome for psychosis.MethodResponse to points of critique.ResultsWe agree that inconsistency in CHR nomenclature should be minimized. We respectfully disagree on other points. In our view: a) individuals with CHR and their families need help, using existing interventions, even though we do not yet fully understand disease mechanisms; b) substantial progress has been made in identification of biomarkers; c) symptoms used to identify CHR are specific to psychotic illnesses; d) CHR diagnosis is not "extremely difficult"; e) the pattern of progression, although heterogenous, is discernible; f) "psychosis-like symptoms" are common but are not used to identify CHR; and g) on the point described as 'the real risk,' CHR diagnosis does not frequently cause harmful stigma.DiscussionMalhi et al.'s arguments do not fairly characterize progress in the CHR field nor efforts to minimize stigma. That said, much work remains in areas of consistent nomenclature, mechanisms of disease, dissecting heterogeneity, and biomarkers. With regard to what the authors term the "real risk" of stigma associated with a CHR "label," however, our view is that avoiding words like "risk" and "psychosis" reinforces the stigma that both they and we mean to oppose. Moreover, patients and their families benefit from being given a term that describes what is happening to them.
Published: 2021

42. Toward Generalizable and Transdiagnostic Tools for Psychosis Prediction: An Independent Validation and Improvement of the NAPLS-2 Risk Calculator in the Multisite PRONIA Cohort

Author: Koutsouleris, Nikolaos, Worthington, Michelle, Dwyer, Dominic B., Kambeitz-Ilankovic, Lana, Sanfelici, Rachele, Fusar-Poli, Paolo, Rosen, Marlene, Ruhrmann, Stephan, Anticevic, Alan, Addington, Jean, Perkins, Diana O., Bearden, Carrie E., Cornblatt, Barbara A., Cadenhead, Kristin S., Mathalon, Daniel H., McGlashan, Thomas, Seidman, Larry, Tsuang, Ming, Walker, Elaine F., Woods, Scott W., Falkai, Peter, Lencer, Rebekka, Bertolino, Alessandro, Kambeitz, Joseph, Schultze-Lutter, Frauke, Meisenzahl, Eva, Salokangas, Raimo K. R., Hietala, Jarmo, Brambilla, Paolo, Upthegrove, Rachel, Borgwardt, Stefan, Wood, Stephen, Gur, Raquel E., McGuire, Philip, Cannon, Tyrone D., Koutsouleris, Nikolaos, Worthington, Michelle, Dwyer, Dominic B., Kambeitz-Ilankovic, Lana, Sanfelici, Rachele, Fusar-Poli, Paolo, Rosen, Marlene, Ruhrmann, Stephan, Anticevic, Alan, Addington, Jean, Perkins, Diana O., Bearden, Carrie E., Cornblatt, Barbara A., Cadenhead, Kristin S., Mathalon, Daniel H., McGlashan, Thomas, Seidman, Larry, Tsuang, Ming, Walker, Elaine F., Woods, Scott W., Falkai, Peter, Lencer, Rebekka, Bertolino, Alessandro, Kambeitz, Joseph, Schultze-Lutter, Frauke, Meisenzahl, Eva, Salokangas, Raimo K. R., Hietala, Jarmo, Brambilla, Paolo, Upthegrove, Rachel, Borgwardt, Stefan, Wood, Stephen, Gur, Raquel E., McGuire, Philip, and Cannon, Tyrone D.
Abstract: BACKGROUND: Transition to psychosis is among the most adverse outcomes of clinical high-risk (CHR) syndromes encompassing ultra-high risk (UHR) and basic symptom states. Clinical risk calculators may facilitate an early and individualized interception of psychosis, but their real-world implementation requires thorough validation across diverse risk populations, including young patients with depressive syndromes. METHODS: We validated the previously described NAPLS-2 (North American Prodrome Longitudinal Study 2) calculator in 334 patients (26 with transition to psychosis) with CHR or recent-onset depression (ROD) drawn from the multisite European PRONIA (Personalised Prognostic Tools for Early Psychosis Management) study. Patients were categorized into three risk enrichment levels, ranging from UHR, over CHR, to a broad-risk population comprising patients with CHR or ROD (CHR|ROD). We assessed how risk enrichment and different predictive algorithms influenced prognostic performance using reciprocal external validation. RESULTS: After calibration, the NAPLS-2 model predicted psychosis with a balanced accuracy (BAC) (sensitivity, specificity) of 68% (73%, 63%) in the PRONIA-UHR cohort, 67% (74%, 60%) in the CHR cohort, and 70% (73%, 66%) in patients with CHR|ROD. Multiple model derivation in PRONIA-CHR|ROD and validation in NAPLS-2-UHR patients confirmed that broader risk definitions produced more accurate risk calculators (CHR|ROD-based vs. UHR-based performance: 67% [68%, 66%] vs. 58% [61%, 56%]). Support vector machines were superior in CHR|ROD (BAC = 71%), while ridge logistic regression and support vector machines performed similarly in CHR (BAC = 67%) and UHR cohorts (BAC = 65%). Attenuated psychotic symptoms predicted psychosis across risk levels, while younger age and reduced processing speed became increasingly relevant for broader risk cohorts. CONCLUSIONS: Clinical-neurocognitive machine learning models operating in young patients with affective and CHR syn
Published: 2021

43. A framework for the investigation of rare genetic disorders in neuropsychiatry

Author: McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Sanders, Stephan J., Sahin, Mustafa, Hostyk, Joseph, Thurm, Audrey, Jacquemont, Sebastien, Avillach, Paul, Douard, Elise, Martin, Christa L., Modi, Meera E., Moreno-De-Luca, Andres, Raznahan, Armin, Anticevic, Alan, Dolmetsch, Ricardo, Feng, Guoping, Geschwind, Daniel H., Glahn, David C., Goldstein, David B., Ledbetter, David H., Mulle, Jennifer G., Pasca, Sergiu P., Samaco, Rodney, Sebat, Jonathan, Pariser, Anne, Lehner, Thomas, Gur, Raquel E., Bearden, Carrie E., McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Sanders, Stephan J., Sahin, Mustafa, Hostyk, Joseph, Thurm, Audrey, Jacquemont, Sebastien, Avillach, Paul, Douard, Elise, Martin, Christa L., Modi, Meera E., Moreno-De-Luca, Andres, Raznahan, Armin, Anticevic, Alan, Dolmetsch, Ricardo, Feng, Guoping, Geschwind, Daniel H., Glahn, David C., Goldstein, David B., Ledbetter, David H., Mulle, Jennifer G., Pasca, Sergiu P., Samaco, Rodney, Sebat, Jonathan, Pariser, Anne, Lehner, Thomas, Gur, Raquel E., and Bearden, Carrie E.
Abstract: De novo and inherited rare genetic disorders (RGDs) are a major cause of human morbidity, frequently involving neuropsychiatric symptoms. Recent advances in genomic technologies and data sharing have revolutionized the identification and diagnosis of RGDs, presenting an opportunity to elucidate the mechanisms underlying neuropsychiatric disorders by investigating the pathophysiology of high-penetrance genetic risk factors. Here we seek out the best path forward for achieving these goals. We think future research will require consistent approaches across multiple RGDs and developmental stages, involving both the characterization of shared neuropsychiatric dimensions in humans and the identification of neurobiological commonalities in model systems. A coordinated and concerted effort across patients, families, researchers, clinicians and institutions, including rapid and broad sharing of data, is now needed to translate these discoveries into urgently needed therapies.
Published: 2021

44. Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome

Author: Onderzoek, Beeldverwerking ISI, Chair, Directie Raad van Bestuur, Psychosociale zorg patientenzorg, Brain, Child Health, Onderzoeksgroep 11, Davies, Robert W., Fiksinski, Ania M., Breetvelt, Elemi J., Williams, Nigel M., Hooper, Stephen R., Monfeuga, Thomas, Bassett, Anne S., Owen, Michael J., Gur, Raquel E., Morrow, Bernice E., McDonald-McGinn, Donna M., Swillen, Ann, Chow, Eva W.C., van den Bree, Marianne, Emanuel, Beverly S., Vermeesch, Joris R., van Amelsvoort, Therese, Arango, Celso, Armando, Marco, Campbell, Linda E., Cubells, Joseph F., Eliez, Stephan, Garcia-Minaur, Sixto, Gothelf, Doron, Kates, Wendy R., Murphy, Kieran C., Murphy, Clodagh M., Murphy, Declan G., Philip, Nicole, Repetto, Gabriela M., Shashi, Vandana, Simon, Tony J., Suñer, Damiàn Heine, Vicari, Stefano, Scherer, Stephen W., Epstein, Michael P., Warren, Stephen T., Morrison, Sinead, Chawner, Samuel, Vingerhoets, Claudia, Breckpot, Jeroen, Vergaelen, Elfi, Vogels, Annick, Monks, Stephen, Prasad, Sarah E., Schneider, Maude, Duijff, Sasja N., Kahn, René S., Houben, Michiel, Vorstman, Jacob A.S., International 22q11.2 Brain and Behavior Consortium, Onderzoek, Beeldverwerking ISI, Chair, Directie Raad van Bestuur, Psychosociale zorg patientenzorg, Brain, Child Health, Onderzoeksgroep 11, Davies, Robert W., Fiksinski, Ania M., Breetvelt, Elemi J., Williams, Nigel M., Hooper, Stephen R., Monfeuga, Thomas, Bassett, Anne S., Owen, Michael J., Gur, Raquel E., Morrow, Bernice E., McDonald-McGinn, Donna M., Swillen, Ann, Chow, Eva W.C., van den Bree, Marianne, Emanuel, Beverly S., Vermeesch, Joris R., van Amelsvoort, Therese, Arango, Celso, Armando, Marco, Campbell, Linda E., Cubells, Joseph F., Eliez, Stephan, Garcia-Minaur, Sixto, Gothelf, Doron, Kates, Wendy R., Murphy, Kieran C., Murphy, Clodagh M., Murphy, Declan G., Philip, Nicole, Repetto, Gabriela M., Shashi, Vandana, Simon, Tony J., Suñer, Damiàn Heine, Vicari, Stefano, Scherer, Stephen W., Epstein, Michael P., Warren, Stephen T., Morrison, Sinead, Chawner, Samuel, Vingerhoets, Claudia, Breckpot, Jeroen, Vergaelen, Elfi, Vogels, Annick, Monks, Stephen, Prasad, Sarah E., Schneider, Maude, Duijff, Sasja N., Kahn, René S., Houben, Michiel, Vorstman, Jacob A.S., and International 22q11.2 Brain and Behavior Consortium
Published: 2020

45. Greater male than female variability in regional brain structure across the lifespan

Author: Wierenga, Lara M., Doucet, Gaelle E., Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn, I, Andreassen, Ole A., Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret, I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Calhoun, Vince D., Canales-Rodriguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Clark, Vincent P., Conrod, Patricia J., Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G., Dickie, Erin W., Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco J. C., Di Giorgio, Annabella, Glahn, David C., Gotlib, Ian H., Grabe, Hans J., Gruber, Oliver, Gruner, Patricia, Gur, Raquel E., Gur, Ruben C., Gurholt, Tiril P., de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J., Hartman, Catharina A., Hatton, Sean N., Heslenfeld, Dirk J., van den Heuvel, Odile A., Hickie, Ian B., Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Pol, Hilleke E. Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony C., Jiang, Jiyang, Jonsson, Erik G., Joska, John A., Kalnin, Andrew J., Klein, Marieke, Koenders, Laura, Kolskar, Knut K., Kramer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S., Lee, Phil H., Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martinez-Zalacain, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C., McDonald, Colm, McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, van der Meer, Dennis, Menchon, Jose M., Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Radua, Joaquim, Reif, Andreas, Richard, Genevieve, Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sarro, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Sim, Kang, Simmons, Andrew, Smoller, Jordan W., Sommer, Iris E., Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Szeszko, Philip R., Temmingh, Henk S., Thomopoulos, Sophia, I, Tomyshev, Alexander S., Trollor, Julian N., Uhlmann, Anne, Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Volzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather C., Williams, Steven C. R., Wittfeld, Katharina, Wolf, Daniel H., Wright, Margaret J., Yoncheva, Yuliya N., Zanetti, Marcus, V, Ziegler, Georg C., de Zubicaray, Greig, I, Thompson, Paul M., Crone, Eveline A., Frangou, Sophia, Tamnes, Christian K., Wierenga, Lara M., Doucet, Gaelle E., Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn, I, Andreassen, Ole A., Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret, I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Calhoun, Vince D., Canales-Rodriguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Clark, Vincent P., Conrod, Patricia J., Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G., Dickie, Erin W., Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco J. C., Di Giorgio, Annabella, Glahn, David C., Gotlib, Ian H., Grabe, Hans J., Gruber, Oliver, Gruner, Patricia, Gur, Raquel E., Gur, Ruben C., Gurholt, Tiril P., de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J., Hartman, Catharina A., Hatton, Sean N., Heslenfeld, Dirk J., van den Heuvel, Odile A., Hickie, Ian B., Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Pol, Hilleke E. Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony C., Jiang, Jiyang, Jonsson, Erik G., Joska, John A., Kalnin, Andrew J., Klein, Marieke, Koenders, Laura, Kolskar, Knut K., Kramer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S., Lee, Phil H., Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martinez-Zalacain, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C., McDonald, Colm, McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, van der Meer, Dennis, Menchon, Jose M., Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Radua, Joaquim, Reif, Andreas, Richard, Genevieve, Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sarro, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Sim, Kang, Simmons, Andrew, Smoller, Jordan W., Sommer, Iris E., Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Szeszko, Philip R., Temmingh, Henk S., Thomopoulos, Sophia, I, Tomyshev, Alexander S., Trollor, Julian N., Uhlmann, Anne, Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Volzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather C., Williams, Steven C. R., Wittfeld, Katharina, Wolf, Daniel H., Wright, Margaret J., Yoncheva, Yuliya N., Zanetti, Marcus, V, Ziegler, Georg C., de Zubicaray, Greig, I, Thompson, Paul M., Crone, Eveline A., Frangou, Sophia, and Tamnes, Christian K.
Abstract: For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
Published: 2020
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46. Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome: Convergence with idiopathic psychosis and effects of deletion size.

Author: Sun, Daqiang, Sun, Daqiang, Ching, Christopher RK, Lin, Amy, Forsyth, Jennifer K, Kushan, Leila, Vajdi, Ariana, Jalbrzikowski, Maria, Hansen, Laura, Villalon-Reina, Julio E, Qu, Xiaoping, Jonas, Rachel K, van Amelsvoort, Therese, Bakker, Geor, Kates, Wendy R, Antshel, Kevin M, Fremont, Wanda, Campbell, Linda E, McCabe, Kathryn L, Daly, Eileen, Gudbrandsen, Maria, Murphy, Clodagh M, Murphy, Declan, Craig, Michael, Vorstman, Jacob, Fiksinski, Ania, Koops, Sanne, Ruparel, Kosha, Roalf, David R, Gur, Raquel E, Schmitt, J Eric, Simon, Tony J, Goodrich-Hunsaker, Naomi J, Durdle, Courtney A, Bassett, Anne S, Chow, Eva WC, Butcher, Nancy J, Vila-Rodriguez, Fidel, Doherty, Joanne, Cunningham, Adam, van den Bree, Marianne BM, Linden, David EJ, Moss, Hayley, Owen, Michael J, Murphy, Kieran C, McDonald-McGinn, Donna M, Emanuel, Beverly, van Erp, Theo GM, Turner, Jessica A, Thompson, Paul M, Bearden, Carrie E, Sun, Daqiang, Sun, Daqiang, Ching, Christopher RK, Lin, Amy, Forsyth, Jennifer K, Kushan, Leila, Vajdi, Ariana, Jalbrzikowski, Maria, Hansen, Laura, Villalon-Reina, Julio E, Qu, Xiaoping, Jonas, Rachel K, van Amelsvoort, Therese, Bakker, Geor, Kates, Wendy R, Antshel, Kevin M, Fremont, Wanda, Campbell, Linda E, McCabe, Kathryn L, Daly, Eileen, Gudbrandsen, Maria, Murphy, Clodagh M, Murphy, Declan, Craig, Michael, Vorstman, Jacob, Fiksinski, Ania, Koops, Sanne, Ruparel, Kosha, Roalf, David R, Gur, Raquel E, Schmitt, J Eric, Simon, Tony J, Goodrich-Hunsaker, Naomi J, Durdle, Courtney A, Bassett, Anne S, Chow, Eva WC, Butcher, Nancy J, Vila-Rodriguez, Fidel, Doherty, Joanne, Cunningham, Adam, van den Bree, Marianne BM, Linden, David EJ, Moss, Hayley, Owen, Michael J, Murphy, Kieran C, McDonald-McGinn, Donna M, Emanuel, Beverly, van Erp, Theo GM, Turner, Jessica A, Thompson, Paul M, and Bearden, Carrie E
Abstract: The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date. The imaging data were collected from 10 centers worldwide, including 474 subjects with 22q11DS (age = 18.2 ± 8.6; 46.9% female) and 315 typically developing, matched controls (age = 18.0 ± 9.2; 45.9% female). Compared to controls, 22q11DS individuals showed thicker cortical gray matter overall (left/right hemispheres: Cohen's d = 0.61/0.65), but focal thickness reduction in temporal and cingulate cortex. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d = -1.01/-1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. These consistent cross-site findings highlight the homogeneity of this single genetic etiology, and support the suitability of 22q11DS as a biological model of schizophrenia.
Published: 2020

47. Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry.

Author: Bigdeli, Tim B, Bigdeli, Tim B, Genovese, Giulio, Georgakopoulos, Penelope, Meyers, Jacquelyn L, Peterson, Roseann E, Iyegbe, Conrad O, Medeiros, Helena, Valderrama, Jorge, Achtyes, Eric D, Kotov, Roman, Stahl, Eli A, Abbott, Colony, Azevedo, Maria Helena, Belliveau, Richard A, Bevilacqua, Elizabeth, Bromet, Evelyn J, Byerley, William, Carvalho, Celia Barreto, Chapman, Sinéad B, DeLisi, Lynn E, Dumont, Ashley L, O'Dushlaine, Colm, Evgrafov, Oleg V, Fochtmann, Laura J, Gage, Diane, Kennedy, James L, Kinkead, Becky, Macedo, Antonio, Moran, Jennifer L, Morley, Christopher P, Dewan, Mantosh J, Nemesh, James, Perkins, Diana O, Purcell, Shaun M, Rakofsky, Jeffrey J, Scolnick, Edward M, Sklar, Brooke M, Sklar, Pamela, Smoller, Jordan W, Sullivan, Patrick F, Macciardi, Fabio, Marder, Stephen R, Gur, Ruben C, Gur, Raquel E, Braff, David L, Consortium on the Genetics of Schizophrenia (COGS) Investigators, Nicolini, Humberto, Escamilla, Michael A, Vawter, Marquis P, Sobell, Janet L, Malaspina, Dolores, Lehrer, Douglas S, Buckley, Peter F, Rapaport, Mark H, Knowles, James A, Genomic Psychiatry Cohort (GPC) Consortium, Fanous, Ayman H, Pato, Michele T, McCarroll, Steven A, Pato, Carlos N, Bigdeli, Tim B, Bigdeli, Tim B, Genovese, Giulio, Georgakopoulos, Penelope, Meyers, Jacquelyn L, Peterson, Roseann E, Iyegbe, Conrad O, Medeiros, Helena, Valderrama, Jorge, Achtyes, Eric D, Kotov, Roman, Stahl, Eli A, Abbott, Colony, Azevedo, Maria Helena, Belliveau, Richard A, Bevilacqua, Elizabeth, Bromet, Evelyn J, Byerley, William, Carvalho, Celia Barreto, Chapman, Sinéad B, DeLisi, Lynn E, Dumont, Ashley L, O'Dushlaine, Colm, Evgrafov, Oleg V, Fochtmann, Laura J, Gage, Diane, Kennedy, James L, Kinkead, Becky, Macedo, Antonio, Moran, Jennifer L, Morley, Christopher P, Dewan, Mantosh J, Nemesh, James, Perkins, Diana O, Purcell, Shaun M, Rakofsky, Jeffrey J, Scolnick, Edward M, Sklar, Brooke M, Sklar, Pamela, Smoller, Jordan W, Sullivan, Patrick F, Macciardi, Fabio, Marder, Stephen R, Gur, Ruben C, Gur, Raquel E, Braff, David L, Consortium on the Genetics of Schizophrenia (COGS) Investigators, Nicolini, Humberto, Escamilla, Michael A, Vawter, Marquis P, Sobell, Janet L, Malaspina, Dolores, Lehrer, Douglas S, Buckley, Peter F, Rapaport, Mark H, Knowles, James A, Genomic Psychiatry Cohort (GPC) Consortium, Fanous, Ayman H, Pato, Michele T, McCarroll, Steven A, and Pato, Carlos N
Abstract: Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke's R2 = 0.032; liability R2 = 0.017; P < 10-52), Latino (Nagelkerke's R2 = 0.089; liability R2 = 0.021; P < 10-58), and European individuals (Nagelkerke's R2 = 0.089; liability R2 = 0.037; P < 10-113), further highlighting the advantages of incorporating data from diverse human populations.
Published: 2020

48. Altered white matter microstructure in 22q11.2 deletion syndrome: a multisite diffusion tensor imaging study.

Author: Villalón-Reina, Julio E, Villalón-Reina, Julio E, Martínez, Kenia, Qu, Xiaoping, Ching, Christopher RK, Nir, Talia M, Kothapalli, Deydeep, Corbin, Conor, Sun, Daqiang, Lin, Amy, Forsyth, Jennifer K, Kushan, Leila, Vajdi, Ariana, Jalbrzikowski, Maria, Hansen, Laura, Jonas, Rachel K, van Amelsvoort, Therese, Bakker, Geor, Kates, Wendy R, Antshel, Kevin M, Fremont, Wanda, Campbell, Linda E, McCabe, Kathryn L, Daly, Eileen, Gudbrandsen, Maria, Murphy, Clodagh M, Murphy, Declan, Craig, Michael, Emanuel, Beverly, McDonald-McGinn, Donna M, Vorstman, Jacob AS, Fiksinski, Ania M, Koops, Sanne, Ruparel, Kosha, Roalf, David, Gur, Raquel E, Eric Schmitt, J, Simon, Tony J, Goodrich-Hunsaker, Naomi J, Durdle, Courtney A, Doherty, Joanne L, Cunningham, Adam C, van den Bree, Marianne, Linden, David EJ, Owen, Michael, Moss, Hayley, Kelly, Sinead, Donohoe, Gary, Murphy, Kieran C, Arango, Celso, Jahanshad, Neda, Thompson, Paul M, Bearden, Carrie E, Villalón-Reina, Julio E, Villalón-Reina, Julio E, Martínez, Kenia, Qu, Xiaoping, Ching, Christopher RK, Nir, Talia M, Kothapalli, Deydeep, Corbin, Conor, Sun, Daqiang, Lin, Amy, Forsyth, Jennifer K, Kushan, Leila, Vajdi, Ariana, Jalbrzikowski, Maria, Hansen, Laura, Jonas, Rachel K, van Amelsvoort, Therese, Bakker, Geor, Kates, Wendy R, Antshel, Kevin M, Fremont, Wanda, Campbell, Linda E, McCabe, Kathryn L, Daly, Eileen, Gudbrandsen, Maria, Murphy, Clodagh M, Murphy, Declan, Craig, Michael, Emanuel, Beverly, McDonald-McGinn, Donna M, Vorstman, Jacob AS, Fiksinski, Ania M, Koops, Sanne, Ruparel, Kosha, Roalf, David, Gur, Raquel E, Eric Schmitt, J, Simon, Tony J, Goodrich-Hunsaker, Naomi J, Durdle, Courtney A, Doherty, Joanne L, Cunningham, Adam C, van den Bree, Marianne, Linden, David EJ, Owen, Michael, Moss, Hayley, Kelly, Sinead, Donohoe, Gary, Murphy, Kieran C, Arango, Celso, Jahanshad, Neda, Thompson, Paul M, and Bearden, Carrie E
Abstract: 22q11.2 deletion syndrome (22q11DS)-a neurodevelopmental condition caused by a hemizygous deletion on chromosome 22-is associated with an elevated risk of psychosis and other developmental brain disorders. Prior single-site diffusion magnetic resonance imaging (dMRI) studies have reported altered white matter (WM) microstructure in 22q11DS, but small samples and variable methods have led to contradictory results. Here we present the largest study ever conducted of dMRI-derived measures of WM microstructure in 22q11DS (334 22q11.2 deletion carriers and 260 healthy age- and sex-matched controls; age range 6-52 years). Using harmonization protocols developed by the ENIGMA-DTI working group, we identified widespread reductions in mean, axial and radial diffusivities in 22q11DS, most pronounced in regions with major cortico-cortical and cortico-thalamic fibers: the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations, and sagittal stratum (Cohen's d's ranging from -0.9 to -1.3). Only the posterior limb of the internal capsule (IC), comprised primarily of corticofugal fibers, showed higher axial diffusivity in 22q11DS. 22q11DS patients showed higher mean fractional anisotropy (FA) in callosal and projection fibers (IC and corona radiata) relative to controls, but lower FA than controls in regions with predominantly association fibers. Psychotic illness in 22q11DS was associated with more substantial diffusivity reductions in multiple regions. Overall, these findings indicate large effects of the 22q11.2 deletion on WM microstructure, especially in major cortico-cortical connections. Taken together with findings from animal models, this pattern of abnormalities may reflect disrupted neurogenesis of projection neurons in outer cortical layers.
Published: 2020

49. Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry.

Author: Bigdeli, Tim B, Bigdeli, Tim B, Genovese, Giulio, Georgakopoulos, Penelope, Meyers, Jacquelyn L, Peterson, Roseann E, Iyegbe, Conrad O, Medeiros, Helena, Valderrama, Jorge, Achtyes, Eric D, Kotov, Roman, Stahl, Eli A, Abbott, Colony, Azevedo, Maria Helena, Belliveau, Richard A, Bevilacqua, Elizabeth, Bromet, Evelyn J, Byerley, William, Carvalho, Celia Barreto, Chapman, Sinéad B, DeLisi, Lynn E, Dumont, Ashley L, O'Dushlaine, Colm, Evgrafov, Oleg V, Fochtmann, Laura J, Gage, Diane, Kennedy, James L, Kinkead, Becky, Macedo, Antonio, Moran, Jennifer L, Morley, Christopher P, Dewan, Mantosh J, Nemesh, James, Perkins, Diana O, Purcell, Shaun M, Rakofsky, Jeffrey J, Scolnick, Edward M, Sklar, Brooke M, Sklar, Pamela, Smoller, Jordan W, Sullivan, Patrick F, Macciardi, Fabio, Marder, Stephen R, Gur, Ruben C, Gur, Raquel E, Braff, David L, Consortium on the Genetics of Schizophrenia (COGS) Investigators, Nicolini, Humberto, Escamilla, Michael A, Vawter, Marquis P, Sobell, Janet L, Malaspina, Dolores, Lehrer, Douglas S, Buckley, Peter F, Rapaport, Mark H, Knowles, James A, Genomic Psychiatry Cohort (GPC) Consortium, Fanous, Ayman H, Pato, Michele T, McCarroll, Steven A, Pato, Carlos N, Bigdeli, Tim B, Bigdeli, Tim B, Genovese, Giulio, Georgakopoulos, Penelope, Meyers, Jacquelyn L, Peterson, Roseann E, Iyegbe, Conrad O, Medeiros, Helena, Valderrama, Jorge, Achtyes, Eric D, Kotov, Roman, Stahl, Eli A, Abbott, Colony, Azevedo, Maria Helena, Belliveau, Richard A, Bevilacqua, Elizabeth, Bromet, Evelyn J, Byerley, William, Carvalho, Celia Barreto, Chapman, Sinéad B, DeLisi, Lynn E, Dumont, Ashley L, O'Dushlaine, Colm, Evgrafov, Oleg V, Fochtmann, Laura J, Gage, Diane, Kennedy, James L, Kinkead, Becky, Macedo, Antonio, Moran, Jennifer L, Morley, Christopher P, Dewan, Mantosh J, Nemesh, James, Perkins, Diana O, Purcell, Shaun M, Rakofsky, Jeffrey J, Scolnick, Edward M, Sklar, Brooke M, Sklar, Pamela, Smoller, Jordan W, Sullivan, Patrick F, Macciardi, Fabio, Marder, Stephen R, Gur, Ruben C, Gur, Raquel E, Braff, David L, Consortium on the Genetics of Schizophrenia (COGS) Investigators, Nicolini, Humberto, Escamilla, Michael A, Vawter, Marquis P, Sobell, Janet L, Malaspina, Dolores, Lehrer, Douglas S, Buckley, Peter F, Rapaport, Mark H, Knowles, James A, Genomic Psychiatry Cohort (GPC) Consortium, Fanous, Ayman H, Pato, Michele T, McCarroll, Steven A, and Pato, Carlos N
Abstract: Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke's R2 = 0.032; liability R2 = 0.017; P < 10-52), Latino (Nagelkerke's R2 = 0.089; liability R2 = 0.021; P < 10-58), and European individuals (Nagelkerke's R2 = 0.089; liability R2 = 0.037; P < 10-113), further highlighting the advantages of incorporating data from diverse human populations.
Published: 2020

50. Greater male than female variability in regional brain structure across the lifespan

Author: Wierenga, Lara M, Doucet, Gaelle E, Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N, Albajes-Eizagirre, Anton, Alnæs, Dag, Alpert, Kathryn I, Andreassen, Ole A, Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M, Buitelaar, Jan K, Busatto, Geraldo F, Calhoun, Vince D, Canales-Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Castellanos, Francisco X, Chaim-Avancini, Tiffany M, Ching, Christopher R. K, Clark, Vincent P, Conrod, Patricia, Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher, Dickie, Erin W, Ehrlich, Stefan, van't Ent, Dennis, Fisher, Simon E, Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco J. C, Di Giorgio, Annabella, Glahn, David C, Gotlib, Ian H, Grabe, Hans J, Gruber, Oliver, Gruner, Patricia, Gur, Raquel E, Gur, Ruben C, Gurholt, Tiril P, de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J, Hartman, Catharina A, Hatton, Sean N, Heslenfeld, Dirk J, van den Heuvel, Odile A, Hickie, Ian B, Hoekstra, Pieter J, Hohmann, Sarah, Holmes, Avram J, Hoogman, Martine, Hosten, Norbert, Howells, Fleur M, Hulshoff Pol, Hilleke E, Huyser, Chaim, Jahanshad, Neda, James, Anthony C, Jiang, Jiyang, Jönsson, Erik G, Joska, John A, Kalnin, Andrew J, Klein, Marieke, Koenders, Laura, Kolskår, Knut K, Krämer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S, Lee, Phil H, Lochner, Christine, Machielsen, Marise WJ, Maingault, Sophie, Martin, Nicholas G, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C, McDonald, Colm, McIntosh, Andrew M, McMahon, Katie L, McPhilemy, Genevieve, van der Meer, Dennis, Menchón, José M, Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J, Radua, Joaquim, Reif, Andreas, Richard, Geneviève, Roffman, Joshua L, Rosa, Pedro GP, Sacchet, Matthew D, Sachdev, Perminder S, Salvador, Raymond, Sarró, Salvador, Satterthwaite, Theodore D, Saykin, Andrew J, Serpa, Mauricio H, Sim, Kang, Simmons, Andrew, Smoller, Jordan W, Sommer, Iris E, Soriano-Mas, Carles, Stein, Dan J, Strike, Lachlan T, Szeszko, Philip R, Temmingh, Henk S, Thomopoulos, Sophia I, Tomyshev, Alexander S, Trollor, Julian N, Uhlmann, Anne, Veer, Ilya M, Veltman, Dick J, Voineskos, Aristotle, Völzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D, Westlye, Lars T, Whalley, Heather C, Williams, Steven CR, Wittfeld, Katharina, Wolf, Daniel H, Wright, Margaret J, Yoncheva, Yuliya N, Zanetti, Marcus V, Ziegler, Georg C, de Zubicaray, Greig I, Thompson, Paul M, Crone, Eveline A, Frangou, Sophia, Tamnes, Christian K, Wierenga, Lara M, Doucet, Gaelle E, Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N, Albajes-Eizagirre, Anton, Alnæs, Dag, Alpert, Kathryn I, Andreassen, Ole A, Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M, Buitelaar, Jan K, Busatto, Geraldo F, Calhoun, Vince D, Canales-Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Castellanos, Francisco X, Chaim-Avancini, Tiffany M, Ching, Christopher R. K, Clark, Vincent P, Conrod, Patricia, Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher, Dickie, Erin W, Ehrlich, Stefan, van't Ent, Dennis, Fisher, Simon E, Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco J. C, Di Giorgio, Annabella, Glahn, David C, Gotlib, Ian H, Grabe, Hans J, Gruber, Oliver, Gruner, Patricia, Gur, Raquel E, Gur, Ruben C, Gurholt, Tiril P, de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J, Hartman, Catharina A, Hatton, Sean N, Heslenfeld, Dirk J, van den Heuvel, Odile A, Hickie, Ian B, Hoekstra, Pieter J, Hohmann, Sarah, Holmes, Avram J, Hoogman, Martine, Hosten, Norbert, Howells, Fleur M, Hulshoff Pol, Hilleke E, Huyser, Chaim, Jahanshad, Neda, James, Anthony C, Jiang, Jiyang, Jönsson, Erik G, Joska, John A, Kalnin, Andrew J, Klein, Marieke, Koenders, Laura, Kolskår, Knut K, Krämer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S, Lee, Phil H, Lochner, Christine, Machielsen, Marise WJ, Maingault, Sophie, Martin, Nicholas G, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C, McDonald, Colm, McIntosh, Andrew M, McMahon, Katie L, McPhilemy, Genevieve, van der Meer, Dennis, Menchón, José M, Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J, Radua, Joaquim, Reif, Andreas, Richard, Geneviève, Roffman, Joshua L, Rosa, Pedro GP, Sacchet, Matthew D, Sachdev, Perminder S, Salvador, Raymond, Sarró, Salvador, Satterthwaite, Theodore D, Saykin, Andrew J, Serpa, Mauricio H, Sim, Kang, Simmons, Andrew, Smoller, Jordan W, Sommer, Iris E, Soriano-Mas, Carles, Stein, Dan J, Strike, Lachlan T, Szeszko, Philip R, Temmingh, Henk S, Thomopoulos, Sophia I, Tomyshev, Alexander S, Trollor, Julian N, Uhlmann, Anne, Veer, Ilya M, Veltman, Dick J, Voineskos, Aristotle, Völzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D, Westlye, Lars T, Whalley, Heather C, Williams, Steven CR, Wittfeld, Katharina, Wolf, Daniel H, Wright, Margaret J, Yoncheva, Yuliya N, Zanetti, Marcus V, Ziegler, Georg C, de Zubicaray, Greig I, Thompson, Paul M, Crone, Eveline A, Frangou, Sophia, and Tamnes, Christian K
Abstract: Altres ajuts: The Marató TV3 Foundation #091710, For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
Published: 2020

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