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1. Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis.

Author

Kennedy, Eamonn, Liebel, Spencer, Lindsey, Hannah, Vadlamani, Shashank, Lei, Pui-Wa, Adamson, Maheen, Alda, Martin, Alonso-Lana, Silvia, Anderson, Tim, Arango, Celso, Asarnow, Robert, Avram, Mihai, Ayesa-Arriola, Rosa, Babikian, Talin, Banaj, Nerisa, Bird, Laura, Borgwardt, Stefan, Brodtmann, Amy, Brosch, Katharina, Caeyenberghs, Karen, Calhoun, Vince, Chiaravalloti, Nancy, Cifu, David, Crespo-Facorro, Benedicto, Dalrymple-Alford, John, Dams-OConnor, Kristen, Dannlowski, Udo, Darby, David, Davenport, Nicholas, DeLuca, John, Diaz-Caneja, Covadonga, Disner, Seth, Dobryakova, Ekaterina, Ehrlich, Stefan, Esopenko, Carrie, Ferrarelli, Fabio, Frank, Lea, Franz, Carol, Fuentes-Claramonte, Paola, Genova, Helen, Giza, Christopher, Goltermann, Janik, Grotegerd, Dominik, Gruber, Marius, Gutierrez-Zotes, Alfonso, Ha, Minji, Haavik, Jan, Hinkin, Charles, Hoskinson, Kristen, Hubl, Daniela, Irimia, Andrei, Jansen, Andreas, Kaess, Michael, Kang, Xiaojian, Kenney, Kimbra, Keřková, Barbora, Khlif, Mohamed, Kim, Minah, Kindler, Jochen, Kircher, Tilo, Knížková, Karolina, Kolskår, Knut, Krch, Denise, Kremen, William, Kuhn, Taylor, Kumari, Veena, Kwon, Junsoo, Langella, Roberto, Laskowitz, Sarah, Lee, Jungha, Lengenfelder, Jean, Liou-Johnson, Victoria, Lippa, Sara, Løvstad, Marianne, Lundervold, Astri, Marotta, Cassandra, Marquardt, Craig, Mattos, Paulo, Mayeli, Ahmad, McDonald, Carrie, Meinert, Susanne, Melzer, Tracy, Merchán-Naranjo, Jessica, Michel, Chantal, Morey, Rajendra, Mwangi, Benson, Myall, Daniel, Nenadić, Igor, Newsome, Mary, Nunes, Abraham, OBrien, Terence, Oertel, Viola, Ollinger, John, Olsen, Alexander, Ortiz García de la Foz, Victor, Ozmen, Mustafa, Pardoe, Heath, Parent, Marise, Piras, Fabrizio, and Piras, Federica

Subjects
Parkinson’s disease, attention-deficit/hyperactivity disorder, bipolar disorder, dementia, depression, memory, schizophrenia, stroke, traumatic brain injury, verbal learning
Abstract

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinsons disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

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, 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

Subjects
clinical high risk, consortium, early detection, prediction, prevention, psychosis, Humans, Psychotic Disorders, Schizophrenia, Prospective Studies, Adult, Prodromal Symptoms, Young Adult, International Cooperation, Adolescent, Research Design, Male, Female
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

4. Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study

Author

Si, Shuqing, Bi, Anbreen, Yu, Zhaoying, See, Cheryl, Kelly, Sinead, Ambrogi, Sonia, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Berk, Michael, Castro-Fornieles, Josefina, Crespo-Facorro, Benedicto, Crouse, Jacob J., Díaz-Caneja, Covadonga M., Fett, Anne-Kathrin, Fortea, Adriana, Frangou, Sophia, Goldstein, Benjamin I., Hickie, Ian B., Janssen, Joost, Kennedy, Kody G., Krabbendam, Lydia, Kyriakopoulos, Marinos, MacIntosh, Bradley J., Morgado, Pedro, Nerland, Stener, Pascual-Diaz, Saül, Picó-Pérez, Maria, Piras, Fabrizio, Rund, Bjørn Rishovd, de la Serna, Elena, Spalletta, Gianfranco, Sugranyes, Gisela, Suo, Chao, Tordesillas-Gutiérrez, Diana, Vecchio, Daniela, Radua, Joaquim, McGuire, Philip, Thomopoulos, Sophia I., Jahanshad, Neda, Thompson, Paul M., Barth, Claudia, Agartz, Ingrid, James, Anthony, and Kempton, Matthew J.

Published
2024
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5. In vivo white matter microstructure in adolescents with early-onset psychosis: a multi-site mega-analysis

Author

Barth, Claudia, Kelly, Sinead, Nerland, Stener, Jahanshad, Neda, Alloza, Clara, Ambrogi, Sonia, Andreassen, Ole A, Andreou, Dimitrios, Arango, Celso, Baeza, Inmaculada, Banaj, Nerisa, Bearden, Carrie E, Berk, Michael, Bohman, Hannes, Castro-Fornieles, Josefina, Chye, Yann, Crespo-Facorro, Benedicto, de la Serna, Elena, Díaz-Caneja, Covadonga M, Gurholt, Tiril P, Hegarty, Catherine E, James, Anthony, Janssen, Joost, Johannessen, Cecilie, Jönsson, Erik G, Karlsgodt, Katherine H, Kochunov, Peter, Lois, Noemi G, Lundberg, Mathias, Myhre, Anne M, Pascual-Diaz, Saül, Piras, Fabrizio, Smelror, Runar E, Spalletta, Gianfranco, Stokkan, Therese S, Sugranyes, Gisela, Suo, Chao, Thomopoulos, Sophia I, Tordesillas-Gutiérrez, Diana, Vecchio, Daniela, Wedervang-Resell, Kirsten, Wortinger, Laura A, Thompson, Paul M, and Agartz, Ingrid

Subjects
Brain Disorders, Serious Mental Illness, Pediatric, Biomedical Imaging, Clinical Research, Neurosciences, Mental Health, Schizophrenia, Mental health, Good Health and Well Being, Female, Humans, Male, Adolescent, White Matter, Diffusion Tensor Imaging, Brain, Psychotic Disorders, Anisotropy, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Emerging evidence suggests brain white matter alterations in adolescents with early-onset psychosis (EOP; age of onset

Published
2023

6. Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium.

Author

Constantinides, Constantinos, Han, Laura KM, Alloza, Clara, Antonucci, Linda Antonella, Arango, Celso, Ayesa-Arriola, Rosa, Banaj, Nerisa, Bertolino, Alessandro, Borgwardt, Stefan, Bruggemann, Jason, Bustillo, Juan, Bykhovski, Oleg, Calhoun, Vince, Carr, Vaughan, Catts, Stanley, Chung, Young-Chul, Crespo-Facorro, Benedicto, Díaz-Caneja, Covadonga M, Donohoe, Gary, Plessis, Stefan Du, Edmond, Jesse, Ehrlich, Stefan, Emsley, Robin, Eyler, Lisa T, Fuentes-Claramonte, Paola, Georgiadis, Foivos, Green, Melissa, Guerrero-Pedraza, Amalia, Ha, Minji, Hahn, Tim, Henskens, Frans A, Holleran, Laurena, Homan, Stephanie, Homan, Philipp, Jahanshad, Neda, Janssen, Joost, Ji, Ellen, Kaiser, Stefan, Kaleda, Vasily, Kim, Minah, Kim, Woo-Sung, Kirschner, Matthias, Kochunov, Peter, Kwak, Yoo Bin, Kwon, Jun Soo, Lebedeva, Irina, Liu, Jingyu, Mitchie, Patricia, Michielse, Stijn, Mothersill, David, Mowry, Bryan, de la Foz, Víctor Ortiz-García, Pantelis, Christos, Pergola, Giulio, Piras, Fabrizio, Pomarol-Clotet, Edith, Preda, Adrian, Quidé, Yann, Rasser, Paul E, Rootes-Murdy, Kelly, Salvador, Raymond, Sangiuliano, Marina, Sarró, Salvador, Schall, Ulrich, Schmidt, André, Scott, Rodney J, Selvaggi, Pierluigi, Sim, Kang, Skoch, Antonin, Spalletta, Gianfranco, Spaniel, Filip, Thomopoulos, Sophia I, Tomecek, David, Tomyshev, Alexander S, Tordesillas-Gutiérrez, Diana, van Amelsvoort, Therese, Vázquez-Bourgon, Javier, Vecchio, Daniela, Voineskos, Aristotle, Weickert, Cynthia S, Weickert, Thomas, Thompson, Paul M, Schmaal, Lianne, van Erp, Theo GM, Turner, Jessica, Cole, James H, ENIGMA Schizophrenia Consortium, Dima, Danai, and Walton, Esther

Subjects
ENIGMA Schizophrenia Consortium, Brain, Humans, Magnetic Resonance Imaging, Prospective Studies, Schizophrenia, Aging, Adolescent, Adult, Aged, Middle Aged, Female, Male, Young Adult, Mental Health, Serious Mental Illness, Brain Disorders, Neurosciences, Biomedical Imaging, Clinical Research, Behavioral and Social Science, Neurological, Mental health, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen's d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.

Published
2023

7. Emotion recognition profiles in clusters of youth based on levels of callous-unemotional traits and reactive and proactive aggression

Author

Kleine Deters, Renee, Naaijen, Jilly, Holz, Nathalie E., Banaschewski, Tobias, Schulze, Ulrike M. E., Sethi, Arjun, Craig, Michael C., Sagar-Ouriaghli, Ilyas, Santosh, Paramala, Rosa, Mireia, Castro-Fornieles, Josefina, Penzol, María José, Arango, Celso, Brandeis, Daniel, Franke, Barbara, Glennon, Jeffrey C., Buitelaar, Jan K., Hoekstra, Pieter J., and Dietrich, Andrea

Published
2023
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8. The relationship between genetic liability, childhood maltreatment, and IQ: findings from the EU-GEI multicentric case–control study

Author

Sideli, Lucia, Aas, Monica, Quattrone, Diego, La Barbera, Daniele, La Cascia, Caterina, Ferraro, Laura, Alameda, Luis, Velthorst, Eva, Trotta, Giulia, Tripoli, Giada, Schimmenti, Adriano, Fontana, Andrea, Gayer-Anderson, Charlotte, Stilo, Simona, Seminerio, Fabio, Sartorio, Crocettarachele, Marrazzo, Giovanna, Lasalvia, Antonio, Tosato, Sarah, Tarricone, Ilaria, Berardi, Domenico, D’Andrea, Giuseppe, Arango, Celso, Arrojo, Manuel, Bernardo, Miguel, Bobes, Julio, Sanjuán, Julio, Santos, Jose Luis, Menezes, Paulo Rossi, Del-Ben, Cristina Marta, Jongsma, Hannah E., Jones, Peter B., Kirkbride, James B., Llorca, Pierre-Michel, Tortelli, Andrea, Pignon, Baptiste, de Haan, Lieuwe, Selten, Jean-Paul, Van Os, Jim, Rutten, Bart P., Bentall, Richard, Di Forti, Marta, Murray, Robin M., Morgan, Craig, and Fisher, Helen L.

Published
2023
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9. Oxytocin Exposure in Labor and Its Relationship with Cognitive Impairment and the Genetic Architecture of Autism

Author

García-Alcón, Alicia, González-Peñas, Javier, Weckx, Elisa, Penzol, M. J., Gurriarán, Xaquín, Costas, Javier, Díaz-Caneja, Covadonga M., Moreno, Carmen, Hernández, Patricia, Arango, Celso, and Parellada, Mara

Abstract

Whether there is a relationship between oxytocin (OXT) use in labor and the risk of autism (ASD), and the nature of such relationship, is unclear. By integrating genetic and clinical data in a sample of 176 ASD participants, we tested the hypothesis that OXT is a marker for abnormal prenatal development which leads to impairments in the process of labor. OXT-exposed ASD had more obstetric complications (P = 0.031), earlier onset of symptoms (P = 0.027), poorer cognitive development (P = 0.011), higher mutation burden across neurodevelopment genes (P = 0.020; OR = 5.33) and lower transmission of polygenic risk for ASD (P = 0.0319), than non-exposed ASD. OXT seems to constitute a risk indicator rather than a risk factor for ASD, which is relevant for diagnostic and genetic counselling.

Published
2023
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10. Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Author

Patel, Yash, Shin, Jean, Abé, Christoph, Agartz, Ingrid, Alloza, Clara, Alnæs, Dag, Ambrogi, Sonia, Antonucci, Linda A, Arango, Celso, Arolt, Volker, Auzias, Guillaume, Ayesa-Arriola, Rosa, Banaj, Nerisa, Banaschewski, Tobias, Bandeira, Cibele, Başgöze, Zeynep, Cupertino, Renata Basso, Bau, Claiton HD, Bauer, Jochen, Baumeister, Sarah, Bernardoni, Fabio, Bertolino, Alessandro, Bonnin, Caterina Del Mar, Brandeis, Daniel, Brem, Silvia, Bruggemann, Jason, Bülow, Robin, Bustillo, Juan R, Calderoni, Sara, Calvo, Rosa, Canales-Rodríguez, Erick J, Cannon, Dara M, Carmona, Susanna, Carr, Vaughan J, Catts, Stanley V, Chenji, Sneha, Chew, Qian Hui, Coghill, David, Connolly, Colm G, Conzelmann, Annette, Craven, Alexander R, Crespo-Facorro, Benedicto, Cullen, Kathryn, Dahl, Andreas, Dannlowski, Udo, Davey, Christopher G, Deruelle, Christine, Díaz-Caneja, Covadonga M, Dohm, Katharina, Ehrlich, Stefan, Epstein, Jeffery, Erwin-Grabner, Tracy, Eyler, Lisa T, Fedor, Jennifer, Fitzgerald, Jacqueline, Foran, William, Ford, Judith M, Fortea, Lydia, Fuentes-Claramonte, Paola, Fullerton, Janice, Furlong, Lisa, Gallagher, Louise, Gao, Bingchen, Gao, Si, Goikolea, Jose M, Gotlib, Ian, Goya-Maldonado, Roberto, Grabe, Hans J, Green, Melissa, Grevet, Eugenio H, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Haavik, Jan, Hahn, Tim, Harrison, Ben J, Heindel, Walter, Henskens, Frans, Heslenfeld, Dirk J, Hilland, Eva, Hoekstra, Pieter J, Hohmann, Sarah, Holz, Nathalie, Howells, Fleur M, Ipser, Jonathan C, Jahanshad, Neda, Jakobi, Babette, Jansen, Andreas, Janssen, Joost, Jonassen, Rune, Kaiser, Anna, Kaleda, Vasiliy, Karantonis, James, King, Joseph A, Kircher, Tilo, Kochunov, Peter, Koopowitz, Sheri-Michelle, Landén, Mikael, Landrø, Nils Inge, and Lawrie, Stephen

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Schizophrenia, Neurosciences, Brain Disorders, Biotechnology, Perinatal Period - Conditions Originating in Perinatal Period, Infant Mortality, Pediatric, Serious Mental Illness, Intellectual and Developmental Disabilities (IDD), Genetics, Mental Health, Preterm, Low Birth Weight and Health of the Newborn, 2.3 Psychological, social and economic factors, Aetiology, 2.1 Biological and endogenous factors, Neurological, Mental health, Reproductive health and childbirth, Good Health and Well Being, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Bipolar Disorder, Cerebral Cortex, Child, Depressive Disorder, Major, Female, Humans, Infant, Newborn, Magnetic Resonance Imaging, Pregnancy, Premature Birth, Cortical growth, Cortical surface area, Mental illness, Neurodevelopment, Neurogenesis, Psychiatric disorders, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences
Abstract

BackgroundMorphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life.MethodsInterregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed.ResultsAcross the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth.ConclusionsOur findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.

Published
2022

12. Social dysfunction relates to shifts within socioaffective brain systems among Schizophrenia and Alzheimer's disease patients

Author

Braak, Simon, Penninx, Brenda WJH, Su, Tanja, Pijnenburg, Yolande, Nijland, Daphne, Campos, Alba Vieira, de la Torre-Luque, Alejandro, Saris, Ilja M.J., Reus, Lianne M., Beckenstrom, Amy Christine, Malik, Asad, Dawson, Gerard R., Marston, Hugh, Alvarez-Linera, Juan, Ayuso-Mateos, Jose-Luis L., Arango, Celso, van der Wee, Nic, Kas, Martien J., and Aghajani, Moji

Published
2024
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13. Accelerated Cortical Thinning in Schizophrenia Is Associated With Rare and Common Predisposing Variation to Schizophrenia and Neurodevelopmental Disorders

Author

González-Peñas, Javier, Díaz-Caneja, Covadonga M., Costas, Javier, Gurriarán, Xaquín, Andreu-Bernabeu, Álvaro, Fañanas, Lourdes, Rosa de la Cruz, Araceli, Arias, Bárbara, Bobes, Julio, Pinto, Ana González, Crespo-Facorro, B., Martorell, L., Vilella, Elisabet, Muntané, Gerard, Moltó, María Dolores, Escartí, María José, Rivero, Olga, Parellada, Mara, Moreno, Carmen, Arango, Celso, Alloza, Clara, Brouwer, Rachel, González-Lois, Noemí, Gallego, Ana Guil, de Hoyos, Lucía, Romero-García, Rafael, Fañanás, Lourdes, González-Pinto, Ana, Crespo-Facorro, Benedicto, Martorell, Lourdes, Arrojo, Manuel, Gutiérrez-Zotes, Alfonso, Perez-Rando, Marta, Buimer, Elizabeth, van Haren, Neeltje, Cahn, Wiepke, O’Donovan, Michael, Kahn, René S., Pol, Hilleke Hulshoff, Janssen, Joost, and Schnack, Hugo

Published
2024
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14. PsyCog: A computerised mini battery for assessing cognition in psychosis

Author

Gifford, George, Cullen, Alexis E., Vieira, Sandra, Searle, Anja, McCutcheon, Robert A., Modinos, Gemma, Stone, William S., Hird, Emily, Barnett, Jennifer, van Hell, Hendrika H., Catalan, Ana, Millgate, Edward, Taptiklis, Nick, Cormack, Francesca, Slot, Margot E., Dazzan, Paola, Maat, Arija, de Haan, Lieuwe, Facorro, Benedicto Crespo, Glenthøj, Birte, Lawrie, Stephen M., McDonald, Colm, Gruber, Oliver, van Amelsvoort, Thérèse, Arango, Celso, Kircher, Tilo, Nelson, Barnaby, Galderisi, Silvana, Bressan, Rodrigo A., Kwon, Jun Soo, Weiser, Mark, Mizrahi, Romina, Sachs, Gabriele, Kirschner, Matthias, Reichenberg, Abraham, Kahn, René, and McGuire, Philip

Published
2024
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16. A normative chart for cognitive development in a genetically selected population

Author

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, Vorstman, Jacob, and Breetvelt, Elemi J

Subjects
Brain Disorders, Serious Mental Illness, Pediatric, Mental Health, Schizophrenia, Clinical Research, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Mental health, Adult, Cognition, DiGeorge Syndrome, Humans, Intelligence Tests, 22q11DS International Consortium on Brain and Behavior, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
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

Published
2022

19. A naturalistic cohort study of first-episode schizophrenia spectrum disorder: A description of the early phase of illness in the PSYSCAN cohort

Author

Slot, Margot I.E., van Hell, Hendrika H., Rossum, Inge Winter-van, Dazzan, Paola, Maat, Arija, de Haan, Lieuwe, Crespo-Facorro, Benedicto, Glenthøj, Birte, Lawrie, Stephen M., McDonald, Colm, Gruber, Oliver, van Amelsvoort, Thérèse, Arango, Celso, Kircher, Tilo, Nelson, Barnaby, Galderisi, Silvana, Weiser, Mark, Sachs, Gabriele, Maatz, Anke, Bressan, Rodrigo A., Kwon, Jun Soo, Mizrahi, Romina, McGuire, Philip, and Kahn, René S.

Published
2024
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20. Humanization in mental health plans in Spain

Author

Fraguas, David, Zarco, Julio, Balanzá-Martínez, Vicent, Blázquez García, Juan Francisco, Borràs Murcia, Cecilia, Cabrera, Ana, Carretero, Julián, Crespo, Agustina, Díaz-Marsá, Marina, Gasul, Vicente, González, Miguel A., Grande, Iria, Muela, Carmen, de las Heras Liñero, Elena, Mayoral, Fermín, Morales Cano, Guadalupe, Pagés-Lluyot, José Ramón, Romo, José, Serrano Marín, Bibiana, Sauceda, Antonio Lozano, and Arango, Celso

Published
2024
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21. Extreme deviations from the normative model reveal cortical heterogeneity and associations with negative symptom severity in first-episode psychosis from the OPTiMiSE and GAP studies

Author

Worker, Amanda, Berthert, Pierre, Lawrence, Andrew J., Kia, Seyed Mostafa, Arango, Celso, Dinga, Richard, Galderisi, Silvana, Glenthøj, Birte, Kahn, René S., Leslie, Anoushka, Murray, Robin M., Pariante, Carmine M., Pantelis, Christos, Weiser, Mark, Winter-van Rossum, Inge, McGuire, Philip, Dazzan, Paola, and Marquand, Andre F.

Published
2023
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22. Correction: Common genetic variants contribute to heritability of age at onset of schizophrenia

Author

Sada-Fuente, Ester, Aranda, Selena, Papiol, Sergi, Heilbronner, Urs, Moltó, María Dolores, Aguilar, Eduardo J., González-Peñas, Javier, Andreu-Bernabeu, Álvaro, Arango, Celso, Crespo-Facorro, Benedicto, González-Pinto, Ana, Fañanás, Lourdes, Arias, Barbara, Bobes, Julio, Costas, Javier, Martorell, Lourdes, Schulze, Thomas G., Kalman, Janos L., Vilella, Elisabet, and Muntané, Gerard

Published
2023
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23. Recent natural selection conferred protection against schizophrenia by non-antagonistic pleiotropy

Author

González-Peñas, Javier, de Hoyos, Lucía, Díaz-Caneja, Covadonga M., Andreu-Bernabeu, Álvaro, Stella, Carol, Gurriarán, Xaquín, Fañanás, Lourdes, Bobes, Julio, González-Pinto, Ana, Crespo-Facorro, Benedicto, Martorell, Lourdes, Vilella, Elisabet, Muntané, Gerard, Molto, María Dolores, Gonzalez-Piqueras, Jose Carlos, Parellada, Mara, Arango, Celso, and Costas, Javier

Published
2023
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25. Common genetic variants contribute to heritability of age at onset of schizophrenia

Author

Sada-Fuente, Ester, Aranda, Selena, Papiol, Sergi, Heilbronner, Urs, Moltó, María Dolores, Aguilar, Eduardo J., González-Peñas, Javier, Andreu-Bernabeu, Álvaro, Arango, Celso, Crespo-Facorro, Benedicto, González-Pinto, Ana, Fañanás, Lourdes, Arias, Barbara, Bobes, Julio, Costas, Javier, Martorell, Lourdes, Schulze, Thomas G., Kalman, Janos L., Vilella, Elisabet, and Muntané, Gerard

Published
2023
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26. 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 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, Pol, Hilleke E Hulshoff, 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, Sánchez, Jennifer Monereo, Moreau, Clara A, Mühleisen, Thomas W, Paus, Tomas, Pausova, Zdenka, Prieto, Carlos, Ragothaman, Anjanibhargavi, Reinbold, Céline S, Marques, Tiago Reis, 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

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Mental Health, Clinical Research, Pediatric, Genetics, Basic Behavioral and Social Science, Human Genome, Prevention, Brain Disorders, Behavioral and Social Science, Neurosciences, Aetiology, 2.1 Biological and endogenous factors, Mental health, Neurological, Brain, DNA Copy Number Variations, Humans, Magnetic Resonance Imaging, Mental Disorders, Multicenter Studies as Topic, Neurodevelopmental Disorders, Neuroimaging, brain structural imaging, copy number variant, diffusion tensor imaging, evolution, genetics-first approach, neurodevelopmental disorders, psychiatric disorders, ENIGMA-CNV Working Group, ENIGMA 22q11.2 Deletion Syndrome Working Group, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
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

27. Intracranial and subcortical volumes in adolescents with early-onset psychosis: A multisite mega-analysis from the ENIGMA consortium.

Author

Gurholt, Tiril P, Lonning, Vera, Nerland, Stener, Jørgensen, Kjetil N, Haukvik, Unn K, Alloza, Clara, Arango, Celso, Barth, Claudia, Bearden, Carrie E, Berk, Michael, Bohman, Hannes, Dandash, Orwa, Díaz-Caneja, Covadonga M, Edbom, Carl T, van Erp, Theo GM, Fett, Anne-Kathrin J, Frangou, Sophia, Goldstein, Benjamin I, Grigorian, Anahit, Jahanshad, Neda, James, Anthony C, Janssen, Joost, Johannessen, Cecilie, Karlsgodt, Katherine H, Kempton, Matthew J, Kochunov, Peter, Krabbendam, Lydia, Kyriakopoulos, Marinos, Lundberg, Mathias, MacIntosh, Bradley J, Rund, Bjørn Rishovd, Smelror, Runar E, Sultan, Alysha, Tamnes, Christian K, Thomopoulos, Sophia I, Vajdi, Ariana, Wedervang-Resell, Kirsten, Myhre, Anne M, Andreassen, Ole A, Thompson, Paul M, Agartz, Ingrid, and ENIGMA-EOP Working Group

Subjects
ENIGMA-EOP Working Group, Brain, Hippocampus, Globus Pallidus, Humans, Magnetic Resonance Imaging, Adolescent Development, Affective Disorders, Psychotic, Psychotic Disorders, Schizophrenia, Age of Onset, Adolescent, adolescence, antipsychotics, brain structure, early-onset, intracranial volume, psychosis spectrum, Mental Health, Clinical Research, Serious Mental Illness, Biomedical Imaging, Brain Disorders, Pediatric, Pediatric Research Initiative, Neurosciences, Mental health, Good Health and Well Being, Cognitive Sciences, Experimental Psychology
Abstract

Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = -0.39) and hippocampal (d = -0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = -0.34) and affective psychosis (d = -0.42), and early-onset schizophrenia showed lower hippocampal (d = -0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = -0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.

Published
2022

28. Exploring the mediation of DNA methylation across the epigenome between childhood adversity and First Episode of Psychosis—findings from the EU-GEI study

Author

Alameda, Luis, Liu, Zhonghua, Sham, Pak C., Aas, Monica, Trotta, Giulia, Rodriguez, Victoria, Di Forti, Marta, Stilo, Simona A., Kandaswamy, Radhika, Arango, Celso, Arrojo, Manuel, Bernardo, Miguel, Bobes, Julio, de Haan, Lieuwe, Del-Ben, Cristina Marta, Gayer-Anderson, Charlotte, Sideli, Lucia, Jones, Peter B., Jongsma, Hannah E., Kirkbride, James B., La Cascia, Caterina, Lasalvia, Antonio, Tosato, Sarah, Llorca, Pierre-Michel, Menezes, Paulo Rossi, van Os, Jim, Quattrone, Diego, Rutten, Bart P., Santos, Jose Luis, Sanjuán, Julio, Selten, Jean-Paul, Szöke, Andrei, Tarricone, Ilaria, Tortelli, Andrea, Velthorst, Eva, Morgan, Craig, Dempster, Emma, Hannon, Eilis, Burrage, Joe, Dwir, Daniella, Arumuham, Atheeshaan, Mill, Jonathan, Murray, Robin M., and Wong, Chloe C. Y.

Published
2023
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30. Psychopharmacology in children and adolescents: unmet needs and opportunities

Author

Cortese, Samuele, Purper-Ouakil, Diane, Apter, Alan, Arango, Celso, Baeza, Inmaculada, Banaschewski, Tobias, Buitelaar, Jan, Castro-Fornieles, Josefina, Coghill, David, Cohen, David, Correll, Christoph U, Grünblatt, Edna, Hoekstra, Pieter J, James, Anthony, Jeppesen, Pia, Nagy, Péter, Pagsberg, Anne Katrine, Parellada, Mara, Persico, Antonio M, Roessner, Veit, Santosh, Paramala, Simonoff, Emily, Stevanovic, Dejan, Stringaris, Argyris, Vitiello, Benedetto, Walitza, Susanne, Weizman, Abraham, Wong, Ian C K, Zalsman, Gil, Zuddas, Alessandro, Carucci, Sara, Butlen-Ducuing, Florence, Tome, Maria, Bea, Myriam, Getin, Christine, Hovén, Nina, Konradsson-Geuken, Asa, Lamirell, Daphne, Olisa, Nigel, Nafria Escalera, Begonya, and Moreno, Carmen

Published
2024
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32. Relapse in clinically stable adult patients with schizophrenia or schizoaffective disorder: evidence-based criteria derived by equipercentile linking and diagnostic test accuracy meta-analysis

Author

Siafis, Spyridon, Brandt, Lasse, McCutcheon, Robert A, Gutwinski, Stefan, Schneider-Thoma, Johannes, Bighelli, Irene, Kane, John M, Arango, Celso, Kahn, René S, Fleischhacker, W Wolfgang, McGorry, Patrick, Carpenter, William T, Falkai, Peter, Hasan, Alkomiet, Marder, Stephen R, Schooler, Nina, Engel, Rolf R, Honer, William G, Buchanan, Robert W, Davidson, Michael, Weiser, Mark, Priller, Josef, Davis, John M, Howes, Oliver D, Correll, Christoph U, and Leucht, Stefan

Published
2024
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34. Drug development for Autism Spectrum Disorder (ASD): Progress, challenges, and future directions

Author

McCracken, James T, Anagnostou, Evdokia, Arango, Celso, Dawson, Geraldine, Farchione, Tiffany, Mantua, Valentina, McPartland, James, Murphy, Declan, Pandina, Gahan, Veenstra-VanderWeele, Jeremy, and Group, the ISCTM ECNP ASD Working

Subjects
Biological Psychology, Psychology, Brain Disorders, Neurosciences, Pediatric, Intellectual and Developmental Disabilities (IDD), Mental Health, Autism, Mental health, Good Health and Well Being, Autism Spectrum Disorder, Biomarkers, Communication, Drug Development, Humans, Phenotype, Endpoints, Children, Drug development, Treatment, Clinical trials, ISCTM/ECNP ASD Working Group, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological psychology
Abstract

In 2017, facing lack of progress and failures encountered in targeted drug development for Autism Spectrum Disorder (ASD) and related neurodevelopmental disorders, the ISCTM with the ECNP created the ASD Working Group charged to identify barriers to progress and recommending research strategies for the field to gain traction. Working Group international academic, regulatory and industry representatives held multiple in-person meetings, teleconferences, and subgroup communications to gather a wide range of perspectives on lessons learned from extant studies, current challenges, and paths for fundamental advances in ASD therapeutics. This overview delineates the barriers identified, and outlines major goals for next generation biomedical intervention development in ASD. Current challenges for ASD research are many: heterogeneity, lack of validated biomarkers, need for improved endpoints, prioritizing molecular targets, comorbidities, and more. The Working Group emphasized cautious but unwavering optimism for therapeutic progress for ASD core features given advances in the basic neuroscience of ASD and related disorders. Leveraging genetic data, intermediate phenotypes, digital phenotyping, big database discovery, refined endpoints, and earlier intervention, the prospects for breakthrough treatments are substantial. Recommendations include new priorities for expanded research funding to overcome challenges in translational clinical ASD therapeutic research.

Published
2021

35. Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations

Author

Liu, Dongjing, Meyer, Dara, Fennessy, Brian, Feng, Claudia, Cheng, Esther, Johnson, Jessica S., Park, You Jeong, Rieder, Marysia-Kolbe, Ascolillo, Steven, de Pins, Agathe, Dobbyn, Amanda, Lebovitch, Dannielle, Moya, Emily, Nguyen, Tan-Hoang, Wilkins, Lillian, Hassan, Arsalan, Burdick, Katherine E., Buxbaum, Joseph D., Domenici, Enrico, Frangou, Sophia, Hartmann, Annette M., Laurent-Levinson, Claudine, Malhotra, Dheeraj, Pato, Carlos N., Pato, Michele T., Ressler, Kerry, Roussos, Panos, Rujescu, Dan, Arango, Celso, Bertolino, Alessandro, Blasi, Giuseppe, Bocchio-Chiavetto, Luisella, Campion, Dominique, Carr, Vaughan, Fullerton, Janice M., Gennarelli, Massimo, González-Peñas, Javier, Levinson, Douglas F., Mowry, Bryan, Nimgaokar, Vishwajit L., Pergola, Giulio, Rampino, Antonio, Cervilla, Jorge A., Rivera, Margarita, Schwab, Sibylle G., Wildenauer, Dieter B., Daly, Mark, Neale, Benjamin, Singh, Tarjinder, O’Donovan, Michael C., Owen, Michael J., Walters, James T., Ayub, Muhammad, Malhotra, Anil K., Lencz, Todd, Sullivan, Patrick F., Sklar, Pamela, Stahl, Eli A., Huckins, Laura M., and Charney, Alexander W.

Published
2023
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38. Counterpoint. Early intervention for psychosis risk syndromes: Minimizing risk and maximizing benefit.

Author

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

Subjects
Humans, Syndrome, Psychotic Disorders, Social Stigma, Autonomy, Beneficence, Biomarkers, Clinical high risk, Psychosis, Stigma, Clinical Research, Mental Health, Serious Mental Illness, Pediatric Research Initiative, Prevention, Good Health and Well Being, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
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

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

Author

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 WC, 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, Bearden, Carrie E, and Vorstman, Jacob AS

Subjects
Biomedical and Clinical Sciences, Health Sciences, Genetics, Schizophrenia, Serious Mental Illness, Behavioral and Social Science, Prevention, Brain Disorders, Clinical Research, Mental Health, Aetiology, 2.1 Biological and endogenous factors, Mental health, Adolescent, Adult, Aged, Child, Child, Preschool, Cognitive Dysfunction, Cohort Studies, DiGeorge Syndrome, Female, Genetic Variation, Humans, Intellectual Disability, Male, Middle Aged, Multifactorial Inheritance, Phenotype, Risk Factors, Young Adult, International 22q11.2 Brain and Behavior Consortium, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

The 22q11.2 deletion syndrome (22q11DS) is associated with a 20-25% risk of schizophrenia. In a cohort of 962 individuals with 22q11DS, we examined the shared genetic basis between schizophrenia and schizophrenia-related early trajectory phenotypes: sub-threshold symptoms of psychosis, low baseline intellectual functioning and cognitive decline. We studied the association of these phenotypes with two polygenic scores, derived for schizophrenia and intelligence, and evaluated their use for individual risk prediction in 22q11DS. Polygenic scores were not only associated with schizophrenia and baseline intelligence quotient (IQ), respectively, but schizophrenia polygenic score was also significantly associated with cognitive (verbal IQ) decline and nominally associated with sub-threshold psychosis. Furthermore, in comparing the tail-end deciles of the schizophrenia and IQ polygenic score distributions, 33% versus 9% of individuals with 22q11DS had schizophrenia, and 63% versus 24% of individuals had intellectual disability. Collectively, these data show a shared genetic basis for schizophrenia and schizophrenia-related phenotypes and also highlight the future potential of polygenic scores for risk stratification among individuals with highly, but incompletely, penetrant genetic variants.

Published
2020

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

Author

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

Subjects
Paediatrics, Biomedical and Clinical Sciences, Neurosciences, Pediatric, Biomedical Imaging, Mental Health, Clinical Research, Brain Disorders, Mental health, Adolescent, Adult, Anisotropy, Child, DiGeorge Syndrome, Diffusion Magnetic Resonance Imaging, Female, Humans, Male, Middle Aged, White Matter, Young Adult, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
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

44. The future of child and adolescent clinical psychopharmacology: A systematic review of phase 2, 3, or 4 randomized controlled trials of pharmacologic agents without regulatory approval or for unapproved indications

Author

Cortese, Samuele, McGinn, Katherine, Højlund, Mikkel, Apter, Alan, Arango, Celso, Baeza, Immaculada, Banaschewski, Tobias, Buitelaar, Jan, Castro-Fornieles, Josefina, Coghill, David, Cohen, David, Grünblatt, Edna, Hoekstra, Pieter J., James, Anthony, Jeppesen, Pia, Nagy, Péter, Pagsberg, Anne Katrine, Parellada, Mara, Persico, Antonio M., Purper-Ouakil, Diane, Roessner, Veit, Santosh, Paramala, Simonoff, Emily, Stevanovic, Dejan, Stringaris, Argyris, Vitiello, Benedetto, Walitza, Susanne, Weizman, Abraham, Wohlfarth, Tamar, Wong, Ian C.K., Zalsman, Gil, Zuddas, Alessandro, Moreno, Carmen, Solmi, Marco, and Correll, Christoph U.

Published
2023
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45. Examining the association between exposome score for schizophrenia and cognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study

Author

Fusar-Poli, Laura, Prachason, Thanavadee, Erzin, Gamze, Pries, Lotta-Katrin, Brondino, Natascia, Politi, Pierluigi, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Andric-Petrovic, Sanja, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, Maria Paz, Sanjuan, Julio, Escarti, Maria Jose, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Üçok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, O'Donovan, Michael, van Os, Jim, Rutten, Bart PF, and Guloksuz, Sinan

Published
2023
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46. Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups

Author

Boedhoe, Premika SW, van Rooij, Daan, Hoogman, Martine, Twisk, Jos WR, Schmaal, Lianne, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Anikin, Anatoly, Anticevic, Alan, Arango, Celso, Arnold, Paul D, Asherson, Philip, Assogna, Francesca, Auzias, Guillaume, Banaschewski, Tobias, Baranov, Alexander, Batistuzzo, Marcelo C, Baumeister, Sarah, Baur-Streubel, Ramona, Behrmann, Marlene, Bellgrove, Mark A, Benedetti, Francesco, Beucke, Jan C, Biederman, Joseph, Bollettini, Irene, Bose, Anushree, Bralten, Janita, Bramati, Ivanei E, Brandeis, Daniel, Brem, Silvia, Brennan, Brian P, Busatto, Geraldo F, Calderoni, Sara, Calvo, Anna, Calvo, Rosa, Castellanos, Francisco X, Cercignani, Mara, Chaim-Avancini, Tiffany M, Chantiluke, Kaylita C, Cheng, Yuqi, Cho, Kang Ik K, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Cubillo, Ana I, Dale, Anders M, Dallaspezia, Sara, Daly, Eileen, Denys, Damiaan, Deruelle, Christine, Di Martino, Adriana, Dinstein, Ilan, Doyle, Alysa E, Durston, Sarah, Earl, Eric A, Ecker, Christine, Ehrlich, Stefan, Ely, Benjamin A, Epstein, Jeffrey N, Ethofer, Thomas, Fair, Damien A, Fallgatter, Andreas J, Faraone, Stephen V, Fedor, Jennifer, Feng, Xin, Feusner, Jamie D, Fitzgerald, Jackie, Fitzgerald, Kate D, Fouche, Jean-Paul, Freitag, Christine M, Fridgeirsson, Egill A, Frodl, Thomas, Gabel, Matt C, Gallagher, Louise, Gogberashvili, Tinatin, Gori, Ilaria, Gruner, Patricia, Gürsel, Deniz A, Haar, Shlomi, Haavik, Jan, Hall, Geoffrey B, Harrison, Neil A, Hartman, Catharina A, Heslenfeld, Dirk J, Hirano, Yoshiyuki, Hoekstra, Pieter J, Hoexter, Marcelo Q, Hohmann, Sarah, Høvik, Marie F, Hu, Hao, Huyser, Chaim, Jahanshad, Neda, Jalbrzikowski, Maria, James, Anthony, Janssen, Joost, Jaspers-Fayer, Fern, Jernigan, Terry L, Kapilushniy, Dmitry, and Kardatzki, Bernd

Subjects
Attention Deficit Hyperactivity Disorder (ADHD), Behavioral and Social Science, Clinical Research, Mental Health, Neurosciences, Pediatric, Autism, Intellectual and Developmental Disabilities (IDD), Brain Disorders, 2.1 Biological and endogenous factors, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Neurological, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Cerebrum, Child, Female, Human Development, Humans, Male, Neuroimaging, Obsessive-Compulsive Disorder, Organ Size, Psychopathology, Research Report, Systems Analysis, ENIGMA ADHD working group, ENIGMA ASD working group, ENIGMA OCD working group, Attention Deficit Hyperactivity Disorder, ENIGMA, Structural MRI, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

ObjectiveAttention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data.MethodsStructural T1-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures).ResultsNo shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood.ConclusionsThe study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.

Published
2020

47. Publisher Correction: Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

Author

Lim, Elaine T, Uddin, Mohammed, De Rubeis, Silvia, Chan, Yingleong, Kamumbu, Anne S, Zhang, Xiaochang, D’Gama, Alissa M, Kim, Sonia N, Hill, Robert Sean, Goldberg, Arthur P, Poultney, Christopher, Minshew, Nancy J, Kushima, Itaru, Aleksic, Branko, Ozaki, Norio, Parellada, Mara, Arango, Celso, Penzol, Maria J, Carracedo, Angel, Kolevzon, Alexander, Hultman, Christina M, Weiss, Lauren A, Fromer, Menachem, Chiocchetti, Andreas G, Freitag, Christine M, Church, George M, Scherer, Stephen W, Buxbaum, Joseph D, and Walsh, Christopher A

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Autism Sequencing Consortium, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

48. Increased power by harmonizing structural MRI site differences with the ComBat batch adjustment method in ENIGMA

Author

Radua, Joaquim, Vieta, Eduard, Shinohara, Russell, Kochunov, Peter, Quidé, Yann, Green, Melissa J, Weickert, Cynthia S, Weickert, Thomas, Bruggemann, Jason, Kircher, Tilo, Nenadić, Igor, Cairns, Murray J, Seal, Marc, Schall, Ulrich, Henskens, Frans, Fullerton, Janice M, Mowry, Bryan, Pantelis, Christos, Lenroot, Rhoshel, Cropley, Vanessa, Loughland, Carmel, Scott, Rodney, Wolf, Daniel, Satterthwaite, Theodore D, Tan, Yunlong, Sim, Kang, Piras, Fabrizio, Spalletta, Gianfranco, Banaj, Nerisa, Pomarol-Clotet, Edith, Solanes, Aleix, Albajes-Eizagirre, Anton, Canales-Rodríguez, Erick J, Sarro, Salvador, Di Giorgio, Annabella, Bertolino, Alessandro, Stäblein, Michael, Oertel, Viola, Knöchel, Christian, Borgwardt, Stefan, du Plessis, Stefan, Yun, Je-Yeon, Kwon, Jun Soo, Dannlowski, Udo, Hahn, Tim, Grotegerd, Dominik, Alloza, Clara, Arango, Celso, Janssen, Joost, Díaz-Caneja, Covadonga, Jiang, Wenhao, Calhoun, Vince, Ehrlich, Stefan, Yang, Kun, Cascella, Nicola G, Takayanagi, Yoichiro, Sawa, Akira, Tomyshev, Alexander, Lebedeva, Irina, Kaleda, Vasily, Kirschner, Matthias, Hoschl, Cyril, Tomecek, David, Skoch, Antonin, van Amelsvoort, Therese, Bakker, Geor, James, Anthony, Preda, Adrian, Weideman, Andrea, Stein, Dan J, Howells, Fleur, Uhlmann, Anne, Temmingh, Henk, López-Jaramillo, Carlos, Díaz-Zuluaga, Ana, Fortea, Lydia, Martinez-Heras, Eloy, Solana, Elisabeth, Llufriu, Sara, Jahanshad, Neda, Thompson, Paul, Turner, Jessica, van Erp, Theo, collaborators, ENIGMA Consortium, Glahn, David, Pearlson, Godfrey, Hong, Elliot, Krug, Axel, Carr, Vaughan, Tooney, Paul, Cooper, Gavin, Rasser, Paul, Michie, Patricia, Catts, Stanley, Gur, Raquel, Gur, Ruben, Yang, Fude, Fan, Fengmei, Chen, Jingxu, and Guo, Hua

Subjects
Brain Disorders, Biomedical Imaging, Mental Health, Schizophrenia, Neurosciences, Mental health, Adult, Algorithms, Cerebral Cortex, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Meta-Analysis as Topic, Middle Aged, Neuroimaging, Young Adult, Brain, Cortical thickness, Gray matter, Mega-analysis, Volume, ENIGMA Consortium collaborators, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning).

Published
2020

49. Elevated Extracellular Free-Water in a Multicentric First-Episode Psychosis Sample, Decrease During the First 2 Years of Illness.

Author

Bergé, Daniel, Mané, Anna, Lesh, Tyler A, Bioque, Miquel, Barcones, Fe, Gonzalez-Pinto, Ana Maria, Parellada, Mara, Vieta, Eduard, Castro-Fornieles, Josefina, Rodriguez-Jimenez, Roberto, García-Portilla, Maria Paz, Usall, Judith, Carter, Cameron S, Cabrera, Bibiana, Bernardo, Miguel, Janssen, Joost, Mezquida, Gisela, Amoretti, Silvia, Pina-Camacho, Laura, Arango, Celso, González-Ortega, I, García, S, De-la-Cámara, C, Fayed, N, Sanjuan, Julio, Aguilar, EJ, Guo, Joyce Y, Salgado, Purificación, Raduà, Joquim, Sánchez-Moreno, J, de la Serna, Elena, Baeza, Ima, Contreras-Fernández, Fernando, Saiz-Masvidal, C, González-Blanco, L, Jiménez-Treviño, L, Dompablo, M, Torío, I, Butjosa, A, Rubio-Abadel, E, Sarró, S, and Pomarol-Clotet, E

Subjects
Clinical Research, Prevention, Neurosciences, Schizophrenia, Mental Health, Brain Disorders, Serious Mental Illness, Biomedical Imaging, 2.1 Biological and endogenous factors, Aetiology, Mental health, Adolescent, Adult, Body Water, Child, Cross-Sectional Studies, Female, Gray Matter, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Psychotic Disorders, White Matter, Young Adult, PEPs group, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Recent diffusion imaging studies using free-water (FW) elimination have shown increased FW in gray matter (GM) and white matter (WM) in first-episode psychosis (FEP) and lower corrected fractional anisotropy (FAt) in WM in chronic schizophrenia. However, little is known about the longitudinal stability and clinical significance of these findings. To determine tissue-specific FW and FAt abnormalities in FEP, as part of a multicenter Spanish study, 132 FEP and 108 healthy controls (HC) were clinically characterized and underwent structural and diffusion-weighted MRI scanning. FEP subjects were classified as schizophrenia spectrum disorder (SSD) or non-SSD. Of these subjects, 45 FEP and 41 HC were longitudinally assessed and rescanned after 2 years. FA and FW tissue-specific measurements were cross-sectional and longitudinally compared between groups using voxel-wise analyses in the skeletonized WM and vertex-wise analyses in the GM surface. SSD and non-SSD subjects showed (a) higher baseline FW in temporal regions and in whole GM average (P.adj(SSD vs HC) = .003, P.adj(Non-SSD vs HC) = .040) and (b) lower baseline FAt in several WM tracts. SSD, but not non-SSD, showed (a) higher FW in several WM tracts and in whole WM (P.adj(SSD vs HC)= .049) and (b) a significant FW decrease over time in temporal cortical regions and in whole GM average (P.adj = .011). Increased extracellular FW in the brain is a reliable finding in FEP, and in SSD appears to decrease over the early course of the illness. FAt abnormalities are stable during the first years of psychosis.

Published
2020

50. The Relationship Between White Matter Microstructure and General Cognitive Ability in Patients With Schizophrenia and Healthy Participants in the ENIGMA Consortium

Author

Holleran, Laurena, Kelly, Sinead, Alloza, Clara, Agartz, Ingrid, Andreassen, Ole A, Arango, Celso, Banaj, Nerisa, Calhoun, Vince, Cannon, Dara, Carr, Vaughan, Corvin, Aiden, Glahn, David C, Gur, Ruben, Hong, Elliot, Hoschl, Cyril, Howells, Fleur M, James, Anthony, Janssen, Joost, Kochunov, Peter, Lawrie, Stephen M, Liu, Jingyu, Martinez, Covadonga, McDonald, Colm, Morris, Derek, Mothersill, David, Pantelis, Christos, Piras, Fabrizio, Potkin, Steven, Rasser, Paul E, Roalf, David, Rowland, Laura, Satterthwaite, Theodore, Schall, Ulrich, Spalletta, Gianfranco, Spaniel, Filip, Stein, Dan J, Uhlmann, Anne, Voineskos, Aristotle, Zalesky, Andrew, van Erp, Theo GM, Turner, Jessica A, Deary, Ian J, Thompson, Paul M, Jahanshad, Neda, and Donohoe, Gary

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Prevention, Neurosciences, Behavioral and Social Science, Clinical Research, Brain Disorders, Serious Mental Illness, Schizophrenia, Mental Health, Mental health, Adult, Anisotropy, Brain, Case-Control Studies, Cognition, Diffusion Tensor Imaging, Factor Analysis, Statistical, Female, Healthy Volunteers, Humans, Intelligence, Male, Middle Aged, Neural Pathways, Principal Component Analysis, Schizophrenic Psychology, Wechsler Scales, White Matter, ENIGMA, Meta-Analysis, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Clinical and health psychology
Abstract

ObjectiveSchizophrenia has recently been associated with widespread white matter microstructural abnormalities, but the functional effects of these abnormalities remain unclear. Widespread heterogeneity of results from studies published to date preclude any definitive characterization of the relationship between white matter and cognitive performance in schizophrenia. Given the relevance of deficits in cognitive function to predicting social and functional outcomes in schizophrenia, the authors carried out a meta-analysis of available data through the ENIGMA Consortium, using a common analysis pipeline, to elucidate the relationship between white matter microstructure and a measure of general cognitive performance, IQ, in patients with schizophrenia and healthy participants.MethodsThe meta-analysis included 760 patients with schizophrenia and 957 healthy participants from 11 participating ENIGMA Consortium sites. For each site, principal component analysis was used to calculate both a global fractional anisotropy component (gFA) and a fractional anisotropy component for six long association tracts (LA-gFA) previously associated with cognition.ResultsMeta-analyses of regression results indicated that gFA accounted for a significant amount of variation in cognition in the full sample (effect size [Hedges' g]=0.27, CI=0.17-0.36), with similar effects sizes observed for both the patient (effect size=0.20, CI=0.05-0.35) and healthy participant groups (effect size=0.32, CI=0.18-0.45). Comparable patterns of association were also observed between LA-gFA and cognition for the full sample (effect size=0.28, CI=0.18-0.37), the patient group (effect size=0.23, CI=0.09-0.38), and the healthy participant group (effect size=0.31, CI=0.18-0.44).ConclusionsThis study provides robust evidence that cognitive ability is associated with global structural connectivity, with higher fractional anisotropy associated with higher IQ. This association was independent of diagnosis; while schizophrenia patients tended to have lower fractional anisotropy and lower IQ than healthy participants, the comparable size of effect in each group suggested a more general, rather than disease-specific, pattern of association.

Published
2020

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