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5. Cerebrospinal fluid concentration of complement component 4A is increased in first episode schizophrenia

Author

Gracias, Jessica, Orhan, Funda, Hörbeck, Elin, Holmén-Larsson, Jessica, Khanlarkani, Neda, Malwade, Susmita, Goparaju, Sravan K., Schwieler, Lilly, Demirel, İlknur Ş., Fu, Ting, Fatourus-Bergman, Helena, Pelanis, Aurimantas, Goold, Carleton P., Goulding, Anneli, Annerbrink, Kristina, Isgren, Anniella, Sparding, Timea, Schalling, Martin, Yañez, Viviana A. Carcamo, Göpfert, Jens C., Nilsson, Johanna, Brinkmalm, Ann, Blennow, Kaj, Zetterberg, Henrik, Engberg, Göran, Piehl, Fredrik, Sheridan, Steven D., Perlis, Roy H., Cervenka, Simon, Erhardt, Sophie, Landen, Mikael, and Sellgren, Carl M.

Published
2022
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6. Identification of cerebrospinal fluid and serum metabolomic biomarkers in first episode psychosis patients

Author

Shang, Pei, Ho, Ada Man-Choi, Tufvesson-Alm, Maximilian, Lindberg, Daniel R., Grant, Caroline W., Orhan, Funda, Eren, Feride, Bhat, Maria, Engberg, Göran, Schwieler, Lilly, Fatouros-Bergman, Helena, Imbeault, Sophie, Iverson, Ryan M., Dasari, Surendra, Piehl, Fredrik, Cervenka, Simon, Sellgren, Carl M., Erhardt, Sophie, and Choi, Doo-Sup

Published
2022
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7. GRK3 deficiency elicits brain immune activation and psychosis

Author

Sellgren, Carl M., Imbeault, Sophie, Larsson, Markus K., Oliveros, Alfredo, Nilsson, Ida A. K., Codeluppi, Simone, Orhan, Funda, Bhat, Maria, Tufvesson-Alm, Maximilian, Gracias, Jessica, Kegel, Magdalena E., Zheng, Yiran, Faka, Anthi, Svedberg, Marie, Powell, Susan B., Caldwell, Sorana, Kamenski, Mary E., Vawter, Marquis P., Schulmann, Anton, Goiny, Michel, Svensson, Camilla I., Hökfelt, Tomas, Schalling, Martin, Schwieler, Lilly, Cervenka, Simon, Choi, Doo-Sup, Landén, Mikael, Engberg, Göran, and Erhardt, Sophie

Published
2021
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8. Lower complement C1q levels in first-episode psychosis and in schizophrenia

Author

Koskuvi, Marja, Malwade, Susmita, Gracias Lekander, Jessica, Hörbeck, Elin, Bruno, Sanna, Holmen Larsson, Jessica, Pelanis, Aurimantas, Isgren, Anniella, Goulding, Anneli, Fatouros-Bergman, Helena, Samudyata, Samudyata, Schalling, Martin, Piehl, Fredrik, Erhardt, Sophie, Landen, Mikael, Cervenka, Simon, Orhan, Funda, Sellgren, Carl M, Koskuvi, Marja, Malwade, Susmita, Gracias Lekander, Jessica, Hörbeck, Elin, Bruno, Sanna, Holmen Larsson, Jessica, Pelanis, Aurimantas, Isgren, Anniella, Goulding, Anneli, Fatouros-Bergman, Helena, Samudyata, Samudyata, Schalling, Martin, Piehl, Fredrik, Erhardt, Sophie, Landen, Mikael, Cervenka, Simon, Orhan, Funda, and Sellgren, Carl M

Abstract

Recent evidence has implicated complement component (C) 4A in excessive elimination of synapses in schizophrenia. C4A is believed to contribute to physiological synapse removal through signaling within the C1q initiated classical activation axis of the complement system. So far, a potential involvement of C1q in the pathophysiology of schizophrenia remains unclear. In this study, we first utilized large-scale gene expression datasets (n = 586 patients with schizophrenia and n = 986 controls) to observe lower C1QA mRNA expression in prefrontal cortex tissue of individuals with schizophrenia (P = 4.8x10-05), while C1QA seeded co-expression networks displayed no enrichment for schizophrenia risk variants beyond C4A. We then used targeted liquid chromatography-mass spectrometry (LS-MS) to measure cerebrospinal fluid (CSF) levels of C1qA in 113 individuals with first-episode psychosis (FEP), among which 66 individuals was later diagnosed with schizophrenia, and 87 healthy controls. CSF concentrations of C1qA were lower in individuals diagnosed with FEP (P = 0.0001), also after removing subjects with a short-term prescription of an antipsychotic agent (P = 0.0005). We conclude that C1q mRNA and protein levels are lower in schizophrenia and that further experimental studies are needed to understand the functional implications.

Published
2024
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9. Kynurenine Metabolites in CSF and Plasma in Healthy Males

Author

Orhan, Funda, Schwieler, Lilly, Engberg, Goran, Samuelsson, Martin, Orhan, Funda, Schwieler, Lilly, Engberg, Goran, and Samuelsson, Martin

Abstract

In recent years, kynurenine metabolites generated by tryptophan catabolism have gained increasing attention in the context of brain diseases. The question of importance is whether there is a relationship between peripheral and central levels of these metabolites. Some of these compounds do not cross the blood-brain barrier; in particular, kynurenic acid, and most analyses of kynurenines from psychiatric patients have been performed using plasma samples. In the present study, we recruited 30 healthy volunteers with no history of psychiatric or neurological diagnosis, to analyze tryptophan, kynurenine, kynurenic acid, and quinolinic acid levels in CSF and plasma. In addition, kynurenic acid was analyzed in urine. The most important finding of this study is that CSF kynurenic acid levels do not correlate with those in plasma or urine. However, we found a correlation between plasma kynurenine and CSF kynurenic acid. Further, plasma kynurenine and plasma quinolinic acid were correlated. Our findings clarify the distribution of tryptophan and its metabolites in various body compartments and may serve as a guide for the analysis of these metabolites in humans. The most significant finding of the present study is that a prediction of brain kynurenic acid by of the analysis of the compound in plasma cannot be made., Funding Agencies|Swedish Medical Research Council [2019:01452]; Swedish Brain Foundation [PS2018-0058]; Swedish Society for Medical Research [P18-0120]; OEstergoetland County Council; Ahlen-stiftelsen

Published
2024
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13. Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium

Author

Farde, Lars, Flyckt, Lena, Engberg, Göran, Erhardt, Sophie, Fatouros-Bergman, Helena, Cervenka, Simon, Schwieler, Lilly, Piehl, Fredrik, Agartz, Ingrid, Collste, Karin, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, van Erp, Theo G.M., Walton, Esther, Hibar, Derrek P., Schmaal, Lianne, Jiang, Wenhao, Glahn, David C., Pearlson, Godfrey D., Yao, Nailin, Fukunaga, Masaki, Hashimoto, Ryota, Okada, Naohiro, Yamamori, Hidenaga, Bustillo, Juan R., Clark, Vincent P., Mueller, Bryon A., Cahn, Wiepke, de Zwarte, Sonja M.C., Hulshoff Pol, Hilleke E., Kahn, René S., Ophoff, Roel A., van Haren, Neeltje E.M., Andreassen, Ole A., Dale, Anders M., Doan, Nhat Trung, Gurholt, Tiril P., Hartberg, Cecilie B., Haukvik, Unn K., Jørgensen, Kjetil N., Lagerberg, Trine V., Melle, Ingrid, Westlye, Lars T., Gruber, Oliver, Kraemer, Bernd, Richter, Anja, Zilles, David, Calhoun, Vince D., Crespo-Facorro, Benedicto, Roiz-Santiañez, Roberto, Tordesillas-Gutiérrez, Diana, Loughland, Carmel, Carr, Vaughan J., Catts, Stanley, Cropley, Vanessa L., Fullerton, Janice M., Green, Melissa J., Henskens, Frans A., Jablensky, Assen, Lenroot, Rhoshel K., Mowry, Bryan J., Michie, Patricia T., Pantelis, Christos, Quidé, Yann, Schall, Ulrich, Scott, Rodney J., Cairns, Murray J., Seal, Marc, Tooney, Paul A., Rasser, Paul E., Cooper, Gavin, Shannon Weickert, Cynthia, Weickert, Thomas W., Morris, Derek W., Hong, Elliot, Kochunov, Peter, Beard, Lauren M., Gur, Raquel E., Gur, Ruben C., Satterthwaite, Theodore D., Wolf, Daniel H., Belger, Aysenil, Brown, Gregory G., Ford, Judith M., Macciardi, Fabio, Mathalon, Daniel H., O’Leary, Daniel S., Potkin, Steven G., Preda, Adrian, Voyvodic, James, Lim, Kelvin O., McEwen, Sarah, Yang, Fude, Tan, Yunlong, Tan, Shuping, Wang, Zhiren, Fan, Fengmei, Chen, Jingxu, Xiang, Hong, Tang, Shiyou, Guo, Hua, Wan, Ping, Wei, Dong, Bockholt, Henry J., Ehrlich, Stefan, Wolthusen, Rick P.F., King, Margaret D., Shoemaker, Jody M., Sponheim, Scott R., De Haan, Lieuwe, Koenders, Laura, Machielsen, Marise W., van Amelsvoort, Therese, Veltman, Dick J., Assogna, Francesca, Banaj, Nerisa, de Rossi, Pietro, Iorio, Mariangela, Piras, Fabrizio, Spalletta, Gianfranco, McKenna, Peter J., Pomarol-Clotet, Edith, Salvador, Raymond, Corvin, Aiden, Donohoe, Gary, Kelly, Sinead, Whelan, Christopher D., Dickie, Erin W., Rotenberg, David, Voineskos, Aristotle N., Ciufolini, Simone, Radua, Joaquim, Dazzan, Paola, Murray, Robin, Reis Marques, Tiago, Simmons, Andrew, Borgwardt, Stefan, Egloff, Laura, Harrisberger, Fabienne, Riecher-Rössler, Anita, Smieskova, Renata, Alpert, Kathryn I., Wang, Lei, Jönsson, Erik G., Koops, Sanne, Sommer, Iris E.C., Bertolino, Alessandro, Bonvino, Aurora, Di Giorgio, Annabella, Neilson, Emma, Mayer, Andrew R., Stephen, Julia M., Kwon, Jun Soo, Yun, Je-Yeon, Cannon, Dara M., McDonald, Colm, Lebedeva, Irina, Tomyshev, Alexander S., Akhadov, Tolibjohn, Kaleda, Vasily, Busatto, Geraldo F., Rosa, Pedro G.P., Serpa, Mauricio H., Zanetti, Marcus V., Hoschl, Cyril, Skoch, Antonin, Spaniel, Filip, Tomecek, David, Hagenaars, Saskia P., McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., Knöchel, Christian, Oertel-Knöchel, Viola, Stäblein, Michael, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Uhlmann, Anne, Lopez-Jaramillo, Carlos, Dima, Danai, McMahon, Agnes, Faskowitz, Joshua I., Gutman, Boris A., Jahanshad, Neda, Thompson, Paul M., and Turner, Jessica A.

Published
2018
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14. Correction: GRK3 deficiency elicits brain immune activation and psychosis

Author

Sellgren, Carl M., Imbeault, Sophie, Larsson, Markus K., Oliveros, Alfredo, Nilsson, Ida A. K., Codeluppi, Simone, Orhan, Funda, Bhat, Maria, Tufvesson-Alm, Maximilian, Gracias, Jessica, Kegel, Magdalena E., Zheng, Yiran, Faka, Anthi, Svedberg, Marie, Powell, Susan B., Caldwell, Sorana, Kamenski, Mary E., Vawter, Marquis P., Schulmann, Anton, Goiny, Michel, Svensson, Camilla I., Hökfelt, Tomas, Schalling, Martin, Schwieler, Lilly, Cervenka, Simon, Choi, Doo-Sup, Landén, Mikael, Engberg, Göran, and Erhardt, Sophie

Published
2022
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16. Preanalytic handling of clinical blood samples in assessing immunological proteins - Role of storage duration

Author

Eren, Feride, Schwieler, Lilly, Orhan, Funda, Malmqvist, Anna, Piehl, Fredrik, Cervenka, Simon, Sellgren, Carl M, Fatouros-Bergman, Helena, Engberg, Göran, Erhardt, Sophie, Eren, Feride, Schwieler, Lilly, Orhan, Funda, Malmqvist, Anna, Piehl, Fredrik, Cervenka, Simon, Sellgren, Carl M, Fatouros-Bergman, Helena, Engberg, Göran, and Erhardt, Sophie

Published
2023
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18. Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Author

Kong, Xiang-Zhen, Francks, Clyde, Allen, Nicholas B., Heslenfeld, Dirk, Hester, Robert, Hibar, Derrek Paul, Ho, Beng-Choon, Ho, Tiffany C., Hoekstra, Pieter J., Holst, Ruth J., Hoogman, Martine, Høvik, Marie F., Howells, Fleur M., Ames, David, Hugdahl, Kenneth, Huyser, Chaim, Ingvar, Martin, Ishikawa, Akari, James, Anthony, Jahanshad, Neda, Jernigan, Terry L., Jönsson, Erik G, Kaleda, Vasily, Kelly, Clare, Andreassen, Ole A., Kerich, Michael, Keshavan, Matcheri S., Khadka, Sabin, Kircher, Tilo, Kohls, Gregor, Konrad, Kerstin, Korucuoglu, Ozlem, Krämer, Bernd, Krug, Axel, Kuntsi, Jonna, Vasquez, Alejandro Arias, Kwon, Jun Soo, Lambregts-Rommelse, Nanda, Landén, Mikael, Lázaro, Luisa, Lebedeva, Irina, Lenroot, Rhoshel, Lesch, Klaus-Peter, Li, Qinqin, Lim, Kelvin O., Liu, Jia, Armstrong, Nicola J., Lochner, Christine, London, Edythe D., Lorenzetti, Valentina, Luciano, Michelle, Luijten, Maartje, Lundervold, Astri J., Mackey, Scott, MacMaster, Frank P., Maingault, Sophie, Malpas, Charles B., Asherson, Phil, Malt, Ulrik F., Mataix-Cols, David, Martin-Santos, Rocio, Mayer, Andrew R., McCarthy, Hazel, Medland, Sarah, Metha, Mitul, Mitchell, Philip B., Mueller, Bryon A., Maniega, Susana Muñoz, Bergo, Felipe, Mazoyer, Bernard, McDonald, Colm, McLellan, Quinn, McMahon, Katie L., McPhilemy, Genevieve, Momenan, Reza, Morales, Angelica M., Narayanaswamy, Janardhanan C., Moreira, José Carlos Vasques, Nerland, Stener, Bastin, Mark E., Nestor, Liam, Newman, Erik, Nigg, Joel T., Nordvik, Jan Egil, Novotny, Stephanie, Weiss, Eileen Oberwelland, O'Gorman, Ruth L., Oosterlaan, Jaap, Oranje, Bob, Orr, Catherine, Batalla, Albert, Overs, Bronwyn, Paloyelis, Yannis, Pauli, Paul, Paulus, Martin, Plessen, Kerstin Jessica, Polier, Georg G., Pomarol-Clotet, Edith, Portella, Maria J., Qiu, Jiang, Radua, Joaquim, Bauer, Jochen, Ramos-Quiroga, Josep Antoni, Reddy, Y. C. Janardhan, Reif, Andreas, Roberts, Gloria, Rosa, Pedro, Rubia, Katya, Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Schmaal, Lianne, Baune, Bernhard T, Schulte-Rüther, Martin, Schweren, Lizanne, Seitz, Jochen, Serpa, Mauricio Henriques, Shaw, Philip, Shumskaya, Elena, Silk, Timothy J., Simmons, Alan N., Simulionyte, Egle, Sinha, Rajita, Baur-Streubel, Ramona, Sjoerds, Zsuzsika, Smelror, Runar Elle, Soliva, Joan Carlos, Solowij, Nadia, Souza-Duran, Fabio Luisde, Sponheim, Scott R., Stein, Dan J., Stein, Elliot A., Stevens, Michael, Strike, Lachlan T., Biederman, Joseph, Sudre, Gustavo, Sui, Jing, Tamm, Leanne, Temmingh, Hendrik S., Thoma, Robert J., Tomyshev, Alexander, Tronchin, Giulia, Turner, Jessica, Uhlmann, Anne, Erp, Theo G. M., Blaine, Sara K., Heuvel, Odile A., Meer, Dennis, Eijk, Liza, Vance, Alasdair, Veer, Ilya M., Veltman, Dick J., Venkatasubramanian, Ganesan, Vilarroya, Oscar, Vives-Gilabert, Yolanda, Voineskos, Aristotle N, Boedhoe, Premika, Völzke, Henry, Vuletic, Daniella, Walitza, Susanne, Walter, Henrik, Walton, Esther, Wardlaw, Joanna M., Wen, Wei, Westlye, Lars T., Whelan, Christopher D., White, Tonya, Bøen, Erlend, Wiers, Reinout W., Wright, Margaret J., Wittfeld, Katharina, Yang, Tony T., Yasuda, Clarissa L., Yoncheva, Yuliya, Yücel, Murat, Yun, Je-Yeon, Zanetti, Marcus Vinicius, Zhen, Zonglei, Bose, Anushree, Zhu, Xing-xing, Ziegler, Georg C., Zubicaray, Greig I., Zwiers, Marcel, Project, Karolinska Schizophrenia, Glahn, David C., Crivello, Fabrice, Fisher, Simon E., Thompson, Paul M., Bralten, Janita, Farde, Lars, Flyckt, Lena, Engberg, Göran, Erhardt, Sophie, Fatouros-Bergman, Helena, Cervenka, Simon, Schwieler, Lilly, Piehl, Fredrik, Agartz, Ingrid, Collste, Karin, Brandeis, Daniel, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, Sellgren, Carl, Brem, Silvia, Mathias, Samuel R., Brodaty, Henry, Yüksel, Dilara, Brooks, Samantha J., Buitelaar, Jan, Bürger, Christian, Bülow, Robin, Calhoun, Vince, Calvo, Anna, Canales-Rodríguez, Erick Jorge, Cannon, Dara M., Guadalupe, Tulio, Caparelli, Elisabeth C., Castellanos, Francisco X., Cendes, Fernando, Chaim-Avancini, Tiffany Moukbel, Chantiluke, Kaylita, Chen, Qun-lin, Chen, Xiayu, Cheng, Yuqi, Christakou, Anastasia, Clark, Vincent P., Abé, Christoph, Coghill, David, Connolly, Colm G., Conzelmann, Annette, Córdova-Palomera, Aldo, Cousijn, Janna, Crow, Tim, Cubillo, Ana, Dannlowski, Udo, Bruttopilo, Sara Ambrosino, Zeeuw, Patrick, Deary, Ian J., Demeter, Damion V., Di Martino, Adriana, Dickie, Erin W, Dietsche, Bruno, Doan, Nhat Trung, Doherty, Colin P., Doyle, Alysa, Durston, Sarah, Earl, Eric, Akudjedu, Theophilus N., Ehrlich, Stefan, Ekman, Carl Johan, Elvsåshagen, Torbjørn, Epstein, Jeffery N., Fair, Damien A., Faraone, Stephen V., Fernández, Guillén, Flint, Claas, Filho, Geraldo Busatto, Förster, Katharina, Aleman, Andre, Fouche, Jean-Paul, Foxe, John J., Frodl, Thomas, Fuentes-Claramonte, Paola, Fullerton, Janice M., Garavan, Hugh, Santos Garcia, Danielle, Gotlib, Ian H., Goudriaan, Anna E., Grabe, Hans Jörgen, Alhusaini, Saud, Groenewold, Nynke A., Grotegerd, Dominik, Gruber, Oliver, Gurholt, Tiril, Haavik, Jan, Hahn, Tim, Hansell, Narelle K., Harris, Mathew A., Hartman, Catharina A., Carmen Valdés Hernández, Maria, Alhusaini, Saud, Del Carmen Valdés Hernández, Maria, Heslenfeld, Dirk, Hester, Robert, Hibar, Derrek Paul, Ho, Beng-Choon, Ho, Tiffany C., Hoekstra, Pieter J., van Holst, Ruth J., Hoogman, Martine, Høvik, Marie F., Allen, Nicholas B., Howells, Fleur M., Hugdahl, Kenneth, Huyser, Chaim, Ingvar, Martin, Ishikawa, Akari, James, Anthony, Jahanshad, Neda, Jernigan, Terry L., Jönsson, Erik G., Kaleda, Vasily, Ames, David, Kelly, Clare, Kerich, Michael, Keshavan, Matcheri S., Khadka, Sabin, Kircher, Tilo, Kohls, Gregor, Konrad, Kerstin, Korucuoglu, Ozlem, Krämer, Bernd, Krug, Axel, Andreassen, Ole A., Kuntsi, Jonna, Kwon, Jun Soo, Lambregts-Rommelse, Nanda, Landén, Mikael, Lázaro, Luisa, Lebedeva, Irina, Lenroot, Rhoshel, Lesch, Klaus-Peter, Li, Qinqin, Lim, Kelvin O., Vasquez, Alejandro Arias, Liu, Jia, Lochner, Christine, London, Edythe D., Lorenzetti, Valentina, Luciano, Michelle, Luijten, Maartje, Lundervold, Astri J., Mackey, Scott, MacMaster, Frank P., Maingault, Sophie, Armstrong, Nicola J., Malpas, Charles B., Malt, Ulrik F., Mataix-Cols, David, Martin-Santos, Rocio, Mayer, Andrew R., McCarthy, Hazel, Medland, Sarah, Metha, Mitul, Mitchell, Philip B., Mueller, Bryon A., Asherson, Phil, Maniega, Susana Muñoz, Mazoyer, Bernard, McDonald, Colm, McLellan, Quinn, McMahon, Katie L., McPhilemy, Genevieve, Momenan, Reza, Morales, Angelica M., Narayanaswamy, Janardhanan C., Moreira, José Carlos Vasques, Bergo, Felipe, Nerland, Stener, Nestor, Liam, Newman, Erik, Nigg, Joel T., Nordvik, Jan Egil, Novotny, Stephanie, Weiss, Eileen Oberwelland, O'Gorman, Ruth L., Oosterlaan, Jaap, Oranje, Bob, Bastin, Mark E., Orr, Catherine, Overs, Bronwyn, Paloyelis, Yannis, Pauli, Paul, Paulus, Martin, Plessen, Kerstin Jessica, von Polier, Georg G., Pomarol-Clotet, Edith, Portella, Maria J., Qiu, Jiang, Batalla, Albert, Radua, Joaquim, Ramos-Quiroga, Josep Antoni, Reddy, Y. C. Janardhan, Reif, Andreas, Roberts, Gloria, Rosa, Pedro, Rubia, Katya, Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Bauer, Jochen, Schmaal, Lianne, Schulte-Rüther, Martin, Schweren, Lizanne, Seitz, Jochen, Serpa, Mauricio Henriques, Shaw, Philip, Shumskaya, Elena, Silk, Timothy J., Simmons, Alan N., Simulionyte, Egle, Baune, Bernhard T., Sinha, Rajita, Sjoerds, Zsuzsika, Smelror, Runar Elle, Soliva, Joan Carlos, Solowij, Nadia, Souza-Duran, Fabio Luisde, Sponheim, Scott R., Stein, Dan J., Stein, Elliot A., Stevens, Michael, Baur-Streubel, Ramona, Strike, Lachlan T., Sudre, Gustavo, Sui, Jing, Tamm, Leanne, Temmingh, Hendrik S., Thoma, Robert J., Tomyshev, Alexander, Tronchin, Giulia, Turner, Jessica, Uhlmann, Anne, Biederman, Joseph, van Erp, Theo G. M., van den Heuvel, Odile A., van der Meer, Dennis, van Eijk, Liza, Vance, Alasdair, Veer, Ilya M., Veltman, Dick J., Venkatasubramanian, Ganesan, Vilarroya, Oscar, Vives-Gilabert, Yolanda, Blaine, Sara K., Voineskos, Aristotle N., Völzke, Henry, Vuletic, Daniella, Walitza, Susanne, Walter, Henrik, Walton, Esther, Wardlaw, Joanna M., Wen, Wei, Westlye, Lars T., Whelan, Christopher D., Boedhoe, Premika, White, Tonya, Wiers, Reinout W., Wright, Margaret J., Wittfeld, Katharina, Yang, Tony T., Yasuda, Clarissa L., Yoncheva, Yuliya, Yücel, Murat, Yun, Je-Yeon, Zanetti, Marcus Vinicius, Bøen, Erlend, Zhen, Zonglei, Zhu, Xing-Xing, Ziegler, Georg C., de Zubicaray, Greig I., Zwiers, Marcel, Project, Karolinska Schizophrenia, Glahn, David C., Crivello, Fabrice, Fisher, Simon E., Thompson, Paul M., Bose, Anushree, Francks, Clyde, Farde, Lars, Flyckt, Lena, Engberg, Göran, Erhardt, Sophie, Fatouros-Bergman, Helena, Cervenka, Simon, Schwieler, Lilly, Piehl, Fredrik, Agartz, Ingrid, Bralten, Janita, Collste, Karin, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, Sellgren, Carl, Brandeis, Daniel, Kong, Xiang-Zhen, Brem, Silvia, Brodaty, Henry, Yüksel, Dilara, Brooks, Samantha J., Buitelaar, Jan, Bürger, Christian, Bülow, Robin, Calhoun, Vince, Calvo, Anna, Canales-Rodríguez, Erick Jorge, Mathias, Samuel R., Cannon, Dara M., Caparelli, Elisabeth C., Castellanos, Francisco X., Cendes, Fernando, Chaim-Avancini, Tiffany Moukbel, Chantiluke, Kaylita, Chen, Qun-Lin, Chen, Xiayu, Cheng, Yuqi, Christakou, Anastasia, Guadalupe, Tulio, Clark, Vincent P., Coghill, David, Connolly, Colm G., Conzelmann, Annette, Córdova-Palomera, Aldo, Cousijn, Janna, Crow, Tim, Cubillo, Ana, Dannlowski, Udo, de Bruttopilo, Sara Ambrosino, Abé, Christoph, de Zeeuw, Patrick, Deary, Ian J., Demeter, Damion V., Di Martino, Adriana, Dickie, Erin W., Dietsche, Bruno, Doan, Nhat Trung, Doherty, Colin P., Doyle, Alysa, Durston, Sarah, Earl, Eric, Ehrlich, Stefan, Ekman, Carl Johan, Elvsåshagen, Torbjørn, Epstein, Jeffery N., Fair, Damien A., Faraone, Stephen V., Fernández, Guillén, Flint, Claas, Filho, Geraldo Busatto, Akudjedu, Theophilus N., Förster, Katharina, Fouche, Jean-Paul, Foxe, John J., Frodl, Thomas, Fuentes-Claramonte, Paola, Fullerton, Janice M., Garavan, Hugh, do Santos Garcia, Danielle, Gotlib, Ian H., Goudriaan, Anna E., Aleman, Andre, Grabe, Hans Jörgen, Groenewold, Nynke A., Grotegerd, Dominik, Gruber, Oliver, Gurholt, Tiril, Haavik, Jan, Hahn, Tim, Hansell, Narelle K., Harris, Mathew A., Hartman, Catharina A., Ontwikkelingspsychologie (Psychologie, FMG), Adult Psychiatry, APH - Mental Health, ANS - Compulsivity, Impulsivity & Attention, Child and Adolescent Psychiatry & Psychosocial Care, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, Laboratory Genetic Metabolic Diseases, Paediatrics, General Paediatrics, ARD - Amsterdam Reproduction and Development, Paediatric Pulmonology, Graduate School, and APH - Digital Health

Subjects
P‐hacking, Datasets as Topic, Publication bias, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, Statistics, team science, Brain asymmetry, Multicenter Studies as Topic, Cervell, Research Articles, Cerebral Cortex, Radiological and Ultrasound Technology, P-hacking, 05 social sciences, Brain, Cerebral cortex, Middle Aged, Magnetic Resonance Imaging, Discoveries in science, Escorça cerebral, Neurology, Biaix de publicació, Anatomy, Psychology, Research Article, Neuroinformatics, Adult, Adolescent, Neuroimaging, Descobriments científics, 050105 experimental psychology, Statistical power, 03 medical and health sciences, Young Adult, Magnetic resonance imaging, Imatges per ressonància magnètica, multisite collaboration, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, ddc:610, reproducibility, Aged, publication bias, Reproducibility, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Perspective (graphical), Reproducibility of Results, Brain Cortical Thickness, Research data, Sample size determination, Dades de recerca, Neurology (clinical), Scale (map), Developmental Psychopathology, 030217 neurology & neurosurgery
Abstract

The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p‐hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left–right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta‐analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an “ideal publishing environment,” that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically‐used sample sizes., Region‐wise effect sizes and reproducibility rates of hemispheric asymmetry effects. In general, effects with higher effect sizes showed higher reproducibility, given the same conditions (e.g., sample size and data heterogeneity).

Published
2022
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19. Increased Levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia--significance for activation of the kynurenine pathway

Author

Schwieler, Lilly, Larsson, Markus K., Skogh, Elisabeth, Kegel, Magdalena E., Orhan, Funda, Abdelmoaty, Sally, Finn, Anja, Bhat, Maria, Samuelsson, Martin, Lundberg, Kristina, Dahl, Marja-Liisa, Sellgren, Carl, Schuppe-Koistinen, Ina, Svensson, Camilla I., Erhardt, Sophie, and Engberg, Goran

Subjects
Schizophrenics -- Physiological aspects, Interleukins -- Health aspects, Cerebrospinal fluid -- Health aspects, Tryptophan -- Health aspects, Health, Psychology and mental health
Abstract

Background: Accumulating evidence indicates that schizophrenia is associated with brain immune activation. While a number of reports suggest increased cytokine levels in patients with schizophrenia, many of these studies have been limited by their focus on peripheral cytokines or confounded by various antipsychotic treatments. Here, well-characterized patients with schizophrenia, all receiving olanzapine treatment, and healthy volunteers were analyzed with regard to cerebrospinal fluid (CSF) levels of cytokines. We correlated the CSF cytokine levels to previously analyzed metabolites of the kynurenine (KYN) pathway. Methods: We analyzed the CSF from patients and controls using electrochemiluminescence detection with regard to cytokines. Cell culture media from human cortical astrocytes were analyzed for KYN and kynurenic acid (KYNA) using high-pressure I iquid chromatography or liquid chromatography/mass spectrometry. Results: We included 23 patients and 37 controls in our study. Patients with schizophrenia had increased CSF levels of interleukin (IL)-6 compared with healthy volunteers. In patients, we also observed a positive correlation between IL-6 and the tryptophan:KYNA ratio, indicating that IL-6 activates the KYN pathway. In line with this, application of IL-6 to cultured human astrocytes increased cell medium concentration of KYNA. Limitations: The CSF samples had been frozen and thawed twice before analysis of cytokines. Median age differed between patients and controls. When appropriate, all present analyses were adjusted for age. Conclusion: We have shown that IL-6, KYN and KYNA are elevated in patients with chronic schizophrenia, strengthening the idea of brain immune activation in patients with this disease. Our concurrent cell culture and clinical findings suggest that IL-6 induces the KYN pathway, leading to increased production of the N-methyl-D-aspartate receptor antagonist KYNA in patients with schizophrenia., Introduction The role of immune activation in schizophrenia has received increasing interest in recent years. Epidemiological studies have shown that infections and autoimmune diseases are clinically important risk factors for [...]

Published
2015
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21. Correction: GRK3 deficiency elicits brain immune activation and psychosis

Author

Sellgren, Carl M., primary, Imbeault, Sophie, additional, Larsson, Markus K., additional, Oliveros, Alfredo, additional, Nilsson, Ida A. K., additional, Codeluppi, Simone, additional, Orhan, Funda, additional, Bhat, Maria, additional, Tufvesson-Alm, Maximilian, additional, Gracias, Jessica, additional, Kegel, Magdalena E., additional, Zheng, Yiran, additional, Faka, Anthi, additional, Svedberg, Marie, additional, Powell, Susan B., additional, Caldwell, Sorana, additional, Kamenski, Mary E., additional, Vawter, Marquis P., additional, Schulmann, Anton, additional, Goiny, Michel, additional, Svensson, Camilla I., additional, Hökfelt, Tomas, additional, Schalling, Martin, additional, Schwieler, Lilly, additional, Cervenka, Simon, additional, Choi, Doo-Sup, additional, Landén, Mikael, additional, Engberg, Göran, additional, and Erhardt, Sophie, additional

Published
2021
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22. Cerebrospinal fluid concentration of complement component 4A is increased in first-episode schizophrenia

Author

Gracias, Jessica, primary, Orhan, Funda, additional, Hörbeck, Elin, additional, Holmén-Larsson, Jessica, additional, Khanlarkani, Neda, additional, Malwade, Susmita, additional, Goparaju, Sravan K., additional, Schwieler, Lilly, additional, Fatourus-Bergman, Helena, additional, Pelanis, Aurimantas, additional, Goold, Carleton P., additional, Goulding, Anneli, additional, Annerbrink, Kristina, additional, Isgren, Anniella, additional, Sparding, Timea, additional, Schalling, Martin, additional, Yañez, Viviana A. Carcamo, additional, Göpfert, Jens C., additional, Nilsson, Johanna, additional, Brinkmalm, Ann, additional, Blennow, Kaj, additional, Zetterberg, Henrik, additional, Engberg, Göran, additional, Piehl, Fredrik, additional, Sheridan, Steven D., additional, Perlis, Roy H., additional, Cervenka, Simon, additional, Erhardt, Sophie, additional, Landen, Mikael, additional, and Sellgren, Carl M., additional

Published
2021
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24. GRK3 deficiency elicits brain immune activation and psychosis.

Author

Sellgren, Carl M, Imbeault, Sophie, Larsson, Markus K, Oliveros, Alfredo, Nilsson, Ida A K, Codeluppi, Simone, Orhan, Funda, Bhat, Maria, Tufvesson-Alm, Maximilian, Gracias, Jessica, Kegel, Magdalena E, Zheng, Yiran, Faka, Anthi, Svedberg, Marie, Powell, Susan B, Caldwell, Sorana, Kamenski, Mary E, Vawter, Marquis P, Schullman, Anton, Goiny, Michel, Svensson, Camilla I, Hökfelt, Tomas, Schalling, Martin, Schwieler, Lilly, Cervenka, Simon, Choi, Doo-Sup, Landén, Mikael, Engberg, Göran, Erhardt, Sophie, Sellgren, Carl M, Imbeault, Sophie, Larsson, Markus K, Oliveros, Alfredo, Nilsson, Ida A K, Codeluppi, Simone, Orhan, Funda, Bhat, Maria, Tufvesson-Alm, Maximilian, Gracias, Jessica, Kegel, Magdalena E, Zheng, Yiran, Faka, Anthi, Svedberg, Marie, Powell, Susan B, Caldwell, Sorana, Kamenski, Mary E, Vawter, Marquis P, Schullman, Anton, Goiny, Michel, Svensson, Camilla I, Hökfelt, Tomas, Schalling, Martin, Schwieler, Lilly, Cervenka, Simon, Choi, Doo-Sup, Landén, Mikael, Engberg, Göran, and Erhardt, Sophie

Abstract

The G protein-coupled receptor kinase (GRK) family member protein GRK3 has been linked to the pathophysiology of schizophrenia and bipolar disorder. Expression, as well as protein levels, of GRK3 are reduced in post-mortem prefrontal cortex of schizophrenia subjects. Here, we investigate functional behavior and neurotransmission related to immune activation and psychosis using mice lacking functional Grk3 and utilizing a variety of methods, including behavioral, biochemical, electrophysiological, molecular, and imaging methods. Compared to wildtype controls, the Grk3-/- mice show a number of aberrations linked to psychosis, including elevated brain levels of IL-1β, increased turnover of kynurenic acid (KYNA), hyper-responsiveness to D-amphetamine, elevated spontaneous firing of midbrain dopamine neurons, and disruption in prepulse inhibition. Analyzing human genetic data, we observe a link between psychotic features in bipolar disorder, decreased GRK expression, and increased concentration of CSF KYNA. Taken together, our data suggest that Grk3-/- mice show face and construct validity relating to the psychosis phenotype with glial activation and would be suitable for translational studies of novel immunomodulatory agents in psychotic disorders.

Published
2021
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25. Publisher Correction:Common brain disorders are associated with heritable patterns of apparent aging of the brain (Nature Neuroscience, (2019), 22, 10, (1617-1623), 10.1038/s41593-019-0471-7)

Author

Kaufmann, Tobias, van der Meer, Dennis, Doan, Nhat Trung, Schwarz, Emanuel, Lund, Martina J., Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Bettella, Francesco, Beyer, Mona K., Bøen, Erlend, Borgwardt, Stefan, Brandt, Christine L., Buitelaar, Jan, Celius, Elisabeth G., Cervenka, Simon, Conzelmann, Annette, Córdova-Palomera, Aldo, Dale, Anders M., de Quervain, Dominique J.F., Di Carlo, Pasquale, Djurovic, Srdjan, Dørum, Erlend S., Eisenacher, Sarah, Elvsåshagen, Torbjørn, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Haatveit, Beathe, Håberg, Asta K., Harbo, Hanne F., Hartman, Catharina A., Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jernigan, Terry L., Jonassen, Rune, Jönsson, Erik G., Farde, Lars, Engberg, Göran, Erhardt, Sophie, Schwieler, Lilly, Piehl, Fredrik, Collste, Karin, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, Kirsch, Peter, Kłoszewska, Iwona, Kolskår, Knut K., Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus Peter, Lovestone, Simon, Lundervold, Arvid, Lundervold, Astri J., Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Norbom, Linn B., Nordvik, Jan Egil, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, Richard, Geneviève, Rokicki, Jaroslav, Sanders, Anne Marthe, Selbæk, Geir, Shadrin, Alexey A., Smeland, Olav B., Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Ulrichsen, Kristine M., Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., and Westlye, Lars T.

Subjects
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING
Abstract

In the version of this article initially published, spaces were missing in the names of Stephanie Le Hellard and Pasquale Di Carlo. The errors have been corrected in the HTML and PDF versions of the article.

Published
2020
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26. Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

Author

Farde, Lars, Flyckt, Lena, Fatouros-Bergman, Helena, Cervenka, Simon, Agartz, Ingrid, Collste, Karin, Victorsson, Pauliina, Engberg, Göran, Erhardt, Sophie, Schwieler, Lilly, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, Piehl, Fredrik, van Erp, Theo G.M., Walton, Esther, Hibar, Derrek P., Schmaal, Lianne, Jiang, Wenhao, Glahn, David C., Pearlson, Godfrey D., Yao, Nailin, Fukunaga, Masaki, Hashimoto, Ryota, Okada, Naohiro, Yamamori, Hidenaga, Clark, Vincent P., Mueller, Bryon A., de Zwarte, Sonja M.C., Ophoff, Roel A., van Haren, Neeltje E.M., Andreassen, Ole A., Gurholt, Tiril P., Gruber, Oliver, Kraemer, Bernd, Richter, Anja, Calhoun, Vince D., Crespo-Facorro, Benedicto, Roiz-Santiañez, Roberto, Tordesillas-Gutiérrez, Diana, Loughland, Carmel, Catts, Stanley, Fullerton, Janice M., Green, Melissa J., Henskens, Frans, Jablensky, Assen, Mowry, Bryan J., Pantelis, Christos, Quidé, Yann, Schall, Ulrich, Scott, Rodney J., Cairns, Murray J., Seal, Marc, Tooney, Paul A., Rasser, Paul E., Cooper, Gavin, Shannon Weickert, Cynthia, Weickert, Thomas W., Hong, Elliot, Kochunov, Peter, Gur, Raquel E., Gur, Ruben C., Ford, Judith M., Macciardi, Fabio, Mathalon, Daniel H., Potkin, Steven G., Preda, Adrian, Fan, Fengmei, Ehrlich, Stefan, King, Margaret D., De Haan, Lieuwe, Veltman, Dick J., Assogna, Francesca, Banaj, Nerisa, de Rossi, Pietro, Iorio, Mariangela, Piras, Fabrizio, Spalletta, Gianfranco, Pomarol-Clotet, Edith, Kelly, Sinead, Ciufolini, Simone, Radua, Joaquim, Murray, Robin, Marques, Tiago Reis, Simmons, Andrew, Borgwardt, Stefan, Schönborn-Harrisberger, Fabienne, Riecher-Rössler, Anita, Smieskova, Renata, Alpert, Kathryn I., Bertolino, Alessandro, Bonvino, Aurora, Di Giorgio, Annabella, Neilson, Emma, Mayer, Andrew R., Yun, Je-Yeon, Cannon, Dara M., Lebedeva, Irina, Tomyshev, Alexander S., Akhadov, Tolibjohn, Kaleda, Vasily, Rosa, Pedro G.P., Serpa, Mauricio H., Zanetti, Marcus V., Hoschl, Cyril, Skoch, Antonin, Spaniel, Filip, Tomecek, David, McIntosh, Andrew M., Whalley, Heather C., Knöchel, Christian, Oertel-Knöchel, Viola, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Uhlmann, Anne, Lopez-Jaramillo, Carlos, Dima, Danai, Faskowitz, Joshua I., Gutman, Boris A., Jahanshad, Neda, Thompson, Paul M., and Turner, Jessica A.

Published
2019
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27. Serum concentration of zinc is elevated in clinically stable bipolar disorder patients.

Author

Jonsson, Bo H., Orhan, Funda, Bruno, Sanna, Oliveira, Ana Osório, Sparding, Timea, Landen, Mikael, and Sellgren, Carl M.

Subjects
*BIPOLAR disorder, *ZINC, *ENZYME-linked immunosorbent assay, *EXECUTIVE function, *NEURAL transmission
Abstract

Background: Bipolar disorder (BD) is a chronic psychiatric disorder characterized by recurrent mood episodes interspersed with euthymic periods. A growing number of studies have indicated that zinc plays an important role in coordinating immune responses, as well as being involved in synaptic transmission. In the current study, we set out to measure serum levels of zinc in a meticulously phenotyped cohort of 121 euthymic BD subjects and 30 matched controls. Methods: Serum levels of zinc were measured by photometry. To assess the interplay between zinc levels and immune activation in BD, we measured serum levels of high‐sensitive C‐reactive protein (hsCRP) levels by immunoturbidimetric assay, and serum levels of monocyte chemoattractant protein‐1 (MCP‐1), chitinase 3‐like protein 1 (YKL‐40), and soluble cluster of differentiation 14 (sCD14) by electrochemiluminescence enzyme‐linked immunosorbent assays. The baseline clinical diagnostic instrument for BD was the Affective Disorder Evaluation, and executive functioning was assessed by using the Delis–Kaplan Executive Function System. Results: Controlling for potential confounding factors, BD patients displayed increased serum levels of zinc unrelated to hsCRP, MCP‐1, YKL‐40, and sCD14 levels. Serum levels of zinc did not associate with executive functioning or measurements of disease severity. Discussion: This study suggests that the zinc homeostasis is disturbed in BD and that this dyshomeostasis is not related to ongoing mood symptoms or immune activation. Of note, serum levels were increased and hence do not support continuous zinc supplementation in BD. [ABSTRACT FROM AUTHOR]

Published
2022
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28. Common brain disorders are associated with heritable patterns of apparent aging of the brain

Author

Kaufmann, Tobias, van der Meer, Dennis, Doan, Nhat Trung, Schwarz, Emanuel, Lund, Martina J., Agartz, Ingrid, Alnaes, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Bettella, Francesco, Beyer, Mona K., Boen, Erlend, Borgwardt, Stefan, Brandt, Christine L., Buitelaar, Jan, Celius, Elisabeth G., Cervenka, Simon, Conzelmann, Annette, Cordova-Palomera, Aldo, Dale, Anders M., de Quervain, Dominique J. F., Carlo, PasqualeDi, Djurovic, Srdjan, Dorum, Erlend S., Eisenacher, Sarah, Elvsashagen, Torbjorn, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Haatveit, Beathe, Haberg, Asta K., Harbo, Hanne F., Hartman, Catharina A., Heslenfeld, Dirk, Hoekstra, Pieter J., Hogestol, Einar A., Jernigan, Terry L., Jonassen, Rune, Jonsson, Erik G., Kirsch, Peter, Ktoszewska, Iwona, Kolskar, Knut K., Landro, Nils Inge, Hellard, StephanieLe, Lesch, Klaus-Peter, Lovestone, Simon, Lundervold, Arvid, Lundervold, Astri J., Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Norbom, Linn B., Nordvik, Jan Egil, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, Richard, Genevieve, Rokicki, Jaroslav, Sanders, Anne-Marthe, Selbaek, Geir, Shadrin, Alexey A., Smeland, Olav B., Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Ulrichsen, Kristine M., Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Farde, Lars, Flyckts, Lena, Engberg, Goran, Erhardt, Sophie, Fatouros-Bergmann, Helena, Schwieler, Lilly, Piehl, Fredrik, Collste, Karin, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, Kaufmann, Tobias, van der Meer, Dennis, Doan, Nhat Trung, Schwarz, Emanuel, Lund, Martina J., Agartz, Ingrid, Alnaes, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Bettella, Francesco, Beyer, Mona K., Boen, Erlend, Borgwardt, Stefan, Brandt, Christine L., Buitelaar, Jan, Celius, Elisabeth G., Cervenka, Simon, Conzelmann, Annette, Cordova-Palomera, Aldo, Dale, Anders M., de Quervain, Dominique J. F., Carlo, PasqualeDi, Djurovic, Srdjan, Dorum, Erlend S., Eisenacher, Sarah, Elvsashagen, Torbjorn, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Haatveit, Beathe, Haberg, Asta K., Harbo, Hanne F., Hartman, Catharina A., Heslenfeld, Dirk, Hoekstra, Pieter J., Hogestol, Einar A., Jernigan, Terry L., Jonassen, Rune, Jonsson, Erik G., Kirsch, Peter, Ktoszewska, Iwona, Kolskar, Knut K., Landro, Nils Inge, Hellard, StephanieLe, Lesch, Klaus-Peter, Lovestone, Simon, Lundervold, Arvid, Lundervold, Astri J., Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Norbom, Linn B., Nordvik, Jan Egil, Nyberg, Lars, Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, Richard, Genevieve, Rokicki, Jaroslav, Sanders, Anne-Marthe, Selbaek, Geir, Shadrin, Alexey A., Smeland, Olav B., Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Ulrichsen, Kristine M., Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Farde, Lars, Flyckts, Lena, Engberg, Goran, Erhardt, Sophie, Fatouros-Bergmann, Helena, Schwieler, Lilly, Piehl, Fredrik, Collste, Karin, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, and Orhan, Funda

Abstract

Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.

Published
2019
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29. Brain Heterogeneity in Schizophrenia and Its Association With Polygenic Risk

Author

Alnaes, Dag, Kaufmann, Tobias, van der Meer, Dennis, Cordova-Palomera, Aldo, Rokicki, Jaroslav, Moberget, Torgeir, Bettella, Francesco, Agartz, Ingrid, Barch, Deanna M., Bertolino, Alessandro, Brandt, Christine L., Cervenka, Simon, Djurovic, Srdjan, Doan, Nhat Trung, Eisenacher, Sarah, Fatouros-Bergman, Helena, Flyckt, Lena, Di Giorgio, Annabella, Haatveit, Beathe, Jonsson, Erik G., Kirsch, Peter, Lund, Martina J., Meyer-Lindenberg, Andreas, Pergola, Giulio, Schwarz, Emanuel, Smeland, Olav B., Quarto, Tiziana, Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Farde, Lars, Collste, Karin, Victorsson, Pauliina, Engberg, Goran, Erhardt, Sophie, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, Sellgren, Carl M., Schwieler, Lilly, Piehl, Fredrik, Alnaes, Dag, Kaufmann, Tobias, van der Meer, Dennis, Cordova-Palomera, Aldo, Rokicki, Jaroslav, Moberget, Torgeir, Bettella, Francesco, Agartz, Ingrid, Barch, Deanna M., Bertolino, Alessandro, Brandt, Christine L., Cervenka, Simon, Djurovic, Srdjan, Doan, Nhat Trung, Eisenacher, Sarah, Fatouros-Bergman, Helena, Flyckt, Lena, Di Giorgio, Annabella, Haatveit, Beathe, Jonsson, Erik G., Kirsch, Peter, Lund, Martina J., Meyer-Lindenberg, Andreas, Pergola, Giulio, Schwarz, Emanuel, Smeland, Olav B., Quarto, Tiziana, Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Farde, Lars, Collste, Karin, Victorsson, Pauliina, Engberg, Goran, Erhardt, Sophie, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, Sellgren, Carl M., Schwieler, Lilly, and Piehl, Fredrik

Abstract

ImportanceBetween-individual variability in brain structure is determined by gene-environment interactions, possibly reflecting differential sensitivity to environmental and genetic perturbations. Magnetic resonance imaging (MRI) studies have revealed thinner cortices and smaller subcortical volumes in patients with schizophrenia. However, group-level comparisons may mask considerable within-group heterogeneity, which has largely remained unnoticed in the literature. ObjectivesTo compare brain structural variability between individuals with schizophrenia and healthy controls and to test whether respective variability reflects the polygenic risk score (PRS) for schizophrenia in an independent sample of healthy controls. Design, Setting, and ParticipantsThis case-control and polygenic risk analysis compared MRI-derived cortical thickness and subcortical volumes between healthy controls and patients with schizophrenia across 16 cohorts and tested for associations between PRS and MRI features in a control cohort from the UK Biobank. Data were collected from October 27, 2004, through April 12, 2018, and analyzed from December 3, 2017, through August 1, 2018. Main Outcomes and MeasuresMean and dispersion parameters were estimated using double generalized linear models. Vertex-wise analysis was used to assess cortical thickness, and regions-of-interest analyses were used to assess total cortical volume, total surface area, and white matter, subcortical, and hippocampal subfield volumes. Follow-up analyses included within-sample analysis, test of robustness of the PRS threshold, population covariates, outlier removal, and control for image quality. ResultsA comparison of 1151 patients with schizophrenia (mean [SD] age,33.8[10.6] years; 68.6% male [n=790] and 31.4% female [n=361]) with 2010 healthy controls (mean [SD] age,32.6[10.4] years; 56.0% male [n=1126] and 44.0% female [n=884]) revealed higher heterogeneity in schizophrenia for cortical thickness and area (t = 3.34)

Published
2019
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31. Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium

Author

Kong, Xiang-Zhen, Mathias, Samuel R, Francks, Clyde, Grabe, Hans, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Gurholt, Tiril, Haavik, Jan, Hahn, Tim, Hansell, Narelle K, Harris, Mathew A, Hartman, Catharina A, Hernández, Maria Del Carmen Valdés, Heslenfeld, Dirk, Hester, Robert, Hibar, Derrek Paul, Ho, Beng-Choon, Ho, Tiffany C, Hoekstra, Pieter J, van Holst, Ruth J, Hoogman, Martine, Høvik, Marie F, Howells, Fleur M, Hugdahl, Kenneth, Huyser, Chaim, Ingvar, Martin, Irwin, Lourdes, Ishikawa, Akari, James, Anthony, Jahanshad, Neda, Jernigan, Terry L, Jönsson, Erik G, Guadalupe, Tulio, Kähler, Claas, Kaleda, Vasily, Kelly, Clare, Kerich, Michael, Keshavan, Matcheri S, Khadka, Sabin, Kircher, Tilo, Kohls, Gregor, Konrad, Kerstin, Korucuoglu, Ozlem, Abé, Christoph, Krämer, Bernd, Krug, Axel, Kwon, Jun Soo, Lambregts-Rommelse, Nanda, Landén, Mikael, Lázaro, Luisa, Lebedeva, Irina, Lenroot, Rhoshel, Lesch, Klaus-Peter, Li, Qinqin, Agartz, Ingrid, Lim, Kelvin O, Liu, Jia, Lochner, Christine, London, Edythe D, Lonning, Vera, Lorenzetti, Valentina, Luciano, Michelle, Luijten, Maartje, Lundervold, Astri J, Mackey, Scott, Akudjedu, Theophilus N, MacMaster, Frank P, Maingault, Sophie, Malpas, Charles B, Malt, Ulrik F, Mataix-Cols, David, Martin-Santos, Rocio, Mayer, Andrew R, McCarthy, Hazel, Mitchell, Philip B, Mueller, Bryon A, Aleman, Andre, Maniega, Susana Muñoz, Mazoyer, Bernard, McDonald, Colm, McLellan, Quinn, McMahon, Katie L, McPhilemy, Genevieve, Momenan, Reza, Morales, Angelica M, Narayanaswamy, Janardhanan C, Moreira, José Carlos Vasques, Alhusaini, Saud, Nerland, Stener, Nestor, Liam, Newman, Erik, Nigg, Joel T, Nordvik, Jan Egil, Novotny, Stephanie, Weiss, Eileen Oberwelland, O'Gorman, Ruth L, Oosterlaan, Jaap, Oranje, Bob, Allen, Nicholas B, Orr, Catherine, Overs, Bronwyn, Pauli, Paul, Paulus, Martin, Plessen, Kerstin Jessica, von Polier, Georg G, Pomarol-Clotet, Edith, Portella, Maria J, Qiu, Jiang, Radua, Joaquim, Ames, David, Ramos-Quiroga, Josep Antoni, Reddy, Y C Janardhan, Reif, Andreas, Roberts, Gloria, Rosa, Pedro, Rubia, Katya, Sacchet, Matthew D, Sachdev, Perminder S, Salvador, Raymond, Schmaal, Lianne, Andreassen, Ole A, Schulte-Rüther, Martin, Schweren, Lizanne, Seidman, Larry, Seitz, Jochen, Serpa, Mauricio Henriques, Shaw, Philip, Shumskaya, Elena, Silk, Timothy J, Simmons, Alan N, Simulionyte, Egle, Vasquez, Alejandro Arias, Sinha, Rajita, Sjoerds, Zsuzsika, Smelror, Runar Elle, Soliva, Joan Carlos, Solowij, Nadia, Souza-Duran, Fabio Luisde, Sponheim, Scott R, Stein, Dan J, Stein, Elliot A, Stevens, Michael, Armstrong, Nicola J, Strike, Lachlan T, Sudre, Gustavo, Sui, Jing, Tamm, Leanne, Temmingh, Hendrik S, Thoma, Robert J, Tomyshev, Alexander, Tronchin, Giulia, Turner, Jessica, Uhlmann, Anne, Bergo, Felipe, van Erp, Theo G M, van den Heuvel, Odile A, van der Meer, Dennis, van Eijk, Liza, Vance, Alasdair, Veer, Ilya M, Veltman, Dick J, Venkatasubramanian, Ganesan, Vilarroya, Oscar, Vives-Gilabert, Yolanda, Bastin, Mark E, Voineskos, Aristotle N, Völzke, Henry, Vuletic, Daniella, Walitza, Susanne, Walter, Henrik, Walton, Esther, Wardlaw, Joanna M, Wen, Wei, Westlye, Lars T, Whelan, Christopher D, Batalla, Albert, White, Tonya, Wiers, Reinout W, Wright, Margaret J, Wittfeld, Katharina, Yang, Tony T, Yasuda, Clarissa L, Yoncheva, Yuliya, Yücel, Murat, Yun, Je-Yeon, Zanetti, Marcus Vinicius, Bauer, Jochen, Zhen, Zonglei, Zhu, Xing-Xing, Ziegler, Georg C, Zierhut, Kathrin, de Zubicaray, Greig I, Zwiers, Marcel, Glahn, David C, Franke, Barbara, Crivello, Fabrice, Tzourio-Mazoyer, Nathalie, Baune, Bernhard T, Fisher, Simon E, Thompson, Paul M, Farde, Lars, Flyckt, Lena, Engberg, Göran, Erhardt, Sophie, Fatouros-Bergman, Helena, Cervenka, Simon, Schwieler, Lilly, Baur-Streubel, Ramona, Piehl, Fredrik, Collste, Karin, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, Group, ENIGMA Laterality Working, Biederman, Joseph, Blaine, Sara K, Boedhoe, Premika, Bøen, Erlend, Bose, Anushree, Bralten, Janita, Brandeis, Daniel, Brem, Silvia, Brodaty, Henry, Yüksel, Dilara, Brooks, Samantha J, Buitelaar, Jan, Bürger, Christian, Bülow, Robin, Calhoun, Vince, Calvo, Anna, Canales-Rodríguez, Erick Jorge, Canive, Jose M, Cannon, Dara M, Caparelli, Elisabeth C, Castellanos, Francisco X, Cavalleri, Gianpiero L, Cendes, Fernando, Chaim-Avancini, Tiffany Moukbel, Chantiluke, Kaylita, Chen, Qun-Lin, Chen, Xiayu, Cheng, Yuqi, Christakou, Anastasia, Clark, Vincent P, Coghill, David, Connolly, Colm G, Conzelmann, Annette, Córdova-Palomera, Aldo, Cousijn, Janna, Crow, Tim, Cubillo, Ana, Dale, Anders, Dannlowski, Udo, Ambrosino de Bruttopilo, Sara, de Zeeuw, Patrick, Deary, Ian J, Delanty, Norman, Demeter, Damion V, Di Martino, Adriana, Dickie, Erin W, Dietsche, Bruno, Doan, N Trung, Doherty, Colin P, Doyle, Alysa, Durston, Sarah, Earl, Eric, Ehrlich, Stefan, Ekman, Carl Johan, Elvsåshagen, Torbjørn, Epstein, Jeffery N, Fair, Damien A, Faraone, Stephen V, Fernández, Guillén, Filho, Geraldo Busatto, Förster, Katharina, Fouche, Jean-Paul, Foxe, John J, Frodl, Thomas, Fuentes-Claramonte, Paola, Fullerton, Janice, Garavan, Hugh, Garcia, Danielle do Santos, Gotlib, Ian H, Goudriaan, Anna E, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Stochastics, Clinical Neuropsychology, Cognitive Psychology, IBBA, APH - Mental Health, Ontwikkelingspsychologie (Psychologie, FMG), Anatomy and neurosciences, Psychiatry, Pediatric surgery, Amsterdam Neuroscience - Brain Imaging, Child Psychiatry, Adult Psychiatry, ANS - Brain Imaging, AGEM - Endocrinology, metabolism and nutrition, Graduate School, AGEM - Inborn errors of metabolism, ARD - Amsterdam Reproduction and Development, General Paediatrics, APH - Digital Health, Radiology & Nuclear Medicine, Child and Adolescent Psychiatry / Psychology, and Universitat de Barcelona

Subjects
Dominància cerebral, Male, Databases, Factual, Planum temporale, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], 0302 clinical medicine, Transverse temporal gyrus, 130 000 Cognitive Neurology & Memory, diagnostic imaging [Cerebral Cortex], 80 and over, Brain asymmetry, Neuroimaging/methods, Child, ENIGMA Laterality Working Group, Aged, 80 and over, Cerebral Cortex, Multidisciplinary, Laterality, 05 social sciences, Human brain, Middle Aged, Databases, Factual/statistics & numerical data, medicine.anatomical_structure, Mental Health, PNAS Plus, Lateralitat, Child, Preschool, Brain size, Neurological, Biomedical Imaging, Female, ddc:500, methods [Neuroimaging], Parahippocampal gyrus, Neuroinformatics, Adult, statistics & numerical data [Databases, Factual], Adolescent, Cerebral Cortex/diagnostic imaging, 1.1 Normal biological development and functioning, BF, Inferior frontal gyrus, Neuroimaging, and over, Biology, 050105 experimental psychology, Lateralization of brain function, 03 medical and health sciences, Databases, Young Adult, All institutes and research themes of the Radboud University Medical Center, Clinical Research, Underpinning research, Journal Article, medicine, Humans, lateralization, 0501 psychology and cognitive sciences, General, Preschool, Factual, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], [SCCO.NEUR]Cognitive science/Neuroscience, Neurosciences, Infant, surface area, cortical thickness, Brain Disorders, meta-analysis, Cerebral dominance, brain asymmetry, Neuroscience, Developmental Psychopathology, 030217 neurology & neurosurgery
Abstract

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here the ENIGMA consortium presents the largest ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and brain size (indexed by intracranial volume). Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (N = 1,443 and 1,113, respectively), we found several asymmetries showing modest but highly reliable heritability. The structural asymmetries identified, and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.Significance StatementLeft-right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population, and how biological factors such as age, sex and genetic variation affect these asymmetries. Here we describe by far the largest ever study of cerebral cortical brain asymmetry, based on data from 17,141 participants. We found a global anterior-posterior 'torque' pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an on-line resource that will serve future studies of human brain anatomy in health and disease.

Published
2018
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32. Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

Author

van Erp, Theo G.M., primary, Walton, Esther, additional, Hibar, Derrek P., additional, Schmaal, Lianne, additional, Jiang, Wenhao, additional, Glahn, David C., additional, Pearlson, Godfrey D., additional, Yao, Nailin, additional, Fukunaga, Masaki, additional, Hashimoto, Ryota, additional, Okada, Naohiro, additional, Yamamori, Hidenaga, additional, Clark, Vincent P., additional, Mueller, Bryon A., additional, de Zwarte, Sonja M.C., additional, Ophoff, Roel A., additional, van Haren, Neeltje E.M., additional, Andreassen, Ole A., additional, Gurholt, Tiril P., additional, Gruber, Oliver, additional, Kraemer, Bernd, additional, Richter, Anja, additional, Calhoun, Vince D., additional, Crespo-Facorro, Benedicto, additional, Roiz-Santiañez, Roberto, additional, Tordesillas-Gutiérrez, Diana, additional, Loughland, Carmel, additional, Catts, Stanley, additional, Fullerton, Janice M., additional, Green, Melissa J., additional, Henskens, Frans, additional, Jablensky, Assen, additional, Mowry, Bryan J., additional, Pantelis, Christos, additional, Quidé, Yann, additional, Schall, Ulrich, additional, Scott, Rodney J., additional, Cairns, Murray J., additional, Seal, Marc, additional, Tooney, Paul A., additional, Rasser, Paul E., additional, Cooper, Gavin, additional, Shannon Weickert, Cynthia, additional, Weickert, Thomas W., additional, Hong, Elliot, additional, Kochunov, Peter, additional, Gur, Raquel E., additional, Gur, Ruben C., additional, Ford, Judith M., additional, Macciardi, Fabio, additional, Mathalon, Daniel H., additional, Potkin, Steven G., additional, Preda, Adrian, additional, Fan, Fengmei, additional, Ehrlich, Stefan, additional, King, Margaret D., additional, De Haan, Lieuwe, additional, Veltman, Dick J., additional, Assogna, Francesca, additional, Banaj, Nerisa, additional, de Rossi, Pietro, additional, Iorio, Mariangela, additional, Piras, Fabrizio, additional, Spalletta, Gianfranco, additional, Pomarol-Clotet, Edith, additional, Kelly, Sinead, additional, Ciufolini, Simone, additional, Radua, Joaquim, additional, Murray, Robin, additional, Marques, Tiago Reis, additional, Simmons, Andrew, additional, Borgwardt, Stefan, additional, Schönborn-Harrisberger, Fabienne, additional, Riecher-Rössler, Anita, additional, Smieskova, Renata, additional, Alpert, Kathryn I., additional, Bertolino, Alessandro, additional, Bonvino, Aurora, additional, Di Giorgio, Annabella, additional, Neilson, Emma, additional, Mayer, Andrew R., additional, Yun, Je-Yeon, additional, Cannon, Dara M., additional, Lebedeva, Irina, additional, Tomyshev, Alexander S., additional, Akhadov, Tolibjohn, additional, Kaleda, Vasily, additional, Fatouros-Bergman, Helena, additional, Flyckt, Lena, additional, Rosa, Pedro G.P., additional, Serpa, Mauricio H., additional, Zanetti, Marcus V., additional, Hoschl, Cyril, additional, Skoch, Antonin, additional, Spaniel, Filip, additional, Tomecek, David, additional, McIntosh, Andrew M., additional, Whalley, Heather C., additional, Knöchel, Christian, additional, Oertel-Knöchel, Viola, additional, Howells, Fleur M., additional, Stein, Dan J., additional, Temmingh, Henk S., additional, Uhlmann, Anne, additional, Lopez-Jaramillo, Carlos, additional, Dima, Danai, additional, Faskowitz, Joshua I., additional, Gutman, Boris A., additional, Jahanshad, Neda, additional, Thompson, Paul M., additional, Turner, Jessica A., additional, Farde, Lars, additional, Cervenka, Simon, additional, Agartz, Ingrid, additional, Collste, Karin, additional, Victorsson, Pauliina, additional, Engberg, Göran, additional, Erhardt, Sophie, additional, Schwieler, Lilly, additional, Malmqvist, Anna, additional, Hedberg, Mikael, additional, Orhan, Funda, additional, and Piehl, Fredrik, additional

Published
2019
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33. Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium

Author

van Erp, Theo G.M., primary, Walton, Esther, additional, Hibar, Derrek P., additional, Schmaal, Lianne, additional, Jiang, Wenhao, additional, Glahn, David C., additional, Pearlson, Godfrey D., additional, Yao, Nailin, additional, Fukunaga, Masaki, additional, Hashimoto, Ryota, additional, Okada, Naohiro, additional, Yamamori, Hidenaga, additional, Bustillo, Juan R., additional, Clark, Vincent P., additional, Agartz, Ingrid, additional, Mueller, Bryon A., additional, Cahn, Wiepke, additional, de Zwarte, Sonja M.C., additional, Hulshoff Pol, Hilleke E., additional, Kahn, René S., additional, Ophoff, Roel A., additional, van Haren, Neeltje E.M., additional, Andreassen, Ole A., additional, Dale, Anders M., additional, Doan, Nhat Trung, additional, Gurholt, Tiril P., additional, Hartberg, Cecilie B., additional, Haukvik, Unn K., additional, Jørgensen, Kjetil N., additional, Lagerberg, Trine V., additional, Melle, Ingrid, additional, Westlye, Lars T., additional, Gruber, Oliver, additional, Kraemer, Bernd, additional, Richter, Anja, additional, Zilles, David, additional, Calhoun, Vince D., additional, Crespo-Facorro, Benedicto, additional, Roiz-Santiañez, Roberto, additional, Tordesillas-Gutiérrez, Diana, additional, Loughland, Carmel, additional, Carr, Vaughan J., additional, Catts, Stanley, additional, Cropley, Vanessa L., additional, Fullerton, Janice M., additional, Green, Melissa J., additional, Henskens, Frans A., additional, Jablensky, Assen, additional, Lenroot, Rhoshel K., additional, Mowry, Bryan J., additional, Michie, Patricia T., additional, Pantelis, Christos, additional, Quidé, Yann, additional, Schall, Ulrich, additional, Scott, Rodney J., additional, Cairns, Murray J., additional, Seal, Marc, additional, Tooney, Paul A., additional, Rasser, Paul E., additional, Cooper, Gavin, additional, Shannon Weickert, Cynthia, additional, Weickert, Thomas W., additional, Morris, Derek W., additional, Hong, Elliot, additional, Kochunov, Peter, additional, Beard, Lauren M., additional, Gur, Raquel E., additional, Gur, Ruben C., additional, Satterthwaite, Theodore D., additional, Wolf, Daniel H., additional, Belger, Aysenil, additional, Brown, Gregory G., additional, Ford, Judith M., additional, Macciardi, Fabio, additional, Mathalon, Daniel H., additional, O’Leary, Daniel S., additional, Potkin, Steven G., additional, Preda, Adrian, additional, Voyvodic, James, additional, Lim, Kelvin O., additional, McEwen, Sarah, additional, Yang, Fude, additional, Tan, Yunlong, additional, Tan, Shuping, additional, Wang, Zhiren, additional, Fan, Fengmei, additional, Chen, Jingxu, additional, Xiang, Hong, additional, Tang, Shiyou, additional, Guo, Hua, additional, Wan, Ping, additional, Wei, Dong, additional, Bockholt, Henry J., additional, Ehrlich, Stefan, additional, Wolthusen, Rick P.F., additional, King, Margaret D., additional, Shoemaker, Jody M., additional, Sponheim, Scott R., additional, De Haan, Lieuwe, additional, Koenders, Laura, additional, Machielsen, Marise W., additional, van Amelsvoort, Therese, additional, Veltman, Dick J., additional, Assogna, Francesca, additional, Banaj, Nerisa, additional, de Rossi, Pietro, additional, Iorio, Mariangela, additional, Piras, Fabrizio, additional, Spalletta, Gianfranco, additional, McKenna, Peter J., additional, Pomarol-Clotet, Edith, additional, Salvador, Raymond, additional, Corvin, Aiden, additional, Donohoe, Gary, additional, Kelly, Sinead, additional, Whelan, Christopher D., additional, Dickie, Erin W., additional, Rotenberg, David, additional, Voineskos, Aristotle N., additional, Ciufolini, Simone, additional, Radua, Joaquim, additional, Dazzan, Paola, additional, Murray, Robin, additional, Reis Marques, Tiago, additional, Simmons, Andrew, additional, Borgwardt, Stefan, additional, Egloff, Laura, additional, Harrisberger, Fabienne, additional, Riecher-Rössler, Anita, additional, Smieskova, Renata, additional, Alpert, Kathryn I., additional, Wang, Lei, additional, Jönsson, Erik G., additional, Koops, Sanne, additional, Sommer, Iris E.C., additional, Bertolino, Alessandro, additional, Bonvino, Aurora, additional, Di Giorgio, Annabella, additional, Neilson, Emma, additional, Mayer, Andrew R., additional, Stephen, Julia M., additional, Kwon, Jun Soo, additional, Yun, Je-Yeon, additional, Cannon, Dara M., additional, McDonald, Colm, additional, Lebedeva, Irina, additional, Tomyshev, Alexander S., additional, Akhadov, Tolibjohn, additional, Kaleda, Vasily, additional, Fatouros-Bergman, Helena, additional, Flyckt, Lena, additional, Busatto, Geraldo F., additional, Rosa, Pedro G.P., additional, Serpa, Mauricio H., additional, Zanetti, Marcus V., additional, Hoschl, Cyril, additional, Skoch, Antonin, additional, Spaniel, Filip, additional, Tomecek, David, additional, Hagenaars, Saskia P., additional, McIntosh, Andrew M., additional, Whalley, Heather C., additional, Lawrie, Stephen M., additional, Knöchel, Christian, additional, Oertel-Knöchel, Viola, additional, Stäblein, Michael, additional, Howells, Fleur M., additional, Stein, Dan J., additional, Temmingh, Henk S., additional, Uhlmann, Anne, additional, Lopez-Jaramillo, Carlos, additional, Dima, Danai, additional, McMahon, Agnes, additional, Faskowitz, Joshua I., additional, Gutman, Boris A., additional, Jahanshad, Neda, additional, Thompson, Paul M., additional, Turner, Jessica A., additional, Farde, Lars, additional, Engberg, Göran, additional, Erhardt, Sophie, additional, Cervenka, Simon, additional, Schwieler, Lilly, additional, Piehl, Fredrik, additional, Collste, Karin, additional, Victorsson, Pauliina, additional, Malmqvist, Anna, additional, Hedberg, Mikael, additional, and Orhan, Funda, additional

Published
2018
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34. Minimal atomik zincir kompleksler

Author

Orhan, Funda, Pak, Sedat, and Matematik Ana Bilim Dalı

Subjects
Matematik, Mathematics
Abstract

Bu tezde, üçüncü kısımda m maksimal ideale sahip yerel komütatif noetherian R halkası üzerinde sonlu tipten sınırlı alt zincir komplekslerinin D_(+(fg)) (R) da türetilmiş kategorisini ve K cisminin rezidüsünü bazı yeni notasyonlarını ve bunların birbiri arasındaki ilişkilerini göstereceğiz. Aynı zamanda dördüncü kısımda D_(+(fg) ) (R) da zincir kompleks için Adams spektral dizsini oluşturup bunların terslerini inceleyeceğiz.Bunları göstermek için iki alt bölüm vereceğiz. Bölüm birde birkaç zincir kompleks vereceğiz. Bazı temel homolojik cebirlerini gözden geçirip, zincir komplekslerin tanımlarının ve temel özelliklerini vereceğiz. Daha sonra ise zincir komplekslerin homotopi kategorilerini verip bölüm biri spektral dizilerle ilgili kısımla bitireceğiz.Bölüm iki bir komütatif halkanın türetilmiş kategorileri hakkındadır. Birinci kısım kategorilerin lokalleştirilmesi ve sol ve sağ bölmeler hakkındadır. Daha sonra ikinci kısımda üçgenleştirilmiş kategorilerin tanımlarını ve bunların temel özelliklerini verip bu kısmı limitlerin ve kolimitlerin homotopi tanımlarıyla sonlandıracağız. Üçüncü kısımda ise türetilmiş kategorinin bir üçgenleştirilmiş kategori olduğunu göstereceğiz. Dördüncü kısımda türetilmiş funktorların, türetilmiş tensör çarpımın ve türetilmiş Hom un tanımlarını vereceğiz.Üçüncü bölümde kısım bire yerel halkaların bazı özelliklerini verip bu kısmı sonlu tipteki sınırlı alt zincir komplekslerinin bir minimal free çözümlemesine sahip olduğunu göstererek bitireceğiz. İkinci kısımda Whitehead teoreminin türetilmiş versiyonunu göstereceğiz. Üçüncü kısımda ise zincir kompleksler için Postnikov kulelerini oluşturacağız. Dördüncü kısımda Steenrod cebirini tanımlayacağız. 5. , 6. ve 7.kısımda bir zincir kompleksin çekirdeğini, nükleer zincir kompleksi, H*-monojenik, detectable mod m olmayan homoloji, minimal atomik ve indirgenemezliği tanımlayacağız. Bu notasyonların birbirleriyle olan ilişkilerinin bazı çeşitli sonuçlarını gösterip, birkaç örnek vereceğiz. In this thesis, we introduce some new notions in the derived category D_(+(fg)) (R) of bounded below chain complexes of finite type over local commutative noetherian ring R with maximal ideal m and residue K in chapter three and study their relations to each other. Also, we set up the Adams spectral sequence for chain complexes in D_(+(fg)) (R) in chapter four and study its convergence.To accomplish this task, we give two background chapters. We give some good account of chain complexes in chapter one. We rewiev some basic homological algebra and give definition and basic properties of chain complexes. Then we study the homotopy caategory of chain complexes and we end chapter one with section about spectral sequences.Chapter two is about the derived category of a commutative ring. Section one is about localization of categories and left and right fractions. Then in section two, we give definition of triangulated categories and some of its basic properties and we end section two with definitions of homotopy limits and colimits. In section three, we show that the derived category is a triangulated category. In section four, we give definitions of the derived functors, the derived tensor product and the derived Hom.In chapter three, we start section one by giving some facts about local rings and we end this section by showing that every bounded below chain complex of finite type has a minimal free solutions. In section two, we show a derived analog of the Whitehead Theorem. In section three, we construct Postnikov towers for chain complexes. In section four, we define the Steenrod algebra. In section five, six and seven, we define irreducible, atomic, minimal atomic, no mod m detectable homology, H^⋆- monogenic, nuclear chain complexes and the core of a chain complex. We show some various results relating these notions to each other and give some examples. 105

Published
2014

35. Skeletal Muscle PGC-1α1 Modulates Kynurenine Metabolism and Mediates Resilience to Stress-Induced Depression

Author

Agudelo, Leandro Z., primary, Femenía, Teresa, additional, Orhan, Funda, additional, Porsmyr-Palmertz, Margareta, additional, Goiny, Michel, additional, Martinez-Redondo, Vicente, additional, Correia, Jorge C., additional, Izadi, Manizheh, additional, Bhat, Maria, additional, Schuppe-Koistinen, Ina, additional, Pettersson, Amanda, additional, Ferreira, Duarte M.S., additional, Krook, Anna, additional, Barres, Romain, additional, Zierath, Juleen R., additional, Erhardt, Sophie, additional, Lindskog, Maria, additional, and Ruas, Jorge L., additional

Published
2015
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36. Kynurenic Acid levels in cerebrospinal fluid from patients with Alzheimer's disease or dementia with lewy bodies.

Author

Wennström, Malin, Nielsen, Henrietta, Orhan, Funda, Londos, Elisabet, Minthon, Lennart, Erhardt, Sophie, Wennström, Malin, Nielsen, Henrietta, Orhan, Funda, Londos, Elisabet, Minthon, Lennart, and Erhardt, Sophie

Abstract

Kynurenic acid (KYNA) is implicated in cognitive functions. Altered concentrations of the compound are found in serum and cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD). Further studies to determine whether KYNA serves as a biomarker for cognitive decline and dementia progression are required. In this study, we measured CSF KYNA levels in AD patients (n = 19), patients with dementia with Lewy bodies (DLB) (n = 18), and healthy age-matched controls (Ctrls)) (n = 20) to further explore possible correlations between KYNA levels, cognitive decline, and well-established AD and inflammatory markers. Neither DLB patients nor AD patients showed significantly altered CSF KYNA levels compared to Ctrls. However, female AD patients displayed significantly higher KYNA levels compared to male AD patients, a gender difference not seen in the Ctrl or DLB group. Levels of KYNA significantly correlated with the AD-biomarker P-tau and the inflammation marker soluble intercellular adhesion molecule-1 (sICAM-1) in the AD patient group. No associations between KYNA and cognitive functions were found. Our study shows that, although KYNA was not associated with cognitive decline in AD or DLB patients, it may be implicated in AD-related hyperphosphorylation of tau and inflammation. Further studies on larger patient cohorts are required to understand the potential role of KYNA in AD and DLB.

Published
2014

37. Skeletal Muscle PGC-1α1 Modulates Kynurenine Metabolism and Mediates Resilience to Stress-Induced Depression

Author

Agudelo, Leandro Z., primary, Femenía, Teresa, additional, Orhan, Funda, additional, Porsmyr-Palmertz, Margareta, additional, Goiny, Michel, additional, Martinez-Redondo, Vicente, additional, Correia, Jorge C., additional, Izadi, Manizheh, additional, Bhat, Maria, additional, Schuppe-Koistinen, Ina, additional, Pettersson, Amanda T., additional, Ferreira, Duarte M.S., additional, Krook, Anna, additional, Barres, Romain, additional, Zierath, Juleen R., additional, Erhardt, Sophie, additional, Lindskog, Maria, additional, and Ruas, Jorge L., additional

Published
2014
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39. Central and peripheral kynurenine pathway metabolites in COVID-19: Implications for neurological and immunological responses.

Author

Li X, Edén A, Malwade S, Cunningham JL, Bergquist J, Weidenfors JA, Sellgren CM, Engberg G, Piehl F, Gisslen M, Kumlien E, Virhammar J, Orhan F, Rostami E, Schwieler L, and Erhardt S

Abstract

Long-term symptoms such as pain, fatigue, and cognitive impairments are commonly observed in individuals affected by coronavirus disease 2019 (COVID-19). Metabolites of the kynurenine pathway have been proposed to account for cognitive impairment in COVID-19 patients. Here, cerebrospinal fluid (CSF) and plasma levels of kynurenine pathway metabolites in 53 COVID-19 patients and 12 non-inflammatory neurological disease controls in Sweden were measured with an ultra-performance liquid chromatography-tandem mass spectrometry system (UPLC-MS/MS) and correlated with immunological markers and neurological markers. Single cell transcriptomic data from a previous study of 130 COVID-19 patients was used to investigate the expression of key genes in the kynurenine pathway. The present study reveals that the neuroactive kynurenine pathway metabolites quinolinic acid (QUIN) and kynurenic acid (KYNA) are increased in CSF in patients with acute COVID-19. In addition, CSF levels of kynurenine, ratio of kynurenine/tryptophan (rKT) and QUIN correlate with neurodegenerative markers. Furthermore, tryptophan is significantly decreased in plasma but not in the CSF. In addition, the kynurenine pathway is strongly activated in the plasma and correlates with the peripheral immunological marker neopterin. Single-cell transcriptomics revealed upregulated gene expressions of the rate-limiting enzyme indoleamine 2,3- dioxygenase1 (IDO1) in CD14 + and CD16 + monocytes that correlated with type II-interferon response exclusively in COVID-19 patients. In summary, our study confirms significant activation of the peripheral kynurenine pathway in patients with acute COVID-19 and, notably, this is the first study to identify elevated levels of kynurenine metabolites in the central nervous system associated with the disease. Our findings suggest that peripheral inflammation, potentially linked to overexpression of IDO1 in monocytes, activates the kynurenine pathway. Increased plasma kynurenine, crossing the blood-brain barrier, serves as a source for elevated brain KYNA and neurotoxic QUIN. We conclude that blocking peripheral-to-central kynurenine transport could be a promising strategy to protect against neurotoxic effects of QUIN in COVID-19 patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Published
2024
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40. Lower complement C1q levels in first-episode psychosis and in schizophrenia.

Author

Koskuvi M, Malwade S, Gracias Lekander J, Hörbeck E, Bruno S, Holmen Larsson J, Pelanis A, Isgren A, Goulding A, Fatouros-Bergman H, Samudyata, Schalling M, Piehl F, Erhardt S, Landen M, Cervenka S, Orhan F, and Sellgren CM

Subjects
Humans, Complement C1q, RNA, Messenger, Schizophrenia, Psychotic Disorders, Antipsychotic Agents therapeutic use
Abstract

Recent evidence has implicated complement component (C) 4A in excessive elimination of synapses in schizophrenia. C4A is believed to contribute to physiological synapse removal through signaling within the C1q initiated classical activation axis of the complement system. So far, a potential involvement of C1q in the pathophysiology of schizophrenia remains unclear. In this study, we first utilized large-scale gene expression datasets (n = 586 patients with schizophrenia and n = 986 controls) to observe lower C1QA mRNA expression in prefrontal cortex tissue of individuals with schizophrenia (P = 4.8x10 -05 ), while C1QA seeded co-expression networks displayed no enrichment for schizophrenia risk variants beyond C4A. We then used targeted liquid chromatography-mass spectrometry (LS-MS) to measure cerebrospinal fluid (CSF) levels of C1qA in 113 individuals with first-episode psychosis (FEP), among which 66 individuals was later diagnosed with schizophrenia, and 87 healthy controls. CSF concentrations of C1qA were lower in individuals diagnosed with FEP (P = 0.0001), also after removing subjects with a short-term prescription of an antipsychotic agent (P = 0.0005). We conclude that C1q mRNA and protein levels are lower in schizophrenia and that further experimental studies are needed to understand the functional implications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2024
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