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5. Association between age of cannabis initiation and gray matter covariance networks in recent onset psychosis

Author

Penzel, N., Antonucci, L. A., Betz, L. T., Sanfelici, R., Weiske, J., Pogarell, O., Cumming, P., Quednow, B. B., Howes, O., Falkai, P., Upthegrove, R., Bertolino, A., Borgwardt, S., Brambilla, P., Lencer, R., Meisenzahl, E., Rosen, M., Haidl, T., Kambeitz-Ilankovic, L., Ruhrmann, S., Salokangas, R. R. K., Pantelis, C., Wood, S. J., Koutsouleris, N., Kambeitz, J., Sen Dong, M., Erkens, A., Gussmann, E., Haas, S., Hasan, A., Hoff, C., Khanyaree, I., Melo, A., Muckenhuber-Sternbauer, S., Kohler, J., Ozturk, O. F., Popovic, D., Rangnick, A., von Saldern, S., Spangemacher, M., Tupac, A., Urquijo, M. F., Wosgien, A., Betz, L., Blume, K., Seves, M., Kaiser, N., Pilgram, T., Lichtenstein, T., Wenzel, J., Woopen, C., Andreou, C., Egloff, L., Harrisberger, F., Lenz, C., Leanza, L., Mackintosh, A., Smieskova, R., Studerus, E., Walter, A., Widmayer, S., Chisholm, K., Day, C., Griffiths, S. L., Iqbal, M., Pelton, M., Mallikarjun, P., Stainton, A., Lin, A., Salokangas, R. K. R., Denissoff, A., Ellila, A., From, T., Heinimaa, M., Ilonen, T., Jalo, P., Laurikainen, H., Lehtinen, M., Luutonen, A., Makela, A., Paju, J., Pesonen, H., Armio (Saila), R. -L., Sormunen, E., Toivonen, A., Turtonen, O., Solana, A. B., Abraham, M., Hehn, N., Schirmer, T., Altamura, C., Belleri, M., Bottinelli, F., Ferro, A., Re, M., Monzani, E., Percudani, M., Sberna, M., D'Agostino, A., Del Fabro, L., Perna, G., Nobile, M., Alciati, A., Balestrieri, M., Bonivento, C., Cabras, G., Fabbro, F., Garzitto, M., Piccin, S., Blasi, G., Pergola, G., Caforio, G., Faio, L., Quarto, T., Gelao, B., Romano, R., Andriola, I., Falsetti, A., Barone, M., Passatiore, R., Sangiuliano, M., Surman, M., Bienek, O., Romer, G., Dannlowski, U., Schultze-Lutter, F., Schmidt-Kraepelin, C., Neufang, S., Korda, A., and Rohner, H.

Subjects
Psychosis, Adolescent, Inferior frontal gyrus, 610 Medicine & health, Article, medicine, Humans, Gray Matter, Association (psychology), Cannabis, Pharmacology, biology, business.industry, Confounding, medicine.disease, biology.organism_classification, Magnetic Resonance Imaging, Psychiatry and Mental health, Risk factors, Psychotic Disorders, Schizophrenia, Cohort, business, Insula, Neuroscience, Clinical psychology
Abstract

Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hitherto reported inconclusive findings. We investigated effects of age of cannabis initiation on psychosis using data from the multicentric Personalized Prognostic Tools for Early Psychosis Management (PRONIA) and the Cannabis Induced Psychosis (CIP) studies, yielding a total sample of 102 clinically-relevant cannabis users with recent onset psychosis. GM covariance underlies shared maturational processes. Therefore, we performed source-based morphometry analysis with spatial constraints on structural brain networks showing significant alterations in schizophrenia in a previous multisite study, thus testing associations of these networks with the age of cannabis initiation and with confounding factors. Earlier cannabis initiation was associated with more severe positive symptoms in our cohort. Greater gray matter volume (GMV) in the previously identified cerebellar schizophrenia-related network had a significant association with early cannabis use, independent of several possibly confounding factors. Moreover, GMV in the cerebellar network was associated with lower volume in another network previously associated with schizophrenia, comprising the insula, superior temporal, and inferior frontal gyrus. These findings are in line with previous investigations in healthy cannabis users, and suggest that early initiation of cannabis perturbs the developmental trajectory of certain structural brain networks in a manner imparting risk for psychosis later in life.

Published
2021
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6. Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis

Author

Pollak, TA, Kempton, MJ, Iyegbe, C, Vincent, A, Irani, SR, Coutinho, E, Menassa, DA, Jacobson, L, de Haan, L, Ruhrmann, S, Sachs, G, Riecher-Roessler, A, Krebs, M-O, Amminger, P, Glenthoj, B, Barrantes-Vidal, N, van Os, J, Rutten, BPF, Bressan, RA, van der Gaag, M, Yolken, R, Hotopf, M, Valmaggia, L, Stone, J, David, AS, McGuire, P, Calem, M, Tognin, S, Modinos, G, Velthorst, E, Kraan, TC, van Dam, DS, Burger, N, Nelson, B, McGorry, P, Pantelis, C, Politis, A, Goodall, J, Borgwardt, S, Ittig, S, Studerus, E, Smieskova, R, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Rosa, A, Racioppi, A, Monsonet, M, Hinojosa-Marques, L, Kwapil, TR, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthoj, L, Nordentoft, M, Gebhard, D, Arnhold, J, Klosterkoetter, J, Lasser, I, Winklbaur, B, Delespaul, PA, Pollak, TA, Kempton, MJ, Iyegbe, C, Vincent, A, Irani, SR, Coutinho, E, Menassa, DA, Jacobson, L, de Haan, L, Ruhrmann, S, Sachs, G, Riecher-Roessler, A, Krebs, M-O, Amminger, P, Glenthoj, B, Barrantes-Vidal, N, van Os, J, Rutten, BPF, Bressan, RA, van der Gaag, M, Yolken, R, Hotopf, M, Valmaggia, L, Stone, J, David, AS, McGuire, P, Calem, M, Tognin, S, Modinos, G, Velthorst, E, Kraan, TC, van Dam, DS, Burger, N, Nelson, B, McGorry, P, Pantelis, C, Politis, A, Goodall, J, Borgwardt, S, Ittig, S, Studerus, E, Smieskova, R, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Rosa, A, Racioppi, A, Monsonet, M, Hinojosa-Marques, L, Kwapil, TR, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthoj, L, Nordentoft, M, Gebhard, D, Arnhold, J, Klosterkoetter, J, Lasser, I, Winklbaur, B, and Delespaul, PA

Abstract

Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case-control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2%; OR = 1.50; 95% CI: 0.58-3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs (p < 0.001). Preliminary phenotypic analyses revealed that within the CHR sample, the NMDAR antibody seropositive subjects had higher levels of current depression, performed worse on the Rey Auditory Verbal Learning Task (p < 0.05), and had a markedly lower IQ (p < 0.01). NMDAR IgGs were not more frequent in subjects who later became psychotic than those who did not. NMDAR antibody serostatus and titre was associated with poorer levels of functioning at follow-up (p < 0.05) and the presence of a neuronal autoantibody was associated with larger amygdala volumes (p < 0.05). Altogether, these findings demonstrate that NMDAR autoantibodies are detectable in a subgroup of CHR subjects at equal rates to controls. In the CHR group, they are associated with affective psychopathology, impairments in verbal memory, and overall cognitive function: these findings are qualitatively and individually similar to core features of autoimmune encephalitis and/or animal models of NMDAR antibody-mediated CNS disease. Overall the current

Published
2021

7. Cognitive subtypes in recent onset psychosis: distinct neurobiological fingerprints?

Author

Wenzel, J., Haas, S. S., Dwyer, D. B., Ruef, A., Oeztuerk, O. F., Antonucci, L. A., von Saldern, S., Bonivento, C., Garzitto, M., Ferro, A., Paolini, M., Blautzik, J., Borgwardt, S., Brambilla, P., Meisenzahl, E., Salokangas, R. K. R., Upthegrove, R., Wood, S. J., Kambeitz, J., Koutsouleris, N., Kambeitz-Ilankovic, L., Sen Dong, M., Erkens, A., Gussmann, E., Haas, S., Hasan, A., Hoff, C., Khanyaree, I., Melo, A., Muckenhuber-Sternbauer, S., Kohler, J., Popovic, D., Penzel, N., Rangnick, A., Sanfelici, R., Spangemacher, M., Tupac, A., Urquijo, M. F., Weiske, J., Wosgien, A., Ruhrmann, S., Rosen, M., Betz, L., Haidl, T., Blume, K., Seves, M., Kaiser, N., Pilgram, T., Lichtenstein, T., Woopen, C., Andreou, C., Egloff, L., Harrisberger, F., Lenz, C., Leanza, L., Mackintosh, A., Smieskova, R., Studerus, E., Walter, A., Widmayer, S., Chisholm, K., Day, C., Griffiths, S. L., Iqbal, M., Lalousis, P., Pelton, M., Mallikarjun, P., Stainton, A., Lin, A., Denissoff, A., Ellila, A., Tiina From, R. N., Heinimaa, M., Ilonen, T., Jalo, P., Heikki Laurikainen, R. N., Lehtinen, M., Antti Luutonen, R. N., Makela, A., Paju, J., Pesonen, H., Armio (Saila), R. -L., Sormunen, E., Toivonen, A., Turtonen, O., Solana, A. B., Abraham, M., Hehn, N., Schirmer, T., Altamura, C., Belleri, M., Bottinelli, F., Re, M., Monzani, E., Percudani, M., Sberna, M., D'Agostino, A., Del Fabro, L., Menni, V. S. B., Perna, G., Nobile, M., Alciati, A., Balestrieri, M., Cabras, G., Fabbro, F., Piccin, S., Bertolino, A., Blasi, G., Pergola, G., Caforio, G., Faio, L., Quarto, T., Gelao, B., Romano, R., Andriola, I., Falsetti, A., Barone, M., Passatiore, R., Sangiuliano, M., Lencer, R., Surman, M., Bienek, O., Romer, G., Dannlowski, U., Schultze-Lutter, F., Schmidt-Kraepelin, C., Neufang, S., Korda, A., and Rohner, H.

Subjects
medicine.medical_specialty, Psychosis, Audiology, Article, Cognition, Social cognition, medicine, Humans, Effects of sleep deprivation on cognitive performance, Gray Matter, Pharmacology, medicine.diagnostic_test, business.industry, Brain, Diagnostic markers, Cognitive neuroscience, Neuropsychological test, medicine.disease, Psychiatry and Mental health, Psychotic Disorders, Schizophrenia, Verbal memory, business, Neurocognitive
Abstract

In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated with neuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosis patients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means algorithm to cluster 108 psychosis patients from the multi-site EU PRONIA (Prognostic tools for early psychosis management) study based on cognitive performance and validated the solution independently (N = 53). Cognitive subgroups and healthy controls (HC; n = 195) were classified based on gray matter volume (GMV) using Support Vector Machine classification. A cognitively spared (N = 67) and impaired (N = 41) subgroup were revealed and partially independently validated (Nspared = 40, Nimpaired = 13). Impaired patients showed significantly increased negative symptomatology (pfdr = 0.003), reduced cognitive performance (pfdr pfdr p = 0.01) separating impaired patients from HC revealed increases and decreases across several fronto-temporal-parietal brain areas, including basal ganglia and cerebellum. Cognitive and functional disturbances alongside brain morphological changes in the impaired subgroup are consistent with a neurodevelopmental origin of psychosis. Our findings emphasize the relevance of tailored intervention early in the course of psychosis for patients suffering from the likely stronger neurodevelopmental character of the disease.

Published
2020

8. Association of Adverse Outcomes With Emotion Processing and Its Neural Substrate in Individuals at Clinical High Risk for Psychosis

Author

Modinos, G, Kempton, MJ, Tognin, S, Calem, M, Porffy, L, Antoniades, M, Mason, A, Azis, M, Allen, P, Nelson, B, McGorry, P, Pantelis, C, Riecher-Rossler, A, Borgwardt, S, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Glenthoj, B, Ruhrmann, S, Sachs, G, Rutten, B, van Os, J, de Haan, L, Velthorst, E, van der Gaag, M, Valmaggia, LR, McGuire, P, Kraan, TC, van Dam, DS, Burger, N, Amminger, GP, Politis, A, Goodall, J, Rapp, C, Ittig, S, Studerus, E, Smieskova, R, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Dominguez-Martinez, T, Monsonet, M, Hinojosa, L, Racioppi, A, Kwapil, TR, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthoj, LB, Gebhard, D, Arnhold, J, Klosterkotter, J, Lasser, I, Winklbaur, B, Delespaul, PA, Modinos, G, Kempton, MJ, Tognin, S, Calem, M, Porffy, L, Antoniades, M, Mason, A, Azis, M, Allen, P, Nelson, B, McGorry, P, Pantelis, C, Riecher-Rossler, A, Borgwardt, S, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Glenthoj, B, Ruhrmann, S, Sachs, G, Rutten, B, van Os, J, de Haan, L, Velthorst, E, van der Gaag, M, Valmaggia, LR, McGuire, P, Kraan, TC, van Dam, DS, Burger, N, Amminger, GP, Politis, A, Goodall, J, Rapp, C, Ittig, S, Studerus, E, Smieskova, R, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Dominguez-Martinez, T, Monsonet, M, Hinojosa, L, Racioppi, A, Kwapil, TR, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthoj, LB, Gebhard, D, Arnhold, J, Klosterkotter, J, Lasser, I, Winklbaur, B, and Delespaul, PA

Abstract

IMPORTANCE: The development of adverse clinical outcomes in patients with psychosis has been associated with behavioral and neuroanatomical deficits related to emotion processing. However, the association between alterations in brain regions subserving emotion processing and clinical outcomes remains unclear. OBJECTIVE: To examine the association between alterations in emotion processing and regional gray matter volumes in individuals at clinical high risk (CHR) for psychosis, and the association with subsequent clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: This naturalistic case-control study with clinical follow-up at 12 months was conducted from July 1, 2010, to August 31, 2016, and collected data from 9 psychosis early detection centers (Amsterdam, Basel, Cologne, Copenhagen, London, Melbourne, Paris, The Hague, and Vienna). Participants (213 individuals at CHR and 52 healthy controls) were enrolled in the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) project. Data were analyzed from October 1, 2018, to April 24, 2019. MAIN MEASURES AND OUTCOMES: Emotion recognition was assessed with the Degraded Facial Affect Recognition Task. Three-Tesla magnetic resonance imaging scans were acquired from all participants, and gray matter volume was measured in regions of interest (medial prefrontal cortex, amygdala, hippocampus, and insula). Clinical outcomes at 12 months were evaluated for transition to psychosis using the Comprehensive Assessment of At-Risk Mental States criteria, and the level of overall functioning was measured through the Global Assessment of Functioning [GAF] scale. RESULTS: A total of 213 individuals at CHR (105 women [49.3%]; mean [SD] age, 22.9 [4.7] years) and 52 healthy controls (25 women [48.1%]; mean [SD] age, 23.3 [4.0] years) were included in the study at baseline. At the follow-up within 2 years of baseline, 44 individuals at CHR (20.7%) had developed psychosis and 169 (79.3%) had n

Published
2020

11. 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, TGM, Walton, E, Hibar, DP, Schmaal, L, Jiang, W, Glahn, DC, Pearlson, GD, Yao, N, Fukunaga, M, Hashimoto, R, Okada, N, Yamamori, H, Clark, VP, Mueller, BA, de Zwarte, SMC, Ophoff, RA, van Haren, NEM, Andreassen, OA, Gurholt, TP, Gruber, O, Kraemer, B, Richter, A, Calhoun, VD, Crespo-Facorro, B, Roiz-Santiañez, R, Tordesillas-Gutiérrez, D, Loughland, C, Catts, S, Fullerton, JM, Green, MJ, Henskens, F, Jablensky, A, Mowry, BJ, Pantelis, C, Quidé, Y, Schall, U, Scott, RJ, Cairns, MJ, Seal, M, Tooney, PA, Rasser, PE, Cooper, G, Shannon Weickert, C, Weickert, TW, Hong, E, Kochunov, P, Gur, RE, Gur, RC, Ford, JM, Macciardi, F, Mathalon, DH, Potkin, SG, Preda, A, Fan, F, Ehrlich, S, King, MD, De Haan, L, Veltman, DJ, Assogna, F, Banaj, N, de Rossi, P, Iorio, M, Piras, F, Spalletta, G, Pomarol-Clotet, E, Kelly, S, Ciufolini, S, Radua, J, Murray, R, Marques, TR, Simmons, A, Borgwardt, S, Schönborn-Harrisberger, F, Riecher-Rössler, A, Smieskova, R, Alpert, KI, Bertolino, A, Bonvino, A, Di Giorgio, A, Neilson, E, Mayer, AR, Yun, JY, Cannon, DM, Lebedeva, I, Tomyshev, AS, Akhadov, T, Kaleda, V, Fatouros-Bergman, H, Flyckt, L, Farde, L, Cervenka, S, Agartz, I, Collste, K, Victorsson, P, Engberg, G, Erhardt, S, Schwieler, L, Malmqvist, A, Hedberg, M, Orhan, F, van Erp, TGM, Walton, E, Hibar, DP, Schmaal, L, Jiang, W, Glahn, DC, Pearlson, GD, Yao, N, Fukunaga, M, Hashimoto, R, Okada, N, Yamamori, H, Clark, VP, Mueller, BA, de Zwarte, SMC, Ophoff, RA, van Haren, NEM, Andreassen, OA, Gurholt, TP, Gruber, O, Kraemer, B, Richter, A, Calhoun, VD, Crespo-Facorro, B, Roiz-Santiañez, R, Tordesillas-Gutiérrez, D, Loughland, C, Catts, S, Fullerton, JM, Green, MJ, Henskens, F, Jablensky, A, Mowry, BJ, Pantelis, C, Quidé, Y, Schall, U, Scott, RJ, Cairns, MJ, Seal, M, Tooney, PA, Rasser, PE, Cooper, G, Shannon Weickert, C, Weickert, TW, Hong, E, Kochunov, P, Gur, RE, Gur, RC, Ford, JM, Macciardi, F, Mathalon, DH, Potkin, SG, Preda, A, Fan, F, Ehrlich, S, King, MD, De Haan, L, Veltman, DJ, Assogna, F, Banaj, N, de Rossi, P, Iorio, M, Piras, F, Spalletta, G, Pomarol-Clotet, E, Kelly, S, Ciufolini, S, Radua, J, Murray, R, Marques, TR, Simmons, A, Borgwardt, S, Schönborn-Harrisberger, F, Riecher-Rössler, A, Smieskova, R, Alpert, KI, Bertolino, A, Bonvino, A, Di Giorgio, A, Neilson, E, Mayer, AR, Yun, JY, Cannon, DM, Lebedeva, I, Tomyshev, AS, Akhadov, T, Kaleda, V, Fatouros-Bergman, H, Flyckt, L, Farde, L, Cervenka, S, Agartz, I, Collste, K, Victorsson, P, Engberg, G, Erhardt, S, Schwieler, L, Malmqvist, A, Hedberg, M, and Orhan, F

Published
2019

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

Author

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

Abstract

Background: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This

Published
2018
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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

van Erp, TGM, Walton, E, Hibar, DP, Schmaal, L, Jiang, W, Glahn, DC, Pearlson, GD, Yao, N, Fukunaga, M, Hashimoto, R, Okada, N, Yamamori, H, Bustillo, JR, Clark, VP, Agartz, I, Mueller, BA, Cahn, W, de Zwarte, SMC, Pol, HEH, Kahn, RS, Ophoff, RA, van Haren, NEM, Andreassen, OA, Dale, AM, Nhat, TD, Gurholt, TP, Hartberg, CB, Haukvik, UK, Jorgensen, KN, Lagerberg, T, Melle, I, Westlye, LT, Gruber, O, Kraemer, B, Richter, A, Zilles, D, Calhoun, VD, Crespo-Facorro, B, Roiz-Santianez, R, Tordesillas-Gutierrez, D, Loughland, C, Carr, VJ, Catts, S, Cropley, VL, Fullerton, JM, Green, MJ, Henskens, FA, Jablensky, A, Lenroot, RK, Mowry, BJ, Michie, PT, Pantelis, C, Quide, Y, Schall, U, Scott, RJ, Cairns, MJ, Seal, M, Tooney, PA, Rasser, PE, Cooper, G, Weickert, CS, Weickert, TW, Morris, DW, Hong, E, Kochunov, P, Beard, LM, Gur, RE, Gur, RC, Satterthwaite, TD, Wolf, DH, Belger, A, Brown, GG, Ford, JM, Macciardi, F, Mathalon, DH, O'Leary, DS, Potkin, SG, Preda, A, Voyvodic, J, Lim, KO, McEwen, S, Yang, F, Tan, Y, Tan, S, Wang, Z, Fan, F, Chen, J, Xiang, H, Tang, S, Guo, H, Wan, P, Wei, D, Bockholt, HJ, Ehrlich, S, Wolthusen, RPF, King, MD, Shoemaker, JM, Sponheim, SR, De Haan, L, Koenders, L, Machielsen, MW, van Amelsvoort, T, Veltman, DJ, Assogna, F, Banaj, N, de Rossi, P, Iorio, M, Piras, F, Spalletta, G, McKenna, PJ, Pomarol-Clotet, E, Salvador, R, Corvin, A, Donohoe, G, Kelly, S, Whelan, CD, Dickie, EW, Rotenberg, D, Voineskos, AN, Ciufolini, S, Radua, J, Dazzan, P, Murray, R, Marques, TR, Simmons, A, Borgwardt, S, Egloff, L, Harrisberger, F, Riecher-Roessler, A, Smieskova, R, Alpert, K, Wang, L, Jonsson, EG, Koops, S, Sommer, IEC, Bertolino, A, Bonvino, A, Di Giorgio, A, Neilson, E, Mayer, AR, Stephen, JM, Kwon, JS, Yun, J-Y, Cannon, DM, McDonald, C, Lebedeva, I, Tomyshev, AS, Akhadov, T, Kaleda, V, Fatouros-Bergman, H, Flyckt, L, Busatto, GF, Rosa, PGP, Serpa, MH, Zanetti, M, Hoschl, C, Skoch, A, Spaniel, F, Tomecek, D, Hagenaars, SP, McIntosh, AM, Whalley, HC, Lawrie, SM, Knoechel, C, Oertel-Knoechel, V, Staeblein, M, Howells, FM, Stein, DJ, Temmingh, HS, Uhlmann, A, Lopez-Jaramillo, C, Dima, D, McMahon, A, Faskowitz, J, Gutman, BA, Jahanshad, N, Thompson, PM, Turner, JA, van Erp, TGM, Walton, E, Hibar, DP, Schmaal, L, Jiang, W, Glahn, DC, Pearlson, GD, Yao, N, Fukunaga, M, Hashimoto, R, Okada, N, Yamamori, H, Bustillo, JR, Clark, VP, Agartz, I, Mueller, BA, Cahn, W, de Zwarte, SMC, Pol, HEH, Kahn, RS, Ophoff, RA, van Haren, NEM, Andreassen, OA, Dale, AM, Nhat, TD, Gurholt, TP, Hartberg, CB, Haukvik, UK, Jorgensen, KN, Lagerberg, T, Melle, I, Westlye, LT, Gruber, O, Kraemer, B, Richter, A, Zilles, D, Calhoun, VD, Crespo-Facorro, B, Roiz-Santianez, R, Tordesillas-Gutierrez, D, Loughland, C, Carr, VJ, Catts, S, Cropley, VL, Fullerton, JM, Green, MJ, Henskens, FA, Jablensky, A, Lenroot, RK, Mowry, BJ, Michie, PT, Pantelis, C, Quide, Y, Schall, U, Scott, RJ, Cairns, MJ, Seal, M, Tooney, PA, Rasser, PE, Cooper, G, Weickert, CS, Weickert, TW, Morris, DW, Hong, E, Kochunov, P, Beard, LM, Gur, RE, Gur, RC, Satterthwaite, TD, Wolf, DH, Belger, A, Brown, GG, Ford, JM, Macciardi, F, Mathalon, DH, O'Leary, DS, Potkin, SG, Preda, A, Voyvodic, J, Lim, KO, McEwen, S, Yang, F, Tan, Y, Tan, S, Wang, Z, Fan, F, Chen, J, Xiang, H, Tang, S, Guo, H, Wan, P, Wei, D, Bockholt, HJ, Ehrlich, S, Wolthusen, RPF, King, MD, Shoemaker, JM, Sponheim, SR, De Haan, L, Koenders, L, Machielsen, MW, van Amelsvoort, T, Veltman, DJ, Assogna, F, Banaj, N, de Rossi, P, Iorio, M, Piras, F, Spalletta, G, McKenna, PJ, Pomarol-Clotet, E, Salvador, R, Corvin, A, Donohoe, G, Kelly, S, Whelan, CD, Dickie, EW, Rotenberg, D, Voineskos, AN, Ciufolini, S, Radua, J, Dazzan, P, Murray, R, Marques, TR, Simmons, A, Borgwardt, S, Egloff, L, Harrisberger, F, Riecher-Roessler, A, Smieskova, R, Alpert, K, Wang, L, Jonsson, EG, Koops, S, Sommer, IEC, Bertolino, A, Bonvino, A, Di Giorgio, A, Neilson, E, Mayer, AR, Stephen, JM, Kwon, JS, Yun, J-Y, Cannon, DM, McDonald, C, Lebedeva, I, Tomyshev, AS, Akhadov, T, Kaleda, V, Fatouros-Bergman, H, Flyckt, L, Busatto, GF, Rosa, PGP, Serpa, MH, Zanetti, M, Hoschl, C, Skoch, A, Spaniel, F, Tomecek, D, Hagenaars, SP, McIntosh, AM, Whalley, HC, Lawrie, SM, Knoechel, C, Oertel-Knoechel, V, Staeblein, M, Howells, FM, Stein, DJ, Temmingh, HS, Uhlmann, A, Lopez-Jaramillo, C, Dima, D, McMahon, A, Faskowitz, J, Gutman, BA, Jahanshad, N, Thompson, PM, and Turner, JA

Abstract

BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.

Published
2018

15. Insular volume abnormalities associated with different transition probabilities to psychosis

Author

Smieskova, R., Fusar-Poli, P., Aston, J., Simon, A., Bendfeldt, K., Lenz, C., Stieglitz, R.-D, McGuire, P., Riecher-Rössler, A., Borgwardt, S. J., Smieskova, R., Fusar-Poli, P., Aston, J., Simon, A., Bendfeldt, K., Lenz, C., Stieglitz, R.-D, McGuire, P., Riecher-Rössler, A., and Borgwardt, S. J.

Abstract

Background Although individuals vulnerable to psychosis show brain volumetric abnormalities, structural alterations underlying different probabilities for later transition are unknown. The present study addresses this issue by means of voxel-based morphometry (VBM). Method We investigated grey matter volume (GMV) abnormalities by comparing four neuroleptic-free groups: individuals with first episode of psychosis (FEP) and with at-risk mental state (ARMS), with either long-term (ARMS-LT) or short-term ARMS (ARMS-ST), compared to the healthy control (HC) group. Using three-dimensional (3D) magnetic resonance imaging (MRI), we examined 16 FEP, 31 ARMS, clinically followed up for on average 3 months (ARMS-ST, n=18) and 4.5 years (ARMS-LT, n=13), and 19 HC. Results The ARMS-ST group showed less GMV in the right and left insula compared to the ARMS-LT (Cohen's d 1.67) and FEP groups (Cohen's d 1.81) respectively. These GMV differences were correlated positively with global functioning in the whole ARMS group. Insular alterations were associated with negative symptomatology in the whole ARMS group, and also with hallucinations in the ARMS-ST and ARMS-LT subgroups. We found a significant effect of previous antipsychotic medication use on GMV abnormalities in the FEP group. Conclusions GMV abnormalities in subjects at high clinical risk for psychosis are associated with negative and positive psychotic symptoms, and global functioning. Alterations in the right insula are associated with a higher risk for transition to psychosis, and thus may be related to different transition probabilities

Published
2017

16. Identifying gene-environment interactions in schizophrenia: Contemporary challenges for integrated, large-scale investigations

Author

Van Os, J. Rutten, B.P. Myin-Germeys, I. Delespaul, P. Viechtbauer, W. Van Zelst, C. Bruggeman, R. Reininghaus, U. Morgan, C. Murray, R.M. Di Forti, M. McGuire, P. Valmaggia, L.R. Kempton, M.J. Gayer-Anderson, C. Hubbard, K. Beards, S. Stilo, S.A. Onyejiaka, A. Bourque, F. Modinos, G. Tognin, S. Calem, M. O'Donovan, M.C. Owen, M.J. Holmans, P. Williams, N. Craddock, N. Richards, A. Humphreys, I. Meyer-Lindenberg, A. Leweke, F.M. Tost, H. Akdeniz, C. Rohleder, C. Bumb, J.M. Schwarz, E. Alptekin, K. Üçok, A. Saka, M.C. Atbagoǧlu, E.C. Gülöksüz, S. Gumus-Akay, G. Cihan, B. Karadaǧ, H. Soygür, H. Cankurtaran, E.S. Ulusoy, S. Akdede, B. Binbay, T. Ayer, A. Noyan, H. Karadayi, G. Akturan, E. Ulaş, H. Arango, C. Parellada, M. Bernardo, M. Sanjuán, J. Bobes, J. Arrojo, M. Santos, J.L. Cuadrado, P. Solano, J.J.R. Carracedo, A. Bernardo, E.G. Roldán, L. López, G. Cabrera, B. Cruz, S. Mesa, E.M.D. Pouso, M. Jiménez, E. Sánchez, T. Rapado, M. González, E. Martínez, C. Sánchez, E. Olmeda, M.S. De Haan, L. Velthorst, E. Van Der Gaag, M. Selten, J.-P. Van Dam, D. Van Der Ven, E. Van Der Meer, F. Messchaert, E. Kraan, T. Burger, N. Leboyer, M. Szoke, A. Schürhoff, F. Llorca, P.-M. Jamain, S. Tortelli, A. Frijda, F. Vilain, J. Galliot, A.-M. Baudin, G. Ferchiou, A. Richard, J.-R. Bulzacka, E. Charpeaud, T. Tronche, A.-M. De Hert, M. Van Winkel, R. Decoster, J. Derom, C. Thiery, E. Stefanis, N.C. Sachs, G. Aschauer, H. Lasser, I. Winklbaur, B. Schlögelhofer, M. Riecher-Rössler, A. Borgwardt, S. Walter, A. Harrisberger, F. Smieskova, R. Rapp, C. Ittig, S. Soguel-Dit-Piquard, F. Studerus, E. Klosterkötter, J. Ruhrmann, S. Paruch, J. Julkowski, D. Hilboll, D. Sham, P.C. Cherny, S.S. Chen, E.Y.H. Campbell, D.D. Li, M. Romeo-Casabona, C.M. Cirión, A.E. Mora, A.U. Jones, P. Kirkbride, J. Cannon, M. Rujescu, D. Tarricone, I. Berardi, D. Bonora, E. Seri, M. Marcacci, T. Chiri, L. Chierzi, F. Storbini, V. Braca, M. Minenna, M.G. Donegani, I. Fioritti, A. La Barbera, D. La Cascia, C.E. Mulè, A. Sideli, L. Sartorio, R. Ferraro, L. Tripoli, G. Seminerio, F. Marinaro, A.M. McGorry, P. Nelson, B. Amminger, G.P. Pantelis, C. Menezes, P.R. Del-Ben, C.M. Tenan, S.H.G. Shuhama, R. Ruggeri, M. Tosato, S. Lasalvia, A. Bonetto, C. Ira, E. Nordentoft, M. Krebs, M.-O. Barrantes-Vidal, N. Cristóbal, P. Kwapil, T.R. Brietzke, E. Bressan, R.A. Gadelha, A. Maric, N.P. Andric, S. Mihaljevic, M. Mirjanic, T.

Abstract

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. © 2014 The Author.

Published
2014

19. Cognitive functioning in prodromal psychosis: A meta-analysis

Author

Fusar-Poli, P, Deste, G, Smieskova, R, Barlati, S, Yung, Alison, Howes, O, Stieglitz, RD, Vita, A, McGuire, P, Borgwardt, S, Fusar-Poli, P, Deste, G, Smieskova, R, Barlati, S, Yung, Alison, Howes, O, Stieglitz, RD, Vita, A, McGuire, P, and Borgwardt, S

Published
2012

24. Vorhersage von Psychosen durch stufenweise Mehrebenenabklärung - Das Basler FePsy(Früherkennung von Psychosen)-Projekt

Author

Riecher-Rössler, A., additional, Aston, J., additional, Borgwardt, S., additional, Bugra, H., additional, Fuhr, P., additional, Gschwandtner, U., additional, Koutsouleris, N., additional, Pflueger, M., additional, Tamagni, C., additional, Radü, E.-W., additional, Rapp, C., additional, Smieskova, R., additional, Studerus, E., additional, Walter, A., additional, and Zimmermann, R., additional

Published
2013
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32. Neuroanatomical markers of genetic liability to psychosis and first episode psychosis: A voxelwise meta-analytical comparison.

Author

Fusar-Poli, P., Smieskova, R., Serafini, G., Politi, P., and Borgwardt, S.

Subjects
*META-analysis, *PSYCHOSES, *CEREBELLUM, *BRAIN anatomy, PSYCHIATRIC research
Abstract

Objectives. To address at a meta-analytical level the neuroanatomical markers of genetic liability to psychosis and a of first episode of psychosis. Methods. Fifteen voxel-based morphometry (VBM) studies of antipsychotic-naive subjects at genetic high-risk (HR) for psychosis or with a first-episode psychosis (FEP) were included in a Signed Differential Mapping (SDM) meta-analysis. Publication bias was assessed with funnel plots and Egger's intercept. Heterogeneity was assessed with Q statistics and I 2 index. Results. The database comprised 458 HR and 206 antipsychotic-naïve FEP subjects, matched with controls. Gray matter (GM) reductions as compared to controls, were observed in the left parahippocampal gyrus and in the bilateral anterior cingulate gyrus in the HR group, and in the right superior temporal gyrus, in the left insula and in the left cerebellum in the FEP group. Further GM decreases were observed in the FEP group as compared to the HR group in the left anterior cingulate, in the right precuneus, in the left cerebellum and in the right superior temporal gyrus. Limitations. The cross-sectional nature of the included studies prevented the comparison of high risk subjects who later did or did not develop a psychotic episode. Other caveats are based on the methodological heterogeneity across individual imaging studies. Conclusions. GM reductions in the anterior cingulate are markers of genetic liability to psychosis while reductions in the superior temporal gyrus and cerebellum can be interpreted as markers of a first onset of the illness. [ABSTRACT FROM AUTHOR]

Published
2014
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38. Insular volume abnormalities associated with different transition probabilities to psychosis

Author

Smieskova, R., Fusar-Poli, P., Aston, J., Simon, A., Bendfeldt, K., Lenz, C., Stieglitz, R.-D, McGuire, P., Riecher-Rössler, A., Borgwardt, S. J., Smieskova, R., Fusar-Poli, P., Aston, J., Simon, A., Bendfeldt, K., Lenz, C., Stieglitz, R.-D, McGuire, P., Riecher-Rössler, A., and Borgwardt, S. J.

Abstract

Background Although individuals vulnerable to psychosis show brain volumetric abnormalities, structural alterations underlying different probabilities for later transition are unknown. The present study addresses this issue by means of voxel-based morphometry (VBM). Method We investigated grey matter volume (GMV) abnormalities by comparing four neuroleptic-free groups: individuals with first episode of psychosis (FEP) and with at-risk mental state (ARMS), with either long-term (ARMS-LT) or short-term ARMS (ARMS-ST), compared to the healthy control (HC) group. Using three-dimensional (3D) magnetic resonance imaging (MRI), we examined 16 FEP, 31 ARMS, clinically followed up for on average 3 months (ARMS-ST, n=18) and 4.5 years (ARMS-LT, n=13), and 19 HC. Results The ARMS-ST group showed less GMV in the right and left insula compared to the ARMS-LT (Cohen's d 1.67) and FEP groups (Cohen's d 1.81) respectively. These GMV differences were correlated positively with global functioning in the whole ARMS group. Insular alterations were associated with negative symptomatology in the whole ARMS group, and also with hallucinations in the ARMS-ST and ARMS-LT subgroups. We found a significant effect of previous antipsychotic medication use on GMV abnormalities in the FEP group. Conclusions GMV abnormalities in subjects at high clinical risk for psychosis are associated with negative and positive psychotic symptoms, and global functioning. Alterations in the right insula are associated with a higher risk for transition to psychosis, and thus may be related to different transition probabilities

40. Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations

Author

Rosana Shuhama, Gonzalo López, Viviana Storbini, Tolga Binbay, Ma Soledad Olmeda, Maria Calem, Marina Mihaljevic, Christos Pantelis, Halis Ulaş, Eva Velthorst, Jeroen Decoster, J. Malte Bumb, Ruud van Winkel, E. Cem Atbasoglu, Wolfgang Viechtbauer, Mirella Ruggeri, Erich Studerus, Daniele La Barbera, Domenico Berardi, Anita Riecher-Rössler, Stefan Borgwardt, Elsje van der Ven, Charlotte Rapp, Desiree Hilboll, Mark van der Gaag, Chiara Bonetto, Marie-Odile Krebs, Silvia Tenan, Monika Schlögelhofer, Robin M. Murray, Caterina La Cascia, Philip McGuire, Simona A. Stilo, Desmond Campbell, Fabienne Harrisberger, Teresa Sánchez, Catherine Derom, Franck Schürhoff, Philippe Delespaul, Jose Luis Santos, Emilio Sánchez, Stephan Ruhrmann, Luigi Rocco Chiri, Sabrina Cruz, Handan Noyan, Dominika Julkowski, Celso Arango, Merete Nordentoft, Stacey S. Cherny, Anne-Marie Galliot, Daniella van Dam, María Pouso, Asier Urruela Mora, G. Paul Amminger, Enrique García Bernardo, Ahmet Ayer, Tijana Mirjanic, Andrei Szöke, Anna Walter, Antonio Lasalvia, Isla Humphreys, Flora Frijda, Lieuwe de Haan, Neus Barrantes-Vidal, Nigel Williams, Burçin Cihan, Matthew J. Kempton, Ceren Akdeniz, Tamar Kraan, Andrea Tortelli, Barnaby Nelson, Marta Di Forti, Angelo Fioritti, Pedro Cuadrado, Eylem Sahin Cankurtaran, Emanuel Schwarz, Andreas Meyer-Lindenberg, Ilaria Tarricone, Laura Ferraro, Dan Rujescu, Anne-Marie Tronche, Laura Roldan, Bibiana Cabrera, Alp Üçok, Craig Morgan, Julio Sanjuán, Mauro Braca, Julio Bobes, Eric Y.H. Chen, Michael Conlon O'Donovan, Peter Holmans, Harald N. Aschauer, Sarah Ittig, Covadonga Martínez, Iris Lasser, Emiliano González, Aitziber Emaldi Cirión, Rachele Sartorio, F. Seminerio, Rodrigo A. Bressan, Ulrich Reininghaus, Elisa Brietzke, François Bourque, G Tripoli, Inez Myin-Germeys, Aziz Ferchiou, Gemma Modinos, Grégoire Baudin, Fabienne Soguel-Dit-Piquard, Cristina Marta Del-Ben, Gabriele Sachs, Elçin Akturan, Manuel Arrojo, Thomas R. Kwapil, Alice Mulè, Eva Mª Díaz Mesa, Federico Chierzi, Köksal Alptekin, Floor J. van der Meer, Pak C. Sham, Jim van Os, Adanna Onyejiaka, Mara Parellada, Bart P. F. Rutten, Jeanne Vilain, Michael John Owen, Sarah Tosato, Haldan Soygür, A.M. Marinaro, Stefania Tognin, Evert Thiery, Cathrin Rohleder, Mary Cannon, Miaoxin Li, F. Markus Leweke, Marc De Hert, Marta Rapado, Maria Gabriella Minenna, Pierre-Michel Llorca, Alexander Richards, Stéphane Jamain, Elles Messchaert, Nadja P. Maric, Semra Ulusoy, Elisa Ira, Peter G. Jones, Paulo Rossi Menezes, Patrick D. McGorry, Bernadette Winklbaur, Stephanie Beards, Nadine Burger, Güvem Gümüş-Akay, Marion Leboyer, James B. Kirkbride, Sinan Guloksuz, Ary Gadelha, E. Bulzacka, Carlos M. Romeo-Casabona, Gülşah Karadayı, Jean-Paul Selten, José Juan Rodríguez Solano, Kathryn Hubbard, Estela Jiménez, Thomas Charpeaud, Nikos C. Stefanis, Lucia Sideli, Miguel Bernardo, Jean-Romain Richard, Ivonne Donegani, Marco Seri, Lucia Valmaggia, Julia Paruch, Catherine van Zelst, Meram Can Saka, Heike Tost, Renata Smieskova, Thomas Marcacci, Nicholas John Craddock, Berna Binnur Akdede, Joachim Klosterkötter, Richard Bruggeman, Charlotte Gayer-Anderson, Sanja Andric, Elena Bonora, Angel Carracedo, Hasan Karadağ, Paula Cristobal, ANS - Amsterdam Neuroscience, Adult Psychiatry, Graduate School, Perceptual and Cognitive Neuroscience (PCN), Maastricht Univ, Kings Coll London, Mondriaan Mental Hlth Trust, Univ Groningen, Cardiff Univ, Cent Inst Mental Hlth, Dokuz Eylul Univ, Istanbul Univ, Ankara Univ, Yale Univ, Middle E Tech Univ, Diskapi YB Res & Training Hosp, Turkish Federat Schizophrenia Assoc, Ataturk Training & Res Hosp, Manisa Mental Hlth Hosp, Univ Complutense, Univ Barcelona, Univ Valencia, Univ Oviedo, Univ Santiago de Compostela, Hosp Virgen de la Luz, Hosp Univ Infanta Leonor Hosp Virgen Torre, Hosp Clin Univ, Hosp Psiquiatr Conxo, Univ Amsterdam, Vrije Univ Amsterdam, EMGO Inst Hlth & Care Res, Parnassia Psychiat Inst, Rivierduinen Psychiat Inst, Grp Hosp Mondor, Hop Henri Mondor, Univ Paris Est, Fdn Fondamental, CMP B CHU, Univ Auvergne, EPS Maison Blanche, UPC KU Leuven, UPC, Katholieke Univ Leuven, Assoc Sci Res Multiple Births, Univ Ghent, Univ Athens, Med Univ Vienna, Psychiat Univ Clin Basel, Univ Cologne, Univ Hong Kong, Univ Basque Country, Univ Zaragoza, Univ Cambridge, UCL, Royal Coll Surgeons Ireland, Univ Munich, Univ Bologna, Local Hlth Trust, Univ Palermo, P Giaccone Gen Hosp, Univ Melbourne, Universidade de São Paulo (USP), Univ Verona, Copenhagen Univ Hosp, Univ Paris 05, Univ Autonoma Barcelona, St Pere Claver Fundacio Sanitaria, Univ N Carolina, CIBERSAM, Universidade Federal de São Paulo (UNIFESP), Univ Belgrade, van Os J, Rutten BP, Myin-Germeys I, Delespaul P, Viechtbauer W, van Zelst C, Bruggeman R, Reininghaus U, Morgan C, Murray RM, Di Forti M, McGuire P, Valmaggia LR, Kempton MJ, Gayer-Anderson C, Hubbard K, Beards S, Stilo SA, Onyejiaka A, Bourque F, Modinos G, Tognin S, Calem M, O'Donovan MC, Owen MJ, Holmans P, Williams N, Craddock N, Richards A, Humphreys I, Meyer-Lindenberg A, Leweke FM, Tost H, Akdeniz C, Rohleder C, Bumb JM, Schwarz E, Alptekin K, Üçok A, Saka MC, Atbaşoğlu EC, Gülöksüz S, Gumus-Akay G, Cihan B, Karadağ H, Soygür H, Cankurtaran EŞ, Ulusoy S, Akdede B, Binbay T, Ayer A, Noyan H, Karadayı G, Akturan E, Ulaş H, Arango C, Parellada M, Bernardo M, Sanjuán J, Bobes J, Arrojo M, Santos JL, Cuadrado P, Rodríguez Solano JJ, Carracedo A, García Bernardo E, Roldán L, López G, Cabrera B, Cruz S, Díaz Mesa EM, Pouso M, Jiménez E, Sánchez T, Rapado M, González E, Martínez C, Sánchez E, Olmeda MS, de Haan L, Velthorst E, van der Gaag M, Selten JP, van Dam D, van der Ven E, van der Meer F, Messchaert E, Kraan T, Burger N, Leboyer M, Szoke A, Schürhoff F, Llorca PM, Jamain S, Tortelli A, Frijda F, Vilain J, Galliot AM, Baudin G, Ferchiou A, Richard JR, Bulzacka E, Charpeaud T, Tronche AM, De Hert M, van Winkel R, Decoster J, Derom C, Thiery E, Stefanis NC, Sachs G, Aschauer H, Lasser I, Winklbaur B, Schlögelhofer M, Riecher-Rössler A, Borgwardt S, Walter A, Harrisberger F, Smieskova R, Rapp C, Ittig S, Soguel-dit-Piquard F, Studerus E, Klosterkötter J, Ruhrmann S, Paruch J, Julkowski D, Hilboll D, Sham PC, Cherny SS, Chen EY, Campbell DD, Li M, Romeo-Casabona CM, Emaldi Cirión A, Urruela Mora A, Jones P, Kirkbride J, Cannon M, Rujescu D, Tarricone I, Berardi D, Bonora E, Seri M, Marcacci T, Chiri L, Chierzi F, Storbini V, Braca M, Minenna MG, Donegani I, Fioritti A, La Barbera D, La Cascia CE, Mulè A, Sideli L, Sartorio R, Ferraro L, Tripoli G, Seminerio F, Marinaro AM, McGorry P, Nelson B, Amminger GP, Pantelis C, Menezes PR, Del-Ben CM, Gallo Tenan SH, Shuhama R, Ruggeri M, Tosato S, Lasalvia A, Bonetto C, Ira E, Nordentoft M, Krebs MO, Barrantes-Vidal N, Cristóbal P, Kwapil TR, Brietzke E, Bressan RA, Gadelha A, Maric NP, Andric S, Mihaljevic M, Mirjanic T, Clinical Psychology, EMGO+ - Mental Health, Van Os, J., Rutten, B., Myin Germeys, I., Delespaul, P., Viechtbauer, W., Van Zelst, C., Bruggeman, R., Reininghaus, U., Morgan, C., Murray, R., Di Forti, M., Mcguire, P., Valmaggia, L., Kempton, M., Gayer Anderson, C., Hubbard, K., Beards, S., Stilo, S., Onyejiaka, A., Bourque, F., Modinos, G., Tognin, S., Calem, M., O'Donovan, M., Owen, M., Holmans, P., Williams, N., Craddock, N., Richards, A., Humphreys, I., Meyer Lindenberg, A., Leweke, F., Tost, H., Akdeniz, C., Rohleder, C., Bumb, J., Schwarz, E., Alptekin, K., Üçok, A., Saka, M., Atbagoǧlu, E., Gülöksüz, S., Gumus Akay, G., Cihan, B., Karadaǧ, H., Soygür, H., Cankurtaran, E., Ulusoy, S., Akdede, B., Binbay, T., Ayer, A., Noyan, H., Karadayi, G., Akturan, E., Ulaş, H., Arango, C., Parellada, M., Bernardo, M., Sanjuán, J., Bobes, J., Arrojo, M., Santos, J., Cuadrado, P., Solano, J., Carracedo, A., Bernardo, E., Roldán, L., López, G., Cabrera, B., Cruz, S., Mesa, E., Pouso, M., Jiménez, E., Sánchez, T., Rapado, M., González, E., Martínez, C., Sánchez, E., Olmeda, M., De Haan, L., Velthorst, E., Van Der Gaag, M., Selten, J., Van Dam, D., Van Der Ven, E., Van Der Meer, F., Messchaert, E., Kraan, T., Burger, N., Leboyer, M., Szoke, A., Schürhoff, F., Llorca, P., Jamain, S., Tortelli, A., Frijda, F., Vilain, J., Galliot, A., Baudin, G., Ferchiou, A., Richard, J., Bulzacka, E., Charpeaud, T., Tronche, A., De Hert, M., Van Winkel, R., Decoster, J., Derom, C., Thiery, E., Stefanis, N., Sachs, G., Aschauer, H., Lasser, I., Winklbaur, B., Schlögelhofer, M., Riecher Rössler, A., Borgwardt, S., Walter, A., Harrisberger, F., Smieskova, R., Rapp, C., Ittig, S., Soguel Dit Piquard, F., Studerus, E., Klosterkötter, J., Ruhrmann, S., Paruch, J., Julkowski, D., Hilboll, D., Sham, P., Cherny, S., Chen, E., Campbell, D., Li, M., Romeo Casabona, C., Cirión, A., Mora, A., Jones, P., Kirkbride, J., Cannon, M., Rujescu, D., Tarricone, I., Berardi, D., Bonora, E., Seri, M., Marcacci, T., Chiri, L., Chierzi, F., Storbini, V., Braca, M., Minenna, M., Donegani, I., Fioritti, A., LA BARBERA, D., LA CASCIA, C., Mulè, A., Sideli, L., Sartorio, C., Ferraro, L., Tripoli, G., Seminerio, F., Marinaro, A., Mcgorry, P., Nelson, B., Amminger, G., Pantelis, C., Menezes, P., Del Ben, C., Tenan, S., Shuhama, R., Ruggeri, M., Tosato, S., Lasalvia, A., Bonetto, C., Ira, E., Nordentoft, M., Krebs, M., Barrantes Vidal, N., Cristóbal, P., Kwapil, T., Brietzke, E., Bressan, R., Gadelha, A., Maric, N., Andric, S., Mihaljevic, M., Mirjanic, T., Psychiatrie & Neuropsychologie, Promovendi MHN, and RS: MHeNs - R2 - Mental Health

Subjects
URBANICITY, Schizophrenia (object-oriented programming), CHILDHOOD, Genome-wide association study, VARIANTS, Social Environment, psychosi, 03 medical and health sciences, 0302 clinical medicine, PSYCHOSIS, epidemiology, gene-environment interaction, genetics, psychosis, schizophrenia, SDG 3 - Good Health and Well-being, RISK-FACTOR, Settore M-PSI/08 - Psicologia Clinica, Genetic variation, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Gene, Settore MED/25 - Psichiatria, METAANALYSIS, Scale (chemistry), Psychosis, Genetic variants, Environment and Schizophrenia Invited, CANNABIS USE, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, Evolutionary biology, Identification (biology), Schizophrenic Psychology, Population Risk, genetic, Psychology, FOLLOW-UP, 030217 neurology & neurosurgery, FUTURE-DIRECTIONS, Clinical psychology
Abstract

European Community Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G x E), however, so far, thorough replication of findings is rare and G x E research still faces several conceptual and methodological challenges. in this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G x E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G x E in schizophrenia. While such investigations are now well underway, new challenges emerge for G x E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype. Maastricht Univ, Med Ctr, Dept Psychiat & Neuropsychol, Sch Mental Hlth & Neurosci,South Limburg Mental H, NL-6200 MD Maastricht, Netherlands Kings Coll London, Inst Psychiat, Dept Psychosis Studies, London WC2R 2LS, England Mondriaan Mental Hlth Trust, Maastricht, Heerlen, Netherlands Univ Groningen, Univ Med Ctr Groningen, Rob Giel Clin Res, Univ Ctr Psychiat, Groningen, Netherlands Kings Coll London, Inst Psychiat, Dept Hlth Serv & Populat Res, London WC2R 2LS, England Kings Coll London, Inst Psychiat, Dept Psychol, London WC2R 2LS, England Cardiff Univ, MRC, Ctr Neuropsychiat Genet, Cardiff CF10 3AX, S Glam, Wales Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, Mannheim, Germany Dokuz Eylul Univ, Sch Med, Dept Psychiat, Konak, Turkey Istanbul Univ, Istanbul Fac Med, Dept Psychiat, Psychot Disorders Res Unit, Istanbul, Turkey Ankara Univ, Sch Med, Dept Psychiat, Cebeci Hosp, TR-06100 Ankara, Turkey Ankara Univ, Brain Res Ctr, TR-06100 Ankara, Turkey Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA Middle E Tech Univ, Dept Psychol, TR-06531 Ankara, Turkey Diskapi YB Res & Training Hosp, Ankara, Turkey Turkish Federat Schizophrenia Assoc, Ankara, Turkey Ataturk Training & Res Hosp, Psychiat Clin, Ankara, Turkey Manisa Mental Hlth Hosp, Manisa, Turkey Istanbul Univ, Expt Med Res Inst, Dept Adv Neurol Sci, Istanbul Fac Med, Istanbul, Turkey Univ Complutense, IiSGM CIBERSAM, Dept Child & Adolescent Psychiat, Hosp Gen Univ Gregorio Maranon,Sch Med, E-28040 Madrid, Spain Univ Barcelona, Dept Psychiat, Hosp Clin, IDIBAPS,Ctr Invest Biomed Red Salud Mental CIBERS, Barcelona, Spain Univ Valencia, Sch Med, Dept Psychiat, Ctr Invest Biomed Red Salud Mental CIBERSAM, Valencia, Spain Univ Oviedo, Sch Med, Dept Med,Psychiat Area, Ctr Invest Biomed Red Salud Mental CIBERSAM, Oviedo, Spain Univ Santiago de Compostela, Dept Mental Hlth & Drug Addit Assistance, Hlth Serv Galicia,Psychiat Genet Grp IDIS, Hosp Clin,Ctr Invest Biomedica Red Salud Mental C, Santiago de Compostela 15706, Spain Hosp Virgen de la Luz, Serv Psiquiat, Dept Psychiat, Cuenca, Spain Hosp Univ Infanta Leonor Hosp Virgen Torre, Villa de Vallecas Mental Hlth Ctr, Villa de Vallecas Mental Hlth Dept, Madrid, Spain Hosp Univ Infanta Leonor Hosp Virgen Torre, Puente de Vallecas Mental Hlth Dept, Ctr Salud Mental Puente Vallecas, Madrid, Spain Hosp Clin Univ, Fdn Publ Galega Med Xenomica, Santiago de Compostela, Spain Univ Complutense, Sch Med, Hosp Gen Univ Gregorio Maranon, Dept Psychiat, E-28040 Madrid, Spain Hosp Psiquiatr Conxo, Santiago de Compostela, Spain Univ Amsterdam, Acad Med Ctr, Early Psychosis Sect, Dept Psychiat, NL-1105 AZ Amsterdam, Netherlands Vrije Univ Amsterdam, Dept Clin Psychol, Amsterdam, Netherlands EMGO Inst Hlth & Care Res, Amsterdam, Netherlands Parnassia Psychiat Inst, Dept Psychosis Res, the Hague, Netherlands Rivierduinen Psychiat Inst, Leiden, Netherlands Grp Hosp Mondor, AP HP, Creteil, France Hop Henri Mondor, INSERM, U955, Equipe 15, F-94010 Creteil, France Univ Paris Est, Fac Med, Creteil, France Fdn Fondamental, Creteil, France CMP B CHU, F-63003 Clermont Ferrand 1, France Univ Auvergne, EA 7280, Clermont Ferrand, France EPS Maison Blanche, Paris, France UPC KU Leuven, Dept Neurosci, UPC, Kortenberg, Belgium UPC, Dept Neurosci, Res Grp Psychiat, Leuven, Belgium Katholieke Univ Leuven, Univ Hosp Gasthuisberg, Dept Human Genet, Leuven, Belgium Assoc Sci Res Multiple Births, Ghent, Belgium Univ Ghent, Dept Neurol, Ghent Univ Hosp, B-9000 Ghent, Belgium Univ Athens, Sch Med, Eginit Hosp, Athens 11528, Greece Med Univ Vienna, Dept Psychiat & Psychotherapy, Vienna, Austria Psychiat Univ Clin Basel, Ctr Gender Res & Early Detect, Basel, Switzerland Psychiat Univ Clin Basel, Diagnost & Crisis Intervent Ctr, Basel, Switzerland Univ Cologne, Dept Psychiat & Psychotherapy, D-50931 Cologne, Germany Univ Hong Kong, Li Ka Shing Fac Med, Ctr Genom Sci, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China Univ Hong Kong, Li Ka Shing Fac Med, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China Univ Hong Kong, Queen Mary Hosp, Li Ka Shing Fac Med, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China Univ Hong Kong, Queen Mary Hosp, Li Ka Shing Fac Med, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China Univ Basque Country, Univ Deusto, Interuniv Chair Law & Human Genome Prov Govt Bisk, Bilbao, Bizkaia, Spain Univ Zaragoza, Zaragoza, Spain Univ Cambridge, Dept Psychiat, Cambridge, England UCL, Div Psychiat, London, England Royal Coll Surgeons Ireland, Beaumont Hosp, Educ & Res Ctr, Dept Psychiat, Dublin 9, Ireland Univ Munich, Dept Psychiat, Div Mol & Clin Neurobiol, Munich, Germany Univ Bologna, Alma Mater Studiorium, Psychiat Unit, Dept Med & Surg Sci, Bologna, Italy Univ Bologna, Alma Mater Studiorium, Genet Unit, Dept Med & Surg Sci, Bologna, Italy Local Hlth Trust, Dept Mental Hlth & Pathol Addict, Bologna, Italy Univ Palermo, Sect Psychiat, Dept Expt Biomed & Clin Neurosci, Palermo, Italy P Giaccone Gen Hosp, Unit Psychiat, Palermo, Italy Univ Melbourne, Ctr Youth Mental Hlth, Parkville, Vic 3052, Australia Univ Melbourne, Melbourne Neuropsychiat Ctr, Carlton, Vic, Australia Univ São Paulo, Fac Med, Dept Med Prevent, BR-01246903 São Paulo, Brazil Univ São Paulo, Nucleo Pesquina Saude Mental Populac, São Paulo, Brazil Univ São Paulo, Fac Med Ribeirao Preto, Dept Neurociencias & Ciencias Comportamento, BR-14049 Ribeirao Preto, Brazil Univ Verona, Sect Psychiat, Dept Publ Hlth & Community Med, I-37100 Verona, Italy Copenhagen Univ Hosp, Res Unit, Mental Hlth Ctr Copenhagen, Copenhagen, Denmark Univ Paris 05, Fac Med, Serv Hosp Univ, Hop St Anne, Paris, France Univ Autonoma Barcelona, Dept Psicol Clin & Salut, E-08193 Barcelona, Spain St Pere Claver Fundacio Sanitaria, Dept Salut Mental, Barcelona, Spain Univ N Carolina, Dept Psychol, Greensboro, NC 27412 USA CIBERSAM, Spanish Mental Hlth Res Network, Barcelona, Spain Universidade Federal de São Paulo, Dept Psychiat, PRISMA Early Intervent Program, São Paulo, Brazil Univ Belgrade, Sch Med, Beograd, Serbia Universidade Federal de São Paulo, Dept Psychiat, PRISMA Early Intervent Program, São Paulo, Brazil European Community: HEALTH-F2-2009-241909 Web of Science

Published
2014
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41. Individualized prediction of psychosis in subjects with an at-risk mental state.

Author

Zarogianni E, Storkey AJ, Borgwardt S, Smieskova R, Studerus E, Riecher-Rössler A, and Lawrie SM

Subjects
Adult, Early Diagnosis, Family, Female, Genetic Predisposition to Disease, Humans, Male, Pattern Recognition, Automated methods, Proof of Concept Study, Prospective Studies, Psychotic Disorders drug therapy, Psychotic Disorders genetics, Risk, Young Adult, Brain diagnostic imaging, Image Interpretation, Computer-Assisted methods, Magnetic Resonance Imaging methods, Psychotic Disorders diagnostic imaging, Support Vector Machine
Abstract

Early intervention strategies in psychosis would significantly benefit from the identification of reliable prognostic biomarkers. Pattern classification methods have shown the feasibility of an early diagnosis of psychosis onset both in clinical and familial high-risk populations. Here we were interested in replicating our previous classification findings using an independent cohort at clinical high risk for psychosis, drawn from the prospective FePsy (Fruherkennung von Psychosen) study. The same neuroanatomical-based pattern classification pipeline, consisting of a linear Support Vector Machine (SVM) and a Recursive Feature Selection (RFE) achieved 74% accuracy in predicting later onset of psychosis. The discriminative neuroanatomical pattern underlying this finding consisted of many brain areas across all four lobes and the cerebellum. These results provide proof-of-concept that the early diagnosis of psychosis is feasible using neuroanatomical-based pattern recognition., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Published
2019
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42. No associations between medial temporal lobe volumes and verbal learning/memory in emerging psychosis.

Author

Egloff L, Lenz C, Studerus E, Heitz U, Harrisberger F, Smieskova R, Schmidt A, Leanza L, Andreou C, Borgwardt S, and Riecher-Rössler A

Subjects
Adult, Cognition physiology, Female, Humans, Magnetic Resonance Imaging, Male, Organ Size physiology, Prospective Studies, Young Adult, Memory physiology, Psychotic Disorders diagnostic imaging, Psychotic Disorders psychology, Temporal Lobe diagnostic imaging, Verbal Learning physiology
Abstract

Grey matter (GM) volume alterations have been repeatedly demonstrated in patients with first episode psychosis (FEP). Some of these neuroanatomical abnormalities are already evident in the at-risk mental state (ARMS) for psychosis. Not only GM alterations but also neurocognitive impairments predate the onset of frank psychosis with verbal learning and memory (VLM) being among the most impaired domains. Yet, their interconnection with alterations in GM volumes remains ambiguous. Thus, we evaluated associations of different subcortical GM volumes in the medial temporal lobe with VLM performance in antipsychotic-naïve ARMS and FEP patients. Data from 59 ARMS and 31 FEP patients, collected within the prospective Früherkennung von Psychosen study, were analysed. Structural T1-weighted images were acquired using a 3 Tesla magnetic resonance imaging scanner. VLM was assessed using the California Verbal Learning Test and its factors Attention Span, Learning Efficiency, Delayed Memory and Inaccurate Memory. FEP patients showed significantly enlarged volumes of hippocampus, pallidum, putamen and thalamus compared to ARMS patients. A significant negative association between amygdala and pallidum volume and Attention Span was found in ARMS and FEP patients combined, which however did not withstand correction for multiple testing. Although we found significant between-group differences in subcortical volumes and VLM is among the most impaired cognitive domains in emerging psychosis, we could not demonstrate an association between low performance and subcortical GM volumes alterations in antipsychotic-naïve patients. Hence, deficits in this domain do not appear to stem from alterations in subcortical structures., (© 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Published
2019
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43. Association of antidepressants with brain morphology in early stages of psychosis: an imaging genomics approach.

Author

Bykowsky O, Harrisberger F, Schmidt A, Smieskova R, Hauke DJ, Egloff L, Riecher-Rössler A, Fusar-Poli P, Huber CG, Lang UE, Andreou C, and Borgwardt S

Subjects
Adult, Cerebral Cortex diagnostic imaging, Cerebral Cortex pathology, Female, Humans, Linear Models, Male, Schizophrenia drug therapy, Antidepressive Agents therapeutic use, Brain diagnostic imaging, Brain pathology, Genomics, Psychotic Disorders drug therapy, Psychotic Disorders genetics
Abstract

Depressive symptoms in subjects at Clinical High Risk for Psychosis (CHR-P) or at first-episode psychosis (FEP) are often treated with antidepressants. Our cross-sectional study investigated whether brain morphology is altered by antidepressant medication. High-resolution T 1 -weighted structural MRI scans of 33 CHR-P and FEP subjects treated with antidepressants, 102 CHR-P and FEP individuals without antidepressant treatment and 55 controls, were automatically segmented using Freesurfer 6.0. Linear mixed-effects modelling was applied to assess the differences in subcortical volume, surface area and cortical thickness in treated, non-treated and healthy subjects, taking into account converted dosages of antidepressants. Increasing antidepressant dose was associated with larger volume of the pallidum and the putamen, and larger surface of the left inferior temporal gyrus. In a pilot subsample of separately studied subjects of known genomic risk loci, we found that in the right postcentral gyrus, the left paracentral lobule and the precentral gyrus antidepressant dose-associated surface increase depended on polygenic schizophrenia-related-risk score. As the reported regions are linked to the symptoms of psychosis, our findings reflect the possible beneficial effects of antidepressant treatment on an emerging psychosis.

Published
2019
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44. Gender differences of patients at-risk for psychosis regarding symptomatology, drug use, comorbidity and functioning - Results from the EU-GEI study.

Author

Menghini-Müller S, Studerus E, Ittig S, Heitz U, Egloff L, Andreou C, Valmaggia LR, Kempton MJ, van der Gaag M, de Haan L, Nelson B, Barrantes-Vidal N, Nordentoft M, Ruhrmann S, Sachs G, Rutten BP, Os JV, Riecher-Rössler A, McGuire P, Valmaggia LR, Kempton MJ, Calem M, Tognin S, Modinos G, de Haan L, van der Gaag M, Velthorst E, Kraan TC, van Dam DS, Burger N, Nelson B, McGorry P, Amminger GP, Pantelis C, Politis A, Goodall J, Riecher-Rössler A, Borgwardt S, Rapp C, Ittig S, Studerus E, Smieskova R, Bressan R, Gadelha A, Brietzke E, Asevedo G, Asevedo E, Zugman A, Barrantes-Vidal N, Domínguez-Martínez T, Racioppi A, Cristóbal-Narváez P, Kwapil TR, Monsonet M, Kazes M, Daban C, Bourgin J, Gay O, Mam-Lam-Fook C, Krebs MO, Nordholm D, Randers L, Krakauer K, Glenthøj L, Glenthøj B, Nordentoft M, Ruhrmann S, Gebhard D, Arnhold J, Klosterkötter J, Sachs G, Lasser I, Winklbaur B, Delespaul PA, Rutten BP, and van Os J

Subjects
Adolescent, Adult, Anxiety Disorders epidemiology, Comorbidity, Europe epidemiology, Female, Humans, Male, Psychotic Disorders psychology, Schizophrenia diagnosis, Sex Distribution, Sex Factors, Substance-Related Disorders epidemiology, Young Adult, Early Diagnosis, Psychotic Disorders epidemiology, Schizophrenia epidemiology
Abstract

Background: Gender differences in symptomatology in chronic schizophrenia and first episode psychosis patients have often been reported. However, little is known about gender differences in those at risk of psychotic disorders. This study investigated gender differences in symptomatology, drug use, comorbidity (i.e. substance use, affective and anxiety disorders) and global functioning in patients with an at-risk mental state (ARMS) for psychosis., Methods: The sample consisted of 336 ARMS patients (159 women) from the prodromal work package of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI; 11 centers). Clinical symptoms, drug use, comorbidity and functioning were assessed at first presentation to an early detection center using structured interviews., Results: In unadjusted analyses, men were found to have significantly higher rates of negative symptoms and current cannabis use while women showed higher rates of general psychopathology and more often displayed comorbid affective and anxiety disorders. No gender differences were found for global functioning. The results generally did not change when corrected for possible cofounders (e.g. cannabis use). However, most differences did not withstand correction for multiple testing., Conclusions: Findings indicate that gender differences in symptomatology and comorbidity in ARMS are similar to those seen in overt psychosis and in healthy controls. However, observed differences are small and would only be reliably detected in studies with high statistical power. Moreover, such small effects would likely not be clinically meaningful., (Copyright © 2019. Published by Elsevier Masson SAS.)

Published
2019
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45. 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 TGM, Walton E, Hibar DP, Schmaal L, Jiang W, Glahn DC, Pearlson GD, Yao N, Fukunaga M, Hashimoto R, Okada N, Yamamori H, Clark VP, Mueller BA, de Zwarte SMC, Ophoff RA, van Haren NEM, Andreassen OA, Gurholt TP, Gruber O, Kraemer B, Richter A, Calhoun VD, Crespo-Facorro B, Roiz-Santiañez R, Tordesillas-Gutiérrez D, Loughland C, Catts S, Fullerton JM, Green MJ, Henskens F, Jablensky A, Mowry BJ, Pantelis C, Quidé Y, Schall U, Scott RJ, Cairns MJ, Seal M, Tooney PA, Rasser PE, Cooper G, Shannon Weickert C, Weickert TW, Hong E, Kochunov P, Gur RE, Gur RC, Ford JM, Macciardi F, Mathalon DH, Potkin SG, Preda A, Fan F, Ehrlich S, King MD, De Haan L, Veltman DJ, Assogna F, Banaj N, de Rossi P, Iorio M, Piras F, Spalletta G, Pomarol-Clotet E, Kelly S, Ciufolini S, Radua J, Murray R, Marques TR, Simmons A, Borgwardt S, Schönborn-Harrisberger F, Riecher-Rössler A, Smieskova R, Alpert KI, Bertolino A, Bonvino A, Di Giorgio A, Neilson E, Mayer AR, Yun JY, Cannon DM, Lebedeva I, Tomyshev AS, Akhadov T, Kaleda V, Fatouros-Bergman H, Flyckt L, Rosa PGP, Serpa MH, Zanetti MV, Hoschl C, Skoch A, Spaniel F, Tomecek D, McIntosh AM, Whalley HC, Knöchel C, Oertel-Knöchel V, Howells FM, Stein DJ, Temmingh HS, Uhlmann A, Lopez-Jaramillo C, Dima D, Faskowitz JI, Gutman BA, Jahanshad N, Thompson PM, and Turner JA

Subjects
Brain, Humans, Magnetic Resonance Imaging, Brain Diseases, Schizophrenia
Published
2019
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46. Voxel-Based Morphometry Correlates of an Agitated-Aggressive Syndrome in the At-Risk Mental State for Psychosis and First Episode Psychosis.

Author

Huber CG, Widmayer S, Smieskova R, Egloff L, Riecher-Rössler A, Stieglitz RD, and Borgwardt S

Subjects
Adult, Case-Control Studies, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging methods, Male, Neuroimaging, Prodromal Symptoms, Psychiatric Status Rating Scales, Psychomotor Agitation psychology, Psychotic Disorders psychology, Young Adult, Aggression psychology, Gray Matter diagnostic imaging, Occipital Lobe diagnostic imaging, Psychomotor Agitation diagnostic imaging, Psychotic Disorders diagnostic imaging
Abstract

There are mixed reports on structural neuroimaging correlates of aggression in schizophrenia with weak evidence due to cohort overlaps and lack of replications. To our knowledge, no study examined volumetric neuroimaging correlates of aggression in early stages of psychosis. An agitated-aggressive syndrome is present in at-risk mental state (ARMS) and in first-episode psychosis (FEP) - it is unclear whether this syndrome is associated with structural brain abnormalities in early stages of psychosis. Using three-dimensional magnetic resonance imaging and a whole brain voxel-based morphometry approach, we examined 56 ARMS patients, 55 FEP patients and 25 healthy controls. We operationalized aggression using the Excited Component of the Brief Psychiatric Rating Scale (BPRS-EC) and dichotomized our patient group by median split into "BPRS-EC high" (n = 49) and "BPRS-EC low" groups (n = 62). The "BPRS-EC high" group had significantly smaller left lingual gyrus volume than HC. This finding was not present in the "BPRS-EC low" group. In addition, grey matter volume in the left lingual gyrus showed a negative linear correlation with BPRS-EC over all subjects (ρ = -0.318; p = 0.0001) and in the patient group (ρ = -0.202; p = 0.033). These findings provide first hints on structural brain abnormalities associated with an agitated-aggressive syndrome in ARMS and FEP patients.

Published
2018
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47. 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 TGM, Walton E, Hibar DP, Schmaal L, Jiang W, Glahn DC, Pearlson GD, Yao N, Fukunaga M, Hashimoto R, Okada N, Yamamori H, Bustillo JR, Clark VP, Agartz I, Mueller BA, Cahn W, de Zwarte SMC, Hulshoff Pol HE, Kahn RS, Ophoff RA, van Haren NEM, Andreassen OA, Dale AM, Doan NT, Gurholt TP, Hartberg CB, Haukvik UK, Jørgensen KN, Lagerberg TV, Melle I, Westlye LT, Gruber O, Kraemer B, Richter A, Zilles D, Calhoun VD, Crespo-Facorro B, Roiz-Santiañez R, Tordesillas-Gutiérrez D, Loughland C, Carr VJ, Catts S, Cropley VL, Fullerton JM, Green MJ, Henskens FA, Jablensky A, Lenroot RK, Mowry BJ, Michie PT, Pantelis C, Quidé Y, Schall U, Scott RJ, Cairns MJ, Seal M, Tooney PA, Rasser PE, Cooper G, Shannon Weickert C, Weickert TW, Morris DW, Hong E, Kochunov P, Beard LM, Gur RE, Gur RC, Satterthwaite TD, Wolf DH, Belger A, Brown GG, Ford JM, Macciardi F, Mathalon DH, O'Leary DS, Potkin SG, Preda A, Voyvodic J, Lim KO, McEwen S, Yang F, Tan Y, Tan S, Wang Z, Fan F, Chen J, Xiang H, Tang S, Guo H, Wan P, Wei D, Bockholt HJ, Ehrlich S, Wolthusen RPF, King MD, Shoemaker JM, Sponheim SR, De Haan L, Koenders L, Machielsen MW, van Amelsvoort T, Veltman DJ, Assogna F, Banaj N, de Rossi P, Iorio M, Piras F, Spalletta G, McKenna PJ, Pomarol-Clotet E, Salvador R, Corvin A, Donohoe G, Kelly S, Whelan CD, Dickie EW, Rotenberg D, Voineskos AN, Ciufolini S, Radua J, Dazzan P, Murray R, Reis Marques T, Simmons A, Borgwardt S, Egloff L, Harrisberger F, Riecher-Rössler A, Smieskova R, Alpert KI, Wang L, Jönsson EG, Koops S, Sommer IEC, Bertolino A, Bonvino A, Di Giorgio A, Neilson E, Mayer AR, Stephen JM, Kwon JS, Yun JY, Cannon DM, McDonald C, Lebedeva I, Tomyshev AS, Akhadov T, Kaleda V, Fatouros-Bergman H, Flyckt L, Busatto GF, Rosa PGP, Serpa MH, Zanetti MV, Hoschl C, Skoch A, Spaniel F, Tomecek D, Hagenaars SP, McIntosh AM, Whalley HC, Lawrie SM, Knöchel C, Oertel-Knöchel V, Stäblein M, Howells FM, Stein DJ, Temmingh HS, Uhlmann A, Lopez-Jaramillo C, Dima D, McMahon A, Faskowitz JI, Gutman BA, Jahanshad N, Thompson PM, and Turner JA

Subjects
Adolescent, Adult, Age of Onset, Aged, Brain diagnostic imaging, Case-Control Studies, Child, Female, Frontal Lobe diagnostic imaging, Frontal Lobe pathology, Humans, Linear Models, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Prefrontal Cortex diagnostic imaging, Prefrontal Cortex pathology, Severity of Illness Index, Temporal Lobe diagnostic imaging, Temporal Lobe pathology, Young Adult, Brain pathology, Schizophrenia diagnostic imaging, Schizophrenia pathology
Abstract

Background: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group., Methods: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide., Results: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset., Conclusions: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Published
2018
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48. Sexually dimorphic subcortical brain volumes in emerging psychosis.

Author

Egloff L, Lenz C, Studerus E, Harrisberger F, Smieskova R, Schmidt A, Huber C, Simon A, Lang UE, Riecher-Rössler A, and Borgwardt S

Subjects
Adult, Brain pathology, Female, Humans, Male, Organ Size, Psychotic Disorders pathology, Brain diagnostic imaging, Magnetic Resonance Imaging, Psychotic Disorders diagnostic imaging, Sex Characteristics
Abstract

Background: In schizophrenic psychoses, the normal sexual dimorphism of the brain has been shown to be disrupted or even reversed. Little is known, however, at what time point in emerging psychosis this occurs. We have therefore examined, if these alterations are already present in the at-risk mental state (ARMS) for psychosis and in first episode psychosis (FEP) patients., Methods: Data from 65 ARMS (48 (73.8%) male; age=25.1±6.32) and 50 FEP (37 (74%) male; age=27±6.56) patients were compared to those of 70 healthy controls (HC; 27 (38.6%) male; age=26±4.97). Structural T1-weighted images were acquired using a 3 Tesla magnetic resonance imaging (MRI) scanner. Linear mixed effects models were used to investigate whether subcortical brain volumes are dependent on sex., Results: We found men to have larger total brain volumes (p<0.001), and smaller bilateral caudate (p=0.008) and hippocampus volume (p<0.001) than women across all three groups. Older subjects had more GM and WM volume than younger subjects. No significant sex×group interaction was found., Conclusions: In emerging psychosis there still seem to exist patterns of normal sexual dimorphism in total brain and caudate volume. The only structure affected by reversed sexual dimorphism was the hippocampus, with women showing larger volumes than men even in HC. Thus, we conclude that subcortical volumes may not be primarily affected by disrupted sexual dimorphism in emerging psychosis., (Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2018
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49. Impact on the Onset of Psychosis of a Polygenic Schizophrenia-Related Risk Score and Changes in White Matter Volume.

Author

Harrisberger F, Smieskova R, Egli T, Simon AE, Riecher-Rössler A, Fusar-Poli P, Papassotiropoulos A, and Borgwardt S

Subjects
Adult, Female, Genetic Predisposition to Disease, Genotype, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Odds Ratio, Polymorphism, Single Nucleotide, Psychotic Disorders diagnosis, Psychotic Disorders epidemiology, Psychotic Disorders genetics, Risk Factors, Schizophrenia diagnosis, Schizophrenia epidemiology, Schizophrenia genetics, Young Adult, Brain pathology, Psychotic Disorders pathology, Schizophrenia pathology, White Matter pathology
Abstract

Background: Reductions in the volume of brain white matter are a common feature in schizophrenia and bipolar disorder while the association between white matter and polygenic schizophrenia-related risk is unclear. To look at the intermediate state between health and the full-blown disorder, we investigated this aspect in groups of patients before and after the onset of psychosis., Methods: On a 3 Tesla scanner, total and regional white matter volumes were investigated by structural magnetic resonance imaging (MRI) in the following groups: 37 at-risk mental state patients (ARMS), including 30 with no transition to psychosis (ARMS-NT) and 7 with a transition to psychosis (ARMS-T) pooled with 25 first episode psychosis (FEP) patients. These T1-weighted images were automatically processed with the FreeSurfer software and compared with an odds-ratio-weighted polygenic schizophrenia-related risk score (PSRS) based on the publicly available top white matter single-nucleotide polymorphisms., Results: We found no association, only a trend, between PSRS and white matter volume over all groups (β = 0.24, p = 0.07, 95% confidence interval = [-0.02 - 0.49]). However, a higher PSRS was significantly associated with a higher probability of being assigned to the ARMS-T + FEP group rather than to the ARMS-NT group (β = 0.70, p = 0.02, 95% confidence interval = [0.14 - 1.33]); there was no such association with white matter volume. Additionally, a positive association was found between PSRS and the Brief Psychiatric Rating Scale (BPRS) total score for the pooled ARMS-NT/ARMS-T+FEP sample and for the ARMS-T + FEP group also, but none for the ARMS-NT group only., Conclusion: These findings suggest that at-risk mental state patients with a transition and first-episode psychosis patients have a higher genetic risk for schizophrenia than at-risk mental state patients with no transition to psychosis; this risk was associated with psychopathological symptoms. Further analyses may allow polygenic schizophrenia-related risk scores to be used as biomarkers to predict psychosis., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Published
2018
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50. Age-related brain structural alterations as an intermediate phenotype of psychosis.

Author

Dukart J, Smieskova R, Harrisberger F, Lenz C, Schmidt A, Walter A, Huber C, Riecher-Rössler A, Simon A, Lang UE, Fusar-Poli P, and Borgwardt S

Subjects
Adolescent, Adult, Aging pathology, Brain pathology, Cohort Studies, Cross-Sectional Studies, Female, Gray Matter diagnostic imaging, Gray Matter pathology, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Organ Size, Phenotype, Psychotic Disorders pathology, Risk, Young Adult, Brain diagnostic imaging, Psychotic Disorders diagnostic imaging
Abstract

Background: There is only limited agreement with respect to location, directionality and functional implications of brain structural alterations observed in patients with schizophrenia. Additionally, their link to occurrence of psychotic symptoms remains unclear. A viable way of addressing these questions is to examine populations in an at-risk mental state (ARMS) before the transition to psychosis., Methods: We tested for structural brain alterations in individuals in an ARMS compared with healthy controls and patients with first-episode psychosis (FEP) using voxel-based morphometry and measures of cortical thickness. Furthermore, we evaluated if these alterations were modified by age and whether they were linked to the observed clinical symptoms., Results: Our sample included 59 individuals with ARMS, 26 healthy controls and 59 patients with FEP. We found increased grey matter volume and cortical thickness in individuals with ARMS and a similar pattern of structural alterations in patients with FEP. We further found stronger age-related reductions in grey matter volume and cortical thickness in both patients with FEP and individuals with ARMS, linking these alterations to observed clinical symptoms., Limitations: The ARMS group comprised subgroups with heterogeneous levels of psychosis risk and medication status. Furthermore, the cross-sectional nature of our study and the reduced number of older patients limit conclusions with respect to observed interactions with age., Conclusion: Our findings on consistent structural alterations in individuals with ARMS and patients with FEP and their link to clinical symptoms have major implications for understanding their time of occurrence and relevance to psychotic symptoms. Interactions with age found for these alterations may explain the heterogeneity of findings reported in the literature.

Published
2017
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