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1. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group

Author: Kelly, S, Jahanshad, N, Zalesky, A, Kochunov, P, Agartz, I, Alloza, C, Andreassen, OA, Arango, C, Banaj, N, Bouix, S, Bousman, CA, Brouwer, RM, Bruggemann, J, Bustillo, J, Cahn, W, Calhoun, V, Cannon, D, Carr, V, Catts, S, Chen, J, Chen, J-X, Chen, X, Chiapponi, C, Cho, Kl K, Ciullo, V, Corvin, AS, Crespo-Facorro, B, Cropley, V, De Rossi, P, Diaz-Caneja, CM, Dickie, EW, Ehrlich, S, Fan, F-M, Faskowitz, J, Fatouros-Bergman, H, Flyckt, L, Ford, JM, Fouche, J-P, Fukunaga, M, Gill, M, Glahn, DC, Gollub, R, Goudzwaard, ED, Guo, H, Gur, RE, Gur, RC, Gurholt, TP, Hashimoto, R, Hatton, SN, Henskens, FA, Hibar, DP, Hickie, IB, Hong, LE, Horacek, J, Howells, FM, Hulshoff Pol, HE, Hyde, CL, Isaev, D, Jablensky, A, Jansen, PR, Janssen, J, Jönsson, EG, Jung, LA, Kahn, RS, Kikinis, Z, Liu, K, Klauser, P, Knöchel, C, Kubicki, M, Lagopoulos, J, Langen, C, Lawrie, S, Lenroot, RK, Lim, KO, Lopez-Jaramillo, C, Lyall, A, Magnotta, V, Mandl, RCW, Mathalon, DH, McCarley, RW, McCarthy-Jones, S, McDonald, C, McEwen, S, McIntosh, A, Melicher, T, Mesholam-Gately, RI, Michie, PT, Mowry, B, Mueller, BA, Newell, DT, O'Donnell, P, Oertel-Knöchel, V, Oestreich, L, Paciga, SA, Pantelis, C, Pasternak, O, Pearlson, G, Pellicano, GR, Pereira, A, and Pineda Zapata, J
Subjects: Neurosciences, Brain Disorders, Mental Health, Serious Mental Illness, Biomedical Imaging, Schizophrenia, Clinical Research, Mental health, Adult, Aged, Aged, 80 and over, Brain, Cohort Studies, Corpus Callosum, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, White Matter, Young Adult, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.
Published: 2018

2. Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium.

Author: Walton, E, Hibar, DP, van Erp, TGM, Potkin, SG, Roiz-Santiañez, R, Crespo-Facorro, B, Suarez-Pinilla, P, van Haren, NEM, de Zwarte, SMC, Kahn, RS, Cahn, W, Doan, NT, Jørgensen, KN, Gurholt, TP, Agartz, I, Andreassen, OA, Westlye, LT, Melle, I, Berg, AO, Morch-Johnsen, L, Færden, A, Flyckt, L, Fatouros-Bergman, H, Karolinska Schizophrenia Project Consortium (KaSP), Jönsson, EG, Hashimoto, R, Yamamori, H, Fukunaga, M, Jahanshad, N, De Rossi, P, Piras, F, Banaj, N, Spalletta, G, Gur, RE, Gur, RC, Wolf, DH, Satterthwaite, TD, Beard, LM, Sommer, IE, Koops, S, Gruber, O, Richter, A, Krämer, B, Kelly, S, Donohoe, G, McDonald, C, Cannon, DM, Corvin, A, Gill, M, Di Giorgio, A, Bertolino, A, Lawrie, S, Nickson, T, Whalley, HC, Neilson, E, Calhoun, VD, Thompson, PM, Turner, JA, and Ehrlich, S
Subjects: Karolinska Schizophrenia Project Consortium, Prefrontal Cortex, Humans, Magnetic Resonance Imaging, Linear Models, Schizophrenia, Psychiatric Status Rating Scales, Schizophrenic Psychology, Internationality, Image Processing, Computer-Assisted, Adult, Female, Male, Functional Laterality, Cortical thickness, ENIGMA, FreeSurfer, MRI, PANSS, SANS, medial orbitofrontal cortex, negative symptoms, schizophrenia, Image Processing, Computer-Assisted, Psychiatry, Psychology, Public Health and Health Services, Neurosciences
Abstract: BackgroundOur understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.MethodsThis study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).ResultsMeta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.ConclusionsUsing an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
Published: 2018

3. Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium

Author: Walton, E, Hibar, DP, Erp, TGM, Potkin, SG, Roiz‐Santiañez, R, Crespo‐Facorro, B, Suarez‐Pinilla, P, Van Haren, NEM, Zwarte, SMC, Kahn, RS, Cahn, W, Doan, NT, Jørgensen, KN, Gurholt, TP, Agartz, I, Andreassen, OA, Westlye, LT, Melle, I, Berg, AO, Mørch‐Johnsen, L, Færden, A, Flyckt, L, Fatouros‐Bergman, H, Consortium, Karolinska Schizophrenia Project, Jönsson, EG, Hashimoto, R, Yamamori, H, Fukunaga, M, Preda, A, De Rossi, P, Piras, F, Banaj, N, Ciullo, V, Spalletta, G, Gur, RE, Gur, RC, Wolf, DH, Satterthwaite, TD, Beard, LM, Sommer, IE, Koops, S, Gruber, O, Richter, A, Krämer, B, Kelly, S, Donohoe, G, McDonald, C, Cannon, DM, Corvin, A, Gill, M, Di Giorgio, A, Bertolino, A, Lawrie, S, Nickson, T, Whalley, HC, Neilson, E, Calhoun, VD, Thompson, PM, Turner, JA, and Ehrlich, S
Subjects: Schizophrenia, Mental Health, Brain Disorders, Mental health, Good Health and Well Being, Adult, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Male, Prospective Studies, Psychiatric Status Rating Scales, Schizophrenic Psychology, Temporal Lobe, schizophrenia, positive symptoms, superior temporal gyrus, cortical thickness, ENIGMA, FreeSurfer, MRI, scale for the assessment of positive symptoms, positive and negative syndrome scale, Karolinska Schizophrenia Project Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: ObjectiveBased on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia.MethodThis prospective meta-analysis includes data from 1987 individuals with schizophrenia collected at seventeen centres around the world that contribute to the ENIGMA Schizophrenia Working Group. STG thickness measures were extracted from T1-weighted brain scans using FreeSurfer. The study performed a meta-analysis of effect sizes across sites generated by a model predicting left or right STG thickness with a positive symptom severity score (harmonized SAPS or PANSS-positive scores), while controlling for age, sex and site. Secondary models investigated relationships between antipsychotic medication, duration of illness, overall illness severity, handedness and STG thickness.ResultsPositive symptom severity was negatively related to STG thickness in both hemispheres (left: βstd = -0.052; P = 0.021; right: βstd = -0.073; P = 0.001) when statistically controlling for age, sex and site. This effect remained stable in models including duration of illness, antipsychotic medication or handedness.ConclusionOur findings further underline the important role of the STG in hallmark symptoms in schizophrenia. These findings can assist in advancing insight into symptom-relevant pathophysiological mechanisms in schizophrenia.
Published: 2017

4. Brain Age Prediction Reveals Aberrant Brain White Matter in Schizophrenia and Bipolar Disorder: A Multisample Diffusion Tensor Imaging Study

Author: Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I., Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Sellgren, C., Tønnesen, Siren, Kaufmann, Tobias, de Lange, Ann-Marie G., Richard, Geneviève, Doan, Nhat Trung, Alnæs, Dag, van der Meer, Dennis, Rokicki, Jaroslav, Moberget, Torgeir, Maximov, Ivan I., Agartz, Ingrid, Aminoff, Sofie R., Beck, Dani, Barch, Deanna M., Beresniewicz, Justyna, Cervenka, Simon, Fatouros-Bergman, Helena, Craven, Alexander R., Flyckt, Lena, Gurholt, Tiril P., Haukvik, Unn K., Hugdahl, Kenneth, Johnsen, Erik, Jönsson, Erik G., Kolskår, Knut K., Kroken, Rune Andreas, Lagerberg, Trine V., Løberg, Else-Marie, Nordvik, Jan Egil, Sanders, Anne-Marthe, Ulrichsen, Kristine, Andreassen, Ole A., and Westlye, Lars T.
Published: 2020
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5. Lower levels of the glial cell marker TSPO in drug-naive first-episode psychosis patients as measured using PET and [11C]PBR28

Author: Collste, K, Plavén-Sigray, P, Fatouros-Bergman, H, Victorsson, P, Schain, M, Forsberg, A, Amini, N, Aeinehband, S, Erhardt, S, Halldin, C, Flyckt, L, Farde, L, and Cervenka, S
Published: 2017
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6. The genetic architecture of human brainstem structures and their involvement in common brain disorders

Author: Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Sellgren, C. M., Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., and Sellgren, C. M.
Abstract: Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders. The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.
Published: 2020
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7. The genetic architecture of human brainstem structures and their involvement in common brain disorders

Author: Elvsåshagen, T., Bahrami, S., Meer, D. van der, Agartz, I., Alnæs, D., Barch, D.M., Baur-Streubel, R., Bertolino, A., Beyer, M.K., Blasi, G., Borgwardt, S., Boye, B., Buitelaar, J.K., Bøen, E., Celius, E.G., Cervenka, S., Conzelmann, A., Coynel, D., Carlo, P. di, Djurovic, S., Eisenacher, S., Espeseth, T., Fatouros-Bergman, H., Flyckt, L., Franke, B., Frei, O., Gelao, B., Harbo, H.F., Hartman, Catharina A., Håberg, A., Heslenfeld, D., Hoekstra, P.J., Høgestøl, E.A., Jonassen, R., Jönsson, E.G., Kirsch, P., Kłoszewska, I., Lagerberg, T.V., Landrø, N.I., Hellard, S. Le, Lesch, K.P., Maglanoc, L.A., Malt, U.F., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Moberget, T., Nordvik, J.E., Nyberg, L., Connell, K.S.O., Oosterlaan, J., Papalino, M., Papassotiropoulos, A., Pauli, P., Pergola, G., Persson, K., Quervain, D. de, Reif, A., Rokicki, J., Rooij, D. van, Shadrin, A.A., Schmidt, A., Schwarz, E., Selbæk, G., Soininen, H., Sowa, P., Steen, V.M., Tsolaki, M., Vellas, B., Wang, L, Westman, E., Ziegler, G.C., Zink, M., Andreassen, O.A., Westlye, L.T., Kaufmann, T., Elvsåshagen, T., Bahrami, S., Meer, D. van der, Agartz, I., Alnæs, D., Barch, D.M., Baur-Streubel, R., Bertolino, A., Beyer, M.K., Blasi, G., Borgwardt, S., Boye, B., Buitelaar, J.K., Bøen, E., Celius, E.G., Cervenka, S., Conzelmann, A., Coynel, D., Carlo, P. di, Djurovic, S., Eisenacher, S., Espeseth, T., Fatouros-Bergman, H., Flyckt, L., Franke, B., Frei, O., Gelao, B., Harbo, H.F., Hartman, Catharina A., Håberg, A., Heslenfeld, D., Hoekstra, P.J., Høgestøl, E.A., Jonassen, R., Jönsson, E.G., Kirsch, P., Kłoszewska, I., Lagerberg, T.V., Landrø, N.I., Hellard, S. Le, Lesch, K.P., Maglanoc, L.A., Malt, U.F., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Moberget, T., Nordvik, J.E., Nyberg, L., Connell, K.S.O., Oosterlaan, J., Papalino, M., Papassotiropoulos, A., Pauli, P., Pergola, G., Persson, K., Quervain, D. de, Reif, A., Rokicki, J., Rooij, D. van, Shadrin, A.A., Schmidt, A., Schwarz, E., Selbæk, G., Soininen, H., Sowa, P., Steen, V.M., Tsolaki, M., Vellas, B., Wang, L, Westman, E., Ziegler, G.C., Zink, M., Andreassen, O.A., Westlye, L.T., and Kaufmann, T.
Abstract: Contains fulltext : 225402.pdf (publisher's version ) (Open Access), Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.
Published: 2020

8. Common brain disorders are associated with heritable patterns of apparent aging of the brain

Author: Kaufmann, T., van der Meer, D., Doan, N. T., Schwarz, E., Lund, M. J., Agartz, I., Alnaes, D., Barch, D. M., Baur-Streubel, R., Bertolino, A., Bettella, F., Beyer, M. K., Boen, E., Borgwardt, S., Brandt, C. L., Buitelaar, J., Celius, E. G., Cervenka, S., Conzelmann, A., Cordova-Palomera, A., Dale, A. M., de Quervain, D. J. F., Carlo, P. D., Djurovic, S., Dorum, E. S., Eisenacher, S., Elvsashagen, T., Espeseth, T., Fatouros-Bergman, H., Flyckt, L., Franke, B., Frei, O., Haatveit, B., Haberg, A. K., Harbo, H. F., Hartman, C. A., Heslenfeld, D., Hoekstra, P. J., Hogestol, E. A., Jernigan, T. L., Jonassen, R., Jonsson, E. G., Farde, L., Engberg, G., Erhardt, S., Schwieler, L., Piehl, F., Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Kirsch, P., Kloszewska, I., Kolskar, K. K., Landro, N. I., Hellard, S. L., Lesch, K. -P., Lovestone, S., Lundervold, A., Lundervold, A. J., Maglanoc, L. A., Malt, U. F., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Moberget, T., Norbom, L. B., Nordvik, J. E., Nyberg, L., Oosterlaan, J., Papalino, M., Papassotiropoulos, A., Pauli, P., Pergola, G., Persson, K., Richard, G., Rokicki, J., Sanders, A. -M., Selbaek, G., Shadrin, A. A., Smeland, O. B., Soininen, H., Sowa, P., Steen, V. M., Tsolaki, M., Ulrichsen, K. M., Vellas, B., Wang, L., Westman, E., Ziegler, G. C., Zink, M., Andreassen, O. A., Westlye, L. T., Le Hellard, S., Di Carlo, P., Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), General Paediatrics, ARD - Amsterdam Reproduction and Development, Pediatric surgery, Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, and RS: MHeNs - R2 - Mental Health
Subjects: 0301 basic medicine, Brain age gap, brain disorders, genetic architecture, pleiotropy, Male, Aging, Schizophrenia/genetics, LOCI, Genome-wide association study, Neuropsychological Tests, 0302 clinical medicine, 80 and over, Brain age gap, Aging/genetics, ALZHEIMERS, Child, Aged, 80 and over, Brain Diseases, Sex Characteristics, General Neuroscience, Mental Disorders, Brain, MULTIPLE-SCLEROSIS, brain disorders, Middle Aged, Magnetic Resonance Imaging, 3. Good health, Schizophrenia, Child, Preschool, Female, Alzheimer's disease, Neurovetenskaper, Algorithms, MRI, Adult, Adolescent, Brain Diseases/diagnostic imaging, Brain Structure and Function, Mental Disorders/diagnostic imaging, Biology, Article, 03 medical and health sciences, Young Adult, AGE, pleiotropy, Genetic architecture, Genetic Pleiotropy, medicine, Humans, Preschool, Brain disorders, Aged, Pleiotropy, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Brain age gaps, Multiple sclerosis, Neurosciences, Infant, medicine.disease, Brain/diagnostic imaging, genetic architecture, 030104 developmental biology, Pleiotropy (drugs), Neuroscience, 030217 neurology & neurosurgery, Genome-Wide Association Study
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. The author list between I.A. and M.Z. is in alphabetic order. The authors were funded by the Research Council of Norway (276082 LifespanHealth (T.K.), 213837 (O.A.A), 223273 NORMENT (O.A.A.), 204966 (L.T.W.), 229129 (O.A.A.), 249795 (L.T.W.), 273345 (L.T.W.) and 283798 SYNSCHIZ (O.A.A.)), the South-Eastern Norway Regional Health Authority (2013-123 (O.A.A.), 2014-097 (L.T.W.), 2015-073 (L.T.W.) and 2016083 (L.T.W.)), Stiftelsen Kristian Gerhard Jebsen (SKGJ-MED-008), the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC Starting Grant, Grant agreement No. 802998 BRAINMINT (L.T.W.)), NVIDIA Corporation GPU Grant (T.K.), and the European Commission 7th Framework Programme (602450, IMAGEMEND (A.M.-L.)).
Published: 2019

9. Brain Age Prediction Reveals Aberrant Brain White Matter in Schizophrenia and Bipolar Disorder: A Multisample Diffusion Tensor Imaging Study

Author: Tønnesen, Siren, primary, Kaufmann, Tobias, additional, de Lange, Ann-Marie G., additional, Richard, Geneviève, additional, Doan, Nhat Trung, additional, Alnæs, Dag, additional, van der Meer, Dennis, additional, Rokicki, Jaroslav, additional, Moberget, Torgeir, additional, Maximov, Ivan I., additional, Agartz, Ingrid, additional, Aminoff, Sofie R., additional, Beck, Dani, additional, Barch, Deanna M., additional, Beresniewicz, Justyna, additional, Cervenka, Simon, additional, Fatouros-Bergman, Helena, additional, Craven, Alexander R., additional, Flyckt, Lena, additional, Gurholt, Tiril P., additional, Haukvik, Unn K., additional, Hugdahl, Kenneth, additional, Johnsen, Erik, additional, Jönsson, Erik G., additional, Kolskår, Knut K., additional, Kroken, Rune Andreas, additional, Lagerberg, Trine V., additional, Løberg, Else-Marie, additional, Nordvik, Jan Egil, additional, Sanders, Anne-Marthe, additional, Ulrichsen, Kristine, additional, Andreassen, Ole A., additional, Westlye, Lars T., additional, Farde, L., additional, Flyckt, L., additional, Engberg, G., additional, Erhardt, S., additional, Fatouros-Bergman, H., additional, Cervenka, S., additional, Schwieler, L., additional, Piehl, F., additional, Agartz, I., additional, Collste, K., additional, Victorsson, P., additional, Malmqvist, A., additional, Hedberg, M., additional, Orhan, F., additional, and Sellgren, C., additional
Published: 2020
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10. Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder

Author: Schwarz, E., Doan, N. T., Pergola, G., Westlye, L. T., Kaufmann, T., Wolfers, T., Brecheisen, R., Quarto, T., Ing, A. J., Di Carlo, P., Gurholt, T. P., Harms, R. L., Noirhomme, Q., Moberget, T., Agartz, I., Andreassen, O. A., Bellani, M., Bertolino, A., Blasi, G., Brambilla, P., Buitelaar, J. K., Cervenka, S., Flyckt, L., Frangou, S., Franke, B., Hall, J., Heslenfeld, D. J., Kirsch, P., Mcintosh, A. M., Nothen, M. M., Papassotiropoulos, A., de Quervain, D. J. -F., Rietschel, M., Schumann, G., Tost, H., Witt, S. H., Zink, M., Meyer-Lindenberg, A., Bettella, F., Brandt, C. L., Clarke, T. -K., Coynel, D., Degenhardt, F., Djurovic, S., Eisenacher, S., Fastenrath, M., Fatouros-Bergman, H., Forstner, A. J., Frank, J., Gambi, F., Gelao, B., Geschwind, L., Di Giannantonio, M., Di Giorgio, A., Hartman, C. A., Heilmann-Heimbach, S., Herms, S., Hoekstra, P. J., Hoffmann, P., Hoogman, M., Jonsson, E. G., Loos, E., Maggioni, E., Oosterlaan, J., Papalino, M., Rampino, A., Romaniuk, L., Selvaggi, P., Sepede, G., Sonderby, I. E., Spalek, K., Sussmann, J. E., Thompson, P. M., Vasquez, A. A., Vogler, C., Whalley, H., Farde, L., Engberg, G., Erhardt, S., Schwieler, L., Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Cognitive Psychology, IBBA, Behavioural Sciences, Elvira Brattico / Principal Investigator, Department of Psychology and Logopedics, Cognitive Brain Research Unit, Faculty of Medicine, University of Helsinki, General Paediatrics, ARD - Amsterdam Reproduction and Development, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Multiscale Imaging of Brain Connectivity, RS: FPN CN 11, Vision, and RS: FPN CN 1
Subjects: 0301 basic medicine, Male, Multivariate statistics, Bipolar Disorder, SEGMENTATION, 3124 Neurology and psychiatry, Machine Learning, 0302 clinical medicine, DEFICITS, Gray Matter, Psychiatry, RISK, medicine.diagnostic_test, 220 Statistical Imaging Neuroscience, LIKELIHOOD ESTIMATION, Middle Aged, MRI SCANS, Magnetic Resonance Imaging, Justice and Strong Institutions, 3. Good health, Psychiatry and Mental health, medicine.anatomical_structure, bipolar disorders, Schizophrenia, Female, brain structural patterns, MRI, Adult, SDG 16 - Peace, Adolescent, Brain Structure and Function, Grey matter, Psykiatri, CLASSIFICATION, Article, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, Text mining, medicine, Humans, Bipolar disorder, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, METAANALYSIS, schizophrenia, grey matter alterations, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, 1ST-EPISODE, SDG 16 - Peace, Justice and Strong Institutions, Magnetic resonance imaging, medicine.disease, 030104 developmental biology, Sample size determination, Attention Deficit Disorder with Hyperactivity, Case-Control Studies, VOLUME, business, Neuroscience, 030217 neurology & neurosurgery
Abstract: Contains fulltext : 202693.pdf (Publisher’s version ) (Open Access) Schizophrenia is a severe mental disorder characterized by numerous subtle changes in brain structure and function. Machine learning allows exploring the utility of combining structural and functional brain magnetic resonance imaging (MRI) measures for diagnostic application, but this approach has been hampered by sample size limitations and lack of differential diagnostic data. Here, we performed a multi-site machine learning analysis to explore brain structural patterns of T1 MRI data in 2668 individuals with schizophrenia, bipolar disorder or attention-deficit/ hyperactivity disorder, and healthy controls. We found reproducible changes of structural parameters in schizophrenia that yielded a classification accuracy of up to 76% and provided discrimination from ADHD, through it lacked specificity against bipolar disorder. The observed changes largely indexed distributed grey matter alterations that could be represented through a combination of several global brain-structural parameters. This multi-site machine learning study identified a brain-structural signature that could reproducibly differentiate schizophrenia patients from controls, but lacked specificity against bipolar disorder. While this currently limits the clinical utility of the identified signature, the present study highlights that the underlying alterations index substantial global grey matter changes in psychotic disorders, reflecting the biological similarity of these conditions, and provide a roadmap for future exploration of brain structural alterations in psychiatric patients.
Published: 2019

11. Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder

Author: Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., and Orhan, F.
Abstract: Schizophrenia is a severe mental disorder characterized by numerous subtle changes in brain structure and function. Machine learning allows exploring the utility of combining structural and functional brain magnetic resonance imaging (MRI) measures for diagnostic application, but this approach has been hampered by sample size limitations and lack of differential diagnostic data. Here, we performed a multi-site machine learning analysis to explore brain structural patterns of T1 MRI data in 2668 individuals with schizophrenia, bipolar disorder or attention-deficit/hyperactivity disorder, and healthy controls. We found reproducible changes of structural parameters in schizophrenia that yielded a classification accuracy of up to 76% and provided discrimination from ADHD, through it lacked specificity against bipolar disorder. The observed changes largely indexed distributed grey matter alterations that could be represented through a combination of several global brain-structural parameters. This multi-site machine learning study identified a brain-structural signature that could reproducibly differentiate schizophrenia patients from controls, but lacked specificity against bipolar disorder. While this currently limits the clinical utility of the identified signature, the present study highlights that the underlying alterations index substantial global grey matter changes in psychotic disorders, reflecting the biological similarity of these conditions, and provide a roadmap for future exploration of brain structural alterations in psychiatric patients.
Published: 2019
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12. 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

13. Increased peripheral levels of TARC/CCL17 in first episode psychosis patients

Author: Malmqvist, Anna, Schwieler, Lilly, Orhan, Funda, Fatouros-Bergman, Helena, Bauer, Markus, Flyckt, Lena, Cervenka, Simon, Engberg, Goran, Piehl, Fredrik, Erhardt, Sophie, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Malmqvist, Anna, Schwieler, Lilly, Orhan, Funda, Fatouros-Bergman, Helena, Bauer, Markus, Flyckt, Lena, Cervenka, Simon, Engberg, Goran, Piehl, Fredrik, Erhardt, Sophie, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., and Orhan, F.
Abstract: Background: Evidence for a link between the pathophysiology of schizophrenia and the immune system is mounting. Altered levels of chemokines in plasma have previously been reported in patients with schizophrenia under antipsychotic medication. Here we aimed to study both peripheral and central chemokine levels in drugnaive or short-time medicated first episode psychosis (FEP) patients. Method: We analyzed nine chemokines in plasma and CSF from 41 FEP patients and 22 healthy controls using electrochemiluminescence assay. Results: In plasma four chemokines; TARC/CCL17, eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 and in CSF one chemokine; IP-10/CXCL10 showed reliable detection in N50% of the cases. FEP patients displayed increased levels of TARC/CCL17 in plasma compared to healthy controls, 89.6 (IQR 66.2-125.8) pg/mL compared to 48.6 (IQR 28.0-71.7) pg/mL (p = 0.001). The difference was not attributed to confounding factors. Plasma TARC/CCL17 was not associated with PANSS, CGI or GAF scores, neither with cognitive functions. The chemokines eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 in plasma and IP-10/CXCL10 in CSF did not differ between FEP patients and controls. Conclusion: In line with a previous study showing that chronic patients with schizophrenia display increased plasma TARC/CCL17 levels, we here found an elevation in FEP patients suggesting a role of TARC/CCL17 in early stages of schizophrenia. The exactmechanism of this involvement is still unknown and future longitudinal studies as well as studies of central and peripheral chemokine levels would be of great interest. (C) 2018 Elsevier B.V. All rights reserved.
Published: 2019
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14. Cerebrospinal fluid levels of sphingolipids associate with disease severity in first episode psychosis patients

Author: Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I., Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Checa, Antonio, Malmqvist, Anna, Flyckt, Lena, Schwieler, Lilly, Samuelsson, Martin, Skogh, Elisabeth, Cervenka, Simon, Dahl, Marja-Liisa, Piehl, Fredrik, Erhardt, Sophie, and Wheelock, Craig E.
Published: 2018
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15. CSF GABA is reduced in first-episode psychosis and associates to symptom severity

Author: Orhan, F, Fatouros-Bergman, H, Goiny, M, Malmqvist, A, Piehl, F, Cervenka, Simon, Collste, K, Victorsson, P, Sellgren, C M, Flyckt, L, Erhardt, S, Engberg, G, Orhan, F, Fatouros-Bergman, H, Goiny, M, Malmqvist, A, Piehl, F, Cervenka, Simon, Collste, K, Victorsson, P, Sellgren, C M, Flyckt, L, Erhardt, S, and Engberg, G
Abstract: Schizophrenia is characterized by a multiplicity of symptoms arising from almost all domains of mental function. γ-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain and is increasingly recognized to have a significant role in the pathophysiology of the disorder. In the present study, cerebrospinal fluid (CSF) concentrations of GABA were analyzed in 41 first-episode psychosis (FEP) patients and 21 age- and sex-matched healthy volunteers by high-performance liquid chromatography. We found lower CSF GABA concentration in FEP patients compared with that in the healthy volunteers, a condition that was unrelated to antipsychotic and/or anxiolytic medication. Moreover, lower CSF GABA levels were associated with total and general score of Positive and Negative Syndrome Scale, illness severity and probably with a poor performance in a test of attention. This study offers clinical in vivo evidence for a potential role of GABA in early-stage schizophrenia.
Published: 2018
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16. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group

Author: Kelly, S., Jahanshad, N., Zalesky, A., Kochunov, P., Agartz, I., Alloza, C., Andreassen, O.A., Arango, C., Banaj, N., Bouix, S., Bousman, C.A., Brouwer, R.M., Bruggemann, J., Bustillo, J., Cahn, W., Calhoun, V., Cannon, D., Carr, V., Catts, S., Chen, J., Chen, J.X., Chen, X, Chiapponi, C., Cho, K.K., Ciullo, V., Corvin, A.S., Crespo-Facorro, B., Cropley, V., Rossi, P., Diaz-Caneja, C.M., Dickie, E.W., Ehrlich, S., Fan, F.M., Faskowitz, J., Fatouros-Bergman, H., Flyckt, L., Ford, J.M., Fouche, J.P., Fukunaga, M., Gill, M., Glahn, D.C., Gollub, R., Goudzwaard, E.D., Guo, H, Gur, R.E., Gur, R.C., Gurholt, T.P., Hashimoto, R., Hatton, S.N., Henskens, F.A., Hibar, D.P., Hickie, I.B., Hong, L.E., Horacek, J., Howells, F.M., Pol, H.E., Hyde, C.L., Isaev, D., Jablensky, A., Jansen, P.R., Janssen, J, Jonsson, E.G., Jung, L.A., Kahn, R.S., Kikinis, Z., Liu, K, Klauser, P., Knochel, C., Kubicki, M., Lagopoulos, J., Langen, C., Lawrie, S., Lenroot, R.K., Lim, K.O., Lopez-Jaramillo, C., Lyall, A., Magnotta, V., Mandl, R.C.W., Mathalon, D.H., McCarley, R.W., McCarthy-Jones, S., McDonald, C., McEwen, S., McIntosh, A., Melicher, T., Mesholam-Gately, R.I., Michie, P.T., Mowry, B., Mueller, B.A., Newell, D.T., O'Donnell, P., Oertel-Knochel, V., Oestreich, L., Paciga, S.A., Pantelis, C., Pasternak, O., Pearlson, G., Pellicano, G.R., Pereira, A., Zapata, J., Sprooten, E., Thompson, P.M., Donohoe, G., Kelly, S., Jahanshad, N., Zalesky, A., Kochunov, P., Agartz, I., Alloza, C., Andreassen, O.A., Arango, C., Banaj, N., Bouix, S., Bousman, C.A., Brouwer, R.M., Bruggemann, J., Bustillo, J., Cahn, W., Calhoun, V., Cannon, D., Carr, V., Catts, S., Chen, J., Chen, J.X., Chen, X, Chiapponi, C., Cho, K.K., Ciullo, V., Corvin, A.S., Crespo-Facorro, B., Cropley, V., Rossi, P., Diaz-Caneja, C.M., Dickie, E.W., Ehrlich, S., Fan, F.M., Faskowitz, J., Fatouros-Bergman, H., Flyckt, L., Ford, J.M., Fouche, J.P., Fukunaga, M., Gill, M., Glahn, D.C., Gollub, R., Goudzwaard, E.D., Guo, H, Gur, R.E., Gur, R.C., Gurholt, T.P., Hashimoto, R., Hatton, S.N., Henskens, F.A., Hibar, D.P., Hickie, I.B., Hong, L.E., Horacek, J., Howells, F.M., Pol, H.E., Hyde, C.L., Isaev, D., Jablensky, A., Jansen, P.R., Janssen, J, Jonsson, E.G., Jung, L.A., Kahn, R.S., Kikinis, Z., Liu, K, Klauser, P., Knochel, C., Kubicki, M., Lagopoulos, J., Langen, C., Lawrie, S., Lenroot, R.K., Lim, K.O., Lopez-Jaramillo, C., Lyall, A., Magnotta, V., Mandl, R.C.W., Mathalon, D.H., McCarley, R.W., McCarthy-Jones, S., McDonald, C., McEwen, S., McIntosh, A., Melicher, T., Mesholam-Gately, R.I., Michie, P.T., Mowry, B., Mueller, B.A., Newell, D.T., O'Donnell, P., Oertel-Knochel, V., Oestreich, L., Paciga, S.A., Pantelis, C., Pasternak, O., Pearlson, G., Pellicano, G.R., Pereira, A., Zapata, J., Sprooten, E., Thompson, P.M., and Donohoe, G.
Abstract: Contains fulltext : 193179.pdf (Publisher’s version ) (Open Access), The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.
Published: 2018

17. Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium

Author: Walton, Esther, Hibar, Derrek P., van Erp, Theo G. M., Potkin, Steven G., Roiz-Santiañez, R., Crespo-Facorro, Benedicto, Suarez-Pinilla, P., Van Haren, N. E.M., De Zwarte, S. M.C., Kahn, R. S., Cahn, W., Doan, Nhat Trung, Jorgensen, K. N., Gurholt, T. P., Agartz, I., Andreassen, Ole A., Westlye, Lars T., Melle, I., Berg, A. O., Morch-Johnsen, L, Færden, A., Flyckt, L., Fatouros-Bergman, H., Jönsson, E. G., Hashimoto, Ryota, Yamamori, H., Fukunaga, Masaki, Jahanshad, N., Rossi, P., Piras, F., Banaj, N., Spalletta, G., Gur, Raquel E., Gur, Ruben C., Hanssen-de Wolf, J.E., Satterthwaite, Theodore D., Beard, L. M., Sommer, I. E., Koops, S., Gruber, Oliver, Richter, A., Krämer, B., Kelly, Rachel S., Donohoe, Gary, McDonald, C., Cannon, Dara M., Corvin, A S, Gill, M., Di Giorgio, A., Bertolino, A., Lawrie, Stephen M., Nickson, T., Whalley, Heather C., Neilson, E., Calhoun, Vince D., Thompson, Paul M., Turner, Jessica A., Ehrlich, S., Walton, Esther, Hibar, Derrek P., van Erp, Theo G. M., Potkin, Steven G., Roiz-Santiañez, R., Crespo-Facorro, Benedicto, Suarez-Pinilla, P., Van Haren, N. E.M., De Zwarte, S. M.C., Kahn, R. S., Cahn, W., Doan, Nhat Trung, Jorgensen, K. N., Gurholt, T. P., Agartz, I., Andreassen, Ole A., Westlye, Lars T., Melle, I., Berg, A. O., Morch-Johnsen, L, Færden, A., Flyckt, L., Fatouros-Bergman, H., Jönsson, E. G., Hashimoto, Ryota, Yamamori, H., Fukunaga, Masaki, Jahanshad, N., Rossi, P., Piras, F., Banaj, N., Spalletta, G., Gur, Raquel E., Gur, Ruben C., Hanssen-de Wolf, J.E., Satterthwaite, Theodore D., Beard, L. M., Sommer, I. E., Koops, S., Gruber, Oliver, Richter, A., Krämer, B., Kelly, Rachel S., Donohoe, Gary, McDonald, C., Cannon, Dara M., Corvin, A S, Gill, M., Di Giorgio, A., Bertolino, A., Lawrie, Stephen M., Nickson, T., Whalley, Heather C., Neilson, E., Calhoun, Vince D., Thompson, Paul M., Turner, Jessica A., and Ehrlich, S.
Published: 2018

18. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: Results from the ENIGMA Schizophrenia DTI Working Group.

Author: Faskowitz J., Jablensky A., Jansen P.R., Janssen J., Jonsson E.G., Jung L.A., Kahn R.S., Kikinis Z., Liu K., Klauser P., Knochel C., Kubicki M., Lagopoulos J., Langen C., Lawrie S., Lenroot R.K., Lim K.O., Lopez-Jaramillo C., Lyall A., Magnotta V., Mandl R.C.W., McIntosh A., Melicher T., Mesholam-Gately R.I., Michie P.T., Mowry B., Mueller B.A., Newell D.T., O'Donnell P., Oertel-Knochel V., Oestreich L., Paciga S.A., Pantelis C., Pasternak O., Pearlson G., Pellicano G.R., Pereira A., Pineda Zapata J., Piras F., Potkin S.G., Preda A., Rasser P.E., Roalf D.R., Roiz R., Roos A., Rotenberg D., Satterthwaite T.D., Savadjiev P., Schall U., Scott R.J., Seal M.L., Seidman L.J., Shannon Weickert C., Whelan C.D., Shenton M.E., Kwon J.S., Spalletta G., Spaniel F., Sprooten E., Stablein M., Stein D.J., Tan Y., Tan S., Tang S., Temmingh H.S., Westlye L.T., Tonnesen S., Tordesillas-Gutierrez D., Doan N.T., Vaidya J., Van Haren N.E.M., Vargas C.D., Vecchio D., Velakoulis D., Voineskos A., Voyvodic J.Q., Wang Z., Wan P., Wei D., Weickert T.W., Whalley H., White T., Whitford T.J., Wojcik J.D., Xiang H., Xie Z., Yamamori H., Yang F., Yao N., Zhang G., Zhao J., Van Erp T.G.M., Turner J., Thompson P.M., Donohoe G., Sundram S., Kelly S., Jahanshad N., Zalesky A., Kochunov P., Agartz I., Alloza C., Andreassen O.A., Arango C., Banaj N., Bouix S., Bousman C.A., Brouwer R.M., Bruggemann J., Bustillo J., Cahn W., Calhoun V., Cannon D., Carr V., Catts S., Chen J., Chen J.-X., Chen X., Chiapponi C., Cho K.K., Ciullo V., Corvin A.S., Crespo-Facorro B., Cropley V., De Rossi P., Diaz-Caneja C.M., Dickie E.W., Ehrlich S., Fan F.-M., Fatouros-Bergman H., Flyckt L., Ford J.M., Fouche J.-P., Fukunaga M., Gill M., Glahn D.C., Gollub R., Goudzwaard E.D., Guo H., Gur R.E., Gur R.C., Gurholt T.P., Hashimoto R., Hatton S.N., Henskens F.A., Hibar D.P., Hickie I.B., Hong L.E., Horacek J., Howells F.M., Hulshoff Pol H.E., Hyde C.L., Isaev D., Mathalon D.H., McCarley R.W., McCarthy-Jones S., McDonald C., McEwen S., Faskowitz J., Jablensky A., Jansen P.R., Janssen J., Jonsson E.G., Jung L.A., Kahn R.S., Kikinis Z., Liu K., Klauser P., Knochel C., Kubicki M., Lagopoulos J., Langen C., Lawrie S., Lenroot R.K., Lim K.O., Lopez-Jaramillo C., Lyall A., Magnotta V., Mandl R.C.W., McIntosh A., Melicher T., Mesholam-Gately R.I., Michie P.T., Mowry B., Mueller B.A., Newell D.T., O'Donnell P., Oertel-Knochel V., Oestreich L., Paciga S.A., Pantelis C., Pasternak O., Pearlson G., Pellicano G.R., Pereira A., Pineda Zapata J., Piras F., Potkin S.G., Preda A., Rasser P.E., Roalf D.R., Roiz R., Roos A., Rotenberg D., Satterthwaite T.D., Savadjiev P., Schall U., Scott R.J., Seal M.L., Seidman L.J., Shannon Weickert C., Whelan C.D., Shenton M.E., Kwon J.S., Spalletta G., Spaniel F., Sprooten E., Stablein M., Stein D.J., Tan Y., Tan S., Tang S., Temmingh H.S., Westlye L.T., Tonnesen S., Tordesillas-Gutierrez D., Doan N.T., Vaidya J., Van Haren N.E.M., Vargas C.D., Vecchio D., Velakoulis D., Voineskos A., Voyvodic J.Q., Wang Z., Wan P., Wei D., Weickert T.W., Whalley H., White T., Whitford T.J., Wojcik J.D., Xiang H., Xie Z., Yamamori H., Yang F., Yao N., Zhang G., Zhao J., Van Erp T.G.M., Turner J., Thompson P.M., Donohoe G., Sundram S., Kelly S., Jahanshad N., Zalesky A., Kochunov P., Agartz I., Alloza C., Andreassen O.A., Arango C., Banaj N., Bouix S., Bousman C.A., Brouwer R.M., Bruggemann J., Bustillo J., Cahn W., Calhoun V., Cannon D., Carr V., Catts S., Chen J., Chen J.-X., Chen X., Chiapponi C., Cho K.K., Ciullo V., Corvin A.S., Crespo-Facorro B., Cropley V., De Rossi P., Diaz-Caneja C.M., Dickie E.W., Ehrlich S., Fan F.-M., Fatouros-Bergman H., Flyckt L., Ford J.M., Fouche J.-P., Fukunaga M., Gill M., Glahn D.C., Gollub R., Goudzwaard E.D., Guo H., Gur R.E., Gur R.C., Gurholt T.P., Hashimoto R., Hatton S.N., Henskens F.A., Hibar D.P., Hickie I.B., Hong L.E., Horacek J., Howells F.M., Hulshoff Pol H.E., Hyde C.L., Isaev D., Mathalon D.H., McCarley R.W., McCarthy-Jones S., McDonald C., and McEwen S.
Abstract: The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.Copyright © The Author(s) 2018.
Published: 2018

19. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: Results from the ENIGMA Schizophrenia DTI Working Group

Author: Kelly, S. (S.), Jahanshad, N. (Neda), Zalesky, A. (A.), Kochunov, P. (P.), Agartz, I. (Ingrid), Alloza, C. (C.), Andreassen, O.A. (O. A.), Arango, C. (C.), Banaj, N. (N.), Bouix, S. (S.), Bousman, C.A. (C. A.), Brouwer, R.M. (Rachel), Bruggemann, J. (J.), Bustillo, J., Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cannon, D. (D.), Carr, V.J. (Vaughan), Catts, S.V. (Stanley), Chen, J. (J.), Chen, J.-X. (J. X.), Chen, X. (X.), Chiapponi, C. (C.), Cho, K.K. (Kl K), Ciullo, V. (V.), Corvin, A. (Aiden), Crespo-Facorro, B. (Benedicto), Cropley, V. (V.), De Rossi, P. (P.), Diaz-Caneja, C.M. (C. M.), Dickie, E.W. (E. W.), Ehrlich, S.M. (Stefan), Fan, F.-M. (F. M.), Faskowitz, J. (J.), Fatouros-Bergman, H. (H.), Flyckt, L. (L.), Ford, J.M. (J. M.), Fouche, J.-P. (J. P.), Fukunaga, M. (Masaki), Gill, M. (M.), Glahn, D.C. (David), Gollub, R.L. (Randy), Goudzwaard, E.D. (E. D.), Guo, H. (H.), Gur, R.E. (Raquel), Gur, R.C. (R. C.), Gurholt, T.P. (T. P.), Hashimoto, R. (Ryota), Hatton, W., Henskens, F.A. (Frans), Hibar, D.P. (D. P.), Hickie, I.B. (Ian), Hong, L.E. (L. E.), Horacek, J. (J.), Howells, F.M. (F. M.), Hulshoff Pol, H.E. (Hilleke), Hyde, C.L. (C. L.), Isaev, D. (D.), Jablensky, A. (A.), Jansen, P.R. (P. R.), Janssen, J. (J.), Jönsson, E.G. (Erik), Jung, L.A. (L. A.), Kahn, R.S. (R. S.), Kikinis, Z. (Z.), Liu, K. (K.), Klauser, P. (P.), Knöchel, C. (C.), Kubicki, M. (M.), Lagopoulos, J. (Jim), Langen, C.D. (Carolyn), Lawrie, S. (Stephen), Lenroot, R.K. (Rhoshel), Lim, K.O. (Kelvin), Lopez-Jaramillo, C. (C.), Lyall, A. (A.), Magnotta, V., Mandl, R. (René), Mathalon, D.H. (D. H.), McCarley, R.W. (Robert), McCarthy-Jones, S. (S.), McDonald, C. (Colm), McEwen, S. (S.), McIntosh, A.M. (Andrew), Melicher, T. (T.), Mesholam-Gately, R.I. (Raquelle), Michie, P.T. (Patricia), Mowry, B.J. (Bryan J), Mueller, B.A. (Bryon ), Newell, D.T. (D. T.), O'Donnell, P. (P.), Oertel-Knöchel, V. (V.), Oestreich, L. (L.), Paciga, S.A. (S. A.), Pantelis, C. (Christos), Pasternak, O. (O.), Pearlson, G. (G.), Pellicano, G.R. (G. R.), Pereira, A. (A.), Pineda Zapata, J. (J.), Piras, F. (F.), Potkin, S.G. (Steven), Preda, A. (A.), Rasser, P.E. (P. E.), Roalf, D.R. (D. R.), Roiz, R. (R.), Roos, A. (A.), Rotenberg, D. (D.), Satterthwaite, T.D. (Theodore), Savadjiev, P. (P.), Schall, J.D. (Jeffrey), Scott, R.J. (R. J.), Seal, M.L. (M. L.), Seidman, L.J. (Larry), Shannon Weickert, C. (C.), Whelan, C.D. (Christopher), Shenton, M.E. (M. E.), Kwon, J.S. (J. S.), Spalletta, G. (Gianfranco), Spaniel, F. (F.), Sprooten, R. (Roy), Stäblein, M. (M.), Stein, D.J. (Dan), Sundram, S. (S.), Tan, Y. (Y.), Tan, S. (S.), Tang, S. (S.), Temmingh, H.S. (H. S.), Westlye, L.T. (Lars), Tønnesen, S. (S.), Tordesillas-Gutierrez, D. (Diana), Doan, N.T. (N. T.), Vaidya, J. (J.), Van Haren, N.E.M. (N. E.M.), Vargas, C.D. (C. D.), Vecchio, D. (D.), Velakoulis, D. (D.), Voineskos, A. (A.), Voyvodic, J.Q. (J. Q.), Wang, Z. (Z.), Wan, P. (P.), Wei, D. (D.), Weickert, T.W. (T. W.), Whalley, H. (H.), White, T.J.H. (Tonya), Whitford, T.J. (T. J.), Wojcik, J.D. (J. D.), Xiang, H. (H.), Xie, Z. (Z.), Yamamori, H. (H.), Yang, F. (F.), Yao, N. (N.), Zhang, G. (G.), Zhao, J. (J.), Erp, T.G.M. (Theo G.) van, Turner, J. (Jessica), Thompson, P.M. (P. M.), Donohoe, D.J. (Dennis), Kelly, S. (S.), Jahanshad, N. (Neda), Zalesky, A. (A.), Kochunov, P. (P.), Agartz, I. (Ingrid), Alloza, C. (C.), Andreassen, O.A. (O. A.), Arango, C. (C.), Banaj, N. (N.), Bouix, S. (S.), Bousman, C.A. (C. A.), Brouwer, R.M. (Rachel), Bruggemann, J. (J.), Bustillo, J., Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cannon, D. (D.), Carr, V.J. (Vaughan), Catts, S.V. (Stanley), Chen, J. (J.), Chen, J.-X. (J. X.), Chen, X. (X.), Chiapponi, C. (C.), Cho, K.K. (Kl K), Ciullo, V. (V.), Corvin, A. (Aiden), Crespo-Facorro, B. (Benedicto), Cropley, V. (V.), De Rossi, P. (P.), Diaz-Caneja, C.M. (C. M.), Dickie, E.W. (E. W.), Ehrlich, S.M. (Stefan), Fan, F.-M. (F. M.), Faskowitz, J. (J.), Fatouros-Bergman, H. (H.), Flyckt, L. (L.), Ford, J.M. (J. M.), Fouche, J.-P. (J. P.), Fukunaga, M. (Masaki), Gill, M. (M.), Glahn, D.C. (David), Gollub, R.L. (Randy), Goudzwaard, E.D. (E. D.), Guo, H. (H.), Gur, R.E. (Raquel), Gur, R.C. (R. C.), Gurholt, T.P. (T. P.), Hashimoto, R. (Ryota), Hatton, W., Henskens, F.A. (Frans), Hibar, D.P. (D. P.), Hickie, I.B. (Ian), Hong, L.E. (L. E.), Horacek, J. (J.), Howells, F.M. (F. M.), Hulshoff Pol, H.E. (Hilleke), Hyde, C.L. (C. L.), Isaev, D. (D.), Jablensky, A. (A.), Jansen, P.R. (P. R.), Janssen, J. (J.), Jönsson, E.G. (Erik), Jung, L.A. (L. A.), Kahn, R.S. (R. S.), Kikinis, Z. (Z.), Liu, K. (K.), Klauser, P. (P.), Knöchel, C. (C.), Kubicki, M. (M.), Lagopoulos, J. (Jim), Langen, C.D. (Carolyn), Lawrie, S. (Stephen), Lenroot, R.K. (Rhoshel), Lim, K.O. (Kelvin), Lopez-Jaramillo, C. (C.), Lyall, A. (A.), Magnotta, V., Mandl, R. (René), Mathalon, D.H. (D. H.), McCarley, R.W. (Robert), McCarthy-Jones, S. (S.), McDonald, C. (Colm), McEwen, S. (S.), McIntosh, A.M. (Andrew), Melicher, T. (T.), Mesholam-Gately, R.I. (Raquelle), Michie, P.T. (Patricia), Mowry, B.J. (Bryan J), Mueller, B.A. (Bryon ), Newell, D.T. (D. T.), O'Donnell, P. (P.), Oertel-Knöchel, V. (V.), Oestreich, L. (L.), Paciga, S.A. (S. A.), Pantelis, C. (Christos), Pasternak, O. (O.), Pearlson, G. (G.), Pellicano, G.R. (G. R.), Pereira, A. (A.), Pineda Zapata, J. (J.), Piras, F. (F.), Potkin, S.G. (Steven), Preda, A. (A.), Rasser, P.E. (P. E.), Roalf, D.R. (D. R.), Roiz, R. (R.), Roos, A. (A.), Rotenberg, D. (D.), Satterthwaite, T.D. (Theodore), Savadjiev, P. (P.), Schall, J.D. (Jeffrey), Scott, R.J. (R. J.), Seal, M.L. (M. L.), Seidman, L.J. (Larry), Shannon Weickert, C. (C.), Whelan, C.D. (Christopher), Shenton, M.E. (M. E.), Kwon, J.S. (J. S.), Spalletta, G. (Gianfranco), Spaniel, F. (F.), Sprooten, R. (Roy), Stäblein, M. (M.), Stein, D.J. (Dan), Sundram, S. (S.), Tan, Y. (Y.), Tan, S. (S.), Tang, S. (S.), Temmingh, H.S. (H. S.), Westlye, L.T. (Lars), Tønnesen, S. (S.), Tordesillas-Gutierrez, D. (Diana), Doan, N.T. (N. T.), Vaidya, J. (J.), Van Haren, N.E.M. (N. E.M.), Vargas, C.D. (C. D.), Vecchio, D. (D.), Velakoulis, D. (D.), Voineskos, A. (A.), Voyvodic, J.Q. (J. Q.), Wang, Z. (Z.), Wan, P. (P.), Wei, D. (D.), Weickert, T.W. (T. W.), Whalley, H. (H.), White, T.J.H. (Tonya), Whitford, T.J. (T. J.), Wojcik, J.D. (J. D.), Xiang, H. (H.), Xie, Z. (Z.), Yamamori, H. (H.), Yang, F. (F.), Yao, N. (N.), Zhang, G. (G.), Zhao, J. (J.), Erp, T.G.M. (Theo G.) van, Turner, J. (Jessica), Thompson, P.M. (P. M.), and Donohoe, D.J. (Dennis)
Abstract: The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.
Published: 2018
Full Text: View/download PDF

20. 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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21. 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

22. Increased number of monocytes and plasma levels of MCP-1 and YKL-40 in first-episode psychosis

Author: Orhan, F., Schwieler, L., Fatouros-Bergman, H., Malmqvist, A., Cervenka, Simon, Collste, K., Flyckt, L., Farde, L., Sellgren, C. M., Piehl, F., Engberg, G., Erhardt, S., Orhan, F., Schwieler, L., Fatouros-Bergman, H., Malmqvist, A., Cervenka, Simon, Collste, K., Flyckt, L., Farde, L., Sellgren, C. M., Piehl, F., Engberg, G., and Erhardt, S.
Abstract: ObjectiveMethodAccumulating evidence implicates immune activation in the development of schizophrenia. Here, monocyte numbers, monocyte chemoattractant protein-1 (MCP-1) and chitinase-3-like protein 1 (YKL-40) were investigated in plasma and cerebrospinal fluid (CSF) in first-episode psychosis (FEP) patients. CSF and blood were sampled from 42 first-episode psychosis (FEP) patients and 22 healthy controls. The levels of YKL-40 and MCP-1 were measured using electrochemiluminescence assay, and blood monocytes were counted using an XN-9000-hematology analyzer. ResultsConclusionWe found higher plasma levels of MCP-1 and YKL-40 in FEP patients compared with healthy controls, a condition that was unrelated to antipsychotic and/or anxiolytic medication. This was combined with an increased number of blood monocytes and a borderline significant increase in YKL-40 levels in the CSF of tobacco-free FEP patients. Plasma or CSF chemokines or blood monocytes did not correlate with the severity of symptoms or the level of functioning. These data demonstrate activation of monocytes in FEP and strengthens the idea of an immune dysfunction of psychotic disorders. Further studies are required to perceive a role of YKL-40 and MCP-1 in the initiation and progression of schizophrenia.
Published: 2018
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23. Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium

Author: UMC Utrecht, Onderzoeksgroep 4, Brain, Onderzoeksgroep 11, Affectieve & Psychotische Med., Curr. Onderwijs Huisartsgeneeskunde, Affectieve & Psychotisch Ond., Walton, Esther, Hibar, Derrek P., van Erp, Theo G. M., Potkin, Steven G., Roiz-Santiañez, R., Crespo-Facorro, Benedicto, Suarez-Pinilla, P., Van Haren, N. E.M., De Zwarte, S. M.C., Kahn, R. S., Cahn, W., Doan, Nhat Trung, Jorgensen, K. N., Gurholt, T. P., Agartz, I., Andreassen, Ole A., Westlye, Lars T., Melle, I., Berg, A. O., Morch-Johnsen, L, Færden, A., Flyckt, L., Fatouros-Bergman, H., Jönsson, E. G., Hashimoto, Ryota, Yamamori, H., Fukunaga, Masaki, Jahanshad, N., Rossi, P., Piras, F., Banaj, N., Spalletta, G., Gur, Raquel E., Gur, Ruben C., Hanssen-de Wolf, J.E., Satterthwaite, Theodore D., Beard, L. M., Sommer, I. E., Koops, S., Gruber, Oliver, Richter, A., Krämer, B., Kelly, Rachel S., Donohoe, Gary, McDonald, C., Cannon, Dara M., Corvin, A S, Gill, M., Di Giorgio, A., Bertolino, A., Lawrie, Stephen M., Nickson, T., Whalley, Heather C., Neilson, E., Calhoun, Vince D., Thompson, Paul M., Turner, Jessica A., Ehrlich, S., UMC Utrecht, Onderzoeksgroep 4, Brain, Onderzoeksgroep 11, Affectieve & Psychotische Med., Curr. Onderwijs Huisartsgeneeskunde, Affectieve & Psychotisch Ond., Walton, Esther, Hibar, Derrek P., van Erp, Theo G. M., Potkin, Steven G., Roiz-Santiañez, R., Crespo-Facorro, Benedicto, Suarez-Pinilla, P., Van Haren, N. E.M., De Zwarte, S. M.C., Kahn, R. S., Cahn, W., Doan, Nhat Trung, Jorgensen, K. N., Gurholt, T. P., Agartz, I., Andreassen, Ole A., Westlye, Lars T., Melle, I., Berg, A. O., Morch-Johnsen, L, Færden, A., Flyckt, L., Fatouros-Bergman, H., Jönsson, E. G., Hashimoto, Ryota, Yamamori, H., Fukunaga, Masaki, Jahanshad, N., Rossi, P., Piras, F., Banaj, N., Spalletta, G., Gur, Raquel E., Gur, Ruben C., Hanssen-de Wolf, J.E., Satterthwaite, Theodore D., Beard, L. M., Sommer, I. E., Koops, S., Gruber, Oliver, Richter, A., Krämer, B., Kelly, Rachel S., Donohoe, Gary, McDonald, C., Cannon, Dara M., Corvin, A S, Gill, M., Di Giorgio, A., Bertolino, A., Lawrie, Stephen M., Nickson, T., Whalley, Heather C., Neilson, E., Calhoun, Vince D., Thompson, Paul M., Turner, Jessica A., and Ehrlich, S.
Published: 2018

24. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: Results from the ENIGMA Schizophrenia DTI Working Group

Author: Onderzoeksgroep 1, Brain, Affectieve & Psychotische Med., Research Office, Onderzoek Bob Oranje, Onderzoeksgroep 11, Onderzoeksgroep 8, Onderzoeksgroep 4, Kelly, S., Jahanshad, N., Zalesky, A., Kochunov, P., Agartz, I., Alloza, C., Andreassen, O. A., Arango, C., Banaj, N., Bouix, S., Bousman, C. A., Brouwer, R. M., Bruggemann, J., Bustillo, J., Cahn, W., Calhoun, V., Cannon, D., Carr, V., Catts, S., Chen, J., Chen, J. X., Chen, X., Chiapponi, C., Cho, Kl K., Ciullo, V., Corvin, A. S., Crespo-Facorro, B., Cropley, V., De Rossi, P., Diaz-Caneja, C. M., Dickie, E. W., Ehrlich, S., Fan, F. M., Faskowitz, J., Fatouros-Bergman, H., Flyckt, L., Ford, J. M., Fouche, J. P., Fukunaga, M., Gill, M., Glahn, D. C., Gollub, R., Goudzwaard, E. D., Guo, H., Gur, R. E., Gur, R. C., Gurholt, T. P., Hashimoto, R., Hatton, S. N., Henskens, F. A., Hibar, D. P., Hickie, I. B., Hong, L. E., Horacek, J., Howells, F. M., Hulshoff Pol, H. E., Hyde, C. L., Isaev, D., Jablensky, A., Jansen, P. R., Janssen, J., Jönsson, E. G., Jung, L. A., Kahn, R. S., Kikinis, Z., Liu, K., Klauser, P., Knöchel, C., Kubicki, M., Lagopoulos, J., Langen, C., Lawrie, S., Lenroot, R. K., Lim, K. O., Lopez-Jaramillo, C., Lyall, A., Magnotta, V., Mandl, R. C.W., Mathalon, D. H., McCarley, R. W., McCarthy-Jones, S., McDonald, C., McEwen, S., McIntosh, A., Melicher, T., Mesholam-Gately, R. I., Michie, P. T., Mowry, B., Mueller, B. A., Newell, D. T., O'Donnell, P., Oertel-Knöchel, V., Oestreich, L., Paciga, S. A., Pantelis, C., Pasternak, O., Pearlson, G., Pellicano, G. R., Pereira, A., Pineda Zapata, J., Piras, F., Potkin, S. G., Preda, A., Rasser, P. E., Roalf, D. R., Roiz, R., Roos, A., Rotenberg, D., Satterthwaite, T. D., Savadjiev, P., Schall, U., Scott, R. J., Seal, M. L., Seidman, L. J., Shannon Weickert, C., Whelan, C. D., Shenton, M. E., Kwon, J. S., Spalletta, G., Spaniel, F., Sprooten, E., Stäblein, M., Stein, D. J., Sundram, S., Tan, Y., Tan, S., Tang, S., Temmingh, H. S., Westlye, L. T., Tønnesen, S., Tordesillas-Gutierrez, D., Doan, N. T., Vaidya, J., Van Haren, N. E.M., Vargas, C. D., Vecchio, D., Velakoulis, D., Voineskos, A., Voyvodic, J. Q., Wang, Z., Wan, P., Wei, D., Weickert, T. W., Whalley, H., White, T., Whitford, T. J., Wojcik, J. D., Xiang, H., Xie, Z., Yamamori, H., Yang, F., Yao, N., Zhang, G., Zhao, J., Van Erp, T. G.M., Turner, J., Thompson, P. M., Donohoe, G., Onderzoeksgroep 1, Brain, Affectieve & Psychotische Med., Research Office, Onderzoek Bob Oranje, Onderzoeksgroep 11, Onderzoeksgroep 8, Onderzoeksgroep 4, Kelly, S., Jahanshad, N., Zalesky, A., Kochunov, P., Agartz, I., Alloza, C., Andreassen, O. A., Arango, C., Banaj, N., Bouix, S., Bousman, C. A., Brouwer, R. M., Bruggemann, J., Bustillo, J., Cahn, W., Calhoun, V., Cannon, D., Carr, V., Catts, S., Chen, J., Chen, J. X., Chen, X., Chiapponi, C., Cho, Kl K., Ciullo, V., Corvin, A. S., Crespo-Facorro, B., Cropley, V., De Rossi, P., Diaz-Caneja, C. M., Dickie, E. W., Ehrlich, S., Fan, F. M., Faskowitz, J., Fatouros-Bergman, H., Flyckt, L., Ford, J. M., Fouche, J. P., Fukunaga, M., Gill, M., Glahn, D. C., Gollub, R., Goudzwaard, E. D., Guo, H., Gur, R. E., Gur, R. C., Gurholt, T. P., Hashimoto, R., Hatton, S. N., Henskens, F. A., Hibar, D. P., Hickie, I. B., Hong, L. E., Horacek, J., Howells, F. M., Hulshoff Pol, H. E., Hyde, C. L., Isaev, D., Jablensky, A., Jansen, P. R., Janssen, J., Jönsson, E. G., Jung, L. A., Kahn, R. S., Kikinis, Z., Liu, K., Klauser, P., Knöchel, C., Kubicki, M., Lagopoulos, J., Langen, C., Lawrie, S., Lenroot, R. K., Lim, K. O., Lopez-Jaramillo, C., Lyall, A., Magnotta, V., Mandl, R. C.W., Mathalon, D. H., McCarley, R. W., McCarthy-Jones, S., McDonald, C., McEwen, S., McIntosh, A., Melicher, T., Mesholam-Gately, R. I., Michie, P. T., Mowry, B., Mueller, B. A., Newell, D. T., O'Donnell, P., Oertel-Knöchel, V., Oestreich, L., Paciga, S. A., Pantelis, C., Pasternak, O., Pearlson, G., Pellicano, G. R., Pereira, A., Pineda Zapata, J., Piras, F., Potkin, S. G., Preda, A., Rasser, P. E., Roalf, D. R., Roiz, R., Roos, A., Rotenberg, D., Satterthwaite, T. D., Savadjiev, P., Schall, U., Scott, R. J., Seal, M. L., Seidman, L. J., Shannon Weickert, C., Whelan, C. D., Shenton, M. E., Kwon, J. S., Spalletta, G., Spaniel, F., Sprooten, E., Stäblein, M., Stein, D. J., Sundram, S., Tan, Y., Tan, S., Tang, S., Temmingh, H. S., Westlye, L. T., Tønnesen, S., Tordesillas-Gutierrez, D., Doan, N. T., Vaidya, J., Van Haren, N. E.M., Vargas, C. D., Vecchio, D., Velakoulis, D., Voineskos, A., Voyvodic, J. Q., Wang, Z., Wan, P., Wei, D., Weickert, T. W., Whalley, H., White, T., Whitford, T. J., Wojcik, J. D., Xiang, H., Xie, Z., Yamamori, H., Yang, F., Yao, N., Zhang, G., Zhao, J., Van Erp, T. G.M., Turner, J., Thompson, P. M., and Donohoe, G.
Published: 2018

25. Positive symptoms associate with cortical thinning in the superior temporal gyrus via the enigma schizophrenia consortium

Author: Walton, E., Hibar, D. P., van Erp, T. G M, Potkin, S. G., Roiz-Santiañez, R., Crespo-Facorro, B., Suarez-Pinilla, P., Van Haren, N. E M, de Zwarte, S. M C, Kahn, R. S., Cahn, W., Doan, N. T., Jørgensen, K. N., Gurholt, T. P., Agartz, I., Andreassen, O. A., Westlye, L. T., Melle, I., Berg, A. O., Mørch-Johnsen, L., Færden, A., Flyckt, L., Fatouros-Bergman, H., Jönsson, E. G., Hashimoto, R., Yamamori, H., Fukunaga, M., Preda, A., De Rossi, P., Piras, F., Banaj, N., Ciullo, V., Spalletta, G., Gur, R. E., Gur, R. C., Wolf, D. H., Satterthwaite, T. D., Beard, L. M., Sommer, I. E., Koops, S., Gruber, O., Richter, A., Krämer, B., Kelly, S., Donohoe, G., McDonald, C., Cannon, D. M., Corvin, A., Gill, M., Di Giorgio, A., Bertolino, A., Lawrie, S., Nickson, T., Whalley, H. C., Neilson, E., Calhoun, V. D., Thompson, P. M., Turner, J. A., Ehrlich, S., Farde, L., Engberg, G., Erhardt, S., Cervenka, S., Schwieler, L., Piehl, F., Ikonen, P., Collste, K., Orhan, F., Malmqvist, A., and Hedberg, M.
Subjects: Male, genetic structures, Planum temporale, FreeSurfer, Audiology, Brain mapping, Superior temporal gyrus, 0302 clinical medicine, enigma, Prospective Studies, psychosis, bipolar disorder, Brain Mapping, Positive and Negative Syndrome Scale, positive and negative syndrome scale, ENIGMA, Magnetic Resonance Imaging, Temporal Lobe, Multicenter Study, Psychiatry and Mental health, superior temporal gyrus, Schizophrenia, cerebral-cortex, Female, Schizophrenic Psychology, auditory verbal hallucinations, Psychology, comprehension, MRI, freesurfer, metaanalysis, Adult, medicine.medical_specialty, Psychosis, cortical thickness, positive symptoms, scale for the assessment of positive symptoms, schizophrenia, Humans, Psychiatric Status Rating Scales, Psychiatry and Mental Health, 1st-episode schizophrenia, behavioral disciplines and activities, Article, Temporal lobe, 03 medical and health sciences, Journal Article, medicine, Bipolar disorder, Psychiatry, mri, medicine.disease, thickness, 030227 psychiatry, planum temporale, 1st episode schizophrenia, 030217 neurology & neurosurgery, Meta-Analysis
Abstract: OBJECTIVE: Based on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia.METHOD: This prospective meta-analysis includes data from 1987 individuals with schizophrenia collected at seventeen centres around the world that contribute to the ENIGMA Schizophrenia Working Group. STG thickness measures were extracted from T1-weighted brain scans using FreeSurfer. The study performed a meta-analysis of effect sizes across sites generated by a model predicting left or right STG thickness with a positive symptom severity score (harmonized SAPS or PANSS-positive scores), while controlling for age, sex and site. Secondary models investigated relationships between antipsychotic medication, duration of illness, overall illness severity, handedness and STG thickness.RESULTS: Positive symptom severity was negatively related to STG thickness in both hemispheres (left: βstd = -0.052; P = 0.021; right: βstd = -0.073; P = 0.001) when statistically controlling for age, sex and site. This effect remained stable in models including duration of illness, antipsychotic medication or handedness.CONCLUSION: Our findings further underline the important role of the STG in hallmark symptoms in schizophrenia. These findings can assist in advancing insight into symptom-relevant pathophysiological mechanisms in schizophrenia.
Published: 2017

26. Supplementary Material for: Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia

Author: Comasco, E., Vumma, R., Toffoletto, S., Johansson, J., Flyckt, L., Lewander, T., Oreland, L., Bjerkenstedt, L., Andreou, D., Söderman, E., Terenius, L., Agartz, I., Jönsson, E.G., and Venizelos, N.
Abstract: Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5/LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system L in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters (maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.
Published: 2017
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27. Cerebrospinal fluid levels of sphingolipids associate with disease severity in first episode psychosis patients

Author: Checa, Antonio, primary, Malmqvist, Anna, additional, Flyckt, Lena, additional, Schwieler, Lilly, additional, Samuelsson, Martin, additional, Skogh, Elisabeth, additional, Cervenka, Simon, additional, Dahl, Marja-Liisa, additional, Piehl, Fredrik, additional, Erhardt, Sophie, additional, Wheelock, Craig E., additional, Farde, L., additional, Flyckt, L., additional, Engberg, G., additional, Erhardt, S., additional, Fatouros-Bergman, H., additional, Cervenka, S., additional, Schwieler, L., additional, Piehl, F., additional, Agartz, I., additional, Collste, K., additional, Victorsson, P., additional, Malmqvist, A., additional, Hedberg, M., additional, and Orhan, F., additional
Published: 2018
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28. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group

Author: Kelly, S, primary, Jahanshad, N, additional, Zalesky, A, additional, Kochunov, P, additional, Agartz, I, additional, Alloza, C, additional, Andreassen, O A, additional, Arango, C, additional, Banaj, N, additional, Bouix, S, additional, Bousman, C A, additional, Brouwer, R M, additional, Bruggemann, J, additional, Bustillo, J, additional, Cahn, W, additional, Calhoun, V, additional, Cannon, D, additional, Carr, V, additional, Catts, S, additional, Chen, J, additional, Chen, J-x, additional, Chen, X, additional, Chiapponi, C, additional, Cho, Kl K, additional, Ciullo, V, additional, Corvin, A S, additional, Crespo-Facorro, B, additional, Cropley, V, additional, De Rossi, P, additional, Diaz-Caneja, C M, additional, Dickie, E W, additional, Ehrlich, S, additional, Fan, F-m, additional, Faskowitz, J, additional, Fatouros-Bergman, H, additional, Flyckt, L, additional, Ford, J M, additional, Fouche, J-P, additional, Fukunaga, M, additional, Gill, M, additional, Glahn, D C, additional, Gollub, R, additional, Goudzwaard, E D, additional, Guo, H, additional, Gur, R E, additional, Gur, R C, additional, Gurholt, T P, additional, Hashimoto, R, additional, Hatton, S N, additional, Henskens, F A, additional, Hibar, D P, additional, Hickie, I B, additional, Hong, L E, additional, Horacek, J, additional, Howells, F M, additional, Hulshoff Pol, H E, additional, Hyde, C L, additional, Isaev, D, additional, Jablensky, A, additional, Jansen, P R, additional, Janssen, J, additional, Jönsson, E G, additional, Jung, L A, additional, Kahn, R S, additional, Kikinis, Z, additional, Liu, K, additional, Klauser, P, additional, Knöchel, C, additional, Kubicki, M, additional, Lagopoulos, J, additional, Langen, C, additional, Lawrie, S, additional, Lenroot, R K, additional, Lim, K O, additional, Lopez-Jaramillo, C, additional, Lyall, A, additional, Magnotta, V, additional, Mandl, R C W, additional, Mathalon, D H, additional, McCarley, R W, additional, McCarthy-Jones, S, additional, McDonald, C, additional, McEwen, S, additional, McIntosh, A, additional, Melicher, T, additional, Mesholam-Gately, R I, additional, Michie, P T, additional, Mowry, B, additional, Mueller, B A, additional, Newell, D T, additional, O'Donnell, P, additional, Oertel-Knöchel, V, additional, Oestreich, L, additional, Paciga, S A, additional, Pantelis, C, additional, Pasternak, O, additional, Pearlson, G, additional, Pellicano, G R, additional, Pereira, A, additional, Pineda Zapata, J, additional, Piras, F, additional, Potkin, S G, additional, Preda, A, additional, Rasser, P E, additional, Roalf, D R, additional, Roiz, R, additional, Roos, A, additional, Rotenberg, D, additional, Satterthwaite, T D, additional, Savadjiev, P, additional, Schall, U, additional, Scott, R J, additional, Seal, M L, additional, Seidman, L J, additional, Shannon Weickert, C, additional, Whelan, C D, additional, Shenton, M E, additional, Kwon, J S, additional, Spalletta, G, additional, Spaniel, F, additional, Sprooten, E, additional, Stäblein, M, additional, Stein, D J, additional, Sundram, S, additional, Tan, Y, additional, Tan, S, additional, Tang, S, additional, Temmingh, H S, additional, Westlye, L T, additional, Tønnesen, S, additional, Tordesillas-Gutierrez, D, additional, Doan, N T, additional, Vaidya, J, additional, van Haren, N E M, additional, Vargas, C D, additional, Vecchio, D, additional, Velakoulis, D, additional, Voineskos, A, additional, Voyvodic, J Q, additional, Wang, Z, additional, Wan, P, additional, Wei, D, additional, Weickert, T W, additional, Whalley, H, additional, White, T, additional, Whitford, T J, additional, Wojcik, J D, additional, Xiang, H, additional, Xie, Z, additional, Yamamori, H, additional, Yang, F, additional, Yao, N, additional, Zhang, G, additional, Zhao, J, additional, van Erp, T G M, additional, Turner, J, additional, Thompson, P M, additional, and Donohoe, G, additional
Published: 2017
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29. Associations between central chemokine levels and glial activation in first episode psychosis – a positron emission tomography study

Author: Collste, K., primary, Orhan, F., additional, Erhardt, S., additional, Schwieler, L., additional, Flyckt, L., additional, Farde, L., additional, Engberg, G., additional, and Cervenka, S., additional
Published: 2017
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30. Lower levels of the glial cell marker TSPO in drug-naive first-episode psychosis patients as measured using PET and [C-11]PBR28

Author: Collste, K., Plaven-Sigray, P., Fatouros-Bergman, H., Victorsson, P., Schain, M., Forsberg, A., Amini, N., Aeinehband, S., Erhardt, S., Halldin, C., Flyckt, L., Farde, L., Cervenka, Simon, Collste, K., Plaven-Sigray, P., Fatouros-Bergman, H., Victorsson, P., Schain, M., Forsberg, A., Amini, N., Aeinehband, S., Erhardt, S., Halldin, C., Flyckt, L., Farde, L., and Cervenka, Simon
Abstract: Several lines of evidence are indicative of a role for immune activation in the pathophysiology of schizophrenia. Nevertheless, studies using positron emission tomography (PET) and radioligands for the translocator protein (TSPO), a marker for glial activation, have yielded inconsistent results. Whereas early studies using a radioligand with low signal-to-noise in small samples showed increases in patients, more recent studies with improved methodology have shown no differences or trend-level decreases. Importantly, all patients investigated thus far have been on antipsychotic medication, and as these compounds may dampen immune cell activity, this factor limits the conclusions that can be drawn. Here, we examined 16 drug-naive, first-episode psychosis patients and 16 healthy controls using PET and the TSPO radioligand [C-11]PBR28. Gray matter (GM) volume of distribution (V-T) derived from a two-tissue compartmental analysis with arterial input function was the main outcome measure. Statistical analyses were performed controlling for both TSPO genotype, which is known to affect [C-11]PBR28 binding, and gender. There was a significant reduction of [C-11]PBR28 V-T in patients compared with healthy controls in GM as well as in secondary regions of interest. No correlation was observed between GM V-T and clinical or cognitive measures after correction for multiple comparisons. The observed decrease in TSPO binding suggests reduced numbers or altered function of immune cells in brain in early-stage schizophrenia.
Published: 2017
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31. Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium

Author: Onderzoeksgroep 4, Brain, Onderzoeksgroep 11, Affectieve & Psychotische Med., Curr. Onderwijs Huisartsgeneeskunde, Affectieve & Psychotisch Ond., Risico & Preventie Ond., Walton, E., Hibar, D. P., van Erp, T. G M, Potkin, S. G., Roiz-Santiañez, R., Crespo-Facorro, B., Suarez-Pinilla, P., Van Haren, N. E M, de Zwarte, S. M C, Kahn, R. S., Cahn, W., Doan, N. T., Jørgensen, K. N., Gurholt, T. P., Agartz, I., Andreassen, O. A., Westlye, L. T., Melle, I., Berg, A. O., Mørch-Johnsen, L., Færden, A., Flyckt, L., Fatouros-Bergman, H., Jönsson, E. G., Hashimoto, R., Yamamori, H., Fukunaga, M., Preda, A., De Rossi, P., Piras, F., Banaj, N., Ciullo, V., Spalletta, G., Gur, R. E., Gur, R. C., Wolf, D. H., Satterthwaite, T. D., Beard, L. M., Sommer, I. E., Koops, S., Gruber, O., Richter, A., Krämer, B., Kelly, S., Donohoe, G., McDonald, C., Cannon, D. M., Corvin, A., Gill, M., Di Giorgio, A., Bertolino, A., Lawrie, S., Nickson, T., Whalley, H. C., Neilson, E., Calhoun, V. D., Thompson, P. M., Turner, J. A., Ehrlich, S., Farde, L., Engberg, G., Erhardt, S., Cervenka, S., Schwieler, L., Piehl, F., Ikonen, P., Collste, K., Orhan, F., Malmqvist, A., Hedberg, M., Onderzoeksgroep 4, Brain, Onderzoeksgroep 11, Affectieve & Psychotische Med., Curr. Onderwijs Huisartsgeneeskunde, Affectieve & Psychotisch Ond., Risico & Preventie Ond., Walton, E., Hibar, D. P., van Erp, T. G M, Potkin, S. G., Roiz-Santiañez, R., Crespo-Facorro, B., Suarez-Pinilla, P., Van Haren, N. E M, de Zwarte, S. M C, Kahn, R. S., Cahn, W., Doan, N. T., Jørgensen, K. N., Gurholt, T. P., Agartz, I., Andreassen, O. A., Westlye, L. T., Melle, I., Berg, A. O., Mørch-Johnsen, L., Færden, A., Flyckt, L., Fatouros-Bergman, H., Jönsson, E. G., Hashimoto, R., Yamamori, H., Fukunaga, M., Preda, A., De Rossi, P., Piras, F., Banaj, N., Ciullo, V., Spalletta, G., Gur, R. E., Gur, R. C., Wolf, D. H., Satterthwaite, T. D., Beard, L. M., Sommer, I. E., Koops, S., Gruber, O., Richter, A., Krämer, B., Kelly, S., Donohoe, G., McDonald, C., Cannon, D. M., Corvin, A., Gill, M., Di Giorgio, A., Bertolino, A., Lawrie, S., Nickson, T., Whalley, H. C., Neilson, E., Calhoun, V. D., Thompson, P. M., Turner, J. A., Ehrlich, S., Farde, L., Engberg, G., Erhardt, S., Cervenka, S., Schwieler, L., Piehl, F., Ikonen, P., Collste, K., Orhan, F., Malmqvist, A., and Hedberg, M.
Published: 2017

32. Clinical and biochemical effects of citalopram, a selective 5-HT reuptake inhibitor — a dose-response study in depressed patients

Author: Bjerkenstedt, L., Edman, G., Flyckt, L., Hagenfeldt, L., Sedvall, G., and Wiesel, F. A.
Published: 1985
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33. Relationship between clinical effects, serum drug concentration and serotonin uptake inhibition in depressed patients treated with citalopram: A double-blind comparison of three dose levels

Author: Bjerkenstedt, L., Flyckt, L., Overø, K. Fredricson, and Lingjærde, O.
Published: 1985
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34. Radionuclide cisternography and computed tomography in 30 healthy volunteers

Author: Bergstrand, G., Oxenstierna, G., Flyckt, L., Larsson, S. A., and Sedvall, G.
Published: 1986
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35. P.1.i.053 - Associations between central chemokine levels and glial activation in first episode psychosis – a positron emission tomography study

Author: Collste, K., Orhan, F., Erhardt, S., Schwieler, L., Flyckt, L., Farde, L., Engberg, G., and Cervenka, S.
Published: 2017
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36. Cognitive Performance in Drug-naÏve First Episode Schizophrenia (FES) Patients

Author: Fatouros-Bergman, H., primary, Cervenka, C., additional, Flyckt, L., additional, Edman, G., additional, Schwieler, L., additional, Ikonen, P., additional, Collste, K., additional, Piehl, F., additional, Agartz, I., additional, Engberg, G., additional, Erhardt, S., additional, and Farde, L., additional
Published: 2015
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37. Burden of Informal Care Giving to Patients with Schizophrenia – It's Magnitude and Determinants

Author: Flyckt, L., primary and Fatouros-Bergman, H., additional
Published: 2015
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38. Tryptophan Metabolism Along the Kynurenine Pathway Downstream of Toll-like Receptor Stimulation in Peripheral Monocytes.

Author: Orhan, F., Bhat, M., Sandberg, K., Ståhl, S., Piehl, F., Svensson, C., Erhardt, S., Schwieler, L., Farde, L., Flyckt, L., Engberg, G., Fatouros‐Bergman, H., Cervenka, S., Agartz, I., Ikonen, P., Collste, K., Malmqvist, A., and Hedberg, M.
Subjects: TRYPTOPHAN metabolism, KYNURENINE, TOLL-like receptors, MONOCYTES, QUINOLINIC acid, LIQUID chromatography-mass spectrometry, TARGETED drug delivery
Abstract: Tryptophan degradation along the kynurenine pathway is of central importance for the immune function. Toll-like receptors ( TLRs), representing the first line of immune defence against pathogens, are expressed in various cell types. The most abundant expression is found on monocytes, macrophages and dendritic cells. The aim of this study was to investigate whether stimulation with different TLR ligands induces the kynurenine pathway in human peripheral monocytes. Cell supernatants were analysed using a liquid chromatography/mass spectrometry to measure kynurenine, kynurenic acid ( KYNA), quinolinic acid ( QUIN) and tryptophan. Stimulation of TLR-2, TLR-3, TLR-4, TLR-7/8 and TLR-9 was found to induce the production of kynurenine, but only stimulation of TLR-3 increased levels of further downstream metabolites, such as KYNA and QUIN. Stimulation of TLR-1, TLR-5 and TLR-6 did not induce the kynurenine pathway. Taken together, this study provides novel evidence demonstrating that TLR activation induces a pattern of downstream tryptophan degradation along the kynurenine pathway in monocytes. The results of this study may implicate that TLRs can be used as new drug targets for the regulation of aberrant tryptophan metabolism along this pathway, a potential therapeutic strategy that may be of importance in several disorders. [ABSTRACT FROM AUTHOR]
Published: 2016
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39. Cerebellar volume and cerebellocerebral structural covariance in schizophrenia: a multisite mega-analysis of 983 patients and 1349 healthy controls

Author: Moberget, T, Doan, N T, Alnæs, D, Kaufmann, T, Córdova-Palomera, A, Lagerberg, T V, Diedrichsen, J, Schwarz, E, Zink, M, Eisenacher, S, Kirsch, P, Jönsson, E G, Fatouros-Bergman, H, Flyckt, L, Pergola, G, Quarto, T, Bertolino, A, Barch, D, Meyer-Lindenberg, A, Agartz, I, Andreassen, O A, and Westlye, L T
Abstract: Although cerebellar involvement across a wide range of cognitive and neuropsychiatric phenotypes is increasingly being recognized, previous large-scale studies in schizophrenia (SZ) have primarily focused on supratentorial structures. Hence, the across-sample reproducibility, regional distribution, associations with cerebrocortical morphology and effect sizes of cerebellar relative to cerebral morphological differences in SZ are unknown. We addressed these questions in 983 patients with SZ spectrum disorders and 1349 healthy controls (HCs) from 14 international samples, using state-of-the-art image analysis pipelines optimized for both the cerebellum and the cerebrum. Results showed that total cerebellar grey matter volume was robustly reduced in SZ relative to HCs (Cohens’s d=−0.35), with the strongest effects in cerebellar regions showing functional connectivity with frontoparietal cortices (d=−0.40). Effect sizes for cerebellar volumes were similar to the most consistently reported cerebral structural changes in SZ (e.g., hippocampus volume and frontotemporal cortical thickness), and were highly consistent across samples. Within groups, we further observed positive correlations between cerebellar volume and cerebral cortical thickness in frontotemporal regions (i.e., overlapping with areas that also showed reductions in SZ). This cerebellocerebral structural covariance was strongest in SZ, suggesting common underlying disease processes jointly affecting the cerebellum and the cerebrum. Finally, cerebellar volume reduction in SZ was highly consistent across the included age span (16–66 years) and present already in the youngest patients, a finding that is more consistent with neurodevelopmental than neurodegenerative etiology. Taken together, these novel findings establish the cerebellum as a key node in the distributed brain networks underlying SZ.
Published: 2018
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40. Functional characterization of tyrosine transport in fibroblast cells from healthy controls

Author: Vumma, R., Wiesel, F.-A., Flyckt, L., Bjerkenstedt, Lars, Venizelos, N., Vumma, R., Wiesel, F.-A., Flyckt, L., Bjerkenstedt, Lars, and Venizelos, N.
Abstract: Human fibroblast cells are an advantageous model to study the transport of amino acids across cell membranes, since one can control the environmental factors. A major problem in all earlier studies is the lack of precise and detailed knowledge regarding the expression and functionality of tyrosine transporters in human fibroblasts. This motivated us to perform a systematic functional characterization of the tyrosine transport in fibroblast cells with respect to the isoforms of system-L (LAT1, LAT2, LAT3, LAT4), which is the major transporter of tyrosine. Ten (n = 10) fibroblast cell lines from healthy volunteers were included in the study. Uptake of L-[U-14C] tyrosine in fibroblasts was measured using the cluster tray method in the presence and absence of excess concentrations of various combinations of inhibitors. This study demonstrated that LAT1 is involved in 90% of total uptake of tyrosine and also around 51% of alanine. Not more than 10% can be accounted for by LAT2, LAT3 and LAT4 isoforms. LAT2 seems to be functionally weak in uptake of tyrosine while LAT3 and LAT4 contributed around 7%. 10% could be contributed by system-A (ATA2 isoform). Alanine consequently inhibited the tyrosine transport by up to 60%. Tyrosine transport through the LAT1 isoform has a higher affinity compared to system-L. In conclusion, the LAT1 isoform is the major transporter of tyrosine in human fibroblast cells. Competition between tyrosine and alanine for transport is shown to exist, probably between LAT1 and LAT2 isoforms. This study established fibroblast cells as a suitable experimental model for studying amino acid transport defects in humans. © 2008 Elsevier Ireland Ltd. All rights reserved.
Published: 2008
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41. The complexity of using D2-dopamine antagonists in the treatment of patients with schizophrenia

Author: Wiesel, F.-A., Bjerkenstedt, L., Edman, G., Flyckt, L., Venizelos, Nikolaos, Wiesel, F.-A., Bjerkenstedt, L., Edman, G., Flyckt, L., and Venizelos, Nikolaos
Abstract: Schizophrenia is a complex disorder and the view that schizophrenia is caused by hyperdopaminergic activity is an oversimplification. In fact, there are clinical evidence in accordance with a hypodopaminergic condition. Thus, untreated patients show motor disturbances in line with a decreased dopamine activity in the extrapyramidal system, likewise cognitive deficits and negative symptoms. In our research we have explored the evidence of schizophrenia as a hyper- or hypodopaminergic condition. With Positron Emission Tomography (PET) we have not seen any evidence of increased D2-dopamine receptors in the brain of never medicated patients. The major dopamine metabolite homovanillic acid (HVA) was lowered in CSF in line with a decreased dopamine turnover in the brain. Tyrosine is precursor to the synthesis of dopamine and for that aim we have made transport studies in an in vitro model with fibroblasts to determine tyrosine kinetics. The results demonstrated that tyrosine transport is lower in patients with schizophrenia in comparison to healthy controls. Tyrosine kinetics measured with PET demonstrated dysregulation of tyrosine transport into the brain. We have found evidence of schizophrenia as a hypodopaminergic condition. This fact is a problem realizing that our antipsychotics are D2-dopamine antagonists, thus decreasing dopamine activity even further. The concept of schizophrenia as both a hypo- and hyperdopaminergic condition may explain why clozapine, a week D2-antagonist, works more efficiently than other antipsychotic compounds. It should be recognized that positive symptoms are, at least partly, related to changes in dopamine activity and therefore respond very efficiently to D2-dopamine antagonists.
Published: 2007
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42. Dopamine D3 receptor gene Ser9Gly variant and schizophrenia: association study and meta-analysis

Author: Jonsson, EG, Flyckt, L, Burgert, E, Crocq, M-A, Forslund, K, Mattila-Evenden, M, Rylander, G, Asberg, M, Nimgaonkar, VL, Edman, G, Bjerkenstedt, L, Wiesel, F-A, Sedvall, GC, Jonsson, EG, Flyckt, L, Burgert, E, Crocq, M-A, Forslund, K, Mattila-Evenden, M, Rylander, G, Asberg, M, Nimgaonkar, VL, Edman, G, Bjerkenstedt, L, Wiesel, F-A, and Sedvall, GC
Published: 2003

43. No association between a putative functional promoter variant in the dopamine beta-hydroxylase gene and schizophrenia

Author: Jonsson, E G, Jamra, R A, Schumacher, J, Flyckt, L, Edman, G, Forslund, K, Mattila-Evenden, M, Rylander, G, Aasberg, M, Bjerkenstedt, L, Wiesel, F-A, Propping, P, Cichon, S, Nothen, M M, Sedvall, G C, Jonsson, E G, Jamra, R A, Schumacher, J, Flyckt, L, Edman, G, Forslund, K, Mattila-Evenden, M, Rylander, G, Aasberg, M, Bjerkenstedt, L, Wiesel, F-A, Propping, P, Cichon, S, Nothen, M M, and Sedvall, G C
Published: 2003

44. PMH44 AN OBSERVATIONAL STUDY OF THE BURDEN OF INFORMAL CAREGIVERS TO OUT-PATIENTS WITH SCHIZOPHRENIA SPECTRUM DISORDERS

Author: Flyckt, L, primary, Granström, O, additional, Löthman, A, additional, Jörgensen, L, additional, and Koernig, T, additional
Published: 2010
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45. Aberrant Tyrosine Transport - A Biological Marker for an Inherited Susceptibility to Schizophrenia

Author: Flyckt, L., primary and Edman, G., additional
Published: 2009
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46. Aberrant Tyrosine Transport Across the Cell Membrane in Patients With Schizophrenia

Author: Flyckt, L, Venizelos, N, Edman, G, Bjerkenstedt, L, Hagenfeldt, L, Wiesel, F-A, Flyckt, L, Venizelos, N, Edman, G, Bjerkenstedt, L, Hagenfeldt, L, and Wiesel, F-A
Published: 2001

47. Predicting 5-year outcome in first episode psychosis-construction of a prognostic rating scale

Author: Flyckt, L., primary, Mattsson, M., additional, Edman, G., additional, Carlsson, R., additional, and Cullberg, J., additional
Published: 2008
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48. Muscle biopsy, Macro EMG and clinical characteristics in patients with schizophrenia

Author: Flyckt, L, Borg, J, Borg, K, Ansved, T, Edman, G, Sydow, O, Bjerkenstedt, L, Wiesel, F-A, Flyckt, L, Borg, J, Borg, K, Ansved, T, Edman, G, Sydow, O, Bjerkenstedt, L, and Wiesel, F-A
Published: 2000

49. Neuromuscular and psychomotor abnormalities in patients with schizophrenia and their first-degree relatives

Author: Flyckt, L, Wiesel, F-A, Borg, J, Edman, G, Ansved, T, Sydow, O, Borg, K, Flyckt, L, Wiesel, F-A, Borg, J, Edman, G, Ansved, T, Sydow, O, and Borg, K
Published: 2000

50. The complexity of using D2-dopamine antagonists in the treatment of patients with schizophrenia

Author: Wiesel, F.-A., primary, Bjerkenstedt, L., additional, Edman, G., additional, Flyckt, L., additional, and Venizelos, N., additional
Published: 2007
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