Dataset Information

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

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.

SUBMITTER: van Erp TGM

PROVIDER: S-EPMC6177304 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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

van Erp Theo G M TGM Walton Esther E Hibar Derrek P DP Schmaal Lianne L Jiang Wenhao W Glahn David C DC Pearlson Godfrey D GD Yao Nailin N Fukunaga Masaki M Hashimoto Ryota R Okada Naohiro N Yamamori Hidenaga H Bustillo Juan R JR Clark Vincent P VP Agartz Ingrid I Mueller Bryon A BA Cahn Wiepke W de Zwarte Sonja M C SMC Hulshoff Pol Hilleke E HE Kahn René S RS Ophoff Roel A RA van Haren Neeltje E M NEM Andreassen Ole A OA Dale Anders M AM Doan Nhat Trung NT Gurholt Tiril P TP Hartberg Cecilie B CB Haukvik Unn K UK Jørgensen Kjetil N KN Lagerberg Trine V TV Melle Ingrid I Westlye Lars T LT Gruber Oliver O Kraemer Bernd B Richter Anja A Zilles David D Calhoun Vince D VD Crespo-Facorro Benedicto B Roiz-Santiañez Roberto R Tordesillas-Gutiérrez Diana D Loughland Carmel C Carr Vaughan J VJ Catts Stanley S Cropley Vanessa L VL Fullerton Janice M JM Green Melissa J MJ Henskens Frans A FA Jablensky Assen A Lenroot Rhoshel K RK Mowry Bryan J BJ Michie Patricia T PT Pantelis Christos C Quidé Yann Y Schall Ulrich U Scott Rodney J RJ Cairns Murray J MJ Seal Marc M Tooney Paul A PA Rasser Paul E PE Cooper Gavin G Shannon Weickert Cynthia C Weickert Thomas W TW Morris Derek W DW Hong Elliot E Kochunov Peter P Beard Lauren M LM Gur Raquel E RE Gur Ruben C RC Satterthwaite Theodore D TD Wolf Daniel H DH Belger Aysenil A Brown Gregory G GG Ford Judith M JM Macciardi Fabio F Mathalon Daniel H DH O'Leary Daniel S DS Potkin Steven G SG Preda Adrian A Voyvodic James J Lim Kelvin O KO McEwen Sarah S Yang Fude F Tan Yunlong Y Tan Shuping S Wang Zhiren Z Fan Fengmei F Chen Jingxu J Xiang Hong H Tang Shiyou S Guo Hua H Wan Ping P Wei Dong D Bockholt Henry J HJ Ehrlich Stefan S Wolthusen Rick P F RPF King Margaret D MD Shoemaker Jody M JM Sponheim Scott R SR De Haan Lieuwe L Koenders Laura L Machielsen Marise W MW van Amelsvoort Therese T Veltman Dick J DJ Assogna Francesca F Banaj Nerisa N de Rossi Pietro P Iorio Mariangela M Piras Fabrizio F Spalletta Gianfranco G McKenna Peter J PJ Pomarol-Clotet Edith E Salvador Raymond R Corvin Aiden A Donohoe Gary G Kelly Sinead S Whelan Christopher D CD Dickie Erin W EW Rotenberg David D Voineskos Aristotle N AN Ciufolini Simone S Radua Joaquim J Dazzan Paola P Murray Robin R Reis Marques Tiago T Simmons Andrew A Borgwardt Stefan S Egloff Laura L Harrisberger Fabienne F Riecher-Rössler Anita A Smieskova Renata R Alpert Kathryn I KI Wang Lei L Jönsson Erik G EG Koops Sanne S Sommer Iris E C IEC Bertolino Alessandro A Bonvino Aurora A Di Giorgio Annabella A Neilson Emma E Mayer Andrew R AR Stephen Julia M JM Kwon Jun Soo JS Yun Je-Yeon JY Cannon Dara M DM McDonald Colm C Lebedeva Irina I Tomyshev Alexander S AS Akhadov Tolibjohn T Kaleda Vasily V Fatouros-Bergman Helena H Flyckt Lena L Busatto Geraldo F GF Rosa Pedro G P PGP Serpa Mauricio H MH Zanetti Marcus V MV Hoschl Cyril C Skoch Antonin A Spaniel Filip F Tomecek David D Hagenaars Saskia P SP McIntosh Andrew M AM Whalley Heather C HC Lawrie Stephen M SM Knöchel Christian C Oertel-Knöchel Viola V Stäblein Michael M Howells Fleur M FM Stein Dan J DJ Temmingh Henk S HS Uhlmann Anne A Lopez-Jaramillo Carlos C Dima Danai D McMahon Agnes A Faskowitz Joshua I JI Gutman Boris A BA Jahanshad Neda N Thompson Paul M PM Turner Jessica A JA

Biological psychiatry 20180514 9

<h4>Background</h4>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.<h4>Methods</h4>The study included data from 4474 individuals with schizophrenia (mean age, 32.3 y ...[more]

PMID: 29960671

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Project description:Emerging evidence points to proteoglycan abnormalities in the pathophysiology of schizophrenia (SZ). In particular, markedly abnormal expression of chondroitin sulfate proteoglycans (CSPGs), key components of the extracellular matrix, was observed in the medial temporal lobe. CSPG functions, including regulation of neuronal differentiation and migration, are highly relevant to the pathophysiology of SZ. CSPGs may exert similar functions in the olfactory epithelium (OE), a continuously regenerating neural tissue that shows cell and molecular abnormalities in SZ. We tested the hypothesis that CSPG expression in OE may be altered in SZ. CSPG-positive cells in postmortem OE from non-psychiatric control (n=9) and SZ (n=10) subjects were counted using computer-assisted light microscopy. 'Cytoplasmic' CSPG (c-CSPG) labeling was detected in sustentacular cells and some olfactory receptor neurons (c-CSPG+ORNs), while 'pericellular' CSPG (p-CSPG) labeling was found in basal cells and some ORNs (p-CSPG+ORNs). Dual labeling for CSPG and markers for mature and immature ORNs suggests that c-CSPG+ORNs correspond to mature ORNs, and p-CSPG+ORNs to immature ORNs. Previous studies in the same cohort demonstrated that densities of mature ORNs were unaltered (Arnold et al., 2001). In the present study, numerical densities of c-CSPG+ORNs were significantly decreased in SZ (p<0.025; 99.32% decrease), suggesting a reduction of CSPG expression in mature ORNs. Previous studies showed a striking increase in the ratios of immature neurons with respect to basal cells. In this study, we find that the ratio of p-CSPG+ORNs/CSPG+basal cells was significantly increased (p=0.03) in SZ, while numerical density changes of p-CSPG+ORNs (110.71% increase) or CSPG+basal cells (53.71% decrease), did not reach statistical significance. Together, these results indicate that CSPG abnormalities are present in the OE of SZ and specifically point to a reduction of CSPG expression in mature ORNs in SZ. Given the role CSPGs play in OE cell differentiation and axon guidance, we suggest that altered CSPG expression may contribute to ORN lineage dysregulation, and olfactory identification abnormalities, observed in SZ.

Dataset Information

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

Publications

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

Similar Datasets

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