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.
Bibliographical noteFunding Information:
The ENIGMA project is in part supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (Grant No. U54EB020403). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Acknowledgments for the various participating data contributors are listed in Supplement 1. Author contributions are as follows: protocol design, quality testing, and meta-analysis, TGMvE, EW, DPH, LS, and WJ; data collection, processing, analysis, and funding, TGMvE, EW, DPH, LS, WJ, DCG, GDP, NY, MF, RH, NO, HY, JRB, VPC, IA, BAM, WC, SMCdZ, HEHP, RSK, RAO, NEMvH, OAA, AMD, NTD, TPG, CBH, UKH, KNJ, TVL, IM, LTW, OG, BK, AR, DZ, VDC, BC-F, RR-S, MJC, VJC, SCa, JR, VLC, JMFu, MJG, FAH, AJ, RKL, CL, BJM, PTM, CP, YQ, PER, GC, US, RJS, MSe, PAT, CSW, TWW, DWM, EH, PK, LMB, REG, RCG, TDS, DHW, ABel, GGB, JMFo, FM, DHM, DSO, SGP, AP, JV, KOL, SM, FY, YT, STan, ZW, FF, JC, HX, STang, HG, PW, DW, HJB, SE, RPFW, MDK, JMSh, SRS, LDH, LK, MWM, TvA, DJV, FA, NB, PdR, MI, FP, GS, PJM, EP-C, JR, RSa, AC, GD, SKe, CDW, EWD, DR, ANV, SCi, PD, RM, TRM, ASi, SB, LE, FHa, AR-R, RSm, KIA, LW, EGJ, SKo, IECS, ABer, ABo, ADG, EN, ARM, JMSt, JSK, J-YY, DMC, CM, IL, AST, TA, VK, HF-B, LF, GFB, PGPR, MHS, MVZ, CH, ASk, FS, DT, SPH, AMM, HCW, SML, CK, VO-K, MSt, FMH, DJS, HST, AU, CL-J, DD, AM, JIF, BAG, NJ, PMT, and JAT; manuscript preparation, TGMvE, JAT, and PMT. All authors contributed edits and approved the contents of the manuscript. TGMvE has had a research contract with Otsuka Pharmaceutical. AP has served as a consultant for Boehringer Ingelheim. The remaining authors report no biomedical financial interests or potential conflicts of interest.
The ENIGMA project is in part supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (Grant No. U54EB020403). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Acknowledgments for the various participating data contributors are listed in Supplement 1 .
© 2018 Society of Biological Psychiatry
- Surface area