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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. METHOD. The study included data from 4474 individuals with schizophrenia (mean age=32.3, range: 11–78; 66% male) and 5098 healthy volunteers (mean age=32.8, range: 10–87; 53% male), assessed with standardized methods, at 39 centers worldwide. RESULTS. Compared to 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: 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, the effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were 2 to 3 times larger in antipsychotic medicated 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.

Hallucinations are a characteristic symptom of psychotic mental health conditions that are also experienced by many individuals without a clinical diagnosis. Hallucinations in schizophrenia have been linked to differences in the length of the paracingulate sulcus (PCS), a structure in the medial prefrontal cortex which has previously been associated with the ability to differentiate perceived and imagined information. We investigated whether this putative morphological basis for hallucinations extends to individuals without a clinical diagnosis, by examining whether nonclinical individuals with hallucinations have shorter PCS than nonclinical individuals without hallucinations. Structural MRI scans were examined from 3 demographically matched groups of individuals: 50 patients with psychotic diagnoses who experienced auditory verbal hallucinations (AVHs), 50 nonclinical individuals with AVHs, and 50 healthy control subjects with no life-time history of hallucinations. Results were verified using automated data-driven gyrification analyses. Patients with hallucinations had shorter PCS than both healthy controls and nonclinical individuals with hallucinations, with no difference between nonclinical individuals with hallucinations and healthy controls. These findings suggest that the association of shorter PCS length with hallucinations is specific to patients with a psychotic disorder. This presents challenges for full-continuum models of psychosis and suggests possible differences in the mechanisms underlying hallucinations in clinical and nonclinical groups.