Cortical thickness in first-episode schizophrenia patients and individuals at high familial risk: A cross-sectional comparison

Background: Schizophrenia is associated with cortical thickness reductions in the brain, but it is unclear whether these are present before illness onset, and to what extent they are driven by genetic factors. Methods: In the Edinburgh High Risk Study, structural MRI scans of 150 young individuals at high familial risk for schizophrenia, 34 patients with first-episode schizophrenia and 36 matched controls were acquired, and clinical information was collected for the following 10. years for the high-risk and control group. During this time, 17 high-risk individuals developed schizophrenia, on average 2.5. years after the scan, and 57 experienced isolated or sub-clinical psychotic symptoms. We applied surface-based analysis of the cerebral cortex to this cohort, and extracted cortical thickness in automatically parcellated regions. Results: Analysis of variance revealed widespread thinning of the cerebral cortex in first-episode patients, most pronounced in superior frontal, medial parietal, and lateral occipital regions (corrected p<10^-4). In contrast, cortical thickness reductions were only found in high-risk individuals in the left middle temporal gyrus (corrected p<0.05). There were no significant differences between those at high risk who later developed schizophrenia and those who remained well. Conclusions: These findings confirm cortical thickness reductions in schizophrenia patients. Increased familial risk for schizophrenia is associated with thinning in the left middle temporal lobe, irrespective of subsequent disease onset. The absence of widespread cortical thinning before disease onset implies that the cortical thinning is unlikely to simply reflect genetic liability to schizophrenia but is predominantly driven by disease-associated factors.