Cortical thinning and flattening in schizophrenia and their unaffected parents

Background: Schizophrenia  is a neurodevelopmental disorder with high heritability. Widespread cortical thinning has been identified in schizophrenia, suggesting that it is a result of cortical development deficit. However, the findings of other cortical morphological indexes of patients are inconsistent, and the research on their relationship with genetic risk factors for schizophrenia is rare. Methods: In order to investigate cortical morphology deficits and their disease-related genetic liability in schizophrenia, we analyzed a sample of 33 patients with schizophrenia, 60 biological parents of the patients, as well as 30 young controls for patients and 28 elderly controls for parents with age, sex and education level being well-matched. We calculated vertex-wise measurements of cortical thickness, surface area, local gyrification index, sulcal depth, and their correlation with the clinical and cognitive characteristics. Results: Widespread cortical thinning of the fronto-temporo-parietal region, sulcal flattening of the insula and gyrification reduction of the frontal cortex were observed in schizophrenia patients. Conjunction analysis revealed that patients with schizophrenia and their parents shared significant cortical thinning of bilateral prefrontal and insula, left lateral occipital and fusiform regions (Monte Carlo correction, P<0.05), as well as a trend-level sulcal depth reduction mainly in bilateral insula and occipital cortex. We observed comprehensive cognitive deficits in patients and similar impairment in the speed of processing of their unaffected parents. Significant associations between lower processing speed and thinning of the frontal cortex and flattening of the parahippocampal gyrus were found in patients and their parents, respectively. However, no significant correlation between abnormal measurements of cortical morphology and clinical characteristics was found. Conclusion: The results suggest that cortical morphology may be susceptible to a genetic risk of schizophrenia and could underlie the cognitive dysfunction in patients and their unaffected relatives. The abnormalities shared with unaffected parents allow us to better understand the disease-specific genetic effect on cortical development.