Widespread Reductions of Cortical Thickness in Schizophrenia and Spectrum Disorders and Evidence of Heritability

Context: Schizophrenia is a brain disorder with predominantly genetic risk factors, and previous research has identified heritable cortical and subcortical reductions in local brain volume. To our knowledge, cortical thickness, a measure of particular interest in schizophrenia, has not previously been evaluated in terms of its heritability in relationship to risk for schizophrenia. Objective: To quantify the distribution and heritability of cortical thickness changes in schizophrenia. Design: We analyzed a large sample of normal controls, affected patients, and unaffected siblings using a surface-based approach. Cortical thickness was compared between diagnosis groups on a surfacewide node-by-node basis. Heritability related to disease risk was assessed in regions derived from an automated cortical parcellation algorithm by calculating the Risch lambda. Setting: Research hospital. Participants: One hundred ninety-six normal controls, 115 affected patients with schizophrenia, and 192 unaffected siblings. Main Outcome Measure: Regional cortical thickness. Results: Node-by-node mapping statistics revealed widespread thickness reductions in the patient group, most pronouncedly in the frontal lobe and temporal cortex. Unaffected siblings did not significantly differ from normal controls at the chosen conservative threshold. Risch lambda analysis revealed widespread evidence for heritability for cortical thickness reductions throughout the brain. Conclusions: To our knowledge, the present study provides the first evidence of broadly distributed and heritable reductions of cortical thickness alterations in schizophrenia. However, since only trend-level reductions of thickness were observed in siblings, cortical thickness per se (at least as measured by this approach) is not a strong intermediate phenotype for schizophrenia. Arch Gen Psychiatry. 2009; 66(5):467-477