The contributions of disease and genetic factors towards regional cortical thinning in schizophrenia: The UCLA family study

Abstract

Objective Cortical thickness reductions in prefrontal and temporal cortices have been repeatedly observed in patients with schizophrenia. However, it remains unclear whether regional variations in cortical thickness may be attributable to disease-related or genetic-liability factors. Method The structural magnetic resonance imaging data of 48 adult-onset schizophrenia patients, 66 first-degree non-psychotic relatives of schizophrenia patients, 27 community comparison (CC) probands and 77 CC relatives were examined using cortical pattern matching methods to map and compare highly localized changes in cortical gray matter thickness between groups defined by biological risk for schizophrenia. Results Schizophrenia patients showed marked cortical thinning primarily in frontal and temporal cortices when compared to unrelated CC probands. Results were similar, though less pronounced when patients were compared with their non-psychotic relatives. Cortical thickness reductions observed in unaffected relatives compared to age-similar CC relatives suggestive of schizophrenia-related genetic liability were marginal, surviving correction for the left parahippocampal gyrus and inferior occipital cortex only. Conclusions Observations of pronounced fronto/temporal cortical thinning in schizophrenia patients replicate prior findings. The lack of marked cortical thickness alterations in non-psychotic relatives of patients, suggests that disease processes are primary contributors toward cortical thickness reductions in the disorder. However, genetic factors may have a larger influence on abnormalities in the medial temporal lobe.