Disease and genetic contributions toward local tissue volume disturbances in schizophrenia: a tensor-based morphometry study.

Structural brain deficits, especially frontotemporal volume reduction and ventricular enlargement, have been repeatedly reported in patients with schizophrenia. However, it remains unclear whether brain structural deformations may be attributable to disease-related or genetic factors. In this study, the structural magnetic resonance imaging data of 48 adult-onset schizophrenia patients, 65 first-degree nonpsychotic relatives of schizophrenia patients, 27 community comparison (CC) probands, and 73 CC relatives were examined using tensor-based morphometry (TBM) to isolate global and localized differences in tissue volume across the entire brain between groups. We found brain tissue contractions most prominently in frontal and temporal regions and expansions in the putamen/pallidum, and lateral and third ventricles in schizophrenia patients when compared with unrelated CC probands. Results were similar, though less prominent when patients were compared with their nonpsychotic relatives. Structural deformations observed in unaffected patient relatives compared to age-similar CC relatives were suggestive of schizophrenia-related genetic liability and were pronounced in the putamen/pallidum and medial temporal regions. Schizophrenia and genetic liability effects for the putamen/pallidum were confirmed by regions-of-interest analysis. In conclusion, TBM findings complement reports of frontal, temporal, and ventricular dysmorphology in schizophrenia and further indicate that putamen/pallidum enlargements, originally linked mainly with medication exposure in early studies, also reflect a genetic predisposition for schizophrenia. Thus, brain deformation profiles revealed in this study may help to clarify the role of specific genetic or environmental risk factors toward altered brain morphology in schizophrenia.