Cerebral connectivity, schizophrenia and genetic liability: A diffusion tensor imaging study

Schizophrenia is thought to have its base in cerebral vulnerability such as altered cortical connectivity, which is supported by functional MRI-based findings. Of late, studies using diffusion tensor imaging (DTI) have supported the dysconnectivity theory by showing microstructural white matter changes in neural circuits, specifically in fronto-temporal, fronto-parietal, and fronto-thalamic connections. However, the concept of DTI white matter alteration as a structural endophenotype has yet to be addressed. Diffusion weighted images as well as T1-weighted anatomy volumes were acquired on a 3 Tesla MRI scanner from 30 patients with schizophrenia, 30non-psychotic siblings of these patients and 30 healthy controls. Measures of fractional anisotropy (FA) as indicators of white matter tract integrity were computed using Trackmark and BrainVoyagerQXsoftware (Brain Innovation, Maastricht, The Netherlands). Parametric images of the average FA of the different groups were acquired after transformation to Talairach space. Differences between groups were assessed with voxelwise analysis of variance and t test comparisons, and confirmed in region of interest analyses. Preliminary analyses in a subgroup (n=10 per group) show microstructural (DTI)white matter changes in psychotic patients and, to a lesser extent, in their healthy siblings when compared to controls. This suggests that altered cerebral connectivity may be an endophenotypic marker of schizophrenia liability.