Mapping corticocortical structural integrity in schizophrenia and effects of genetic liability.

Background: Structural and diffusion tensor imaging studies implicate gray and white matter (WM) abnormalities and disruptions of neural circuitry in schizophrenia. However, the structural integrity of the superficial WM, comprising short-range association (U-fibers) and intracortical axons, has not been investigated in schizophrenia.

Methods: High-resolution structural and diffusion tensor images and sophisticated cortical pattern matching methods were used to measure and compare global and local variations in superficial WM fractional anisotropy between schizophrenia patients and their relatives and community comparison subjects and their relatives (n = 150).

Results: Compared with control subjects, patients showed reduced superficial WM fractional anisotropy distributed across each hemisphere, particularly in left temporal and bilateral occipital regions (all p < .05, corrected). Furthermore, by modeling biological risk for schizophrenia in patients, patient relatives, and control subjects, fractional anisotropy was shown to vary in accordance with relatedness to a patient in both hemispheres and in the temporal and occipital lobes (p < .05, corrected). However, effects did not survive correction procedures for two-group comparisons between patient relatives and control subjects.

Conclusions: Results extend previous findings restricted to deep WM pathways to demonstrate that disturbances in corticocortical connectivity are associated with schizophrenia and might indicate a genetic predisposition for the disorder. Because the structural integrity of WM plays a crucial role in the functionality of networks linking gray matter regions, disturbances in the coherence and organization of fibers at the juncture of the neuropil might relate to features of schizophrenia at least partially attributable to disease-related genetic factors.