The COMT Val158Met polymorphism moderates the association between cognitive functions and white matter microstructure in schizophrenia

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Impaired cognitive functioning is a core feature of schizophrenia. Cognitive impairment in schizophrenia has been associated with white-matter (WM) abnormalities and degenerative changes of cortical myelin in the cerebral cortex. Furthermore, findings suggested a role of the COMT gene in affecting both WM and neuropsychological performances.


We thus hypothesized that the COMT Val158Met genotype would affect the association between cognitive functions and WM microstructure in a sample of schizophrenic patients.

Materials and methods

Seventy-eight schizophrenic patients performed the brief assessment of cognition in schizophrenia for assessment of cognitive performances. Sixty-nine patients provided a venous blood sample for genotypic analysis. WM integrity was evaluated using tract-based spatial statistics with threshold-free cluster enhancement (P<0.05).


Analysis indicated an association between cognitive functions and WM microstructure in the Val/Val group, but not in the Met carriers group. WM tracts include the corpus callosum, thalamic radiations, corona radiata, forceps major and minor, superior and inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, corticospinal tract, and cingulum.


Results suggested a moderating effect of the COMT Val158Met polymorphism on the association between cognitive functioning and WM microstructure. Our findings support the importance of myelination in cognition, identifying measures of WM microstructure as important neurobiological features of cognitive performances.

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