Reduced density of oligodendrocytes and oligodendrocyte clusters in the caudate nucleus in major psychiatric illnesses.

Functional dysconnectivity in schizophrenia and affective disorders may be associated with myelin and oligodendrocyte abnormalities. Altered network integration involving the caudate nucleus (CN) and metabolic abnormalities in fronto-striatal-thalamic white matter tracts have been reported in schizophrenia and impaired patterns of cortico-caudate functional connectivity have been found in both bipolar disorder (BPD) and schizophrenia compared to healthy controls. Postmortem studies have found ultrastructural dystrophy and degeneration of oligodendrocytes and dysmyelination in the CN in schizophrenia and BPD. We aimed to test the hypothesis that oligodendrocyte density may be reduced in the CN in major psychiatric disorders and may thereby form the cellular basis for the functional dysconnectivity observed in these disorders. Optical disector was used to estimate the numerical density (Nv) of oligodendrocytes and oligodendrocyte clusters (OLC) in the CN of cases with schizophrenia, BPD and major depressive disorder (MDD) and in normal controls (15 cases per group). A significant reduction in the Nv of oligodendrocytes was found in schizophrenia and BPD as compared to the control group (p < 0.05), and the Nv of OLC was significantly lowered in schizophrenia and BPD compared to controls (p < 0.05). There were no significant differences between MDD and control groups. The Nv of OLC was significantly decreased in the left hemisphere in schizophrenia as compared to the left hemisphere of the control group (-52%, p < 0.01). The data indicates that a decreased density of oligodendrocytes and OLC could contribute to the altered functional connectivity of the CN in subjects with severe mental illnesses.