Schizophrenia is a severe mental disorder with a neurodevelopmental origin whose pathophysiological processes are poorly understood. Magnetic resonance imaging studies have shown structural alterations, such as volume loss in the temporal lobe, including the hippocampus and amygdala, thalamus, and frontal and temporal cortex, while other studies have found reduced oligodendrocyte numbers in the hippocampal CA4 subregion and dorsolateral prefrontal cortex. The decreased number of oligodendrocytes in CA4 was reported to be related to cognitive deficits. The hippocampus and other parts of the limbic system are connected to the white matter of the cingulum bundle, but it had remained unknown whether schizophrenia affects the number of oligodendrocytes also in the cingulum.

In a post mortem study, we applied a design-based stereological approach to investigate the number and density of oligodendrocytes in gallocyanin-stained serial sections in the cingulum of the left and right hemispheres in 12 brains from male donors with schizophrenia and 11 brains from age- and sex-matched controls without mental illness. In addition, we evaluated whether oligodendrocyte numbers and densities in the cingulum correlated with the corresponding data in the hippocampal CA4 subregion of the same brains.

In schizophrenia, both the mean volume of the left cingulum (difference, -12.7%) and the mean total oligodendrocyte number in the left cingulum (difference, -19.9%) were statistically significantly lower than in healthy controls (p = 0.049 and p = 0.037). No correlations were found for covariates (age, post mortem interval, fixation time). The individual oligodendrocyte numbers in the right cingulum correlated with those in the right hippocampal CA4, and the individual oligodendrocyte densities in the left cingulum correlated with that in the left hippocampal CA4.

This post mortem study shows, for the first time, a statistically significant reduction in the mean volume of and the mean oligodendrocyte number in the left cingulum of patients with schizophrenia. Our results support findings of a reduction of oligodendrocytes in limbic regions in schizophrenia, reinforcing the hypothesis that deficits in myelination and trophic support of long projecting axons play a role in the functional disconnectivity of the hippocampus and prefrontal cortex in schizophrenia..