Age-Related Increase in the Number of Oligodendrocytes Is Dysregulated in Schizophrenia and Mood Disorders

Abstract

The postnatal maturation of the human prefrontal cortex is associated with substantial increase of number of oligodendrocytes. Previously, we reported decreased numerical density of oligodendrocytes in the prefrontal cortex in schizophrenia and mood disorders. To gain further understanding of the role oligodendrocytes in pathogenesis of schizophrenia and mood disorders, we examined the effect of the age on the number of oligodendrocytes in the prefrontal cortex in schizophrenia, bipolar disorder, and major depressive disorder. We revealed the age-related increase in numerical density of oligodendrocytes in layer VI and adjacent white matter of BA10 and BA 9 in normal controls but not in schizophrenia, bipolar disorder, and major depressive disorder. The absence of normal increase in the number of oligodendrocytes in gray and white matter with age in schizophrenia and mood disorders suggests that age-related process of oligodendrocyte increase is dysregulated in schizophrenia and mood disorders.

Abnormalities in oligodendrocyte clusters in the inferior parietal cortex in schizophrenia are associated with insight

“…This suggestion supports our previous data showing that the normal age-related increase in the number of oligodendrocytes in the prefrontal cortex was absent in schizophrenia 39 . These abnormalities may contribute to more profound abnormalities in the brain of patients with schizophrenia including abnormal expression of oligodendrocyte-and myelin-related genes, of genes that govern oligodendrocyte development and function, and of genes involved in the cell cycles.…”

Depressive Symptoms in Mild Cognitive Impairment Predict Greater Atrophy in Alzheimer's Disease-Related Regions

“…Some investigators have found reduced white matter volume in depressed individuals (47), and recent investigations using diffusion tensor imaging (DTI) have identified lower fractional anisotropy (FA) in prefrontal regions, anterior cingulate, and temporal regions in depressed subjects (48). Severe depression and other neuropsychiatric disorders have also been associated with abnormal myelination (49,50) and reduced or abnormal oligodendrocytes (51), especially at older ages (52). …”

Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia

“…[63][64][65][66] In the latter, an age-related increase in number of mature oligodendrocytes normally observed in control subjects is absent in SZ patients. 67 Microarray analysis of patients' prefrontal and anterior cingulate cortices reveal a reduced expression of several genes related to myelin and oligodendrocytes [68][69][70] and an altered expression of genes coding for cell-cycle maintenance or arrest. 71 Altogether, these findings point to impaired oligodendrocyte maturation and myelination.…”