Abnormal microglial reactivity in gray matter of the prefrontal cortex in schizophrenia

Microglial activation has been proposed to contribute to the pathogenesis of schizophrenia. The present study addressed the questions of whether microglial reactivity is involved in the course of schizophrenia and is associated with aging. Transmission electron microscopy and morphometry were applied to estimate microglial density and ultrastructural parameters in layer 5 of the prefrontal cortex (BA10) in postmortem 21 chronic schizophrenia and 20 healthy control cases. A significant increase in microglial density was found in the schizophrenia group (+20 %), in young group (≤50 y.o.), in shorter duration of disease (≤26 yrs.) group, in early age at onset of disease (≤ 21 y.o.) group as compared to controls (p < 0.05) and in young schizophrenia group as compared to both young and elderly (>50 y.o.) controls (p < 0.05). Volume fraction (Vv) of mitochondria was significantly lower and area of lipofuscin granules was significantly higher in young and elderly schizophrenia groups as compared to young and elderly controls. Vv of lipofuscin granules strongly positively correlated with age and duration of disease in the schizophrenia group. Vv and the number (N) of lipofuscin granules were higher in longer duration (>26 yrs.) group as compared to shorter duration group (p < 0.01). Vv and N of vacuoles were increased in longer duration group as compared to controls (p < 0.01). The study provides evidence for microgliosis associated with age, duration of disease and age at onset of disease, progressive dystrophy and accelerated aging of microglia in gray matter of the prefrontal cortex in schizophrenia.