Glial cell abnormalities in major psychiatric disorders: The evidence and implications

Recent quantitative post-mortem investigations of the cerebral cortex have convincingly demonstrated cortical glial cell loss in subjects with major d epression. Evidence is also mounting that glial cell loss may also be a fea ture of schizophrenia. These findings coincide with a re-evaluation of the importance of glial cells in normal cortical function. In addition to their traditional roles in neuronal migration and inflammatory processes, glia a re now accepted to have roles in providing trophic support to neurons, neur onal metabolism, and the formation of synapses and neurotransmission. Conse quently, reduced cortical glial cell numbers could be responsible for some of the pathological changes in schizophrenia and depression, including redu ced neuronal size, reduced levels of synaptic proteins, and abnormalities o f cortical neurotransmission. Additionally, as astrocytes provide the energ y requirements of neurons, deficient astrocyte function could account for a spects of the functional magnetic imaging abnormalities found in these diso rders. We discuss the possible basis of glial cell loss in these disorders and suggest that elevated levels of glucocorticoids, due to illness-related stress or to hyperactivity of the hypothalamic-pituitary-adrenal may down- regulate glial activity and so predispose to, or exacerbate psychiatric ill ness through enhanced excitotoxicity. The potential therapeutic impact of a gents which up-regulate glial activity or normalise glial cell numbers is a lso discussed. (C) 2001 Elsevier Science Inc.