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 depression. Evidence is also mounting that glial cell loss may also be a feature 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 are now accepted to have roles in providing trophic support to neurons, neuronal metabolism, and the formation of synapses and neurotransmission. Consequently, reduced cortical glial cell numbers could be responsible for some of the pathological changes in schizophrenia and depression, including reduced neuronal size, reduced levels of synaptic proteins, and abnormalities of cortical neurotransmission. Additionally, as astrocytes provide the energy requirements of neurons, deficient astrocyte function could account for aspects of the functional magnetic imaging abnormalities found in these disorders. 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 illness through enhanced excitotoxicity. The potential therapeutic impact of agents which up-regulate glial activity or normalise glial cell numbers is also discussed.