Histopathology of the prefrontal cortex in major depression: what does it tell us about dysfunctional monoaminergic circuits?

Abstract

This chapter discusses the prefrontal cell pathology in major depression as it relates to biochemical and structural changes detected in studies of the serotonergic and noradrenergic neurons located in the brainstem. Information pertaining to both current and lifetime psychiatric symptoms was gathered using the schedule for affective disorders and schizophrenia. State-of-the-art morphometric and stereological methods were used to assess neuronal and glial cell densities, cell body size and cortical thickness in each of the three prefrontal regions. The validity of studies described is underscored by the fact that the tissues from the prefrontal cortex and brainstem nuclei were examined in the same depressives and control subjects. The cellular changes described in these postmortem studies indicate that both types of brain cells, neurons and glia, are involved in the cortical pathology of major depression. It remains to be determined whether the morphometric changes detected postmortem in subjects with major depressive disorder are trait or state dependent, and whether antidepressant medications have an effect on cell morphology. In the present study, cell pathology was detected even in those subjects who were not taking antidepressant medications; however, further behavioral and morphometric experiments on animals treated with antidepressant medications will shed more light on this issue.