Morphometric methods for studying the prefrontal cortex in suicide victims and psychiatric patients

Neurochemical studies demonstrate altered numbers of monoaminergic receptors in the prefrontal cortex in suicide and depression victims, implicating dysfunction of the prefrontal cortex in the neuropathology of suicide and psychiatric disorders. Neuroimaging studies in vivo have revealed an altered pattern of cortical metabolism and reductions in frontal lobe volume in patients with schizophrenia (SCZ) or depression. However, the precise morphopathology underlying these abnormalities and their relevance to suicide are unknown. Our recent three-dimensional cell counting of dorsolateral prefrontal cortex from 16 postmortem SCZ brains (10 suicide completers) revealed cellular changes (increased neuronal density, and reduced laminar width and neuronal size) that may be associated with neuroimaging observations. Evaluation of the same morphometric parameters in the prefrontal cortex in seven bipolar brains (three committed suicide) revealed similarities (decreased cortical and laminar thickness) and differences (unchanged overall neuronal density and laminar densities) between morphopathology of SCZ and bipolar disorder. In another population of suicide victims with major depression (nonpsychotic), further morphopathological differences from SCZ and similarities to bipolar disorder were observed in the prefrontal cortex. From these data we can conclude that the morphopathology observed in brain tissue from suicide victims appears to vary based on psychiatric symptomatology. In order to confirm this hypothesis and to establish the specificity of morphometric findings in relation to psychiatric disorders and suicide, additional studies are warranted in nonsuicide subjects with SCZ, major depression, or bipolar disorder.