Depression: what we can learn from postmortem studies.

The existence of depression has been recognized for decades, but its precise neurobiological basis remains unknown. Whereas neuroimaging studies unravel the gross morphological localization of dysfunctional brain regions in depression, postmortem studies provide further insights into the cellular and neurochemical substrates of depression. Recent cell-counting studies have established that major depressive disorder and bipolar illness are characterized by alterations in the density and size of neuronal and glial cells in fronto-limbic brain regions. It remains to be fully elucidated to what extent these findings represent neurodevelopmental abnormalities or disease progression and whether the cellular changes observed in depression can be reversed by antidepressant and mood-stabilizing medications. Efforts to unravel specific groups of genes that are compromised in depression have recently been undertaken by investigators in the postmortem research field. Future studies will determine whether these genes may be novel targets of therapeutic medications.