Decreased numbers of progenitor cells but no response to antidepressant drugs in the hippocampus of elderly depressed patients

Abstract

Imaging studies have consistently documented hippocampal volume reductions in depression. Although depressive disorders are traditionally considered to have a neurochemical basis, recent studies suggest that impairments of structural plasticity contribute to the volume reductions and the related cognitive changes. This might result from repeated periods of stress that are a wellknown risk factor for depression. Adult neurogenesis is a prominent example of neuroplasticity that in rodents, is reduced by stress but stimulated by antidepressant drugs. Although reductions in neurogenesis have been proposed to contribute to the etiology of depression, only two studies have so far examined hippocampal cytogenesis in depression, but this was in a limited number of subjects with considerable interindividual variation, and these studies came to different conclusions. We therefore collected hippocampal tissue of 10 elderly control subject and 10 well-matched depressed patients that were highly comparable in terms of age, sex, pH-CSF and postmortem delay, and tested whether the numbers of MCM2-positive progenitors and PH3-positive proliferating cells were altered by depression or antidepressant treatment. A significant reduction was found in MCM2-, but not PH3-immunopositive cells in depression. Although this result is consistent with the concept that structural plasticity is decreased in depression, we could not confirm that antidepressant drugs had a stimulatory effect on these cells. This discrepancy may relate to anatomical differences, in medication, to neurogenesis-independent mechanisms of antidepressant action, or the age of the patients that was higher than in previous studies. Whether the reduction is a cause or consequence of depression awaits to be determined.