Benzodiazepines and the potential trophic effect of antidepressants on dentate gyrus cells in mood disorders.

Modest antidepressant response rates of mood disorders (MD) encourage benzodiazepine (BZD) co-medication with debatable benefit. Adult hippocampal neurogenesis may underlie antidepressant responses, but diazepam co-administration impairs murine neuron maturation and survival in response to fluoxetine. We counted neural progenitor cells (NPCs), mitotic cells, and mature granule neurons post-mortem in dentate gyrus (DG) from subjects with: untreated Diagnostic and Statistical Manual of Mental Disorders (DSM) IV MD (n = 17); antidepressant-treated MD (MDADT, n = 10); benzodiazepine-antidepressant-treated MD (MDADTBZD, n = 7); no psychopathology or treatment (controls, n = 18). MDADTBZD had fewer granule neurons vs. MDADT in anterior DG and vs. controls in mid DG, and did not differ from untreated-MD in any DG subregion. MDADT had more granule neurons than untreated-MD in anterior and mid DG and comparable granule neuron number to controls in all dentate subregions. Untreated-MD had fewer granule neurons than controls in anterior and mid DG, and did not differ from any other group in posterior DG. MDADTBZD had fewer NPCs vs. MDADT in mid DG. MDADT had more NPCs vs. untreated-MD and controls in anterior and mid DG. MDADTBZD and MDADT had more mitotic cells in anterior DG vs. controls and untreated-MD. There were no between-group differences in mid DG in mitotic cells or in posterior DG for any cell type. Our results in mid-dentate, and to some degree anterior dentate, gyrus are consistent with murine findings that benzodiazepines counteract antidepressant-induced increases in neurogenesis by interfering with progenitor proliferation. We also confirmed, in this expanded sample, our previous finding of granule neuron deficit in untreated MD.