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

Int J Neuropsychopharmacol. 2014 Dec;17(12):1923-33. doi: 10.1017/S1461145714000844. Epub 2014 Jun 27.

Abstract

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 (MD*ADT, n = 10); benzodiazepine-antidepressant-treated MD (MD*ADT*BZD, n = 7); no psychopathology or treatment (controls, n = 18). MD*ADT*BZD had fewer granule neurons vs. MD*ADT in anterior DG and vs. controls in mid DG, and did not differ from untreated-MD in any DG subregion. MD*ADT 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. MD*ADT*BZD had fewer NPCs vs. MD*ADT in mid DG. MD*ADT had more NPCs vs. untreated-MD and controls in anterior and mid DG. MD*ADT*BZD and MD*ADT 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use*
  • Benzodiazepines / therapeutic use*
  • Dentate Gyrus / drug effects*
  • Dentate Gyrus / pathology
  • Female
  • Fluoxetine / therapeutic use*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mitosis / drug effects
  • Mood Disorders / drug therapy*
  • Mood Disorders / pathology
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / pathology
  • Neurons / drug effects
  • Neurons / pathology

Substances

  • Antidepressive Agents
  • Fluoxetine
  • Benzodiazepines