title: Benzodiazepines and the potential trophic effect of antidepressants on dentate gyrus cells in mood disorders.
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.
authors: Division of Molecular Imaging and Neuropathology and New York State Psychiatric Institute,New York, NY,USA.
authors: Maura
authors: M
authors: Boldrini
authors: Division of Molecular Imaging and Neuropathology and New York State Psychiatric Institute,New York, NY,USA.
authors: Tanya H
authors: TH
authors: Butt
authors: Division of Molecular Imaging and Neuropathology and New York State Psychiatric Institute,New York, NY,USA.
authors: Adrienne N
authors: AN
authors: Santiago
authors: Division of Molecular Imaging and Neuropathology and New York State Psychiatric Institute,New York, NY,USA.
authors: Hadassah
authors: H
authors: Tamir
authors: Division of Molecular Imaging and Neuropathology and New York State Psychiatric Institute,New York, NY,USA.
authors: Andrew J
authors: AJ
authors: Dwork
authors: Division of Molecular Imaging and Neuropathology and New York State Psychiatric Institute,New York, NY,USA.
authors: Gorazd B
authors: GB
authors: Rosoklija
authors: Division of Molecular Imaging and Neuropathology and New York State Psychiatric Institute,New York, NY,USA.
authors: Victoria
authors: V
authors: Arango
authors: Department of Psychiatry,Columbia University,New York, NY,USA.
authors: René
authors: R
authors: Hen
authors: Division of Molecular Imaging and Neuropathology and New York State Psychiatric Institute,New York, NY,USA.
authors: J John
authors: JJ
authors: Mann
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008938:Mitosis / Q000187:drug effects; D019964:Mood Disorders / Q000188:drug therapy* / Q000473:pathology; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology
chemical_list: D000928:Antidepressive Agents; D005473:Fluoxetine; D001569:Benzodiazepines