Chronic antidepressant treatment exerts sexually dimorphic immunomodulatory effects in an experimental model of major depression: do females lack an advantage?

Int J Neuropsychopharmacol. 2009 Oct;12(9):1157-63. doi: 10.1017/S1461145709990502. Epub 2009 Aug 24.

Abstract

Major depression is a stress-related disorder that affects about 20% of the population, with women outnumbering men by 2:1. However, research focusing on stress/antidepressant-related immunomodulation overlooks sex differences, although an established sexual dimorphism also characterizes the immune system. We report for the first time that both chronic clomipramine treatment (10 mg/kg, twice daily) and chronic mild stress (CMS) application in rats, exert sexually dimorphic effects on cellular immunoreactivity (natural killer and lymphokine-activated killer cell cytotoxicity and interleukin-2-induced T-cell proliferation), with females presenting a relatively immunosuppressed phenotype compared to males. Moreover, following chronic antidepressant treatment, thymic monoamines presented sex-related alterations, as well as intriguing associations with peripheral T-cell responses. This study highlights the sex-related effects of chronic clomipramine treatment and CMS application on the cellular arm of immunity, and represents a preliminary exposé of a thymus-dependent route pertaining to the interactions between antidepressants and the immune system.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents, Tricyclic / administration & dosage*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chronic Disease
  • Clomipramine / administration & dosage*
  • Cytotoxicity, Immunologic / drug effects
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / immunology
  • Depressive Disorder, Major / psychology
  • Disease Models, Animal
  • Dopamine / metabolism
  • Drug Administration Schedule
  • Female
  • Immunity, Cellular / drug effects*
  • Interleukin-2 / metabolism
  • Killer Cells, Lymphokine-Activated / drug effects
  • Killer Cells, Lymphokine-Activated / immunology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Lymphocyte Activation / drug effects
  • Male
  • Norepinephrine / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism
  • Severity of Illness Index
  • Sex Characteristics*
  • Sex Factors
  • Stress, Psychological / immunology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Thymus Gland / drug effects*
  • Thymus Gland / immunology
  • Thymus Gland / metabolism

Substances

  • Antidepressive Agents, Tricyclic
  • Interleukin-2
  • Serotonin
  • Clomipramine
  • Dopamine
  • Norepinephrine