title: Chronic antidepressant treatment exerts sexually dimorphic immunomodulatory effects in an experimental model of major depression: do females lack an advantage?
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.
authors.affiliation: Department of Pharmacology, Medical School, University of Athens, Athens, Greece.
authors.forename: Pothitos M
authors.initials: PM
authors.lastname: Pitychoutis
authors.forename: Eirini
authors.initials: E
authors.lastname: Griva
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Ioannou
authors.forename: Ourania E
authors.initials: OE
authors.lastname: Tsitsilonis
authors.forename: Zeta
authors.initials: Z
authors.lastname: Papadopoulou-Daifoti
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002908:Chronic Disease; D002997:Clomipramine / Q000008:administration & dosage*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000276:immunology / Q000523:psychology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects*; D007376:Interleukin-2 / Q000378:metabolism; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D012720:Severity of Illness Index; D012727:Sex Characteristics; D012737:Sex Factors; D013315:Stress, Psychological / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D000929:Antidepressive Agents, Tricyclic; D007376:Interleukin-2; D012701:Serotonin; D002997:Clomipramine; D004298:Dopamine; D009638:Norepinephrine