The International Journal of Neuropsychopharmacology

Research Article

Of depression and immunity: does sex matter?

Pothitos M. Pitychoutisa1 and Zeta Papadopoulou-Daifotia1 c1

a1 Department of Pharmacology, Medical School, University of Athens, Athens, Greece


It is firmly established that women experience major depression (MD) at roughly twice the rate of men. Contemporary research has indicated that sex hormones comprise crucial orchestrators of the differences in susceptibility associated to sex in MD, as well as in certain infectious and autoimmune diseases. Interestingly, it has been suggested that altered functioning of the immune system may be implicated in the medical morbidity of this affective disorder. To make matters more complicated, data accumulated largely during the last two decades advocate the innate inflammatory immune response as a mechanism that may contribute to the pathophysiology of MD, mainly through alterations in the ability of immune cells to secrete pro-inflammatory cytokines. Although the literature is limited, the bi-directional influences between the brain and the immune system appear to present sex-related motifs whose elucidation is far from being completely achieved but comprises a matter of intensive research. Herein, we provide a first critical glimpse into if and how sex differences in immunity may be implicated in the pathophysiology of MD. The review's major aim is to sensitize clinical scientists of different disciplines to the putative impact of immune sexual dimorphism on MD and to stimulate basic research in a need to delineate the neuroimmunological substrate in the appearance, course and outcome of this stress-related disorder.

(Received January 19 2010)

(Reviewed February 25 2010)

(Revised March 22 2010)

(Accepted March 30 2010)


c1 Address for correspondence: Z. Papadopoulou-Daifoti, Professor of Pharmacology, Chair of the Department of Pharmacology, Medical School, University of Athens, 75, Mikras Asias Street, Goudi, Athens, 115 27, Greece. Tel.: +30210 7462702, +30210 7462579 Fax: +30210 746 2554 Email: