Depression, Estrogens, and Neuroinflammation: A Preclinical Review of Ketamine Treatment for Mood Disorders in Womens

Introduction

Szewczyk and colleagues open by situating the problem: women experience major depressive disorder at roughly twice the rate of men during adolescence and early adulthood, and ovarian steroid hormones (principally 17β-estradiol and progesterone) are implicated in that sex difference. The introduction reviews clinical phenomena linking hormone fluxes to mood—post-partum depression, premenstrual dysphoric disorder and menopause-related mood change—and notes that simple models that equate low ovarian hormones with depression are inadequate because some conditions involve heightened hormone sensitivity rather than absolute deficits. Against this background, the review sets out to synthesise preclinical evidence about how ketamine exerts antidepressant effects in the female brain, with particular attention to interactions with estrogens, progesterone and neuroinflammatory processes (especially microglia and the kynurenine pathway). The authors frame the neuroinflammatory hypothesis of depression as a potentially useful lens for understanding sex-specific ketamine effects and identify the hippocampus as a candidate brain region for hormone–ketamine interactions.