A Reproductive Subtype of Depression

Abstract

The lifetime risk for major depression in women is well known to be twice the risk in men and is especially high during the reproductive years between menarche and menopause. A subset of reproductive-age women experience depressive episodes that are triggered by hormonal fluctuations. Such “reproductive depressions” involve episodes of depression that occur specifically during the premenstrual, postpartum, and perimenopausal phases in women. These reproductive subtypes of depression can be conceptualized as a specific biological response to the effects of hormonal fluctuations in the brain. The different types of reproductive depressions are associated with each other, have unique risk factors that are distinct from nonreproductive depression episodes, and respond to both hormonal and nonhormonal interventions. This review uses a PubMed search of relevant literature to discuss clinical, animal, and genetic evidence for reproductive depression as a specific subtype of major depression. Unique treatment options, such as hormonal interventions, are also discussed, and hypotheses regarding the underlying biology of reproductive depression—including interactions between the serotonergic system and estrogen, as well as specific effects on neurosteroids—are explored. This review will provide evidence supporting reproductive depression as a distinct clinical entity with specific treatment approaches and a unique biology that is separate from nonreproductive depression.

Disruption of fetal hormonal programming (prenatal stress) implicates shared risk for sex differences in depression and cardiovascular disease

“…Changes in women’s reproductive system have been consistently related to mood fluctuations and MDD per se (Rabin et al, 1990; Baischer et al, 1995; Rubinow and Schmidt, 1996; Harlow et al, 2003; Payne, 2003; Roca et al, 2003; Spinelli, 2005; Payne et al, 2009). MDD incidence increases with pubertal onset in females (Angold and Costello, 2006), late luteal menstrual cycle phase (Steiner, 1992), chronic use of oral contraceptives (Young et al, 2007a), the postpartum period (Bloch et al, 2000; Brummelte and Galea, 2010), and postmenopause (Graziottin and Serafini, 2009).…”

Lower allopregnanolone during pregnancy predicts postpartum depression: An exploratory study

“…While now increasingly focused on the immune system as well as genetic and epigenetic factors, the bulk of the existing literature on biological factors has focused on the hormonal fluctuations (especially of estrogen and progesterone) that occur in the immediate postpartum period (Chrousos et al, 1998; Glynn et al, 2013; Moses-Kolko et al, 2009). Our group has previously argued for a “reproductive subtype of depression” (Payne et al, 2009), which affects vulnerable women during reproductive transitions including premenstrual, postpartum, and perimenopausal periods. There is evidence that estrogen fluctuations can trigger mood disturbance throughout the reproductive life cycle in susceptible women (Douma et al, 2005).…”

Ovarian Hormone Fluctuation, Neurosteroids, and HPA Axis Dysregulation in Perimenopausal Depression: A Novel Heuristic Model

“…In addition to any role for psychosocial factors in perimenopausal depression, there is evidence to suggest that women vulnerable to perimenopausal depression exhibit a greater “hormonal sensitivity” to the endocrine profile of the menopause transition (24). First, both a history of PMDD and a history of postpartum depression – two disorders for which reproductive hormonal flux may be pathophysiologically relevant (25, 26) – are each strong predictors of perimenopausal depression (16, 17, 19).…”