The genetic architecture of reproductive subtypes of depression in females

Le résumé fourni par la source

Reproductive subtypes of depression, including premenstrual dysphoric disorder, postpartum depression, and perimenopausal depression are tightly linked to hormonal fluctuations, presenting as windows of vulnerability in females. While it is suggested that these reproductive subtypes present as a stable trait, it remains unclear whether they share an underlying genetic architecture. In this review, we summarize the known genetic etiology of each reproductive subtype of depression, contrast the findings between subtypes, and highlight existing knowledge gaps, challenges, and ways forward. We found that while postpartum depression has been comparatively more studied, genetic studies on premenstrual dysphoric disorder and perimenopausal depression are scarce. Candidate genes commonly studied in major depressive disorder (5-HTT, COMT, MAO-A, and TPH1) as well as ESR1 have been studied across the reproductive subtypes, however, showing inconsistent patterns. No genome-wide association studies currently exist for premenstrual dysphoric disorder or perimenopausal depression. Genome-wide association studies on postpartum depression, although underpowered, point to unique and shared genetic components with other psychiatric disorders, which should be further explored across all reproductive subtypes of depression. To advance this field, well-powered studies with consistent diagnostic criteria across diverse ancestry groups are needed. Identifying whether overlap exists in the genetic architecture of premenstrual dysphoric disorder, postpartum depression, and perimenopausal depression could enhance our understanding of their pathogenesis and foster the development of new therapeutic targets.

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