Neuroendocrine and psychosocial triggers of severe psychiatric onset in women: a systematic review with domain-specific quantitative and narrative synthesis.

AIM: Severe psychiatric onsets in women show pronounced clustering around specific reproductive life stages. This study aimed to systematically evaluate (i) the association between the perimenopausal transition and first-episode mania and (ii) the relationship between intimate partner violence (IPV) and postpartum psychosis (PPP), integrating neuroendocrine and psychosocial perspectives across the female life course. METHODS: A systematic review with domain-specific quantitative and narrative synthesis was conducted in accordance with PRISMA 2020 guidelines. PubMed/MEDLINE, Embase, Web of Science, Scopus, PsycINFO, and Cochrane CENTRAL were searched from inception to December 2024. Observational studies reporting first-onset mania during perimenopause or PPP in relation to IPV exposure were included. Random-effects models were planned where quantitative pooling was feasible. Risk of bias was assessed using the Newcastle-Ottawa Scale, and certainty of evidence was evaluated with the GRADE framework. RESULTS: Three studies met criteria for quantitative synthesis and seven for contextual narrative synthesis. A large population-based cohort demonstrated a significantly increased risk of first-onset mania during the perimenopausal transition (RR = 2.1, 95% CI: 1.30-3.52; low-certainty evidence). In contrast, direct evidence linking IPV to PPP was sparse and heterogeneous, precluding pooled effect estimation (very low-certainty evidence). Contextual evidence from systematic reviews, meta-analyses, and cohort studies consistently associated IPV with adverse perinatal mental health outcomes, particularly postpartum depression and anxiety (moderate-certainty evidence). DISCUSSION: The findings support perimenopause as a clinically meaningful risk window for first-onset mania and highlight a critical evidence gap regarding IPV as a potential trigger for PPP. Although direct quantitative evidence is limited, biological plausibility and consistent contextual findings suggest that intense psychosocial stressors such as IPV may amplify postpartum psychiatric vulnerability in susceptible individuals. Future large-scale, well-phenotyped perinatal cohorts are needed to directly quantify this association.