Biological pathways for sexual minority depression disparities: From life stress to inflammation
BD Smart, JE Pachankis, R BränströmAbstract
Background
Biological mechanisms by which elevated stress facing sexual minority groups lead to depression remain under-investigated, despite theorization. We investigated the extent that stressful life events leading to chronic inflammation explain elevated depression rates based on sexual orientation. We combine biological extensions of minority stress theory with the broader stress biology literature. This includes social safety theory, its claims that “social threats” are mechanically privileged, and that prior life stress sensitizes response to incident stressors.
Methods
Pre-registered analysis of the longitudinal Swedish LifeGene cohort (2009–2021; N = 24,524) linked to national healthcare registers. Questionnaires assessed depressive symptoms, sexual orientation, stressful life events, and health behaviors. Stressors were classified a priori as high, moderate, or non-social threats. Ten stress biomarkers comprised inflammatory and metabolic composite indices. Statistical analyses included interventional decomposition mediation.
Results
Sexual minority and especially bisexual participants had elevated depression rates, stressful life event counts, and biomarker values. High social threats were the largest mediators, explaining 29–45% of the bisexual depression disparity and significantly exceeding moderate and non-social threats, and health behaviors (smoking, heavy alcohol, physical inactivity). Sequential mediation found <4% of the stressor–depression association passed through inflammation. The three-way sensitization interaction was significant (p < .001). Bisexual participants were disproportionately sensitized; equalizing disparities would reduce bisexual depression disparities by 5.0% (women) and 2.7% (men).
Conclusions
Biological processes underlying sexual orientation-based disparities in depression are empirically supported. Interventions preventing life stressors, rather than downstream biological sequelae, are recommended public health goals.