2 - (SYM 7) Threats to Social Safety and Inflammatory Mechanisms Underlying Sexual Orientation Disparities in Depression: A Prospective Population-based Study of Young Adults

Background: Sexual minority individuals have a markedly elevated risk of depression compared to heterosexuals. This disparity is believed to be caused by this group’s disproportionate exposure to stigma-based social stress starting in childhood and persisting over the lifespan. Recent frameworks have put forth biological processes—and inflammation in particular—as potential mechanisms underlying some populations’ greater risk of mental health problems. According to the social safety theory of depression, low-grade chronic inflammation can result from early experiences of threats to social safety and put some individuals at increased risk of depression. Sexual minorities are particularly likely to experience such threats to social safety. We therefore explored the link between early exposure to threats of social safety, chronically elevated inflammation, and depression severity, as well as inflammation’s mechanistic role in sexual orientation disparities in depression.

Methods: We analyzed data from a large, prospective cohort of 1,150 sexual minority and heterosexual young adults that included assessments of depression symptoms over four years, three well-established biomarkers of inflammation (i.e., CRP, IL-6, TNF-alpha) measured at two time points, and a measure of early exposure to threats to social safety in the form of adverse childhood experiences.

Results: Sexual minorities reported more depressive symptoms and more adverse interpersonal experiences during childhood than heterosexuals. Mediation analyses showed a significant indirect serial mediation effect of childhood adversity and chronically elevated inflammation on the association between sexual orientation and depressive symptoms.

Conclusions: Results offer support for the social safety theory of depression by being one of the first longitudinal studies to demonstrate a link between threats to social safety during childhood with chronic inflammation and depression in young adulthood. Findings also provide the strongest evidence to date for early exposure to social threats and chronic inflammation as underlying factors that can partially explain sexual orientation disparities in depression, highlighting potential intervention targets.