Persistent or recurrent depression in young adults: associations with systemic inflammation and early life adversity.

Background There is limited research on persistent or recurrent depression into young adulthood. We examined the prevalence of recurrent/persistent depression in young adults, and associations with childhood trauma/adversity and systemic inflammation, and if inflammatory markers mediated associations between childhood trauma and subsequent depression. Methods ALSPAC participants with ICD-10 depression assessments at ages 18, 24 and 30 were classified as never depressed, transiently depressed (one episode), or persistently/recurrently depressed (≥ 2). Trauma/adversity from birth to age 16/17 was characterised by type, timing and burden. Interleukin-6 (IL-6) and C-reactive protein (CRP) were measured at ages 9, 16, 18 and 24. Analyses used multinomial logistic regression, linear regression and causal mediation models. Results Among 2,014 participants, 78.9% were never depressed, 15.0% had transient depression and 6.1% had persistent/recurrent depression. Trauma/adversity was more strongly associated with persistent/recurrent depression (RRR 3.17, 95% CI 1.98-5.06; FDR-P=6.2x10^-6) than transient depression, with a dose-response pattern and stronger associations for threat adversities. Middle-to-late childhood (11-17 yrs) emerged as a sensitive period for persistent/recurrent (RRR 2.85, 95% CI 1.47-5.52) and transient depression (RRR 1.85, 95% CI 1.25-2.73). Trauma/adversity was associated with modestly higher IL-6 at age 24 (all FDR-adjusted P < 0.05); CRP associations did not survive multiple-testing correction. Neither marker mediated trauma/adversity associations with persistent/recurrent depression. Conclusion Persistent/recurrent depression affects approximately 1 in 20 young adults. Childhood trauma/adversity, particularly during middle-to-late childhood, was associated with persistent/recurrent depression, but measured inflammatory proteins did not mediate this association. Further work is needed to understand biological mechanisms underlying the embedding early life psychosocial stress.