Associations between childhood maltreatment, peripheral immune biomarkers, and psychiatric symptoms in adults: A cohort study of over 138,000 participants

BACKGROUND: Few studies have integrated the impact of individual and cumulative childhood maltreatment on multiple psychiatric symptoms, with the mechanisms underlying these associations largely unknown. This study aims to comprehensively assess the associations between childhood maltreatment, multiple peripheral immune biomarkers, and various psychiatric symptoms in adulthood and to explore whether peripheral immune inflammation plays a mediator role in the associations between childhood maltreatment and psychiatric symptoms in adulthood. METHODS: Using data from the UK Biobank, we constructed a retrospective cohort study of 138,915 participants who provided self-reported childhood maltreatment and had peripheral immune biomarkers assessed. We examined seven types of psychiatric symptoms in adulthood, including depressive symptoms, anxiety symptoms, mania, post-traumatic stress disorder (PTSD), psychotic experiences, self-harm, and alcohol use disorder. Logistic regression models were performed to explore the associations between childhood maltreatment, immune biomarkers, and psychiatric symptoms, calculating the average marginal effects for each indicator of childhood maltreatment. Mediation analyses were conducted to determine the extent to which the immune biomarkers could explain the association between childhood maltreatment and psychiatric symptoms in adulthood. Subgroup and sensitivity analyses were also performed. RESULTS: Among the participants, 77,937 (56.10 %) were female, with a mean age of 55.91 (SD: 7.73) years at baseline. There were dose-response relationships existed between the accumulation of childhood maltreatment indicators and all seven assessed psychiatric symptoms and multimorbidity in adulthood (e.g., for depressive symptoms, OR = 1.67 [95 %CI, 1.57 to 1.78] for one childhood maltreatment indicator; OR = 2.77 [95 % CI, 2.58 to 2.97] for two; OR = 4.91 [95 % CI, 4.61 to 5.24] for three or more). Emotional abuse and physical neglect showed the strongest average marginal effects on psychiatric symptoms. Levels of C-reactive protein (CRP) and counts of leukocytes and neutrophils were positively associated with depressive symptoms (e.g., OR = 1.13 [95 % CI, 1.08 to 1.17] for CRP level), anxiety symptoms, PTSD, and psychotic experiences. Moreover, levels of CRP partially mediated the association between childhood maltreatment scores and psychiatric symptoms, albeit with a relatively low mediation proportion (0.65 %-1.77 %). CONCLUSIONS: Our findings underscore the importance of interventions that address multiple forms of childhood maltreatment to mitigate long-term mental health challenges substantially. While peripheral immunity responses may serve as predictors of mental health problems, they might not to be the primary mechanism through which childhood maltreatment influences psychiatric symptoms in adulthood.