Summary:
Adverse childhood experiences (ACEs) are common and involve significant stress during early life, including experiences such as sexual abuse, physical or emotional neglect, and other forms of maltreatment. These exposures have been linked to poorer mental health outcomes, particularly mood and anxiety symptoms, and may also influence physical health later in life. One proposed mechanism is prolonged activation of stress responses, leading to persistent immune activation and inflammation, which may increase susceptibility to autoimmune disease. Women tend to report more complex and varied ACE patterns than men and may show stronger inflammatory responses, suggesting sex-specific effects. Mental disorders and autoimmune diseases frequently co-occur and are influenced by both environmental and biological factors. While previous research has suggested that mental health symptoms may help explain the link between childhood trauma and autoimmune disease, evidence from large population-based studies remains limited, particularly for common symptoms such as depression and anxiety. This study, a population-based cohort study using data from two large cohorts of adult women, included participants who self-reported exposure to multiple ACEs, including sexual abuse and physical and emotional neglect. The study examined associations between ACE exposure and autoimmune disease prevalence and assessed whether depressive, anxiety, and post-traumatic stress symptoms contributed to the association. ACE exposure was common and showed a clear dose–response relationship with autoimmune disease prevalence. Several autoimmune conditions were more strongly associated with ACEs, and specific ACE types, particularly sexual abuse and neglect, were consistently linked to higher risk. Mental health symptoms accounted for approximately one quarter of the association between ACEs and autoimmune disease. Overall, this study suggests that early-life adversity is associated with autoimmune disease risk in adult women.
Abstract:
Background: Adverse childhood experiences (ACEs) have been associated with increased risks of autoimmune diseases. However, data are scarce on the role of specific ACEs as well as the potential mediating role of adverse mental health symptoms in this association. Methods: A cohort study using the nationwide Icelandic Stress-And-Gene-Analysis (SAGA, 22,423 women) cohort and the UK Biobank (UKB, 86,492 women) was conducted. Participants self-reported on five ACEs. Twelve autoimmune diseases were self-reported in SAGA and identified via hospital records in UKB. Poisson regression was used to assess the cross-sectional association between ACEs and autoimmune diseases in both cohorts. Using longitudinal data on self-reported mental health symptoms in the UKB, we used causal mediation analyses to study potential mediation by depressive, anxiety, and PTSD symptoms in the association between ACEs and autoimmune diseases. Results: The prevalence of ACEs was 50% in SAGA and 35% in UKB, while the prevalence of autoimmune diseases was 29% (self-reported) and 14% (clinically confirmed), respectively. In both cohorts, ACEs were associated with an increased prevalence ratio (PR) of any studied autoimmune disease in a dose–response manner (PR = 1.10 (95%CI = 1.08–1.12) per ACE), particularly for Sjögrens (PR = 1.34), polymyalgia rheumatica (PR = 1.20), rheumatoid arthritis (PR = 1.14), systemic lupus erythematosus (PR = 1.13), and thyroid disease (PR = 1.11). Sexual abuse and physical and emotional neglect were consistently associated with an elevated prevalence of autoimmune diseases when including all ACEs in the model. Approximately one fourth of the association was mediated through depression, anxiety, and PTSD. Conclusions: These findings based on two large cohorts indicate a role of ACEs and corresponding mental health distress in autoimmune diseases among adult women.
Article Publication Date: 11/02/2025
DOI: 10.1017/S0033291724003544
