Immune dysregulation in psychiatric disorders with and without exposure to childhood maltreatment: A transdiagnostic stratified meta-analysis

Childhood maltreatment (CM), i.e. physical, psychological, or sexual abuse and neglect, affects approximately one third of the general population and is an important risk factor for all major psychiatric disorders. Exposure to CM also has a profound impact on immune function, with both factors independently implicated in the development and prognosis of different mental disorders. This study aims to 1) assess differences in immune markers among adults diagnosed with psychiatric disorders with and without a history of CM and 2) explore the role of CM as a mediating factor in immune abnormalities among psychiatric patients compared to non-psychiatric controls. A PRISMA-compliant systematic search of PubMed, Web of Science and Embase databases was performed until October 24th, 2024 for original studies that assessed immune markers in trauma-stratified adult psychiatric patients (PROSPERO ID CRD42021273059). We modelled random-effects meta-analyses to compare levels of pro-inflammatory (PIM), anti-inflammatory (AIM) and cellular immune markers (CIM) between traumatized (CM + ) and non-traumatized (CM-) individuals, and investigated exposure to CM as a mediating factor in the immune abnormalities among adult psychiatric patients compared to non-psychiatric controls. Secondary analyses were performed for diagnostic subgroups and individual immune markers. Study quality was assessed with the Newcastle Ottawa Scale. We included data from 53 studies on n = 12,141 patients with mood disorders (MD), schizophrenia spectrum disorders (SSD), substance use disorders (SUD), eating disorders (ED) and anxiety disorders (AD). We uncovered a consistent transdiagnostic impact of CM on blood-based pro-inflammatory molecules (OR = 1.186; 95 % CI 1.030-1.365, p = 0.018) among patients with psychiatric disorders. This effect was not observed in the non-psychiatric controls included in the same studies. We did not find evidence of specific trauma-induced abnormalities in immune composite scores for separate diagnostic subgroups, except for PIM in SUD patients (OR = 2.324, 95 % CI 1.043-5.182, p = 0.039). Interleukin 6 (IL-6) was identified as a significant mediator between CM exposure and a psychiatric diagnosis in adulthood (OR = 1.609; 95 % CI 1.100-2.353, p = 0.014), while increases in C-reactive protein (CRP) and Interleukin 10 (IL-10) did not appear to be trauma-specific. Our findings confirm a transdiagnostic impact of exposure to CM on increased pro-inflammatory molecular and cellular immune levels in psychiatric patients. IL-6 emerged as a crucial mediator, suggesting that CM leads to specific immune alterations predisposing individuals to psychiatric conditions. This meta-analysis highlights the role of trauma-induced immune abnormalities as a potentially crucial mechanism contributing to increased vulnerability towards mental illness later in life.