Abstract
The experience of childhood life events is associated with higher vulnerability to develop psychiatric disorders. One of the pathways suggested to lead to this vulnerability is activation of the immune system. The aim of this study is to find out whether the association between childhood life events and the development of mood and anxiety disorders is predicted by the activation of the immune system. This study was performed in TRAILS, a large prospective population cohort, from which a subgroup was selected (N=1084, 54.3% female, mean age 19.0 (s.d., 0.6)). Childhood life events before age 16 were assessed using questionnaires at age 12, 14, 16 and 19. Immune activation was assessed at age 16 by elevated high-sensitive C-reactive protein (hsCRP) and by levels of immunoglobulin G antibodies against the herpes viruses herpes simplex virus 1, cytomegalovirus and Epstein–Barr virus. At age 19, the presence of mood and anxiety disorders was determined using the World Health Organization Composite International Diagnostic Interview Version 3.0. Regression analyses were used to study the association between life events, the inflammatory markers and mental health. We found that childhood life events score was associated with risk of mood disorders (B=0.269, P<0.001) and anxiety disorders (B=0.129, P<0.001). Childhood life events score was marginally associated with elevated hsCRP (B=0.076, P=0.006), but not with the antibody levels. This was especially due to separation trauma (P=0.015) and sexual abuse (P=0.019). Associations lost significance after correcting for lifestyle factors such as body mass index and substance abuse (P=0.042). None of the inflammatory markers were associated with development of anxiety disorders or mood disorders. In conclusion, the life event scores predicted the development of anxiety disorders and mood disorders at age 19. Life event scores were associated with elevated hsCRP, which was partly explained by lifestyle factors. Elevated hsCRP was not associated with the development of psychiatric disorders at age 19.
Highlights
Childhood life events are associated with higher vulnerability to develop various psychiatric disorders, and the risk increases with the number of life events subjects have experienced.[1,2] Apart from psychological and social pathways, several biological pathways have been suggested to play a role in this vulnerability.The experience of childhood life events is associated with hypothalamic-pituitary-adrenal axis dysregulation, different genetic and epigenetic influences on stress regulation, and with activation of the immune system.[3]
We studied the association between life events before age 16, activity of the immune system at age 16, as measured by levels of high-sensitive C-reactive protein (hsCRP) and immunoglobulin G antibodies to CMV, Epstein–Barr virus (EBV) and HSV1, and the development of mood and anxiety disorders at age 19
Life events score before age 16 was associated with presence of mood disorders at age 19 (B = 0.269, P o 0.001, odds ratio (OR) 1.93, with a 95% confidence interval of 1.21–1.41) and anxiety disorders (B = 0.129, P o 0.001, OR 1.14, with a 95% confidence interval of 1.06–1.22)
Summary
The experience of childhood life events is associated with hypothalamic-pituitary-adrenal axis dysregulation, different genetic and epigenetic influences on stress regulation, and with activation of the immune system.[3] An activated immune system is associated with the presence of various psychiatric disorders. A recent meta-analysis found similar patterns of activation of the immune system in acute and chronic phases of schizophrenia, bipolar disorder and major depressive disorder. This finding makes it more likely that there is a common underlying pathway for immune disorders across these conditions.[11] A possible explanation is that stress may cause activation of the immune system, which in turn could influence brain functioning and this could contribute to the development of psychiatric disorders. Stressful experiences early in life could lead to a chronic state of immune activation, which would increase the vulnerability for the development of psychiatric disorders
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