Clustering of Depression and Inflammation in Adolescents Previously Exposed to Childhood Adversity

Department of Psychology, University of British Columbia, Vancouver, Canada.
Biological psychiatry (Impact Factor: 10.26). 04/2012; 72(1):34-40. DOI: 10.1016/j.biopsych.2012.02.034
Source: PubMed
There is mounting interest in the hypothesis that inflammation contributes to the pathogenesis of depression and underlies depressed patients' vulnerability to comorbid medical conditions. However, research on depression and inflammation has yielded conflicting findings, fostering speculation that these conditions associate only in certain subgroups, such as patients exposed to childhood adversity.
We studied 147 female adolescents. All were in good health at baseline but at high risk for depression because of family history or cognitive vulnerability. Subjects were assessed every 6 months for 2.5 years, undergoing diagnostic interviews and venipuncture for measurement of two inflammatory biomarkers, C-reactive protein (CRP) and interleukin-6 (IL-6). Childhood adversity was indexed by parental separation, low socioeconomic status, and familial psychopathology.
Multilevel models indicated that childhood adversity promotes clustering of depression and inflammation. Among subjects exposed to high childhood adversity, the transition to depression was accompanied by increases in both CRP and IL-6. Higher CRP remained evident 6 months later, even after depressive symptoms had abated. These lingering effects were bidirectional, such that among subjects with childhood adversity, high IL-6 forecasted depression 6 months later, even after concurrent inflammation was considered. This coupling of depression and inflammation was not apparent in subjects without childhood adversity.
These findings suggest that childhood adversity promotes the formation of a neuroimmune pipeline in which inflammatory signaling between the brain and periphery is amplified. Once established, this pipeline leads to a coupling of depression and inflammation, which may contribute to later affective difficulties and biomedical complications.

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    • "One of the plausible explanations for the lack of expected moderation of the link between childhood abuse and rMDD by IL-1 could lie in the type or the timing of stressor we used. More specifically, depression is a heterogeneous disorder and there is evidence for cytokine disruption in only a subset of depressed individuals (Miller & Cole, 2012; Slavich & Irwin, 2014), or with specific depressive symptoms (Baune et al., 2012; Jokela, Virtanen, Batty, & Kivimäki, 2015 ). In addition , although we focused on childhood abuse in our study, there is evidence from other research that other specific forms of negative life events may impact cytokine levels (e.g., targeted rejection events; for a review, see Slavich & Irwin, 2014). "
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    • "Changes in the circulating levels of these proteins have been associated with many disease states, making them potentially valuable as functional biomarkers. Excessive or diminished cytokine levels are associated with schizophrenia and depression and are associated with a pro-inflammatory phenotype in patients with a history of childhood trauma, but not in patients without such history (Dennison et al., 2012; Miller and Cole, 2012). There are several pathways of active communication that allow controlled immune signaling between the periphery and the brain. "
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    • "To explain this association, severe childhood stress was shown to predispose to persistently high inflammatory status of the body (CRP and IL-6) lasting to adulthood. In subjects with severe childhood adverse events the systemic levels of inflammatory cytokines were also raised higher in response to an adverse event in adulthood when compared to those without childhood adverse events [134, 135]. The persistently activated inflammatory pathways may increase susceptibility to other chronic inflammatory diseases. "
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