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. 2012 Jul 1;72(1):34-40.
doi: 10.1016/j.biopsych.2012.02.034. Epub 2012 Apr 10.

Clustering of depression and inflammation in adolescents previously exposed to childhood adversity

Gregory E Miller  1 , Steve W Cole
Affiliations

Clustering of depression and inflammation in adolescents previously exposed to childhood adversity

Gregory E Miller et al. Biol Psychiatry. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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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Conflict of interest statement

Neither of the authors has a financial holding or conflict of interest to declare related to this work.

Figures

Figure 1
Figure 1
Estimated values of inflammatory outcomes as a function of recent depression and childhood adversity. At visits when subjects had recently experienced depression, they showed higher levels of inflammatory biomarkers, relative to visits when they were euthymic. However, the magnitude of these changes varied in proportion to childhood adversity. To the extent they had been exposed to earlier adversity, subjects displayed progressively larger IL-6 (upper panel) and CRP (middle panel) increases upon transitioning from healthy to depressed states. With recent depression, these subjects also displayed a greater likelihood of having CRP ≥ 3 mg/L, placing them in the elevated risk category for cardiovascular disease as outlined in AHA/CDC guidelines (lower panel). These associations persisted following adjustment for demographic and biobehavioral confounders. The label “non-converters” refers to subjects who did not experience a depressive episode during the study.
Figure 2
Figure 2
Estimated prevalence of depression as a function of interleukin-6 and childhood adversity. Lagged models revealed that when adversity-exposed subjects displayed high IL-6 levels, relative to their average over the project, they had increased depression rates six months forward. These associations persisted following adjustment for standard covariates and concurrent depression, i.e., at time of IL-6 measurement. The label “non-converters” refers to subjects who did not experience a depressive episode during the study.
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