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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    • "As suggested by the results of meta analysis studies, although the association of pro-inflammatory cytokines and depression in adults has been demonstrated yet the same remains to be demonstrated extensively in adolescent and pediatric population. Immune system dysfunction in depression has been observed across different age groups (Penninx et al., 2003; Danese et al., 2008; Viscogliosi et al., 2011) including adolescents (Brambilla et al., 2004; Gabbay et al., 2009a, 2009b; Miller and Cole 2012; Henje Blom et al., 2012; Mcdade et al., 2013). There is also a gender difference. "
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    ABSTRACT: The present study compares the serum cytokine levels between adolescent depression patients and healthy controls and assesses correlation between depression, anxiety scores and serum levels of eight cytokines. Study also checked the variation in serum levels with medication status (medication free/naïve vs. patients on medication). Following clinical and psychometric assessment of 77 adolescent (aged 13-18 years) depression patients (49 males and 28 females; 56 medication free/naïve) and 54 healthy controls (25 males, 29 females), eight cytokines (IL-1β, IL-2, IL-6, IL-10, TNF-α, IFN-γ, TGF-β1 and IL-17A {denoted IL-17 throughout}) were measured in serum using ELISA. Depressed adolescents had significantly high levels of IL-2 (p<0.001) and IL-6 (p=0.03) as compared to controls. The female population skewed the result of one cytokine (IL-6) in patients. Anxiety scores showed positive correlation (only in female patients) with IL-1β, IL-10 and negative correlation with TGF-β1 and IL-17. The gender effect in relationship between anxiety and cytokines was not straightforward. On comparing study groups on the medication/naïve status, IL-2 and TGF-β1 showed significant difference between the groups (p<0.001, p=0.007 higher in medicated). Depression in adolescents was associated with elevation of proinflammatory serum cytokines with a gender bias for females. Anxiety scores correlated negatively with TGF-β1 and IL-17. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    06/2015; 229(1-2). DOI:10.1016/j.psychres.2015.06.036
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    • "Recent efforts have been made to develop integrated theories that connect interpersonal stress to inflammation and major depressive disorder (for a review, see Slavich & Irwin, 2014). However, the links among interpersonal stress, inflammation, and depression are far from simple (Glassman & Miller, 2007), and it is possible that the connection between inflammation and depression is limited to certain subgroups of people with various vulnerability factors (e.g., early adversity or medical illnesses like heart disease or an autoimmune condition; see Danese et al., 2008, 2010; Miller & Cole, 2012; Slavich & Irwin, 2014). Continued research on the links among stress, inflammation , and depression is needed in order to better understand the role that inflammation plays in the risk for psychopathology . "
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    ABSTRACT: Researchers have identified cross-sectional links between interpersonal stress and inflammation. Little is known, however, about how these dynamics unfold over time, what underlying immune pathways might exist, or whether moderators such as race could alter the strength of the connection between interpersonal stress and inflammatory processes. We examined whether adolescent girls whose relationship trajectories were characterized by chronic stress would exhibit a proinflammatory phenotype marked by systemic inflammation, heightened cytokine responses to bacterial challenges, and resistance to the anti-inflammatory properties of cortisol. Significant Stress × Race interactions revealed that family stress trajectories predicted glucocorticoid sensitivity and peer stress trajectories predicted cytokine production for White but not Asian girls. Relationship stress trajectories were not associated with systemic inflammation, however. These findings suggest that particular subgroups of adolescent girls who face chronic and elevated stress in their close relationships may be at risk for disruptions to the immune system.
    Development and Psychopathology 04/2015; -1:1-12. DOI:10.1017/S0954579415000334 · 4.89 Impact Factor
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    • "In sum, these longitudinal studies present heterogeneous findings, calling for more studies examining the interrelation between depression and inflammation in adolescence over time. An important shortcoming of the longitudinal studies conducted thus far (Caserta et al., 2011; Copeland et al., 2012; Elovainio et al., 2006; Miller & Cole, 2012) is that these authors did not look into the within-subjects trajectories of depressive symptoms over time. Examining trajectories over time takes the within-person variability of the symptoms into account and its temporal association with inflammation. "
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    ABSTRACT: In adults, depression and inflammation are bidirectionally related. This association is less clear in adolescents. Moreover, somatic and cognitive depressive symptoms might be differentially related to inflammation. Lifestyle factors, as in adults, may play an important mediating role in adolescents. For the current study we evaluated trajectories of depressive symptoms in adolescence over a 5-year course and their relation with subsequent high-sensitivity C-reactive protein (hsCRP) levels, and examined lifestyle factors as mediators. Participants of the TRacking Adolescents' Individual Lives' Survey (TRAILS; N = 1166) were followed from 2001 until 2008. Three biennial youth self-report (YSR) assessments of depressive symptoms were taken. Demographics, health, and lifestyle factors and levels of hsCRP were assessed at Wave 3. Latent-class analysis was used to determine trajectories of depression and general linear models to determine the association between depression trajectories and hsCRP. Finally, mediation analysis was performed to test mediation of lifestyle factors. Persistently moderate to high depressive symptoms were associated with higher hsCRP levels. Results were unaltered when we adjusted for demographics and health variables. Smoking mediated the association between depressive symptoms total score and hsCRP, in large part. Persistently higher scores on somatic and cognitive symptom subscales were associated with higher levels of hsCRP than persistently low scores. These results were rendered nonsignificant after covariate adjustment. Persistent depressive symptoms were associated with subsequent higher levels of hsCRP, with somatic and cognitive symptoms contributing equally. The association was mediated by smoking behavior. These findings suggest that reducing adolescent depression and smoking are important starting points in the prevention of inflammatory diseases. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
    Health Psychology 03/2015; DOI:10.1037/hea0000210 · 3.59 Impact Factor
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