Article

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

ABSTRACT

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.

Full-text preview

Available from: ncbi.nlm.nih.gov
  • Source
    • "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). "
    [Show abstract] [Hide abstract] ABSTRACT: Extensive evidence highlights the role of inflammatory processes in major depressive disorder (MDD). However, most studies have examined a consistent set of inflammatory cytokines and there is evidence that other immune-derived products may play a role in MDD. In this article, we present data from 3 complimentary studies that support the role of a novel cytokine, interleukin-33 (IL-33), in depression risk. First, we show that a 2-SNP haplotype in the IL-33 gene (rs11792633 and rs7044343) moderated the link between women's history of childhood abuse and their history of recurrent MDD (rMDD), such that the link between childhood abuse and rMDD was stronger among women with fewer copies of the protective IL-33 CT haplotype. Second, linking these findings to differences in circulating cytokine levels, we show in a separate sample that those with a history of rMDD had higher peripheral levels of IL-33 and IL-1β compared with women with a single MDD episode or no history of MDD. Third, providing initial evidence of brain regions underlying these effects using archival rat brain tissue, we show that an acute stressor increased IL-33 expression in the paraventricular nucleus of the hypothalamus and, to a lesser extent, the prefrontal cortex, key brain regions underlying stress response and emotion regulation. These findings provide converging support for the potential role of IL-33 in risk for recurrent MDD. (PsycINFO Database Record
    Full-text · Article · Apr 2016 · Journal of Abnormal Psychology
  • Source
    • "Consistent with previous studies on CRP and depression in adolescence (Copeland et al., 2012; Miller and Cole, 2012), this study found a positive association between CRP and depressive symptoms . Although the effect size was small to moderate (ˇ = 0.23), it is similar to aggregate effect sizes calculated by Howren, et al. (2009) in their meta-analysis of studies examining CRP and depression in adults, which were overall small but significant (d = 0.22, p < 0.001). "
    [Show abstract] [Hide abstract] ABSTRACT: Despite consistent findings of an association between depression and immunity in adult and adolescent populations, little is known about the nature of this relationship at earlier ages. Studies of children have yielded mixed results, suggesting methodological confounds and/or the presence of significant moderating factors. Timing of adrenarche, the first phase of puberty that occurs during late childhood, is a plausible moderator of the depression-immunity relationship in late childhood due to its associations with both the immune system and psychological wellbeing. We hypothesized that: (1) a depression-immunity association exists in children, (2) this association is moderated by adrenarcheal timing, and, (3) this association is also moderated by gender. Data were drawn from a nested study of 103 participants (62 females, Mage=9.5, age range: 8.67-10.21 years) participating in a population based cohort study of the transition from childhood to adolescence (across puberty). Participants in this nested study completed the Children's Depression Inventory 2 (CDI-2) and provided morning saliva samples to measure immune markers (i.e., C-reactive protein, CRP; and secretory immunoglobulin A, SIgA). Using hierarchical regression, inflammation measured by CRP was positively associated with the negative mood/physical symptoms (NM/PS) subscale (β=0.23, t=2.33, p=0.022) of the CDI-2. A significant interaction effect of SIgA x adrenarcheal timing was found for NM/PS (β=-0.39, t=-2.19, p=0.031) and Interpersonal Problems (β=-0.47, t=-2.71, p=0.008). SIgA and NM/PS were positively associated for relatively late developers. SIgA and Interpersonal Problems were positively associated for late developers, and negatively associated for early developers. We suggest that both sets of findings might be partially explained by the immunosuppressive effect of the hormonal changes associated with earlier adrenarche, namely testosterone. These results also suggest that adrenarcheal timing has an effect on the association between depression and immunity, and is therefore an important measure in research with younger populations. Future research should utilize longitudinal designs to demonstrate direction of influence of variables, and use a broader range of pro- and anti-inflammatory markers.
    Full-text · Article · Oct 2015 · Psychoneuroendocrinology
  • Source
    • "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. "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Jun 2015
Show more