Immune system dysregulation in adolescent major depressive disorder

New York University School of Medicine, NYU Child Study Center, NY 10016, United States.
Journal of Affective Disorders (Impact Factor: 3.38). 10/2008; 115(1-2):177-82. DOI: 10.1016/j.jad.2008.07.022
Source: PubMed


A large body of evidence suggests that immune system dysregulation is associated with Major Depressive Disorder (MDD) in adults. This study extends this work to adolescent MDD to examine the hypotheses of immune system dysregulation in adolescents with MDD, as manifested by significantly: (i) elevated plasma levels of cytokines (interferon [IFN]-gamma, tumor necrosis factor-alpha, interleukin [IL]-6, IL-1beta, and IL-4); and (ii) Th1/Th2 cytokine imbalance shifted toward Th1 as indexed by increased IFN-gamma/IL-4.
Thirty adolescents with MDD (19 females; 13 medication-free/naïve; ages 12-19) of at least 6 weeks duration and a minimum severity score of 40 on the Children's Depression Rating Scale-Revised, and 15 healthy comparisons (8 females), group-matched for age, were enrolled. Plasma cytokines were examined using enzyme-linked immunosorbent assay. Mann-Whitney test was used to compare subjects with MDD and controls.
Adolescents with MDD had significantly elevated plasma IFN-gamma levels (3.38+/-11.8 pg/ml versus 0.37+/-0.64 pg/ml; p<0.003), and IFN-gamma/IL-4 ratio (16.6+/-56.5 versus 1.76+/-2.28; p=0.007). A trend for IL-6 to be elevated in the MDD group was also observed (1.52+/-2.88 pg/ml versus 0.49+/-0.90 pg/ml; p=0.09). Importantly, findings remained evident when medicated subjects were excluded.
Findings suggest that immune system dysregulation may be associated with adolescent MDD, with an imbalance of Th1/Th2 shifted toward Th1, as documented in adult MDD. Larger studies with medication-free adolescents should follow.

Download full-text


Available from: Rachel G Klein,
21 Reads
  • Source
    • "There is consistent evidence for a depression-immunity association in both adults and adolescents (Gabbay et al., 2009; Howren et al., 2009); however, this association has not yet been conclusively demonstrated at earlier ages. Three published studies on this topic have included children, but have also included adolescents and/or adults, often without adequate differentiation between the age groups (Brambilla et al., 2004; Copeland et al., 2012; Keller et al., 2010). "
    [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.
    Psychoneuroendocrinology 10/2015; 63:228-234. DOI:10.1016/j.psyneuen.2015.10.003 · 4.94 Impact Factor
  • 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.
    06/2015; 229(1-2). DOI:10.1016/j.psychres.2015.06.036
  • Source
    • "Heritability is estimated around 40% for MDD (Glowinski et al., 2003; Sullivan et al., 2000) and around 80% for schizophrenia (Schwab & Wildenauer, 2013). The presence of plasma pro-inflammatory cytokines (Gabbay et al., 2009; Mills et al., 2013) and variation in vitamin D levels (Tolppanen et al., 2012) in adolescents with mental illness is especially interesting, with both also having a role in the modulation of the immune system (Yin & Agrawal, 2014). Understanding how putative biomarkers vary in a healthy population of adolescents may help in guiding the study of these blood measures in psychiatric disorders in adolescents. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cytokines and vitamin D both have a role in modulating the immune system, and are also potentially useful biomarkers in mental illnesses such as major depressive disorder (MDD) and schizophrenia. Studying the variability of cytokines and vitamin D in a healthy population sample may add to understanding the association between these biomarkers and mental illness. To assess genetic and environmental contributions to variation in circulating levels of cytokines and vitamin D (25-hydroxy vitamin D: 25(OH)D3), we analyzed data from a healthy adolescent twin cohort (mean age 16.2 years; standard deviation 0.25). Plasma cytokine measures were available for 400 individuals (85 MZ, 115 DZ pairs), dried blood spot sample vitamin D measures were available for 378 individuals (70 MZ, 118 DZ pairs). Heritability estimates were moderate but significant for the cytokines transforming growth factor-β1 (TGF-β1), 0.57 (95% CI 0.26-0.80) and tumor necrosis factor-receptor type 1 (TNFR1), 0.50 (95% CI 0.11-0.63) respectively. Measures of 25(OH)D3 were within normal range and heritability was estimated to be high (0.86, 95% CI 0.61-0.94). Assays of other cytokines did not generate meaningful results. These potential biomarkers may be useful in mental illness, with further research warranted in larger sample sizes. They may be particularly important in adolescents with mental illness where diagnostic uncertainty poses a significant clinical challenge.
    Twin Research and Human Genetics 12/2014; 18(01):1-8. DOI:10.1017/thg.2014.70 · 2.30 Impact Factor
Show more