Immune system dysregulation in adolescent major depressive disorder

Abstract

Background-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]-γ, tumor necrosis factor-α, interleukin [IL]-6, IL-1β, and IL-4); and (ii) Th1/Th2 cytokine imbalance shifted toward Th1 as indexed by increased IFN-γ/IL-4.Method-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.Results-Adolescents with MDD had significantly elevated plasma IFN-γ levels (3.38 ± 11.8 pg/ ml versus 0.37 ± 0.64 pg/ml; p<0.003), and IFN-γ/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.Conclusions-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.

Major Depressive Disorder and Bipolar Disorder Predispose Youth to Accelerated Atherosclerosis and Early Cardiovascular Disease

“…Indeed, in a handful of small case-control studies, clinically depressed adolescents have shown higher serum levels of some proinflammatory cytokines (eg, interleukin [IL]-1β and IL-6) than healthy control participants. [88][89][90] The results of larger studies of community youth have been mixed, with most but not all studies demonstrating graded associations between depressive symptoms and inflammatory biomarkers such as IL-6 and C-reactive protein (CRP). 88,[91][92][93] Findings from adults suggest that inflammation may be particularly salient in early-onset BD, 94,95 and there are preliminary findings from youth with BD.…”

“…141 In a 2010 meta-analysis of 18 articles, 150 patients who were clinically depressed had significantly less favorable measures of autonomic dysfunction reflecting parasympathetic function than nondepressed patients; moreover, depression severity was correlated with autonomic dysfunction. Some 90,151,152 but not all 153 studies have suggested that autonomic nervous system functioning, most commonly estimated as parasympathetic withdrawal, is worse in patients with BD than in those without. Although autonomic dysfunction has been identified in the pathway between depressive disorders and CVD in adults, 154 autonomic dysfunction is less likely to lead to end-organ damage in adolescents and young adults because of the decades-long process by which CVD develops over time.…”

The role of neuroinflammation in juvenile bipolar disorder

“…[22][23][24] In addition, studying clinical features of mood disorders at onset in the offspring of adults with depression or BD has become a promising research approach. [25,26] Several reports have shown a relationship between: (1) the dysregulation of inflammatory markers (increased levels of IL-6, IL-1β, IL-2, IL-10, INF-α and TNF); (2) genetic variation in inflammatory genes [C-reactive protein (CRP)-gene polymorphism] and pediatric major depressive disorder; [16] (3) changes in gene expression among subjects with active mood disorders; [16] (4) preliminary evidences of an association between inflammation and suicidality in depressed youths (decreased TNF-α levels in suicidal compared to nonsuicidal depressed adolescents [27] ) as well as increased mRNA and protein expression of IL-1β, IL-6 and TNF-α in Brodmann area 10 of suicide victims relative to controls. [28] Among children and adolescents with BD, there is a high prevalence of conditions associated with inflammation, such as asthma, cardiovascular disorders, diabetes and obesity, [12] often associated with inflammatory markers, [13] including elevated high-sensitivity-C-reactive protein (hsCRP) and IL-6.…”

Heritability of Transforming Growth Factor-β1 and Tumor Necrosis Factor-Receptor Type 1 Expression and Vitamin D Levels in Healthy Adolescent Twins

“…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. Examining the link between psychiatric disorders and immune system dysregulation (Gabbay et al, 2009), and the genetic contribution to these biomarkers, are both required to understand the role of plasma cytokines and vitamin D levels in adolescent psychiatric disorders.…”