Serum cytokines and anxiety in adolescent depression patients: Gender effect
Introduction
The role of the immune system in the pathophysiology of depression is under extensive study in current research. The results support the role of cytokines as modulators of neuroendocrine and neurochemical pathways leading to depressive disorders (Schiepers et al., 2005, Irwin and Miller, 2007). Peripheral cytokines are shown to cross blood−brain-barrier and influence brain cells following several defined mechanisms (Yarlagadda et al., 2009, Tian et al., 2012).
Recent systematic review by Mills et al. (2013) supports the view that depression in adolescents is a low-grade neuro-inflammation state. The role of pro-inflammatory cytokines, such as IL-1β, tumor necrosis factor (TNF)-α and interferon (IFN)-γ, IL-6 etc. in the etiology and pathophysiology of depression is well investigated (O’Brien et al., 2007, Dhabhar et al., 2009, Dowlati et al., 2010, Janelidze et al., 2011) including their role in suicidality (Simon et al., 2008, Gabbay et al., 2009b). In contrast to pro-inflammatory cytokines such as IL-6, considerably less attention has been focused on the potential role of anti- inflammatory (IL-10), immunomodulatory (TGF-β1) and autoimmune (IL-17) cytokines. 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, Gabbay et al., 2009b, Miller and Cole, 2012, Henje Blom et al., 2012, Mcdade et al., 2013). There is also a gender difference. Mood disturbances are the most frequent in female patients as compared to male patients particularly in adolescent age group. Few studies have assessed the role of immune system dysfunction in females with adolescent depressive disorders and the results suggest that pro-inflammatory cytokines are part of the pathophysiology of affective disorders in adolescent females (ter Wolbeek et al., 2007, Henje Blom et al., 2012).
It was also observed that depressed patients responding poorly to antidepressant treatments have elevated levels of proinflammatory cytokines and the levels were seen to remain persistently elevated even on antidepressant treatment (Sluzewska et al., 1996, Kim et al., 2008, Cattaneo et al., 2013). Tumor necrosis factor alpha (TNF-α) levels have been seen to predict non-response to antidepressant therapy (Eller et al., 2008).
In essence, there seems to be a strong indication that depression and interleukins merit further systematic study with special attention to medication status and in vulnerable groups like adolescence.
In the present study we aimed to add to the existing literature using a case-control design among patients of adolescence age group and healthy controls group wherein we measured eight cytokines, from pro-inflammatory (IL-1β, IL-2, IL-6, IFN-γ, TNF-α,), anti-inflammatory (IL-10) and immunomodulatory groups (IL-17, TGF-β1) with a research hypothesis that adolescent depression patients have altered serum cytokine profile with proinflammatory inclination in comparison to the age comparable healthy controls.
Section snippets
Cases
Seventy seven confirmed cases of adolescent depressed subjects (28 females and 49 males) were recruited from the Child-guidance-clinic and Walk-in-clinic of Department of Psychiatry, All India Institute of Medical Sciences (AIIMS), New Delhi during the period of November 2008 to August 2011. The present study was approved by the ethics committee of AIIMS. Participant information sheet having details about the study both in English and local vernacular (Hindi) was made available to all
Demographic and clinical profile
Demographic and clinical characteristics of the patients (n=77) and healthy control group (n=54) are compiled in Table 1. Healthy control subjects were chosen of comparable age with the patients. Both groups belong to comparable socioeconomic status and it is assumed that they are of similar hygiene level. None of the patients or healthy controls reported smoking, alcohol consumption or substance abuse. There was no significant difference (p=0.110) in BMI (kg/m2) between patients (23.8±2.9) and
Discussion
The study measured eight serum cytokines in patients (n=77) and controls (n=54), analyzed their gender based distribution and their correlation with depression and anxiety scores. The study reports elevated levels of two cytokines, IL-2 and IL-6 in depressed patient. Five cytokines namely IL-1β, TNF-α, IL-10, TGF-β1 and IL-17 were found to have correlation with clinical depression and/or anxiety scores. The study reports effect of gender in the cytokine (IL-6) levels of depression patients
Acknowledgments
The authors are grateful to all subjects who participated in this study. We would like to thank Ms. Kalaivani, Department of Biostatistics, AIIMS, New Delhi for helping in statistical analysis of the study. The authors declare no conflict of interest.
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