Janelidze S, Mattei D, Westrin A, Traskman-Bendz L, Brundin L. Cytokine levels in the blood may distinguish suicide attempters from depressed patients. Brain Behav Immun 25: 335-339

Psychoimmunology Unit, Division of Psychiatry, Department of Clinical Sciences, Lund University, Lund, Sweden.
Brain Behavior and Immunity (Impact Factor: 5.89). 10/2010; 25(2):335-9. DOI: 10.1016/j.bbi.2010.10.010
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Elevated plasma cytokines is a common finding in Major Depressive Disorder (MDD), although not consistent. It is currently not known whether the inflammatory changes are confined to any specific subgroup of depressive patients. We here analyzed three inflammatory markers in suicidal and non-suicidal depressed patients, as well as healthy controls. Plasma interleukin (IL)-2, IL-6 and tumor necrosis factor (TNF)-α were measured in 47 suicide attempters, 17 non-suicidal depressed patients and 16 healthy controls. Study participants were evaluated using the Comprehensive Psychopathological Rating Scale (CPRS) with subscales for anxiety and degree of depression, as well as the Suicide Assessment Scale (SUAS). We found increased levels of IL-6 and TNF-α as well as decreased IL-2 concentrations in suicide attempters compared to non-suicidal depressed patients and healthy controls. The results were adjusted for potential confounders of cytokine expression, such as age, sex, body mass index (BMI), degree of depression, anxiety, personality disturbance, abuse and type of medication. These results demonstrate for the first time that suicidal patients display a distinct peripheral blood cytokine profile compared to non-suicidal depressed patients. Thus, our study provides further support for a role of inflammation in the pathophysiology of suicidality.

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    • "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 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. "
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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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    • "Particularly, the critical role of TNF-α in the pathophysiology of depression has been demonstrated in a variety of studies. It was reported that TNF-α levels were significantly higher in the plasma of acutely depressed patients (Himmerich et al., 2008), suicide attempters (Janelidze et al., 2011) and in the postmortem brains of suicide victims (Pandey et al., 2012). In addition, experimental stimulation of TNF-α production leads to a transient significant increase in the levels of anxiety and depressed mood in humans (Reichenberg et al., 2001). "
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    ABSTRACT: We investigated the effects of ascorbic acid on depressive-like behavior induced by tumor necrosis factor (TNF-α) in mice. Additionally, we examined the effects of combined administration of ascorbic acid and antidepressants, MK-801 and 7-nitroindazole in mice exposed or not to TNF-α and the capacity of TNF-α and ascorbic acid to modulate hippocampal and cerebrocortical phosphorylation of extracellular signal-regulated kinase (ERK), p38(MAPK) and c-Jun N-terminal kinase (JNK). In control animals, ascorbic acid reduced the immobility time in the tail suspension test (TST). Unilateral intracerebroventricular administration of TNF-α produced a depressive-like behavior in the TST, and the treatment with ascorbic acid prevented this effect. Sub-effective dose of ascorbic acid combined with sub-effective doses of fluoxetine, imipramine, bupropion, MK-801 or 7-nitroindazole produced a synergistic antidepressant-like effect in mice exposed or not to TNF-α. No treatment caused significant alterations in the locomotor activity of mice. Administration of TNF-α increased the phosphorylation of p38(MAPK) in hippocampus and cerebral cortex, and the treatment with ascorbic acid prevented this effect. Ascorbic acid increased phosphorylation of ERK1 in the hippocampus of saline- and TNF-α-treated animals, however it did not produce alterations in the cerebral cortex. No effects on phosphorylation of ERK2 or JNK were found. The observed effect of ascorbic acid seems to be associated, at least partially, with a reduced p38(MAPK) phosphorylation, activation of the monoaminergic systems as well as inhibition of N-methyl-D-aspartate (NMDA) receptors and nitric oxide (NO) synthesis. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 03/2015; 25(6). DOI:10.1016/j.euroneuro.2015.03.006 · 4.37 Impact Factor
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    • "cytokines (chemokines) in depression [10] [11] [12]. In a study on mice 43 and rats, Haroon et al. [13] described the participation of 44 chemokines: monocyte chemotactic protein-1 (MCP-1), chemo- 45 kine (C-X3-C motif) ligand-1 (CX3CL1; fractalkine), as well as 46 chemokine receptors: CX3C chemokine receptor-1 (CX3CR1; 47 fractalkine receptor), C-C chemokine receptor type 5 (CCR5) 48 and chemokine (C-X-C motif) receptor-4 (CXCR4) in the formation 49 of behavior resembling depression (depressive-like behavior). "
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    ABSTRACT: Background Depression can be perceived as a psychoneuroimmunological disorder in which cytokines affecting the body's neurochemical and neuroendocrine functions play an important role. Among cytokines, chemokines participating in activation of the inflammatory response are considered to be crucial. Methods 160 men and women were enrolled in the study. 120 of them were diagnosed with various types of depression. The mean age was 45.2 ± 4.5 years (range: 19–47 years). The control group consisted of 40 healthy individuals. The average age in this group was 42.4 ± 4.1 years. Plasma levels of chemokines and their receptors (CCL-5 – RANTES and CXCR-5, SDF-1 and CXCR-4), as well as of IL-6, were assessed by ELISA. Results There was an increase in SDF-1 and CCL-5 levels in women and men with different severities of depression, versus the control group. Also, an increase in the IL-6 levels, CXCR4 and CCR-5 receptors was observed in both women and men with all types of depression. Levels of SDF-1 and CCL-5 chemokines, as well as of CCR-5 and CXCR4 chemokine receptors, were higher in women than in men. Conclusions The results of this study indicate the need for assessment of CCL-5 and SDF-1 chemokines levels, as they are likely markers of developing depression. Early measurement of these chemokines levels may be helpful in choosing the best pharmacotherapy.
    Pharmacological reports: PR 10/2014; 66(5). DOI:10.1016/j.pharep.2014.06.001 · 1.93 Impact Factor
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