Interleukin, tumor necrosis factor-α and C-reactive protein profiles in melancholic and non-melancholic depression: A systematic review (original) (raw)
Related papers
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2013
Background and purpose: Growing scientific evidence indicates that there is a correlation between depression and alternations in the immune system. The main aim of the study was to investigate serum levels of Interleukin-6 (IL-6) and Tumour Necrosis Factor-alpha (TNF-α) in melancholic and atypical depressive patients during acute exacerbations of illness, compared to healthy subjects. The secondary aim was to explore a possible association between cytokine levels and clinical characteristics, as well as total duration of prior antidepressant treatment. Method: We measured serum levels of IL-6 and TNF-α in 47 patients suffering from major depressive disorder (MDD) (29 melancholic and 18 atypical) in exacerbation of illness, compared to 39 healthy controls, matched by sex, body mass index (BMI) and smoking habits. Serum levels of IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). The severity of psychopathology was assessed using the Hamilton Depression Rating Scale (HDRS). Results: IL-6 was significantly elevated in melancholic depressive patients (MDD-M) compared to healthy controls, while no difference was found between the patients with atypical depression (MDD-A) and the healthy group. Lower TNF-α serum level was found both in melancholic and in patients with atypical depression, compared with healthy subjects. We detected a positive correlation between cytokine levels in atypical, but not in melancholic subjects. Sex, age, smoking habits and BMI were not associated to cytokine levels in neither group. Clinical parameters (duration of illness, current episode, age of onset) were related to cytokine levels in atypical depression, while the duration of lifetime exposure to antidepressant treatment correlated to IL-6 serum levels in both melancholic and atypical depression. Conclusion: Our results suggest that the difference in pro-inflammatory cytokine levels could reflect a biological difference between melancholic and atypical depression. A positive correlation between the cytokines (TNF-α and IL-6) observed in depressive patients with atypical features, might be influenced by chronic course of illness, while IL-6 elevation could represent a state indicator for acute exacerbation, especially in melancholic patients. Total duration of antidepressant treatment could be a relevant factor influencing the immune status of patients who suffer either from melancholic or atypical depression.
Inflammatory cytokines in major depressive disorder: A case–control study
Australian & New Zealand Journal of Psychiatry, 2016
Introduction: There is mixed evidence in the literature on the role of inflammation in major depressive disorder. Contradictory findings are attributed to lack of rigorous characterization of study subjects, to the presence of concomitant medical illnesses, to the small sample sizes, and to the limited number of cytokines tested. Methods: Subjects aged 18–70 years, diagnosed with major depressive disorder and presenting with chronic course of illness, as well as matched controls ( n = 236), were evaluated by trained raters and provided blood for cytokine measurements. Cytokine levels in EDTA plasma were measured with the MILLIPLEX Multi-Analyte Profiling Human Cytokine/Chemokine Assay employing Luminex technology. The Wilcoxon rank-sum test was used to compare cytokine levels between major depressive disorder subjects and healthy volunteers, before (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α) and after Bonferroni correction for multiple comparisons (IL-1α, IL-2, IL-3, IL...
A Meta-Analysis of Cytokines in Major Depression
Biological Psychiatry, 2010
Background: Major depression occurs in 4.4% to 20% of the general population. Studies suggest that major depression is accompanied by immune dysregulation and activation of the inflammatory response system (IRS). Our objective was to quantitatively summarize the data on concentrations of specific cytokines in patients diagnosed with a major depressive episode and controls.
2020
ABSTRACTMajor depressive disorder (MDD) is a serious psychiatric disorder but there are no reliable risk assessment tools for this condition. The actual reason for affecting depression is still controversial. It is assumed that the dysregulated cytokines are produced due to the hyperactivation of the immune system in depression. We aimed to evaluate the possible alteration and the role of serum interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in MDD patients. The diagnostic and statistical manual of mental disorders, 5th edition was used to diagnose patients and evaluation of healthy controls (HCs). The severity of depression was measured by the Hamilton depression rating scale (Ham-D). Serum IL-1β and TNF-α levels were quantified by enzyme-linked immunosorbent assay kits. Increased levels of serum IL-1β and TNF-α were observed in MDD patients compared to HCs. These higher levels of peripheral markers were positively correlated with the severity of depression. Moreover, fe...
A Review of the Relationship between Proinflammatory Cytokines and Major Depressive Disorder
Background: Determining etiological factors and reviewing advances in diagnostic modalities sensitive and specific to Major Depressive Disorder (MDD) is of importance in its evaluation and treatment. The inflammatory hypothesis is one of the most prevalent topics concerning MDD and may provide insight into the pathogenesis of depression, development of biomarkers, and ultimately production of more effective depression therapies. Method: We reviewed several studies to evaluate contemporary concepts concerning proinflammatory cytokines and their relationship to various depressive disorders, the use of antiinflammatory therapies in MDD treatment, and the application of neuroimaging in conjunction with cytokine profiles from both plasma and CSF as possible diagnostic tools. Results: Proinflammatory cytokines in both plasma and CSF have been found to influence the progression and severity of depressive disorders in different populations. Studies have shown elevated serum levels of IL-1, IL-6, TNF-α, CRP, and MCP-1 in depressed patients, but have presented mixed results with IL-8 serum levels, and with IL-6 and MCP-1 CSF levels. Antiinflammatory treatment of MDD may have adjuvant properties with current depression medications. MRI and NIRS neuroimaging confirm neurological abnormalities in the presence of elevated proinflammatory cytokines in depressed or stressed patients. Limitations: Heterogeneity of MDD and limited CSF cytokine research complicate the study of MDD pathogenesis. Conclusion: There is significant evidence that inflammatory processes influence the development and progression of MDD. Future studies with larger arrays of cytokine profiles aided by neuroimaging may provide more sensitive and specific modes of diagnostics in determining MDD etiology and provide guidance in individual therapies. Highlights Inflammatory hypothesis postulates depression pathogenesis is related to increases in inflammatory cytokine production in peripheral and central nervous systems. Elevated levels of proinflammatory cytokines in both serum and CSF found in different populations with depressive disorders. Anti-inflammatory medications such as NSAIDs and Infliximab reported to decrease depression severity.
2014
Inflammatory processes as well as attenuation of brain-derived neurotrophic factor (BDNF) availability are involved in the pathophysiology of major depressive disorder (MDD). Although it is generally presumed that these two systems interact negatively in the brain, preclinical and human in vitro studies have shown synergistic rather than antagonistic interactions in the periphery. We therefore examined the association between serum levels of BDNF and plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a) in patients with MDD (n = 1070) and non-depressed controls (n = 379) from the Netherlands Study of Depression and Anxiety. We used multiple regression analyses with serum BDNF as the dependent variable and we specifically tested the presence of BDNF-cytokine associations in DSM-IV-assigned melancholic MDD patients, identified by the Inventory of Depressive Symptomatology. After adjustment for sociodemographics, sampling variability, lifestyle indicators, somatic diseases and medication use, BDNF levels were predicted by the interaction between MDD diagnosis and IL-6 (p-interaction = .006). Stratified analyses showed that BDNF levels are indeed positively associated with IL-6 levels in MDD patients (b = .07, p = .02), but not in non-depressed controls (b = À.07, p = .23). When further stratified for melancholic and non-melancholic MDD (p-interaction = .005), IL-6 emerged as a robust positive predictor of BDNF only in the melancholic sample (b = .21, p = .01), wherein serum BDNF levels were accordingly enhanced. Post-hoc exploratory analyses verified an accentuated positive association of BDNF levels with leucocyte counts in melancholia. No significant associations emerged between BDNF and TNF-a. Overall, our cross-sectional approach may have disclosed an allostatic, BDNF-inducing component of peripheral immunity and/or an immunotrophic function of peripheral BDNF. Both scenarios may warrant further exploration, as they could inform new research concepts towards immune-based antidepressive treatment strategies.
To clarify findings of elevated cytokine levels in major depression (MD), this study aimed to investigate the relationship between serum levels of cytokines, symptoms of MD and antidepressant treatment outcome. At baseline (T0) and 4 weeks following initiation of antidepressant treatment (T1), levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, IL-13, gran-ulocyte-macrophage-colony-stimulating-factor (GM-CSF), CRP and depression ratings HAMD-17 and BDI-II were assessed in 30 patients with MD and 30 age-and sex-matched controls. At T0, in the patient group, cytokines, but not CRP, negatively correlated with individual BDI-II-items, factors and severities and showed both negative and positive correlations with HAMD-17 items. At T1 and within the controls, no such relationships were observed. At T0 and T1, levels of both pro-and anti-inflammatory cytokines were significantly higher in treatment responders (ΔHAMD-17 T0-T1 Z50%,n ¼15) compared to non-re-sponders. When controlled for baseline BDI, differences between groups were only found significant for IL-2 at T0. The results suggest cytokines are not generally pro-depressive but rather relate to more specific regulation of symptoms and severities in MD. Together with the association between cytokines and treatment responder status, these data support cytokines as a promising but still controversial biomarker of depression.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2012
Background: Depression is characterized by activation of cell-mediated immunity (CMI), including increased neopterin levels, and increased pro-inflammatory cytokines (PICs), such as interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα). These PICs may induce depressive, melancholic and chronic fatigue (CF) symptoms. Methods: We examined serum neopterin and plasma PIC levels in depressive subgroups in relation to the depressive subtypes and the melancholic and CF symptoms of depression. Participants were 85 patients with depression and in 26 normal controls. Severity of depression was assessed with the Hamilton Depression Rating Scale (HDRS) and severity of CF with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale. Results: Serum neopterin was significantly higher in depressed patients and in particular in those with melancholia. There were positive correlations between serum neopterin, the plasma PICs and the number of previous depressive episodes. Neopterin and TNFα were associated with melancholia, while both PICs were associated with CF. Melancholia-group membership was predicted by the HDRS and neopterin, and CF group membership by age, the FF score and serum TNFα. Discussion: Depression and melancholia are accompanied by CMI activation, suggesting that neopterin plays a role in their pathophysiology, e.g. through activation of oxidative and nitrosative stress and apoptosis pathways. The intertwined CMI and inflammatory responses are potentially associated with the onset of depression and with the melancholic and CF symptoms of depression. Exposure to previous depressive episodes may magnify the size of CMI and PIC responses, possibly increasing the likelihood of new depressive episodes. CMI activation and inflammation may contribute to the staging or recurrence of depression.
Bulletin of Egyptian Society for Physiological Sciences, 2007
A little is known about the relation of plasma cytokines with psychological risk factors, such as hopelessness, and the severity of depressive symptoms. The present work studied the effect of depression on plasma interleukin (IL)-1β, IL-6 and high sensitivity C-reactive protein (hsCRP) in 40 subjects. Participants included two groups; patient group included 20 nonsmoking males (aged 20-40 years), recruited from the psychiatry clinic at Kasr El-Ainy Hospital fulfilling the DSM-IV Axis I disorders criteria for major depression. Control group included 20 healthy, nonsmoking males (age matched with no current or past history of psychiatric disorders). After an overnight fast, blood samples were collected and plasma IL-6, IL-1β, and hsCRP were determined using enzymatic-linked immunosorbent assay (ELISA), also fasting total cholesterol (TC) and high density lipoprotein-cholesterol (HDL-C) were estimated on the same day that the Beck Depression Inventory (BDI), Hopelessness Scale (HS) and full psychiatric sheet were accomplished. The results of the study showed a significant increase in depressed patients compared to normal controls as regards mean scores of BDI, HS, IL-1β, IL-6 and hsCRP. There was, also, a significant increase in both patients with moderate and severe depression compared to patients with mild depression as regards mean scores of BDI, IL-1β, IL-6 and hsCRP. There was, also, a significant difference between patients with mild hopelessness and those with moderate and severe hopelessness as regards mean scores of HS, IL-1β, IL-6 and hsCRP. Conclusion: Patients with major depression revealed high levels of IL-1β, IL-6 and hsCRP. That finding makes such patients more vulnerable to cerebrovascular accidents, where elevation of plasma cytokines and inflammatory markers are considered as risk factors for myocardial infarction.
Journal of Affective Disorders, 2014
Background: Despite an extensive literature on the role of inflammation and depression, few studies have evaluated the association between inflammatory biomarkers and depression in a prospective manner, and results are inconclusive. Methods: We conducted a prospective analysis of blood levels of CRP, IL-6 and TNFα-R2 in 4756 women participating in the Nurses' Health Study who donated blood in 1990 and were depression-free up to 1996. Participants were followed between 1996 and 2008 for reports of clinical diagnosis depression or antidepressant use. Additionally, we conducted cross-sectional analyses for CRP, IL-6 and TNFα-R2 and antidepressant use at time of blood draw. Results: After adjustment for body mass index, menopause status, use of anti-inflammatory drugs and other covariates, no significant associations between CRP, IL-6 and TNFα-R2 and incident depression were observed after a follow-up of 6 À18 years. However, menopause status appears to modify the association between IL-6 and depression risk. In cross-sectional analyses, TNFα-R2 was associated with antidepressant use (OR ¼1.96, 95% CI ¼1.23 À3.13, P-trend¼ 0.001), but no significant associations were found for CRP and IL-6. Limitations: Depression diagnosis was first assessed in 1996, 6 years after blood draw. However the biomarkers have high within-person correlations with measurements 4 years apart.