transforming-growth-factor-beta and Depressive-Disorder--Major

The involvement of an immune process in the pathophysiology of major depression disorder (MDD) was substantiated by studies demonstrating elevated levels of proinflammatory cytokines and prostaglandin E(2) (PGE(2)). Cyclooxygenase-2 (COX-2) inhibitors lead to a reduced production of PGE(2) and have been shown to improve depressive symptoms. We investigated the three immune parameters macrophage migration inhibitory factor (MIF), transforming growth factor-β (TGF-β) and soluble CD14 (sCD14) in a randomized, placebo-controlled trial of the COX-2 inhibitor celecoxib as add-on therapy in patients with MDD treated with reboxetine.. Thirty-two patients with depression and 20 healthy controls participated in the study. The patients were treated with reboxetine and celecoxib or placebo. Immune parameters were measured from serum at baseline, after three and five weeks using ELISA.. Celecoxib as add-on strategy resulted in a significant reduction of Hamilton Depression Scale scores compared to placebo. Depressed patients showed significantly elevated MIF (p < 0.001) and reduced TGF-β (p = 0.006) concentrations at baseline. There was no difference in sCD14-concentrations. There was no difference between the placebo and the celecoxib group and no change over time.. Limitations of the study are the relatively small sample size and lack of functional assessment of HPA axis in parallel.. MIF is a promising new candidate in the neuro-immune interplay that may link depressive symptoms, altered immune state and HPA-axis dysregulation. Reduced levels of TGF-β replicate previous findings and support the importance of this regulatory cytokine in major depressive disorder.

Topics: Adult; Aged; Antidepressive Agents; Celecoxib; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Depression; Depressive Disorder; Depressive Disorder, Major; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intramolecular Oxidoreductases; Macrophage Migration-Inhibitory Factors; Male; Middle Aged; Morpholines; Psychiatric Status Rating Scales; Psychological Tests; Pyrazoles; Reboxetine; Sulfonamides; Transforming Growth Factor beta; Young Adult

It has been postulated that major depression may be accompanied by significant changes in cell-mediated and humoral immunity related to the pathophysiology or pathogenesis of that illness. We explored the role of 2 cytokines, IL-12 and TGF-beta1, which represent the cytokines of the Th1 and Th3 types, in the pathophysiology of major depressive disorder (MDD). Cytokine levels were measured in 30 major depressed patients at the time of admission and 6 weeks after effective antidepressant treatment; levels were measured once in 30 normal controls. At the time of admission, TGF-beta1 levels of MDD patients showed no differences from normal controls, but IL-12 was significantly higher than in normal controls. However, the IL-12/TGF-beta1 (Th1/Th3) ratios of depressed patients were not different from those of controls. In MDD patients, IL-12 values were significantly decreased after treatment, while TGF-beta1 levels were significantly increased. IL-12/TGF-beta1 ratios of patients were significantly decreased after treatment compared with before treatment. There were no significant correlations between changes in the cytokine levels and changes in scores representing the severity of depression. These findings suggest that major depression is accompanied by immune activation during the acute depressed state, and antidepressant treatments have anti-inflammatory effects.

Topics: Adult; Antidepressive Agents, Second-Generation; Cyclohexanols; Depressive Disorder, Major; Female; Fluoxetine; Humans; Interleukin-12; Male; Middle Aged; Paroxetine; Time Factors; Transforming Growth Factor beta; Transforming Growth Factor beta1; Treatment Outcome; Venlafaxine Hydrochloride

Transforming growth factor beta (TGF-β), which has a role as a regulatory cytokine, has not been widely investigated in patients with major depressive disorder (MDD) who experienced childhood trauma. The aim of our study was to investigate the differences in circulating TGF-β levels between the patients with major depressive disorder (MDD) with and without child maltreatment (CM) history, and to compare them to the corresponding control subjects' groups (with or without CM). Blood samples were obtained from 55 patients, fulfilling DSM-IV-R criteria for a current MDD episode without psychotic symptoms, and 45 healthy controls, matched for age and gender. Participants were administered the Childhood Trauma Questionnaire (CTQ). Serum TGF-β concentration was determined by enzyme-linked immunosorbent assay. The concentration of TGF-β was significantly higher in patients with MDD with CM history, compared to MDD patients with no CM, as well as both control groups. Furthermore, we have shown that the combined effect of CM history and MDD affected TGF-β levels in adulthood, which was not observed in the control group with CM. These results indicate that MDD patients with the experience of CM have altered immune-regulatory response, and they may constitute a specific subtype within this heterogenic disorder (ecophenotype).

Topics: Adult; Adult Survivors of Child Abuse; Child; Child Abuse; Cytokines; Depressive Disorder, Major; Humans; Transforming Growth Factor beta

Immune system dysfunction is implicated in the pathophysiology of major depression, and is hypothesized to normalize with successful treatment. We aimed to investigate immune dysfunction in melancholic depression and its response to ECT.. 55 melancholic depressed patients and 26 controls participated. 33 patients (60%) were referred for ECT. Blood samples were taken at baseline, one hour after the first ECT session, and 48h after ECT series completion.. At baseline, melancholic depressed patients had significantly higher levels of the pro-inflammatory cytokine IL-6, and lower levels of the regulatory cytokine TGF-β than controls. A significant surge in IL-6 levels was observed one hour after the first ECT session, but neither IL-6 nor TGF-β levels normalized after completion of ECT series. Seventy per cent (n=23) of ECT recipients showed clinical response and 42% (n=10) reached remission. Neither IL-6 nor TGF-β changes correlated with clinical improvement following ECT. No significant changes in IL-10, TNF-α and CRP levels were found in relation to melancholia or response to ECT.. As a naturalistic study, some potential confounders could not be eliminated or controlled, including medication use.. Melancholic depressed patients demonstrated a peripheral increase in IL-6 and reduction in TGF-β, which did not normalize despite clinical response to ECT. These findings may be consistent with emerging hypotheses of the role of inflammation in mediating neurotrophin expression. The implications of chronic inflammation in the melancholic depressed population for future medical health, particularly cardiovascular risk, are largely unknown and warrant further investigation.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Cytokines; Depressive Disorder; Depressive Disorder, Major; Electroconvulsive Therapy; Female; Humans; Interleukin-10; Interleukin-6; Male; Middle Aged; Transforming Growth Factor beta; Treatment Outcome; Tumor Necrosis Factor-alpha

Patients with major depressive disorder (MDD) who attempt or complete suicide have elevated inflammation compared to nonsuicidal patients with MDD. However, greater severity of depression and the medical lethality of suicide attempts could account for such elevated inflammation in suicide attempters and suicide completers.. To clarify, we measured inflammatory markers in patients with MDD with and without high levels of suicidal ideation and in nondepressed controls (N = 124). Levels of suicidal ideation, depression severity, and recent suicide attempts were assessed by structured clinical interviews. A composite score including the inflammatory markers tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and C-reactive protein (CRP) was used as an inflammatory index. Analysis of covariance models were used to assess group differences with adjustments for age and gender.. Patients with MDD and high suicidal ideation had significantly higher inflammatory index scores than both controls, F(1,53) = 18.08, partial η(2) = .25, P < .001, and patients with MDD and lower suicidal ideation F(1,44) = 7.59, partial η(2) = .15, P = .009. In contrast, patients with lower suicidal ideation were not significantly different from controls on the inflammatory index, F(1,63) = .52, partial η(2) = .01, P = .47. Follow-up analyses indicated that differences between patients with MDD and high versus lower suicidal ideation were independent of depression severity and recent suicide attempts.. Suicidal ideation may be uniquely associated with inflammation in depressed patients.

Topics: Adult; Analysis of Variance; C-Reactive Protein; Case-Control Studies; Depressive Disorder, Major; Female; Humans; Inflammation; Interleukin-10; Interleukin-6; Male; Middle Aged; Self-Injurious Behavior; Severity of Illness Index; Suicidal Ideation; Suicide, Attempted; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha