transforming-growth-factor-beta and Depressive-Disorder

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

Depressive disorder is a common comorbidity of chronic obstructive pulmonary disease (COPD); according to some studies, it occurs in approximately 80% of patients. The presence of depressive symptoms influences the quality of life and affects the course and treatment of this disease. The cause of depressive symptoms in COPD and the linking mechanism between COPD and depressive disorder have not been clearly elucidated, and more studies are warranted. Inflammation and inflammation-related processes and biomarkers are involved in the etiology of COPD and depressive disorder and may be an explanation for the potential occurrence of depressive disorder in patients diagnosed with COPD. The scope of this study was to measure and compare the profiles of IL-18, TGF-β, RANTES, ICAM-1, and uPAR among stable COPD patients, recurrent depressive disorder (rDD) patients, and healthy controls.. Inflammation and inflammation-related factors were evaluated in COPD patients, patients diagnosed with depressive disorder, and control individuals using enzyme-linked immunosorbent assays.. Interleukin (IL)-18, transforming growth factor (TGF)-β, chemokine RANTES, and urokinase plasminogen activator receptor (uPAR) concentrations were higher in patients suffering from COPD and depression than in control patients. Intercellular adhesive molecule (ICAM)-1 levels were significantly higher in COPD patients and lower in depressive disorder patients than in controls.. Higher levels of IL-18, TGF-β, RANTES, and uPAR in patients with COPD might indicate the presence of depressive disorder and suggest the need for further evaluation of the mental state of these patients.

Topics: Biomarkers; Depressive Disorder; Humans; Inflammation; Interleukin-18; Pulmonary Disease, Chronic Obstructive; Quality of Life; Transforming Growth Factor beta

Neuronal activity is altered in several neurological and psychiatric diseases. Upon depolarization not only neurotransmitters are released but also cytokines and other activators of signaling cascades. Unraveling their complex implication in transcriptional control in receiving cells will contribute to understand specific central nervous system (CNS) pathologies and will be of therapeutically interest. In this study we depolarized mature hippocampal neurons in vitro using KCl and revealed increased release not only of brain-derived neurotrophic factor (BDNF) but also of transforming growth factor beta (TGFB). Neuronal activity together with BDNF and TGFB controls transcription of DNA modifying enzymes specifically members of the DNA-damage-inducible (Gadd) family, Gadd45a, Gadd45b, and Gadd45g. MeDIP followed by massive parallel sequencing and transcriptome analyses revealed less DNA methylation upon KCl treatment. Psychiatric disorder-related genes, namely Tshz1, Foxn3, Jarid2, Per1, Map3k5, and Arc are transcriptionally activated and demethylated upon neuronal activation. To analyze whether misexpression of Gadd45 family members are associated with psychiatric diseases, we applied unpredictable chronic mild stress (UCMS) as established model for depression to mice. UCMS led to reduced expression of Gadd45 family members. Taken together, our data demonstrate that Gadd45 family members are new putative targets for UCMS treatments.

Topics: Animals; Autistic Disorder; Brain-Derived Neurotrophic Factor; Cell Cycle Proteins; Cells, Cultured; Chronic Disease; Depressive Disorder; Disease Models, Animal; DNA Methylation; Hippocampus; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Neurons; Nuclear Proteins; Protein Serine-Threonine Kinases; Receptor, Transforming Growth Factor-beta Type I; Receptors, Transforming Growth Factor beta; Signal Transduction; Stress, Psychological; Synaptic Transmission; Transcriptome; 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