Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunotherapy with interferon-alpha (IFNalpha) may induce depressive symptoms, anxiety and major depression when administered for at least 1-3 months at a dose of 3-10 MUI daily, twice or three times a week. Previously, it has been shown that immunotherapy with interleukin-2 (IL-2) significantly induces the cytokine network, as measured by increases in serum IL-6, IL-10 and the IL-2 receptor (IL-2R), and that the immunotherapy-induced changes in the cytokine network are significantly correlated with the increases in depression ratings. The main aim of this study was to examine the effects of immunotherapy with IFNalpha on the cytokine network in relation to changes in depression and anxiety ratings. Fourteen patients, affected by chronic active C-hepatitis, were treated with IFNalpha (3-6 MUI s.c. three/six times a week for 6 months) and had measurements of serum IFN-gamma (IFNgamma), IL-2, IL-6, IL-6R, IL-8 and IL-10 before starting therapy and 2, 4, 16 and 24 weeks after immunotherapy with IFNalpha. Severity of depression and anxiety were measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Repeated measure (RM) design ANOVAs showed significantly higher MADRS and HAM-A scores 2-4 weeks and 4-6 months after starting IFNalpha-based immunotherapy than at baseline. RM design ANOVAs showed significantly higher serum IL-6 and IL-8 levels 2-4 weeks after starting IFNalpha-based immunotherapy and higher serum IL-10 levels 2-4 weeks and 4-6 months after starting therapy than at baseline. There were significant relationships between the IFNalpha-induced changes in serum IL-6 or IL-8 and the depression and anxiety scores. The findings show that IFNalpha-based immunotherapy induces the cytokine network and that IFNalpha-induced increases in IL-6 predicts the development of depressive symptoms. Depressive symptoms following IFNalpha treatment may be secondary to cytokine induction, including that of IL-6.
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PMID:Immunotherapy with interferon-alpha in patients affected by chronic hepatitis C induces an intercorrelated stimulation of the cytokine network and an increase in depressive and anxiety symptoms. 1174 Sep 74

Interleukin 1 receptor accessory protein (IL-1RAcP) is an essential signal-transducing component of the IL-1 receptor type I. The recent availability of IL-1RAcP-deficient (KO) mice allows to study the in vivo function of IL-1RAcP. Animals were injected intraperitoneally with rat recombinant IL-1beta (200 ng/mouse), lipopolysaccharide (LPS, 5 microg/mouse), or subjected to 1-hour restraint stress. Neuroendocrine and immune parameters were measured 2 h after IL-1 or LPS injection or just after restraint. In wild-type controls, IL-1 and LPS activated the hypothalamic-pituitary-adrenal axis and increased plasma IL-6. In KO mice, the plasma levels of corticosterone and IL-6 increased after LPS, but not after rat recombinant IL-1beta. The LPS-induced depression of the lymphoproliferation was similar in wild-type and KO mice. Finally, the 1-hour restraint was able to increase the plasma levels of corticosterone in KO mice. These results show that IL-1RAcP is essential for physiological activities of peripheral IL-1, as it was previously demonstrated for those of brain IL-1. However, using IL-1RAcP KO mice, we were unable to demonstrate a specific role of endogenous IL-1 during LPS-induced inflammation. Moreover, stress-induced activation of the hypothalamic-pituitary-adrenal axis may occur in the absence of the IL-1-transducing receptor, IL-1RAcP.
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PMID:Physiological significance of the interleukin 1 receptor accessory protein. 1184 85

Major depression is associated with both hypothalamic-pituitary-adrenal (HPA) axis overactivity and immune system activation. Depression is a common occurrence following interferon (IFN)-a treatment. While IFN-alpha is known to stimulate the HPA axis, little is known about the effects of exogenous IFN-a in humans on the proinflammatory cytokine interleukin (IL)-6, a marker of immune system activation. This study examined the acute effects of IFN-alpha on cortisol and IL-6 release, and the time course of any changes in these variables. Serum cortisol and plasma IL-6 were assessed in healthy volunteers over an 8-h period following 3 million units subcutaneous IFN-alpha or placebo using a double-blind, placebo-controlled crossover design. IFN-alpha resulted in a significant increase in both cortisol and IL-6. Regular sampling over 8 h did not delineate any sequential effect of the rise in these variables over time. We conclude that IFN-alpha acutely stimulates both the HPA axis and proinflammatory cytokine release. The hypothesis that the effect of IFN-alpha on the HPA axis is indirect and mediated by IL-6 was not supported by this study. Our findings are nonetheless of relevance to the aetiology of depression following IFN-alpha.
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PMID:Acute effects of low-dose interferon-alpha on serum cortisol and plasma interleukin-6. 1223 30

This review article integrates empirical findings from various scientific disciplines into a proposed psychoneuroimmunological (PNI) model of the acute coronary syndrome (ACS). Our starting point is an existing, mild, atherosclerotic plaque and a dysfunctional endothelium. The ACS is triggered by three stages. (1) Plaque instability: Pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha) and chemoattractants (MCP-1, IL-8) induce leukocyte chemoattraction to the endothelium, and together with other triggers such as the CD40L-CD40 co-stimulation system activate plaque monocytes (macrophages). The macrophages then produce matrix metalloproteinases that disintegrate extra-cellular plaque matrix, causing coronary plaque instability. Acute stress, hostility, depression and vital exhaustion (VE) have been associated with elevated pro-inflammatory cytokines and leukocyte levels and their recruitment. (2) Extra-plaque factors promoting rupture: Neuro-endocrinological factors (norepinephrine) and cytokines induce vasoconstriction and elevated blood pressure (BP), both provoking a vulnerable plaque to rupture. Hostility/anger and acute stress can lead to vasoconstriction and elevated BP via catecholamines. (3) Superimposed thrombosis at a ruptured site: Increases in coagulation factors and reductions in anticoagulation factors (e.g. protein C) induced by inflammatory factors enhance platelet aggregation, a key stage in thrombosis. Hostility, depression and VE have been positively correlated with platelet aggregation. Thrombosis can lead to severe coronary occlusion, clinically manifested as an ACS. Thus, PNI processes might, at least in part, contribute to the pathogenesis of the ACS. This chain of events may endure due to lack of neuroendocrine-to-immune negative feedback stemming from cortisol resistance. This model has implications for the use of psychological interventions in ACS patients.
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PMID:Molecular and cellular interface between behavior and acute coronary syndromes. 1223 62

There is some evidence that major depression is accompanied by activation of the inflammatory-response system (IRS). It has been hypothesized that increased production of proinflammatory cytokines may play a role in the etiology of major depression. If increased production of proinflammatory cytokines is at all involved in the etiology of depression, one would expect antidepressive treatments to have negative immunoregulatory effects. This paper reviews the effects of antidepressants, such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), heterocyclic antidepressants (HCAs), serotonin-noradrenaline reuptake inhibitors (SNRIs), lithium, l-5-hydroxytroptophan (L-5-HTP), reversible inhibitors of MAO-A (RIMA) on the production of proinflammatory cytokines, e.g. interferon-gamma (IFNgamma), and negative immunoregulatory cytokines and agents, e.g. interleukin-10 (IL-10). In depressed patients, prolonged treatment with antidepressants and mood stabilizers normalizes signs of activation of the IRS, such as increased serum IL-6 and acute phase protein concentrations. In vitro, it has been shown that various types of antidepressive drugs, including TCAs (imipramine; clomipramine); SSRIs (citalopram, fluoxetine, sertraline); lithium; SNRIs (venlafaxine); HCAs (trazodone); RIMAs (moclobemide) and L-5-HTP significantly suppress the ratio of IFNgamma/IL-10 production by peripheral blood immunocytes. These antidepressant drugs appear to have a common effect on the IRS, i.e. in vitro they increase the production of IL-10 by peripheral blood leukocytes. Thus, the results suggest that antidepressants have negative immunoregulatory effects. It may be speculated that antidepressants exert some of their antidepressant effects through their negative immunoregulatory capacities. Copyright 2001 John Wiley & Sons, Ltd.
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PMID:The immunoregulatory effects of antidepressants. 1240 4

Repetitive transcranial magnetic stimulation (rTMS) has been applied for treatment of several diseases such as depression. However, the safety and biological effects of rTMS have not been fully elucidated. In this study, the effects of rTMS on the levels of inflammatory mediators in the central nervous system (CNS), which may be involved in neurodegenerative disorders, were investigated in comparison with the electric convulsive model. Long-term rTMS (1500 pulses at 30 Hz/day for series of 7 days) stimulation, which did not elicit convulsion, was given to rats (rTMS rats). Single high-frequency electrical stimulation (100 Hz, 0.5-ms pulse width, 1 s duration, 50 mA), which induced convulsion, was given to rats (ES rats). mRNA levels of interleukin (IL)-1beta, IL-6, cyclooxygenase (COX)-2 and inducible nitric oxide synthetase (iNOS) in the brain were evaluated by reverse transcription-polymerase chain reaction before and after these stimulations. mRNA of IL-1beta, IL-6 and COX-2 was induced in the brains of ES rats but not in the brains of long-term rTMS rats. mRNA of iNOS was not induced in the brain of long-term rTMS rats. These results suggest that long-term rTMS may safe and modulate neural function without up-regulation of inflammatory mediators, which may be involved in neurodegenerative disorders.
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PMID:The long-term high-frequency repetitive transcranial magnetic stimulation does not induce mRNA expression of inflammatory mediators in the rat central nervous system. 1244 77

The objective of the present study was to investigate the relation between adipose tissue polyunsaturated fatty acids, an index of long-term or habitual fatty acid dietary intake, and depression. The sample consisted of 247 healthy adults (146 males, 101 females) from the island of Crete. The number of subjects with complete data on all variables studied was 139. Subjects were examined at the Preventive Medicine and Nutrition Clinic of the University of Crete. Depression was assessed through the use of the Zung Self-rating Depression Scale. Mildly depressed subjects had significantly reduced (-34.6%) adipose tissue docosahexaenoic acid (DHA) levels than non-depressed subjects. Multiple linear regression analysis indicated that depression related negatively to adipose tissue DHA levels. In line with the findings of other studies, the observed negative relation between adipose tissue DHA and depression, in the present study, appears to indicate increasing long-term dietary DHA intakes with decreasing depression. This is the first literature report of a relation between adipose tissue DHA and depression. Depression has been reported to be associated with increased cytokine production, such as IL-1, IL-2, IL-6, INF-gamma and INF-alpha. On the other hand, fish oil and omega-3 fatty acids have been reported to inhibit cytokine synthesis. The observed negative relation between adipose DHA and depression, therefore, may stem from the inhibiting effect of DHA on cytokine synthesis.
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PMID:Depression and adipose essential polyunsaturated fatty acids. 1244 91

This Special Section of the International Journal of Neuropsychopharmacology presents papers which review the current status of the relationship between the inflammatory response system (IRS) and major 'endogenous' and 'organic' (due to a medical condition) depression. Studies published over the last 11 years and reviewed in this Special Section begin to test the necessary conditions which are needed to accept the hypothesis that an activation of the IRS is involved in the pathophysiology and aetiology of 'endogenous' and 'organic' depression. This hypothesis suggests that some types of 'endogenous' and 'organic' depression may be related to IRS activation, such as an increased production of pro-inflammatory cytokines, such as interleukin-1beta (IL-1beta), IL-6, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN)-gamma. These cytokines are stress-sensitive, may cause depression, they have specific effects on brain systems involved in the pathogenesis of major depression, such as the serotonergic system and the hypothalamic-pituitary-adrenal (HPA) axis, and their production may be suppressed by antidepressants. Future research should examine whether anti-inflammatory drugs are effective in the treatment of depression and whether naturally occurring variants of the 'IRS' genes confer susceptibility to the development of the depressive phenotype through altered function of the respective gene products.
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PMID:Introduction to the special section. 1246 32

Administration of the cytokines interferon-alpha and interleukin-2 is used for the treatment of various disorders, such as hepatitis C and various forms of cancer. The most serious side-effects are symptoms associated with depression, including fatigue, increased sleepiness, irritability, loss of appetite as well as cognitive changes. However, great differences exist in the prevalence of the development of depressive symptoms across studies. Differences in doses and duration of therapy may be sources of variation as well as individual differences of patients, such as a history of psychiatric illness. In addition, sensitization effects may contribute to differential responses of patients to the administration of cytokines. In animals administration of pro-inflammatory cytokines induces a pattern of behavioural alterations called 'sickness behaviour' which resembles the vegetative symptoms of depression in humans. Changes in serotonin (5-HT) receptors and in levels of 5-HT and its precursor tryptophan in depressed people support a role for 5-HT in the development of depression. In addition, evidence exists for a dysregulation of the noradrenergic system and a hyperactive hypothalamic-pituitary-adrenal (HPA) axis in depression. Some mechanisms exist which make it possible for cytokines to cross the blood-brain barrier. Pro-inflammatory cytokines such as IL-1beta, IFN-alpha, IFN-gamma and TNF-alpha affect the 5-HT metabolism directly and/or indirectly by stimulating the enzyme indoleamine 2,3-dioxygenase which leads to a peripheral depletion of tryptophan. IL-1, IL-2 and TNF-alpha influence noradrenergic activity and IL-1, IL-6 and TNF-alpha are found to be potent stimulators of the HPA axis. Altogether, administration of cytokines may induce alterations in the brain resembling those found in depressed patients, which leads to the hypothesis that cytokines induce depression by their influence on the 5-HT, noradrenergic and HPA system.
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PMID:The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans. 1246 36

In mice, lateralization as assessed by paw preference represents a behavioral trait linked to immune reactivity and stress susceptibility. Right-pawed mice are more reactive to stress than left-pawed animals when brain metabolism, activation of the corticoid axis, and depression of lymphoproliferation are studied. Since stress responses include cytokine production, we address the possibility that lateralization influences the production of cytokines--especially interleukin (IL)-1--responsible for depression of lymphoproliferation and activation of the corticoid axis. Increased plasma IL-1 level that may be considered as a stress marker, was observed in right- but not in left-pawed mice submitted to a 4 h-restraint. Likewise, plasma levels were greater in right- than in left-pawed animals 2 h after the administration of a low dose of lipopolysaccharides (LPS). By contrast, there was no lateralization effect in restraint-induced plasma level of IL-6 or in the LPS-induced increase in plasma IL-10. Prazosin, an alpha1/alpha2 adrenoreceptor antagonist, drastically increased plasma IL-10 induced by LPS, reduced plasma levels of IL-1 and abolished the effect of lateralization observed after LPS alone. This suggests that alpha-adrenergic modulation of IL-1 production depends on lateralization through mechanisms that need further investigation.
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PMID:Cytokine stress responses depend on lateralization in mice. 1263 2


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