Journal ArticleDOI
Cytokines and major depression.
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TLDR
Although the central effects of proinflammatory cytokines appear to be able to account for most of the symptoms occurring in depression, it remains to be established whether cytokines play a causal role in depressive illness or represent epiphenomena without major significance.Abstract:
In the research field of psychoneuroimmunology, accumulating evidence has indicated the existence of reciprocal communication pathways between nervous, endocrine and immune systems. In this respect, there has been increasing interest in the putative involvement of the immune system in psychiatric disorders. In the present review, the role of proinflammatory cytokines, such as interleukin (IL)-1, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma, in the aetiology and pathophysiology of major depression, is discussed. The 'cytokine hypothesis of depression' implies that proinflammatory cytokines, acting as neuromodulators, represent the key factor in the (central) mediation of the behavioural, neuroendocrine and neurochemical features of depressive disorders. This view is supported by various findings. Several medical illnesses, which are characterised by chronic inflammatory responses, e.g. rheumatoid arthritis, have been reported to be accompanied by depression. In addition, administration of proinflammatory cytokines, e.g. in cancer or hepatitis C therapies, has been found to induce depressive symptomatology. Administration of proinflammatory cytokines in animals induces 'sickness behaviour', which is a pattern of behavioural alterations that is very similar to the behavioural symptoms of depression in humans. The central action of cytokines may also account for the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity that is frequently observed in depressive disorders, as proinflammatory cytokines may cause HPA axis hyperactivity by disturbing the negative feedback inhibition of circulating corticosteroids (CSs) on the HPA axis. Concerning the deficiency in serotonergic (5-HT) neurotransmission that is concomitant with major depression, cytokines may reduce 5-HT levels by lowering the availability of its precursor tryptophan (TRP) through activation of the TRP-metabolising enzyme indoleamine-2,3-dioxygenase (IDO). Although the central effects of proinflammatory cytokines appear to be able to account for most of the symptoms occurring in depression, it remains to be established whether cytokines play a causal role in depressive illness or represent epiphenomena without major significance.read more
Citations
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From Stress to Inflammation and Major Depressive Disorder: A Social Signal Transduction Theory of Depression
TL;DR: A biologically plausible, multilevel theory is proposed that describes neural, physiologic, molecular, and genomic mechanisms that link experiences of social-environmental stress with internal biological processes that drive depression pathogenesis and may shed light on several important questions including how depression develops, why it frequently recurs, and why it is strongly predicted by early life stress.
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A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness.
TL;DR: It is concluded that aberrations in O&NS pathways are--together with the inflammatory processes--key components of depression, and the results suggest that depression belongs to the spectrum of (neuro)degenerative disorders.
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The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression
Michael Maes,Raz Yirmyia,Jens Noraberg,Stefan Brené,Joe Hibbeln,Giulia Perini,Marta Kubera,Petr Bob,Bernard Lerer,Mario Maj +9 more
TL;DR: Screening for inflammatory and neurodegenerative processes in depression will allow to discover new I&ND biomarkers, both at the level of gene expression and the phenotype, and elucidate the underlying molecular I &ND pathways causing depression; identify new therapeutic targets in the I& ND pathways; develop new anti-I&ND drugs for these targets; and select existingAnti-I &ND drugs or substances that could augment the efficacy of antidepressants.
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Glycogen Synthase Kinase-3 (GSK3): Inflammation, Diseases, and Therapeutics
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TL;DR: The human and animal results related to immune involvement suggest novel therapeutic avenues based on immune interventions, which could help to explain some of the heterogeneity of schizophrenia.
References
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Journal ArticleDOI
Association between immune activation and early depressive symptoms in cancer patients treated with interleukin-2-based therapy.
Lucile Capuron,Alain Ravaud,Norbert Gualde,Eugene Bosmans,Robert Dantzer,Michael Maes,Pierre J. Neveu +6 more
TL;DR: The hypothesis of close relationship between depressive symptoms and the activation of the cytokine network was supported and the intensity of depressive symptoms at endpoint was positively correlated with the increases measured in serum levels of IL-10 between baseline and endpoint.
Journal ArticleDOI
Depressive and anxiety symptoms in the early puerperium are related to increased degradation of tryptophan into kynurenine, a phenomenon which is related to immune activation
Michael Maes,Robert Verkerk,Stephania Bonaccorso,Willem Ombelet,Eugene Bosmans,Simon Scharpé +5 more
TL;DR: It is concluded that lower plasma kynurenine at the end of term is the consequence of lower plasma tryptophan, and that depressive and anxiety symptoms in the early puerperium are (causally) related to an increased catabolism of tryPTophan into knurenine, a phenomenon which probably results from immune activation.
Journal ArticleDOI
Low levels of circulating inflammatory cytokines--do they affect human brain functions?
TL;DR: Evidence is presented that very low amounts of circulating cytokines are likely to influence brain functions, even under baseline conditions, and it is likely that low levels of cytokines affect the same brain function as high levels do.
Book ChapterDOI
Cytokines, stress, and depression. Conclusions and perspectives.
TL;DR: From the data that are reviewed in this volume, several important points emerge: cytokines administered to patients and laboratory animals induce symptoms of depression, and antidepressants have anti-inflammatory properties and attenuate the behavioral effects of immune challenge.
Book ChapterDOI
Anhedonic and Anxiogenic Effects of Cytokine Exposure
Hymie Anisman,Zul Merali +1 more
TL;DR: The findings indicated that cytokine treatments profoundly influence extrahypothalamic neurochemical functioning and may thus impact on behavioral outputs and particularly TNF alpha treatment.