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.
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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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References
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Journal ArticleDOI
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Journal ArticleDOI
Cytokines in inflammatory bowel disease.
Gerhard Rogler,T. Andus +1 more
TL;DR: The first clinical trials using neutralizing monoclonal antibodies against TNFα (cA2) or the antiinflammatory cytokine IL-10 have shown promising results, however, many questions must be answered before cytokines can be considered standard therapy for IBD.
Journal ArticleDOI
Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy.
TL;DR: Assessment of the relationship between serum concentrations of the amino acids tryptophan and tyrosine, major precursors of serotonin and norepinephrine respectively, and depression symptoms in cancer patients undergoing cytokine therapy indicates that the development of depressive symptoms in patients undergoing chemotherapy could be mediated by a reduced availability of the serotonin relevant amino acid precursor, tryptophile.
Journal ArticleDOI
The stress response and the hypothalamic-pituitary-adrenal axis: from molecule to melancholia.
TL;DR: The response to stress at molecular, cellular, neuroendocrine and behavioural levels is described, and the disease processes that result from a dysregulation of this response are discussed, as well as recent developments in their treatment.