Cited by 116Tryptophan and brain disordersTreatment of Major DepressionStress Responses and Cortisol

Increased autoimmune activity against 5-HT: A key component of depression that is associated with inflammation and activation of cell-mediated immunity, and with severity and staging of depression

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Maes, Michael, Ringel, Karl, Kubera, Marta, Berk, Michael, Rybakowski, Janusz·2012·Journal of Affective Disorders

Abstract

Background Depression is characterized by inflammation and cell-mediated immune (CMI) activation and autoimmune reactions directed against a multitude of self-epitopes. There is evidence that the inflammatory response in depression causes dysfunctions in the metabolism of 5-HT, e.g. lowering the 5-HT precursor tryptophan, and upregulating 5-HT receptor mRNA. This study has been undertaken to examine autoimmune activity directed against 5-HT in relation to CMI activation and inflammation.Methods 5-HT antibodies were examined in major depressed patients (n=109) versus normal controls (n=35) in relation to serum neopterin and lysozyme, and plasma pro-inflammatory cytokines (PIC), i.e. interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα). Severity of depression was assessed with the Hamilton Depression Rating Scale (HDRS) and severity of fatigue and somatic symptoms with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale.Results The incidence of anti-5-HT antibody activity was significantly higher in depressed patients (54.1%), and in particular in those with melancholia (82.9%), than in controls (5.7%). Patients with positive 5-HT antibodies showed increased serum neopterin and lysozyme, and plasma TNFα and IL-1; higher scores on the HDRS and FF scales, and more somatic symptoms, including malaise and neurocognitive dysfunctions. There was a significant association between autoimmune activity to 5-HT and the number of previous depressive episodes.Discussion The autoimmune reactions directed against 5-HT might play a role in the pathophysiology of depression and the onset of severe depression. The strong association between autoimmune activity against 5-HT and inflammation/CMI activation is explained by multiple, reciprocal pathways between these factors. Exposure to previous depressive episodes increases the incidence of autoimmune activity directed against 5-HT, which in turn may increase the likelihood to develop new depressive episodes. These findings suggest that sensitization (kindling) and staging of depression are in part based on progressive autoimmune responses.

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Crossref · 10.1016/j.jad.2011.11.016

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  • These discrepancies may reflect clinical heterogeneity such as illness stage, because greater serotonin dysfunction has been reported in people with more prior major depressive episodes.

    “Discrepancies may be due to clinical heterogeneity, including illness stage, particularly since greater serotonin dysfunction has been described amongst individuals with MDD who have experienced a greater number of past MDEs (120).”

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Authors
Maes, M., Ringel, K., Kubera, M., Berk, M., & Rybakowski, J.
Affiliations
  • Piyavate Hospital (TH)
  • Maj Institute of Pharmacology (PL)
  • Deakin University (AU)
Venue
Journal of Affective Disorders
Publisher
Elsevier BV
Published
2012-02
Volume
136
Issue
3
Pages
386-392
ISSN
0165-0327 (ISSN-L)
OpenAlex
W1994612911
Cited by
116
References
69
Citations by year
2026: 2 · 2025: 5 · 2024: 6 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 8 · 2019: 4 · 2018: 11 · 2017: 9 · 2016: 6 · 2015: 12 · 2014: 15 · 2013: 14 · 2012: 8
FWCI
3.43
Type
journal article
Language
en
Open access
Locations
  • Journal of Affective Disorders (publishedVersion)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion, cc-by)
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
depression, serotonin, autoimmunity, inflammation, cell-mediated immunity, neopterin, lysozyme, inflammatory cytokines, TNF-α, interleukin-1, melancholia, depression severity, somatic symptoms, fatigue, depressive episodes, kindling, neurocognitive impairment
MeSH terms
Adult, Major Depressive Disorder, Depressive Disorder, Female, Humans, Immunity, Cellular, Inflammation, Interleukin-1, Male, Middle Aged, Muramidase, Serotonin, Tumor Necrosis Factor-alpha, Autoimmunity, Neopterin

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