Circulating Tumour Necrosis Factor is highly correlated with brainstem serotonin transporter availability in humans

Krishnadas, R. et al. (2016) Circulating Tumour Necrosis Factor is highly correlated with brainstem serotonin transporter availability in humans. Brain, Behavior, and Immunity, 51, pp. 29-38. (doi: 10.1016/j.bbi.2015.08.005) (PMID:26255693)

Abstract

Preclinical studies demonstrate that pro-inflammatory cytokines increase serotonin transporter availability and function, leading to depressive symptoms in rodent models. Herein we investigate associations between circulating inflammatory markers and brainstem serotonin transporter (5-HTT) availability in humans. We hypothesised that higher circulating inflammatory cytokine concentrations, particularly of tumour necrosis factor (TNF-α), would be associated with greater 5-HTT availability, and that TNF-α inhibition with etanercept (sTNFR:Fc) would in turn reduce 5-HTT availability. In 13 neurologically healthy adult women, plasma TNF-α correlated significantly with 5-HTT availability (rho=0.6; p=0.03) determined by [123I] -beta-CIT SPECT scanning. This association was replicated in an independent sample of 12 patients with psoriasis/psoriatic arthritis (rho=0.76; p=0.003). Indirect effects analysis, showed that there was a significant overlap in the variance explained by 5-HTT availability and TNF-α concentrations on BDI scores. Treatment with etanercept for 6-8 weeks was associated with a significant reduction in 5-HTT availability (Z= 2.09; p=0.03; r=0.6) consistent with a functional link. Our findings confirm an association between TNF-α and 5-HTT in both the basal physiological and pathological condition. Modulation of both TNF-α and 5-HTT by etanercept indicate the presence of a mechanistic pathway whereby circulating inflammatory cytokines are related to central nervous system substrates underlying major depression.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain and Cavanagh, Professor Jonathan and Combet Aspray, Professor Emilie and Sassarini, Dr Jenifer and Pimlott, Dr Sally and Hadley, Professor Donald and Burden, Professor David and Krishnadas, Dr Rajeev
• Authors: Krishnadas, R., Nicol, A., Sassarini, J., Puri, N., Burden, A. D., Leman, J., Combet, E., Pimlott, S., Hadley, D., McInnes, I. B., and Cavanagh, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing; College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Brain, Behavior, and Immunity
• Publisher: Elsevier B.V.
• ISSN: 0889-1591
• ISSN (Online): 1090-2139
• Copyright Holders: Copyright © 2015 Elsevier B.V.
• First Published: First published in Brain, Behavior, and Immunity 51:29-38
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher.