Circulating tumour necrosis factor is highly correlated with brainstem serotonin transporter availability in humans.

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 [(123)I]-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 6-8weeks 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.

• Authors: Rajeev Krishnadas, Alice Nicol, Jen Sassarini, Navesh Puri, A David Burden, Joyce Leman, Emilie Combet, Sally Pimlott, Donald Hadley, Iain B McInnes, Jonathan Cavanagh
• Journal: Brain, behavior, and immunity (Brain Behav Immun) Vol. 51 Pg. 29-38 (Jan 2016) ISSN: 1090-2139 [Electronic] Netherlands
• PMID: 26255693 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• SLC6A4 protein, human
• Serotonin Plasma Membrane Transport Proteins
• Tumor Necrosis Factor-alpha
• Etanercept

Topics

• Arthritis, Psoriatic (diagnostic imaging, metabolism)
• Brain Stem (diagnostic imaging, metabolism)
• Depression (metabolism)
• Etanercept (administration & dosage)
• Female
• Humans
• Middle Aged
• Serotonin Plasma Membrane Transport Proteins (metabolism)
• Tomography, Emission-Computed, Single-Photon
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, blood)