TNF-alpha Antagonist Infliximab Increases Willingness to Expend Effort in Patients with Depression and High Inflammation Open Access

Abstract

Background: Increasing evidence suggests that alterations in inflammation and immunometabolism may contribute to the pathophysiology of motivational anhedonia in major depressive disorder (MDD). To date, only a few studies have explored the impact of pharmaceuticals that target inflammation on motivational anhedonia in depressed patients. Here, we present novel results from a newly completed clinical trial (NCT03006393) aimed at identifying the mechanisms by which inflammation and immunometabolism contribute to motivational anhedonia in depressed patients.

Methods: 33 patients with CRP >3 mg/L were randomized to receive a single infusion of either the TNF-alpha antagonist Infliximab (5mg/kg) or saline solution as part of a double-blind, placebo-controlled, randomized clinical trial. Motivated behavior and peripheral inflammatory markers were assessed prior to infusion and 14 days post infusion. Motivated behavior was assessed using an effort-based decision-making (EBDM) task. A composite measure of TNF soluble receptors (TNFRII) and glucose metabolism was formed using TNFRII and five markers of glucose metabolism.

Results: Patients that received Infliximab showed an increase in effortful options chosen relative to placebo (p= 0.034). Further, post-infusion reductions in plasma TNFRII and glucose metabolism predicted decreases in effort discounting (p = 0.042). Finally, there was trend level evidence that changes in inflammation and immunometabolism mediated the relationship between treatment arm and change in effortful choices at the highest effort level (p=0.094).

Conclusion: Administration of Infliximab to patients experiencing current MDD and high inflammation increases willingness to expend effort, a hallmark of motivational anhedonia. These results highlight the potential for using inflammatory biomarkers and anti-inflammatory treatment strategies to identify and treat motivational impairments. 

Table of Contents

Introduction ...................................................1

Materials and Methods....................................7

Results ...........................................................13

Discussion...................................................... 16

References .....................................................19 

About this Master's Thesis

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School	Laney Graduate School
Department	Psychology
Subfield / Discipline	Clinical Psychology
Degree	M.A.
Submission	Master's Thesis
Language	English
Research Field	Psychology, Clinical
Keyword	Depression Effort Based Decision Making Inflammation
Committee Chair / Thesis Advisor	Michael Treadway, Emory University
Committee Members	Philip Kragel, Emory University Philip Wolff, Emory University

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