Inflammation-Induced CNS Glutamate Changes in Depression

Summary

Increased inflammation has been implicated in the pathophysiology of a number of neuropsychiatric illnesses including mood disorders, which affect almost 30 million adults in the United States alone. One mechanism by which inflammation may alter behavior is through increasing brain glutamate, a neurotransmitter that in excess has been implicated in neuronal toxicity and resistance to conventional antidepressant therapy. The goal of the proposed research is to test the hypothesis that inflammation alters behavior through increasing glutamate in specific brain regions, ultimately leading to behavioral changes.

The proposed research is designed to determine the cause and effect relationship between inflammation and CNS glutamate as well as the relationship between CNS glutamate and specific symptoms. To accomplish these aims, investigators will administer a single infusion of either the tumor necrosis factor (TNF) antagonist infliximab or placebo (n=30 per group) to patients with high inflammation (CRP\>3mg/L). A CRP\>3mg/L was chosen because it is considered high inflammation according to guidelines by the American Heart Association. Moreover, a CRP\>3mg/L is associated with significantly increased basal ganglia glutamate and with a clinical response to infliximab. Inflammatory biomarkers, basal ganglia glutamate as measured by MRS, and motivation and psychomotor activity will be assessed at baseline and days 1 and 3 and weeks 1 and 2 following infliximab or placebo administration.

Conditions

• Depression

Interventions

DRUG

Infliximab

Infliximab will be administered intravenously (IV) as 5 mg/kg body weight over a 2 to 2.5 hour period.

DRUG

Placebo

Saline solution will be administered intravenously over a 2 to 2.5 hour period.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH)

  collaborator NIH

• Emory University

  lead OTHER

Principal Investigators

• Andrew H Miller, MD · Emory University

• Ebrahim Haroon, MD · Emory University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

21 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-05-15

Primary Completion

2019-11-27

Completion

2019-11-27

FDA Drug

Yes

Countries

• United States

Study Locations