Inflammation-Induced CNS Glutamate Changes in Depression
Status:
Recruiting
Trial end date:
2021-11-01
Target enrollment:
Participant gender:
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.