# Does Acute Inhibition of Inflammation Improve Cortico-amygdala Circuitry and Symptoms of Anxiety in Depression?

> **NIH NIH F32** · EMORY UNIVERSITY · 2020 · $69,810

## Abstract

This proposal is designed to provide a mentored clinical research experience for the PI that will facilitate the
development of an independent research career at the interface of neuroscience, psychiatry, and immunology.
The proposed work will examine causal relationships between inflammation, cortico-amygdala circuit
dysfunction, and symptoms of anxiety in patients with major depressive disorder (MDD). Approximately 85% of
MDD patients also suffer from significant anxiety symptoms, yet the pathophysiologic mechanisms of anxiety in
patients with depression are not fully understood. One biological pathway that may contribute to symptoms of
anxiety in depression is the effect of inflammation on anxiety-relevant cortico-limbic circuitry. Neuroimaging
studies have demonstrated that acute inflammatory stimuli given to healthy subjects reduce functional
connectivity between the amygdala and prefrontal cortex (PFC) to lead to temporary symptoms of anxiety.
Disrupted cortico-amygdala circuitry has been consistently reported in patients with anxiety disorders and post-
traumatic stress disorder; a number of these patients also reliably exhibit increased cytokines and acute phase
reactants like C-reactive protein (CRP). We recently reported that high inflammation (as determined by plasma
CRP and cytokines) was associated with decreased functional connectivity between the amygdala and
ventromedial PFC (vmPFC) in patients with MDD. Amygdala-vmPFC connectivity was in turn negatively
correlated with severity of anxiety symptoms, and this relationship was strongest in patients with a comorbid
anxiety disorder and/or PTSD. Relevant to treating anxiety symptoms in MDD, we also previously found that
infliximab, a monoclonal antibody against tumor necrosis factor (TNF), reduced anxiety symptom severity in
depressed patients with high CRP. Together, these findings suggest that inflammation affects cortico-
amygdala connectivity to drive symptoms of anxiety in patients with depression; however, a causal relationship
between inflammation and cortico-amygdala circuit dysfunction in psychiatric patient populations has yet to be
established. The proposed work will utilize resources from an ongoing NIMH-sponsored study to test the
hypothesis that acute inhibition of inflammation with infliximab will improve cortico-amygdala connectivity in
association with reduced symptoms of anxiety in MDD patients with high inflammation. To examine this central
hypothesis, we will assess the impact of acute challenge with infliximab compared to placebo on 1) amygdala-
vmPFC functional connectivity, 2) relationships between amygdala-vmPFC connectivity, anxiety symptoms and
the role of comorbidities, and 3) associations between inflammatory biomarkers, cortico-amygdala connectivity
and anxiety symptoms. This project represents a first step toward developing novel anti-inflammatory and
personalized treatment strategies for symptoms of anxiety in MDD patients with high inflammation. This pr...

## Key facts

- **NIH application ID:** 9835604
- **Project number:** 1F32MH119750-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Mandakh Bekhbat
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $69,810
- **Award type:** 1
- **Project period:** 2020-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9835604

## Citation

> US National Institutes of Health, RePORTER application 9835604, Does Acute Inhibition of Inflammation Improve Cortico-amygdala Circuitry and Symptoms of Anxiety in Depression? (1F32MH119750-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9835604. Licensed CC0.

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