Friday, June 27, 2025 6/27/2025

Neural response to inflammatory challenge in major depressive disorder

Award Number: R01MH123652
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/14/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2026

Group Awards By:

View Award Description

Neural response to inflammatory challenge in major depressive disorder - PROJECT SUMMARY: Chronic inflammation likely underlies the pathogenesis of major depressive disorder (MDD) in a significant number of cases but we do not understand why these individuals get stuck in an inflammatory state. We hypothesize that this subgroup of depressed patients has a defective homeostatic or regulatory response to inflammatory stimuli such that appropriate, acute inflammatory responses fail to resolve, leading to chronic inflammation which increases the risk for (a) developing depression, (b) its recurrence, and (c) treatment failure. To test this hypothesis, we propose challenging the immune system of both MDD subjects and healthy controls (HC) with an inflammatory stimulus (lipopolysaccharide, LPS) to induce a homeostatic response. Specifically, 90 MDD and 90 HC participants will be randomized (2:1) to LPS (0.8ng/kg) or saline. Serial blood draws will be obtained to quantify the pattern of inflammatory response using several inflammatory markers. At the same time, participants will complete clinical ratings and undergo a pre- and post-LPS MRI scan to measure how the transient inflammatory response affects the brain processing of interoceptive (bodily- relevant) stimuli. Participants will also return one day and one week after LPS/saline infusion to complete identical psychometric measures and blood draws. The MDD group, only, will also complete psychological assessments once per month for 6 months in order to determine whether the acute response to LPS predicts the clinical course of MDD. The main hypotheses are that: (1) relative to HC, the MDD group will show a greater acute increase in inflammatory mediators but a blunted acute response of the neural circuitry mediating interoceptive processes (insula and cingulate cortex) in the LPS vs. placebo condition. For the acute outcomes we focus on the changes that occur at the peak of the inflammatory response, i.e. 2 hours post-infusion. (2). Within the MDD group, LPS-associated changes in interoceptive processing and functional connectivity will be correlated with the strength of the acute pro-inflammatory response. (3) These acute effects will be more salient in MDD participants with chronic inflammation (baseline CRP ³3mg/L). That is, relative to the low inflammation MDD group (CRP £1mg/L), the high inflammation MDD group will display a blunted hemodynamic response of the insula and cingulate during internally-focused attention. In exploratory analyses we will also examine whether there is a sex by diagnosis interaction effect on inflammatory and insular response to LPS and whether the acute effects of LPS will relate to depressive symptoms over the 6-month follow-up. This research is innovative and highly impactful because it will open up a new program of research that will allow us to draw strong conclusions about the biological mechanisms underlying the failure to resolve inflammation-related depressive behavior. This knowledge can ultimately be used to develop new brain or immune-based treatments to jump-start the neural circuitry normally engaged by inflammatory stimuli, and to target these interventions at specific patient populations.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $687,903 )
2025	2025	LAUREATE INSTITUTE FOR BRAIN RESEARCH, LLC	6655 S YALE AVE	TULSA	OK	74136	TULSA	USA	Mental Health Research Grants	000	5	5/16/2025	NON-COMPETING CONTINUATION	$687,903
														Subtotal = $687,903

Issue Date FY: 2024 ( Subtotal = $716,247 )
2024	2024	LAUREATE INSTITUTE FOR BRAIN RESEARCH, LLC	6655 S YALE AVE	TULSA	OK	74136	TULSA	USA	Mental Health Research Grants	000	4	4/25/2024	NON-COMPETING CONTINUATION	$716,247
														Subtotal = $716,247

Issue Date FY: 2023 ( Subtotal = $641,500 )
2023	2023	LAUREATE INSTITUTE FOR BRAIN RESEARCH	6655 S YALE AVE	TULSA	OK	74136	TULSA	USA	Mental Health Research Grants	000	3	4/25/2023	NON-COMPETING CONTINUATION	$641,500
														Subtotal = $641,500

Issue Date FY: 2022 ( Subtotal = $687,812 )
2022	2022	LAUREATE INSTITUTE FOR BRAIN RESEARCH, INC.	6655 S YALE AVE	TULSA	OK	74136	TULSA	USA	Mental Health Research Grants	000	2	4/21/2022	NON-COMPETING CONTINUATION	$687,812
														Subtotal = $687,812

Issue Date FY: 2021 ( Subtotal = $751,094 )
2021	2021	LAUREATE INSTITUTE FOR BRAIN RESEARCH, INC.	6655 S YALE AVE	TULSA	OK	74136	TULSA	USA	Mental Health Research Grants	000	1	5/14/2021	NEW	$751,094
														Subtotal = $751,094

Grand Total All Awards = $3,484,556

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Neural response to inflammatory challenge in major depressive disorder

Award Number: R01MH123652

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/14/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer