Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

The role of inflammation in cognitive dysfunction in acute depression as determined by experimental inhibition of tumor necrosis factor-alphasignaling in a randomized controlled trial.

Award Number: K23MH132893
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/01/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2029

Group Awards By:

View Award Description

The role of inflammation in cognitive dysfunction in acute depression as determined by experimental inhibition of tumor necrosis factor-alphasignaling in a randomized controlled trial. - Cognitive dysfunction is a highly prevalent feature of depression that is resistant to anti-depressant treatments and associated with a worse course and outcome. Although a broad range of cognitive deficits are observed in depression, it is psychomotor speed and executive function that are most severely impacted during a depressive episode. A mechanistic understanding of why cognitive deficits emerge in depression is needed to identify treatment targets. Activated inflammatory physiology - a process in which TNF signaling is critical - plays a causal role in a substantial proportion of depressed cases based on genetic, clinical, experimental and observational research. In contrast, evidence that inflammation causes cognitive dysfunction, particularly in the context of depression, is less clearly established. Both theory and observational data, however, indicate that inflammation may account for deficits in psychomotor speed and executive function during a depressive episode. Determining how inflammation relates to cognitive dysfunction in depression is complicated by notable methodological limitations. First, the nature of the associations between inflammation, depression, and cognition is difficult to characterize because multiple, overlapping confounds exist (e.g., stress). Second, cognition is typically assessed intermittently (months/years apart) due to a reliance on in-person, lengthy cognitive measures that lack (“real-time”) temporal sensitivity. To overcome these limitations, this K23 application proposes using an intensive sampling methodology within a randomized controlled trial (RCT) to determine whether administration of an anti-inflammatory agent that inhibits tumor necrosis factor (TNF) signaling improves psychomotor speed and executive function in depressed individuals exhibiting an inflammatory phenotype over two weeks; exploratory analyses will examine whether decreases in inflammatory biomarkers are associated with improvements in cognition. Advances in cognitive neuroscience will be leveraged to assess cognition daily and generate sophisticated estimates of cognitive performance that address known limitations in conventional indices. A TNF antagonist was selected because of its critical role in inflammation, known association with psychomotor speed and executive function and because clinical trials have shown that a TNF antagonist (infliximab) can reduce depressive symptoms and increase effortful motivation after two weeks in depressed individuals exhibiting an inflammatory phenotype. The applicant proposes training in the: conduct of experiment research that is well-equipped to determine causality (i.e. RCT); use of intensive sampling methodologies in clinical samples; use of remote cognitive assessment tools and sophisticated analytic approaches; and further training in immunology. An interdisciplinary team of scientists will provide expert mentorship within the highly resourced environment of the Massachusetts General Hospital. The proposed study will advance the candidate’s long-term career goal of developing a mechanistic understanding of cognitive dysfunction in depression and accelerate the transition to research independence.


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: 2026 ( Subtotal = $197,564 )
2026	2026	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	3	1/14/2026	NON-COMPETING CONTINUATION	$197,564
														Subtotal = $197,564

Issue Date FY: 2025 ( Subtotal = $197,605 )
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	2	1/22/2025	NON-COMPETING CONTINUATION	$197,605
														Subtotal = $197,605

Issue Date FY: 2024 ( Subtotal = $197,115 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	1	2/1/2024	NEW	$197,115
														Subtotal = $197,115

Grand Total All Awards = $592,284

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The role of inflammation in cognitive dysfunction in acute depression as determined by experimental inhibition of tumor necrosis factor-alphasignaling in a randomized controlled trial.

Award Number: K23MH132893

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/01/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer