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Transcriptional differences in human postmortem brain tissue correspond with impulsive behavior in mood disorders

Award Number: F31MH136784
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/17/2025
PERIOD OF PERFORMANCE END DATE: 07/16/2027

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Transcriptional differences in human postmortem brain tissue correspond with impulsive behavior in mood disorders - Project Summary Mood disorders, characterized by reduced affect, can result in and diminished quality of life and are the leading cause of disability worldwide. Within these disorders, impulsive behavior emerges as a crucial endophenotype. Elevated levels of impulsivity in individuals with mood disorders are associated with poorer treatment adherence, worse health outcomes, and an increased risk of suicide. While previous genome-wide association studies have linked certain genes to impulsive behavior, there is a lack of research examining the differential gene expression related to impulsivity in humans, particularly those diagnosed with mood disorders. The current research application aims to address this gap by investigating transcriptomic and epigenetic differences in the dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, and nucleus accumbens of individuals diagnosed with mood disorders alongside healthy control subjects. Additionally, the study will integrate whole genome sequencing data from individuals diagnosed with mood disorders and controls subjects to test association signals. This comprehensive approach will provide valuable insights into the genetic mechanisms underlying impulsivity in mood disorders, improving our understanding and creating targeted treatment options. Based on preliminary data generated from this laboratory, we hypothesize that specific genetic and epigenetic alterations targeting key genes associated with neuroinflammation and synaptic structure within the dorsolateral prefrontal cortex (dlPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and nucleus accumbens (NAc) play a causative role in impulsive behavior in individuals with mood disorders. The proposed study consists of three aims, each contributing to the understanding of genetic and epigenetic factors underlying impulsive behavior in mood disorders. Aim 1 will continue the analysis of RNA expression in key brain regions of individuals with mood disorders and controls. By incorporating samples from various brain banks, the study aims to enhance statistical power, minimize sampling bias, and uncover new differentially expressed genes. Aim 2 will focus on exploring differential DNA methylation patterns in the same individuals studied in Aim 1. Understanding region-specific methylation data will shed light on its role in mood disorders and reveal heritable mechanisms of gene regulation. Aim 3 will create comprehensive network and pathway analyses based upon lists of genes generated from pilot data and previously published data, as well as from Aims 1 and 2. This will provide greater insight to relationships among genes than lists of single genes. Furthermore, this aim will explore connections with the results from Aims 1 and 2 at the molecular level. Each aim contributes to the broader picture of how genetic and epigenetic differences can jointly influence impulsive behavior within the context of mood disorders and the integration of these independent aims will lead to a comprehensive understanding of the underlying mechanisms driving impulsivity in mood disorders.


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 = $39,576 )
2026	2026	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Mental Health Research Grants	000	2	8/5/2026	NON-COMPETING CONTINUATION	$39,576
														Subtotal = $39,576

Issue Date FY: 2025 ( Subtotal = $39,000 )
2025	2025	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Mental Health Research Grants	000	1	7/15/2025	NEW	$39,000
2025	2025	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Mental Health Research Grants	001	1	7/15/2025	NEW	$0
														Subtotal = $39,000

Grand Total All Awards = $78,576

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Transcriptional differences in human postmortem brain tissue correspond with impulsive behavior in mood disorders

Award Number: F31MH136784

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/17/2025

PERIOD OF PERFORMANCE END DATE: 07/16/2027

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