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

Mechanistic Insights into Topiramate Response in Comorbid AUD and PTSD: From patients to cells

Award Number: R01AA033316
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2031

Group Awards By:

View Award Description

Mechanistic Insights into Topiramate Response in Comorbid AUD and PTSD: From patients to cells - Project Summary/Abstract Precision psychiatry is the application of data-driven, biologically grounded methods to improve the accuracy, efficacy, and personalization of mental health care. It has the potential to revolutionize the field of psychiatry by transitioning it from a reactive and symptom-based approach to a proactive, preventive, and highly personalized approach. Dr. Ho has utilized induced pluripotent stem cell (iPSC) technology and multi-omics approaches to investigate the biological mechanisms underlying variability in acamprosate efficacy and their interactions with pathways associated with alcohol relapse. These studies form the foundation for the current MPI R01 proposal in collaboration with Dr. Marmar at NYU. A critical barrier in psychiatry is the absence of objective molecular markers to guide diagnosis and monitor treatment response. Direct study of disease biology is hindered by the inaccessibility of living human brain tissue, and few biomarkers currently exist for predicting treatment response in substance use disorders. Identifying biomarkers linked directly to brain biology could revolutionize psychiatric care. Comorbidity of AUD and post-traumatic stress disorder (PTSD) adds further complexity, as individuals with both conditions often exhibit more severe PTSD symptoms, higher relapse risk, additional psychiatric comorbidities and increased suicide risk. These patients generally experience poorer treatment outcomes than those with either disorder alone. Dr. Marmar and colleagues recently completed a double-blind, placebo- controlled trial of topiramate in patients with comorbid AUD and PTSD (P01 AA27057). This proposal aims to identify biomarkers predictive of topiramate response and uncover underlying mechanisms using iPSC-derived brain-like cells. Preliminary studies show that topiramate alters gene expression, enhancing synaptic plasticity pathways and modulating stress and cortisol signaling. Aim 1 investigates topiramate’s effects on stress regulation and cortisol metabolism in iPSC-derived forebrain neurons, testing the hypothesis that glucocorticoid receptor binding contributes to treatment response. Aim 2 seeks to define molecular mechanisms underlying individual variation in topiramate response using patient-derived forebrain organoids and single-cell sequencing. Aim 3 applies Phenotype Identity Fingerprinting (PIF), an AI-based method, to identify cell type-specific and drug-induced “identity fingerprint genes,” revealing conserved signatures of drug action and new pharmacological avenues. Functional genomic studies will further explore these genes as potential novel targets for AUD+PTSD treatment. In summary, this research integrates cutting-edge iPSC and single-cell technologies with AI analytics to address a major unmet need in AUD treatment. It is innovative, feasible and grounded in strong preliminary data and it lays the foundation for biomarker-driven, mechanistic clinical trials that could transform psychiatric practice for AUD and related comorbidities.


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 = $433,056 )
2026	2026	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Alcohol Research Programs	000	1	8/27/2026	NEW	$433,056
														Subtotal = $433,056

Grand Total All Awards = $433,056

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanistic Insights into Topiramate Response in Comorbid AUD and PTSD: From patients to cells

Award Number: R01AA033316

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer