Monday, June 30, 2025 6/30/2025

1/2 Leveraging electronic health records for pharmacogenomics of psychiatric disorders

Award Number: R01MH116270
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2024

Group Awards By:

View Award Description

1/2 Leveraging electronic health records for pharmacogenomics of psychiatric disorders - Schizophrenia (SCZ) and major depressive disorder (MDD) are highly heritable, debilitating diseases with lifetime prevalences of ~1% and 15%, respectively. Both disorders carry substantial morbidity and mortality and are associated with severe societal and personal costs. Despite the availability of efficacious treatments for both disorders, ~1/3 of individuals will not achieve symptomatic improvement even after multiple rounds of medication. Identifying individuals at greater risk for such treatment nonresponse, or treatment resistance, could facilitate more targeted interventions for these individuals. A burgeoning literature has identified genomic variation associated with treatment response. IN particular, antidepressant response has been suggested to be highly heritable; convergent data from rodent studies likewise suggest that antipsychotic and antidepressant response phenotypes are influenced by genetic variation. However, treatment studies to date have had minimal success in identifying variants associated with psychotropic response, likely as a result of limited sample sizes: prior efforts required sequential treatment trials and prospective assessment to characterize outcomes. Longitudinal electronic health records (EHR) data provide an opportunity to efficiently characterize treatment response in many individuals in real-world settings. Coupled with large and expanding biobanks, these cohorts allow for low- cost, large-scale genomic studies that finally achieve sufficient power to detect realistic effect sizes. The investigators now propose to apply these approaches to the EHRs of two large regional health systems, each linked to a large biobank, to investigate treatment resistance in SCZ and MDD. They will apply canonical indicators of treatment resistance - clozapine treatment for SCZ, and electroconvulsive therapy (ECT) for MDD - to identify coded and uncoded clinical features associated with high probability of treatment resistance in EHR data. These predictors will themselves provide a useful baseline for identifying high risk individuals. Then, they will apply these to study the entire affected population of each biobank, extending existing genomic data with additional genome-wide association, yielding more than 26,000 antidepressant-treated individuals and 2,500 antipsychotic-treated individuals. Rather than simply conducting a case-control study, they will examine treatment resistance as a quantitative trait, applying a method developed by the investigators and shown to substantially increase power for such traits. The project combines expertise in clinical informatics, machine learning, and analysis of large scale genomics, as well as domain-specific expertise in psychiatric treatment resistance. Spanning two distinct health systems, the algorithms and methods developed have maximal portability, facilitating next- step investigations. Successful identification of risk variants will facilitate efforts at clinical risk stratification as well as investigation of the biology underlying treatment resistance.


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 = -$47,159 )
2025	2022	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	4	4/7/2025	NON-COMPETING CONTINUATION	-$47,159
														Subtotal = -$47,159

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	4	2/29/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $421,250 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	001	4	5/16/2022	NON-COMPETING CONTINUATION	$42,125
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	4	11/23/2021	NON-COMPETING CONTINUATION	$379,125
														Subtotal = $421,250

Issue Date FY: 2021 ( Subtotal = $421,250 )
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	3	12/4/2020	NON-COMPETING CONTINUATION	$379,125
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	001	3	4/13/2021	NON-COMPETING CONTINUATION	$42,125
														Subtotal = $421,250

Issue Date FY: 2020 ( Subtotal = $421,250 )
2020	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	001	2	3/11/2020	NON-COMPETING CONTINUATION	$42,125
2020	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	2	12/2/2019	NON-COMPETING CONTINUATION	$379,125
														Subtotal = $421,250

Issue Date FY: 2019 ( Subtotal = $421,250 )
2019	2019	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Mental Health Research Grants	000	1	12/28/2018	NEW	$421,250
														Subtotal = $421,250

Grand Total All Awards = $1,637,841

Top

All Categories

About

Search

Reports

Data Submission

Award Information

1/2 Leveraging electronic health records for pharmacogenomics of psychiatric disorders

Award Number: R01MH116270

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer