Wednesday, January 15, 2025 1/15/2025

Identification of Distinct Biotypes in Clinical High Risk for Psychosis State Using Objective Brain-Based Biomarkers

Award Number: R21MH133001
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Identifying predictors and elucidating mechanisms underlying psychosis onset are critical for the development of targeted interventions. The current symptom-based clinical high risk (CHR) syndrome has been validated as an indicator of future psychosis risk but does not provide accurate predictions regarding individual clinical trajectories or a stratification model that informs outcome or treatment response. The CHR phase is diverse in terms of risk factors and outcomes, with a significant proportion of CHR converters (<30%) developing non-affective psychosis (~73%) and a smaller group developing affective psychoses (~11%). In addition, CHR non- converters have variable outcomes, ranging from full remission to ongoing multifaceted sequelae. Furthermore, substantial neurobiological heterogeneity among CHR individuals is well- documented. Despite this, little research attempted to harness the rich multimodal data collected in large-scale CHR studies to form and validate neurobiologically driven CHR subgroups. Successful parsing of the underlying heterogeneity of CHR may yield more defined subgroups with distinct clinical trajectories and outcomes. Our group’s recent studies examining neurobiological heterogeneity in psychosis spectrum using the Bipolar-Schizophrenia Network for Intermediate Phenotypes dataset, adopted a data-driven cluster analytic method to define biological clusters (or biotypes) using cognitive, and electrophysiological biomarkers agnostic to traditional symptom-based diagnostic categories. The goal was to identify neurobiologically homogeneous biotypes with presumed distinct underlying pathophysiology. However, the sample consisted of chronic psychosis subjects and thus was unable to inform the development of early intervention and prevention applications, and lacked clinically relevant longitudinal outcome data. An approach focusing on CHR to define biotypes and assess them using longitudinal clinical, and functional outcome data has yet to be attempted. The availability of prospectively characterized and deeply phenotyped CHR samples from the North American Prodrome Longitudinal Study 2 and 3 is a unique opportunity to address this question using an objective approach. In the current proposal, we will identify distinct subgroups or ‘biotypes’ for CHR using cluster analysis and will compare, evaluate and validate the resulting biotypes. This proposal will have an important impact on our understanding of how biological heterogeneity contributes to clinical outcomes in CHR and elucidates a way to characterize biological heterogeneity in this population, providing biological targets for more effective diagnosis, and early therapeutic intervention.


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: 2024 ( Subtotal = $155,207 )
2024	2024	BETH ISRAEL DEACONESS MEDICAL CENTER, INC.	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	001	2	5/13/2024	NON-COMPETING CONTINUATION	$15,520
2024	2024	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	2	1/12/2024	NON-COMPETING CONTINUATION	$139,687
														Subtotal = $155,207

Issue Date FY: 2023 ( Subtotal = $191,100 )
2023	2023	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Mental Health Research Grants	000	1	1/31/2023	NEW	$191,100
														Subtotal = $191,100

Grand Total All Awards = $346,307

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Identification of Distinct Biotypes in Clinical High Risk for Psychosis State Using Objective Brain-Based Biomarkers

Award Number: R21MH133001

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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