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EVALUATION OF MOLECULAR MECHANISMS OF TREATMENT RESPONSE IN LATE LIFE DEPRESSION

Award Number: R01MH118311
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2019
PERIOD OF PERFORMANCE END DATE: 03/31/2024

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EVALUATION OF MOLECULAR MECHANISMS OF TREATMENT RESPONSE IN LATE LIFE DEPRESSION - DESCRIPTION: Over the past decades, antidepressants and psychotherapy have been the first-line treatments for LLD. Despite being safe and well-tolerated, a large number of patients do not achieve full and persistent remission after initial treatment. About 50% of patients with LLD do not respond after two antidepressant trials, meeting the consensus definition of treatment resistance (TR-LLD). The persistence of chronic and elevated depressive symptoms in older adults has significant clinical and public health implications. This has been correlated to poor general health, reduced quality of life, and a higher risk of mortality when compared to those with sustained remission after treatment. Despite the relevance to public health of TR-LLD, there is little information about the biological mechanisms and no robust clinical prediction model to evaluate at the outset of antidepressant therapy who will or will not respond to treatment. Leveraging an NIMH funded clinical trial, the Incomplete Response in Late-Life Depression: Getting to Remission” (IRL-GREY), across 3 sites, in this study, we propose to evaluate the biological mechanisms related to treatment response in late-life depression and to develop a machine learning based algorithm for prediction of treatment response in these subjects. We will carry out a comprehensive, multiplexed proteomic analysis on 542 samples from patients who completed phase 1 and phase 2 of the clinical trial. We hypothesise that ageing-related biological pathways (i.e. inflammatory response control, proteostasis control, cell damage response, endothelial function) will be associated with poorer treatment response in LLD. Moreover, we hypothesize that a machine learning derived biomarker panel will have sensitivity and specificity greater than 80% to predict treatment response in LLD. Finally, we will evaluate the biological mechanisms related to different depressive symptoms trajectories after treatment. This work will set the stage for a biologically-driven model of treatment response that will be useful to guide, at the outset of antidepressant treatment, those who will benefit more from a specific treatment. If successful, our work can accelerate therapeutic efforts and innovation targeting depression and reduce suffering for large numbers of elderly and their families.


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 = $0 )
2024	2022	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Mental Health Research Grants	000	5	7/29/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $279,453 )
2022	2022	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Mental Health Research Grants	003	5	5/23/2022	NON-COMPETING CONTINUATION	$27,762
2022	2022	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Mental Health Research Grants	002	5	3/9/2022	NON-COMPETING CONTINUATION	$249,838
2022	2021	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Mental Health Research Grants	001	4	11/9/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$332,340
2022	2020	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON			CAN	Mental Health Research Grants	004	2	9/26/2022	NON-COMPETING CONTINUATION	$1,853
2022	2020	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON			CAN	Mental Health Research Grants	000	2	11/9/2021	NON-COMPETING CONTINUATION	-$332,340
														Subtotal = $279,453

Issue Date FY: 2021 ( Subtotal = $721,224 )
2021	2021	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Mental Health Research Grants	002	4	7/26/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$721,224
2021	2021	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON			CAN	Mental Health Research Grants	000	3	3/17/2021	NON-COMPETING CONTINUATION	$490,569
2021	2021	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON			CAN	Mental Health Research Grants	001	3	7/26/2021	NON-COMPETING CONTINUATION	-$490,569
														Subtotal = $721,224

Issue Date FY: 2020 ( Subtotal = $516,549 )
2020	2020	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON	M6J 1H4		CAN	Mental Health Research Grants	000	2	3/17/2020	NON-COMPETING CONTINUATION	$516,549
														Subtotal = $516,549

Issue Date FY: 2019 ( Subtotal = $518,325 )
2019	2019	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON	M6J 1H4		CAN	Mental Health Research Grants	001	1	9/24/2019	NEW	$0
2019	2019	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON	M6J 1H4		CAN	Mental Health Research Grants	000	1	6/26/2019	NEW	$518,325
														Subtotal = $518,325

Grand Total All Awards = $2,035,551

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EVALUATION OF MOLECULAR MECHANISMS OF TREATMENT RESPONSE IN LATE LIFE DEPRESSION

Award Number: R01MH118311

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2019

PERIOD OF PERFORMANCE END DATE: 03/31/2024

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