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Phenotype Predictors of Cognitive Outcomes in Geriatric Depression

Award Number: R01MH108578
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/13/2016
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Phenotype Predictors of Cognitive Outcomes in Geriatric Depression - In this competing renewal of R01MH108578, we are seeking to extend findings from the initial study to focus on effects of stress in longitudinal mood and cognitive outcomes of late-life depression (LLD) and to examine stress effects on brain structure and function in LLD. Severe or persistent stressors can result in a number of behavioral and mood changes, including anxiety, dysphoric mood, sleep disruption, altered appetite, and withdrawal from social and pleasurable activities. These stress-related consequences are particularly salient when considering longitudinal outcomes of treated LLD. They may be compounded by an individual's longstanding maladaptive patterns of response to stress, embodied in the construct of neuroticism, which we have shown to be related to poor mood and cognitive LLD outcomes. Moreover, Andreescu et al. (2019) introduced a model of depression recurrence that incorporates the homeostatic disequilibrium hypothesis, which proposes that in geriatric remitted depression, neural networks are in fragile homeostasis that is threatened by stress exposure. Networks of particular importance in stress of LLD outcome are the Default Mode Network (DMN), Salience Network (SN) and Executive Control Network (ECN). The Neurobiology of Late Life Depression (NBOLD) study began enrolling older depressed and never- depressed controls in 2013, enrolling 132 depressed and 44 controls, and currently follows 77 depressed and 22 controls. Subjects are well characterized in terms of mood, cognition, personality and stress (including specific measures obtained during the present COVID pandemic). It is well suited to examine stress effects on longitudinal mood and cognitive outcomes. For the renewal, we will follow current subjects and recruit 75 new subjects, who will be followed for up to 5 years with annual cognitive testing, stress measures and baseline and two-year brain fMRI scan. In preliminary data presented in this application, we show that: 1) In depressed elders, compared with those who developed cognitive decline/dementia in 4 years, those who remained cognitively normal had greater 2-year decrease in neuroticism and increase in Conscientiousness. 2) Worsening in stress over two years is associated with two-year decrease in hippocampal volume and is associated with changes in functional connectivity of key brain regions.. 3) In complex statistical modeling, interactions of changes in neuroticism and changes in the number of stressors recently experienced are associated with cognitive outcome. In this competing renewal, we will examine the following specific aims: 1. To study effects of stressors (obtained on a variety of measures) and neuroticism on longitudinal mood and cognitive outcomes in older adults with history of major depressive disorder (MDD). 2. To study effects of stress and neuroticism on brain structure and function in older adults with MDD history. 3. To explore relationships among variables in Aims 1 and 2 with longitudinal multivariable statistical models.


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 = $607,072 )
2025	2025	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Mental Health Research Grants	000	10	4/17/2025	NON-COMPETING CONTINUATION	$607,072
														Subtotal = $607,072

Issue Date FY: 2024 ( Subtotal = $743,495 )
2024	2024	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Mental Health Research Grants	000	9	4/25/2024	NON-COMPETING CONTINUATION	$743,495
														Subtotal = $743,495

Issue Date FY: 2023 ( Subtotal = $663,990 )
2023	2023	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON AVE	FARMINGTON	CT	06030	CAPITOL	USA	Mental Health Research Grants	000	8	5/2/2023	NON-COMPETING CONTINUATION	$663,990
														Subtotal = $663,990

Issue Date FY: 2022 ( Subtotal = $713,805 )
2022	2022	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Mental Health Research Grants	002	7	4/8/2022	NON-COMPETING CONTINUATION	$713,805
2022	2021	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Mental Health Research Grants	001	6	4/1/2022	COMPETING CONTINUATION	$16,394
2022	2020	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Mental Health Research Grants	000	5	4/1/2022	NON-COMPETING CONTINUATION	-$16,394
														Subtotal = $713,805

Issue Date FY: 2021 ( Subtotal = $801,327 )
2021	2021	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Mental Health Research Grants	000	6	5/28/2021	COMPETING CONTINUATION	$801,327
														Subtotal = $801,327

Issue Date FY: 2020 ( Subtotal = $356,420 )
2020	2020	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Mental Health Research Grants	000	5	6/23/2020	NON-COMPETING CONTINUATION	$356,420
														Subtotal = $356,420

Issue Date FY: 2019 ( Subtotal = $366,633 )
2019	2019	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Mental Health Research Grants	000	4	6/14/2019	NON-COMPETING CONTINUATION	$366,633
														Subtotal = $366,633

Issue Date FY: 2018 ( Subtotal = $376,556 )
2018	2018	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Mental Health Research Grants	000	3	6/6/2018	NON-COMPETING CONTINUATION	$376,556
														Subtotal = $376,556

Issue Date FY: 2017 ( Subtotal = $388,057 )
2017	2017	UNIVERSITY OF CONNECTICUT	263 FARMINGTON AVE, ASB #3	FARMINGTON	CT	06032	CAPITOL	USA	Mental Health Research Grants	000	2	6/20/2017	NON-COMPETING CONTINUATION	$388,057
														Subtotal = $388,057

Issue Date FY: 2016 ( Subtotal = $438,399 )
2016	2016	UNIVERSITY OF CONNECTICUT HEALTH CENTER	263 FARMINGTON CENTER	FARMINGTON	CT	06030	CAPITOL	USA	Mental Health Research Grants	000	1	9/13/2016	NEW	$438,399
														Subtotal = $438,399

Grand Total All Awards = $5,455,754

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Phenotype Predictors of Cognitive Outcomes in Geriatric Depression

Award Number: R01MH108578

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/13/2016

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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