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1/2 Inflammation and Stress Response in Familial and Nonfamilial Youth Suicidal Behavior

Award Number: R01MH108039
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/20/2015
PERIOD OF PERFORMANCE END DATE: 10/31/2026

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1/2 Inflammation and Stress Response in Familial and Nonfamilial Youth Suicidal Behavior - Suicide is 2nd leading cause of death in the US youth, and rates have risen 33% in 17 years. Clinical risk factors alone have disappointing predictive power and biological predictors show promise but rarely separated into long- term and short-term predictors due to the challenge of detecting biological profiles shortly before suicide behavior (SB). We propose a novel pragmatic approach of examining biological risk profiles immediately after an acute suicidal crisis and then separating them into familial and nonfamilial risk profiles. Our collaborative work indicates a stress responsive biological phenotype associated with more lethal and familial SB where inflammation activates the kynurenine pathway depleting brain serotonin by shunting tryptophan away from serotonin toward kynurenine synthesis. Inflammation and neuroinflammation can potentially result from HPA axis and mitochondrial dysregulations. We also find HPA axis dysregulation and inflammation to be more pronounced in those with SB and family history of SB. We hypothesize familial factors to be mostly long-term and nonfamilial factors to be mostly short-term risk factors. We propose to examine short-term or proximal biological risk profiles for suicidal behavior (SB) in stress response and inflammatory pathways, peripherally and in the brain, and examine familial and nonfamilial biological mechanisms for SB in young adults. We will recruit 120 young adult psychiatric inpatients or outpatients, aged 18-30 years, 80 at high-risk for SB defined as those presenting to the emergency department (ED) or admitted for suicidal ideation (SI) with a plan and intent or SB in the last two weeks; and 40 at lower risk with no SB or SI with plan/intent in past 3 months. Groups will be frequency-matched on familial risk. We will collect: 1) clinical data; 2) hair to measure hair cortisol concentrations (HCC); 3) conduct the Trier Social Stress Task (TSST) to measure cortisol, peripheral inflammation (cytokines, kynurenine metabolites) and circulating cell free mitochondrial DNA (ccf-mtDNA); 4) PET imaging using [11C]ER176 ligand to measure neuroinflammation; and 5) near-infrared spectroscopy (NIRS) to measure in PFC oxidation state of cytochrome-c-oxidase (oxCOX), a brain marker of mitochondrial function. Patients will be followed up at 1, 3, and 12 months. The year post-hospital/ED discharge is a high-risk period for SB and the first 3 months is the highest risk period. We hypothesize high-risk patients will show higher [11C]ER176 PET binding and lower oxCOX at baseline. They will also show lower HCC and higher cortisol response to stress and higher inflammation and ccf-mtDNA prior and in response to stress at baseline. Offspring of attempters will show more severe biological profiles due to the contribution of short and longer-term risk factors. We will also examine the relationships between peripheral and brain measures and explore whether they predict SB. This study will improve our understanding of familial and nonfamilial biological mechanisms for SB to better separate long-term and short- term risk biological phenotypes, which will help guide risk detection and novel just-in-time approaches.


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 = $398,594 )
2026	2026	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	10	1/16/2026	NON-COMPETING CONTINUATION	$398,594
2026	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	001	9	1/20/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $398,594

Issue Date FY: 2025 ( Subtotal = $316,790 )
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	9	11/21/2024	NON-COMPETING CONTINUATION	$316,790
														Subtotal = $316,790

Issue Date FY: 2024 ( Subtotal = $351,332 )
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	001	8	5/13/2024	NON-COMPETING CONTINUATION	$35,132
2024	2024	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	8	10/17/2023	NON-COMPETING CONTINUATION	$316,200
														Subtotal = $351,332

Issue Date FY: 2023 ( Subtotal = $350,383 )
2023	2023	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	7	11/3/2022	NON-COMPETING CONTINUATION	$315,344
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	001	7	1/18/2023	NON-COMPETING CONTINUATION	$35,039
														Subtotal = $350,383

Issue Date FY: 2022 ( Subtotal = $365,758 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	001	6	6/27/2022	COMPETING CONTINUATION	$34,593
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	6	12/15/2021	COMPETING CONTINUATION	$331,165
														Subtotal = $365,758

Issue Date FY: 2021 ( Subtotal = -$634 )
2021	2019	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	5	9/22/2021	NON-COMPETING CONTINUATION	-$634
														Subtotal = -$634

Issue Date FY: 2019 ( Subtotal = $304,248 )
2019	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Mental Health Research Grants	000	5	4/25/2019	NON-COMPETING CONTINUATION	$304,248
														Subtotal = $304,248

Issue Date FY: 2018 ( Subtotal = $299,396 )
2018	2018	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Mental Health Research Grants	001	4	8/29/2018	NON-COMPETING CONTINUATION	$0
2018	2018	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Mental Health Research Grants	000	4	5/15/2018	NON-COMPETING CONTINUATION	$299,396
														Subtotal = $299,396

Issue Date FY: 2017 ( Subtotal = $300,400 )
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Mental Health Research Grants	001	3	8/15/2017	NON-COMPETING CONTINUATION	$30,041
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Mental Health Research Grants	000	3	5/4/2017	NON-COMPETING CONTINUATION	$270,359
														Subtotal = $300,400

Issue Date FY: 2016 ( Subtotal = $257,886 )
2016	2016	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Mental Health Research Grants	000	2	4/16/2016	NON-COMPETING CONTINUATION	$257,886
														Subtotal = $257,886

Issue Date FY: 2015 ( Subtotal = $269,813 )
2015	2015	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Mental Health Research Grants	000	1	8/20/2015	NEW	$269,813
														Subtotal = $269,813

Grand Total All Awards = $3,213,966

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1/2 Inflammation and Stress Response in Familial and Nonfamilial Youth Suicidal Behavior

Award Number: R01MH108039

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/20/2015

PERIOD OF PERFORMANCE END DATE: 10/31/2026

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