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Neural Systems Underlying Severe Worry in Anxious Adolescents and Young Adults

Award Number: R21MH122808
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2020
PERIOD OF PERFORMANCE END DATE: 09/30/2023

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Neural Systems Underlying Severe Worry in Anxious Adolescents and Young Adults - PROJECT SUMMARY Chronic and severe worry is a key characteristic of Anxiety Disorders (AD), which have the highest prevalence across the lifespan, typically start in childhood and adolescence, and increase risk for depression and suicide during adolescence. Chronic severe worry is also transdiagnostic and has been associated with increased risk of onset, relapse, and treatment resistance in mood disorders in adolescents. Yet, little is known about the neural mechanisms of worry that may contribute to onset of mood disorders. Neuroimaging studies in adults indicate that chronic severe worry is associated with deficits in frontolimbic networks, which undergo important maturational changes in adolescence. Our preliminary fMRI findings in older adults with severe worry show heightened activation in limbic/paralimbic structures during worry induction as well as reduced connectivity be- tween regions of the Salience Network (SN) and the Executive Control Network (ECN) and heightened amyg- dala-paraventricular nucleus (PVN) connectivity during worry reappraisal. Based on findings in depression, such patterns of neural function could represent a neural marker linking chronic worry with increased risk for depression. However, it remains unclear whether these patterns observed in older adults translate in anxious adolescents and young adults and whether they vary with age and sex. Furthermore, given evidence that anxi- ety may be associated with an imbalance in γ-aminobutyrate (GABA) and glutamatergic systems and that these systems undergo important maturational changes during adolescence and early adulthood, we will ex- amine the functioning of these systems as they relate to worry regulation in anxious individuals. This R21 pro- posal will serve to seed a larger, longitudinal R01 proposal that will test an overarching hypothesis that severe worry has distinct and cumulative age-related consequences due to altered neurodevelopment of the coordina- tion within and between neural regions within the SN and ECN in adolescence. These alterations contribute to increases in chronic arousal, ineffective emotion regulation, and lead to outcomes such as depression. Partici- pants will include 40 mid-/late-pubertal adolescents (12-17 yrs; 20 females) and 40 young adults (18-30 yrs; 20 females), recruited transdiagnostically based on worry severity, with 2/3 reporting severe levels of worry. Par- ticipants will complete psychiatric assessments, a worry induction and reappraisal fMRI task and a resting state session. To characterize the molecular underpinnings of frontolimbic networks, we will also acquire novel mag- netic resonance spectroscopy imaging measures of brain metabolites relevant to anxiety (e.g., GABA and glu- tamate) in the prefrontal cortical and limbic/paralimbic subcortical regions. The study aims to characterize age- related patterns of neural activation and functional connectivity during worry induction and regulation and to determine the extent to which GABA and glutamate concentrations are associated with neural functioning and worry and anxiety symptoms. Findings could lead to the identification of targets for novel neurodevelopmental- ly-based interventions of chronic and severe worry and prevention of depression in at-risk individuals.


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 = -$1,598 )
2024	2021	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	001	2	6/6/2024	NON-COMPETING CONTINUATION	-$2
2024	2021	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	2	5/2/2024	NON-COMPETING CONTINUATION	-$1,595
														Subtotal = -$1,598

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	2	4/25/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $218,098 )
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Mental Health Research Grants	000	2	4/13/2021	NON-COMPETING CONTINUATION	$218,098
														Subtotal = $218,098

Issue Date FY: 2020 ( Subtotal = $189,381 )
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Mental Health Research Grants	000	1	7/6/2020	NEW	$189,381
														Subtotal = $189,381

Grand Total All Awards = $405,881

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Neural Systems Underlying Severe Worry in Anxious Adolescents and Young Adults

Award Number: R21MH122808

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/15/2020

PERIOD OF PERFORMANCE END DATE: 09/30/2023

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