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Sleep-dependent Negative Overgeneralization in Adolescent Anxiety

Award Number: R01MH116005
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2018
PERIOD OF PERFORMANCE END DATE: 12/31/2028

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Sleep-dependent Negative Overgeneralization in Adolescent Anxiety - PROJECT SUMMARY Sleep is essential to our well-being, yet sleep problems are pervasive across mental health disorders and are heightened during adolescence – a developmental window of notable biological and social changes coinciding with escalations of anxiety disorders and depression. Consistent with the NIMH strategic plan, we aim to map the longitudinal course of sleep neurophysiology, brain maturation, emotion reactivity, and memory generalization and their relation to emotional health from the onset of adolescence through mid-late adolescence to inform novel treatments and minimize emotional health risks during this critical developmental window. In our ongoing R01, we have focused on mechanisms related to negative overgeneralization – a core dimension of anxiety that is poorly understood. We have found that sleep fails to depotentiate the response of the amygdala to negative stimuli in participants with elevated anxiety and negative overgeneralization emerges from an interplay between the amygdala at encoding and pattern completion supported by activity in the CA1 subfield of the hippocampus during retrieval. This proposal builds on and extends our ongoing R01 by longitudinally following the same individuals to investigate our hypothesis that altered emotional reactivity, sleep neurophysiology, and overgeneralization of negative memories arise from an imbalance between the amygdala and the hippocampus. Further, we posit that the amygdalo-hippocampal imbalance, exacerbated by the emotional and social changes prevalent during adolescence, contributes to the escalation of internalizing symptom severity often noted during this developmental window. The current renewal proposal tests this model using an accelerated longitudinal approach combining multiple methods – detailed clinical assessment, neuroimaging, polysomnography, and emotional memory task – across three time points, collected every ~18 months, in each participant to examine longitudinal maturation from peri-adolescence through mid-late adolescence. Youth (retained: n=140; newly recruited: n=80; total: N=220) across a continuum of anxiety symptoms, assigned to one of four cohorts based on their age at baseline will be enrolled in the proposed renewal study. Aim 1 will utilize the nocturnal polysomnography and structural and functional neuroimaging data collected at baseline and the two follow-up sessions to evaluate the longitudinal relation between amygdalo-hippocampal function and changes in sleep. Aim 2 will focus on behavior from the emotional memory task and functional neuroimaging data collected across waves to evaluate the longitudinal relation between amygdalo-hippocampal function and changes in negative overgeneralization. Aim 3 will incorporate the detailed clinical assessments collected across waves to investigate the longitudinal relation between amygdalo-hippocampal function, sleep neurophysiology, negative overgeneralization, and internalizing symptom severity. This project will provide critically needed data to advance mechanistic understanding of how sleep and neuromaturation influence emotional health in this sensitive period.


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 = $932,155 )
2025	2025	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	002	7	12/12/2024	NON-COMPETING CONTINUATION	$932,155
2025	2024	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	001	6	12/6/2024	COMPETING CONTINUATION	$31,412
2025	2023	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	000	5	12/6/2024	SUPPLEMENT FOR EXPANSION	-$31,412
														Subtotal = $932,155

Issue Date FY: 2024 ( Subtotal = $1,220,642 )
2024	2024	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	004	6	4/30/2024	COMPETING CONTINUATION	$119,690
2024	2024	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	003	6	3/1/2024	COMPETING CONTINUATION	$1,100,952
2024	2023	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	001	5	12/22/2023	SUPPLEMENT FOR EXPANSION	$0
2024	2022	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	002	5	3/1/2024	NON-COMPETING CONTINUATION	$0
2024	2022	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	000	5	12/18/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,220,642

Issue Date FY: 2023 ( Subtotal = $83,473 )
2023	2023	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	000	5	5/5/2023	SUPPLEMENT FOR EXPANSION	$83,473
														Subtotal = $83,473

Issue Date FY: 2022 ( Subtotal = $694,418 )
2022	2022	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	003	5	3/23/2022	SUPPLEMENT FOR EXPANSION	$52,601
2022	2022	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	002	5	3/21/2022	NON-COMPETING CONTINUATION	$641,924
2022	2021	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	000	4	11/4/2021	SUPPLEMENT FOR EXPANSION	$0
2022	2021	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	001	4	12/13/2021	SUPPLEMENT FOR EXPANSION	-$107
														Subtotal = $694,418

Issue Date FY: 2021 ( Subtotal = $691,543 )
2021	2021	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	001	4	8/16/2021	SUPPLEMENT FOR EXPANSION	$44,225
2021	2021	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	000	4	3/10/2021	NON-COMPETING CONTINUATION	$647,318
														Subtotal = $691,543

Issue Date FY: 2020 ( Subtotal = $672,164 )
2020	2020	FLORIDA INTERNATIONAL UNIVERSITY	11200 SW 8TH ST	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	000	3	3/9/2020	NON-COMPETING CONTINUATION	$672,164
														Subtotal = $672,164

Issue Date FY: 2019 ( Subtotal = $685,840 )
2019	2019	FLORIDA INTERNATIONAL UNIVERSITY	11200 S W 8TH ST MARC 430	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	000	2	5/27/2019	NON-COMPETING CONTINUATION	$685,840
														Subtotal = $685,840

Issue Date FY: 2018 ( Subtotal = $737,948 )
2018	2018	FLORIDA INTERNATIONAL UNIVERSITY	11200 S W 8TH ST MARC 430	MIAMI	FL	33199	MIAMI-DADE	USA	Mental Health Research Grants	000	1	5/29/2018	NEW	$737,948
														Subtotal = $737,948

Grand Total All Awards = $5,718,183

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Sleep-dependent Negative Overgeneralization in Adolescent Anxiety

Award Number: R01MH116005

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2018

PERIOD OF PERFORMANCE END DATE: 12/31/2028

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