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Neural and behavioral predictors of cognitive development and internalizing problems in adolescents with autism spectrum disorder

Award Number: R01MH103284
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT: Adolescence is a period of strong cortical plasticity accompanied by significant changes in cognitive, social, and adaptive functioning. Despite the promise characteristic of this period, it is also a time when social relationships and emotion processing may intensify, and depression and other forms of psychopathology first emerge. The lack of longitudinal studies of adolescents with autism spectrum disorder (ASD), coupled with the disorder's heterogeneity, clouds our understanding of development during this complex period, and hinders treatment development. We thus propose to extend our longitudinal investigation of children from the UC Davis MIND Institute Autism Phenome Project cohort into adolescence. In Specific Aim #1, we predict aspects of cognitive development in adolescents with ASD based on grant period studies. We hypothesize that ASD will continue to exhibit at least three trajectories of intellectual functioning (IQ) -- a group with persistently below average IQs (< 75) from early childhood through adolescence (Persistently Low or P-Low), a group with IQs < 75 in early childhood that increase by at least 1 standard deviation by adolescence (Positive Changers or +CHG), and a group with persistently average or better IQs (>75) (Persistently High or P-High). We also predict that preparatory cognitive control will continue to be comparable to TYP, but will be associated with behavioral inflexibility; that all groups will exhibit comparable performance on aspects of episodic memory; and that P-Low will show fewer negative emotional false memories. In Specific Aim #2, we examine social awareness, motivation, and adaptive functioning in between middle childhood and adolescence in ASD. We predict that +CHG will show improved social awareness and functioning compared to P-Low and P-High, while all groups show declining social motivation, and that resting state functional magnetic resonance imaging functional connectivity (FC) between the executive/cognitive control (ECN), default mode (DMN), and salience (SN) networks will be predictive of adolescent social awareness and social functioning while social motivation is predicted by concurrent engagement of the striatum. Specific Aim #3 investigates the emergence of depression in ASD between middle childhood and adolescence. We test a prominent model predicting that increased depression between middle childhood and adolescence will be more common in P-High and +CHG, and will be associated with increased social awareness, greater retention of negative emotional memories, and less flexible cognitive control. Additionally, we predict that during a well-validated task-based fMRI Sadness Introspection Paradigm, functional connectivity between the ECN, DMN, SN, amygdala, and hippocampus during sadness introspection will be associated with adolescent depression in P-High and +CHG. We also predict that parent questionnaires, compared to gold standard clinician interviews, will under-report depression in P-Low. This longitudinal examination of cognition, social functioning, and depression in adolescents with ASD holds the potential to identify early markers of depression and more tailored precision medicine solutions.


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: 2023 ( Subtotal = $738,465 )
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Mental Health Research Grants	000	9	5/11/2023	NON-COMPETING CONTINUATION	$738,465
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Mental Health Research Grants	001	9	6/8/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $738,465

Issue Date FY: 2022 ( Subtotal = $739,355 )
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Mental Health Research Grants	000	8	5/11/2022	NON-COMPETING CONTINUATION	$739,355
														Subtotal = $739,355

Issue Date FY: 2021 ( Subtotal = $736,013 )
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Mental Health Research Grants	000	7	5/3/2021	NON-COMPETING CONTINUATION	$736,013
2021	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Mental Health Research Grants	002	6	6/29/2021	COMPETING CONTINUATION	$16,683
2021	2018	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Mental Health Research Grants	001	5	6/29/2021	NON-COMPETING CONTINUATION	-$16,683
														Subtotal = $736,013

Issue Date FY: 2020 ( Subtotal = $774,751 )
2020	2020	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Mental Health Research Grants	000	6	7/2/2020	COMPETING CONTINUATION	$774,751
														Subtotal = $774,751

Issue Date FY: 2018 ( Subtotal = $504,752 )
2018	2018	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Mental Health Research Grants	000	5	6/13/2018	NON-COMPETING CONTINUATION	$504,752
														Subtotal = $504,752

Issue Date FY: 2017 ( Subtotal = $506,146 )
2017	2017	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Mental Health Research Grants	000	4	7/21/2017	NON-COMPETING CONTINUATION	$506,146
														Subtotal = $506,146

Issue Date FY: 2016 ( Subtotal = $510,456 )
2016	2016	UNIVERSITY OF CALIFORNIA	1850 RESEARCH PARK DRIVE	DAVIS	CA	95618	YOLO	USA	Mental Health Research Grants	000	3	6/25/2016	NON-COMPETING CONTINUATION	$510,456
														Subtotal = $510,456

Issue Date FY: 2015 ( Subtotal = $504,641 )
2015	2015	UNIVERSITY OF CALIFORNIA	1850 RESEARCH PARK DRIVE	DAVIS	CA	95618	YOLO	USA	Mental Health Research Grants	000	2	8/18/2015	NON-COMPETING CONTINUATION	$504,641
														Subtotal = $504,641

Issue Date FY: 2014 ( Subtotal = $557,566 )
2014	2014	UNIVERSITY OF CALIFORNIA	1850 RESEARCH PARK DRIVE	DAVIS	CA	95618	YOLO	USA	Mental Health Research Grants	000	1	9/11/2014	NEW	$557,566
														Subtotal = $557,566

Grand Total All Awards = $5,572,145

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Neural and behavioral predictors of cognitive development and internalizing problems in adolescents with autism spectrum disorder

Award Number: R01MH103284

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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