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Nutritional deficiency and dopamine: A neurodevelopmental study of starvation effects in adolescent anorexia nervosa

Award Number: R01MH131231
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/19/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2030

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Nutritional deficiency and dopamine: A neurodevelopmental study of starvation effects in adolescent anorexia nervosa - Anorexia nervosa (AN) is a severe and potentially life-threating condition that typically emerges in the teenage years. While AN is a complex disorder with myriad symptoms, caloric restriction is the central behavioral disturbance, and is characterized by a specific restriction of dietary fat. Converging data indicate that AN is associated with disturbances in the dopamine system. The dopamine system develops considerably during adolescence, and adequate nutrition plays a role in healthy brain development. Yet the effects of dietary restriction and the associated starved state that is an inherent feature of AN is poorly understood. Individuals with AN typically initiate dietary restrictions that accelerate, with mounting caloric reductions and weight loss and associated symptoms including anxiety and depression. This cascading pattern most commonly unfolds during adolescence and can lead to life-long struggles with eating, body image, and mood disturbance, if not unremitting AN. The restrictive eating pattern leads to decreased availability of many nutrients, some of which are particularly important in adolescent brain development. Here, we focus on polyunsaturated fats (PUFAs) and tyrosine which are specifically known to be critical for the functioning and development of the dopamine system. Our proposal aims to test the overarching hypothesis that among teens who develop AN, dietary restriction which is intrinsic to illness negatively impacts the dopamine (DA) system during a critical window of brain development, with enduring effects. We predict that these nutritional deficits will be associated with structural and functional disturbances in the DA system (baseline MRI scans with tractography, neuromelanin-MRI, and prediction error-fMRI). We predict that these nutritional deficits have enduring effects on the DA system even when weight restoration is successful, as evidenced by repeat MRI at 1 year. To assess the impact of being underweight, we will include individuals with atypical AN, who show all clinical features of AN but are not underweight, and 1-year longitudinal assessments will measure the enduring impact of these nutritional deficits. The proposed research has direct translational therapeutic implications – such as augmenting current treatments (including refeeding) with nutrient supplementation, thereby protecting the developing brain and curtailing the long-term negative sequelae of adolescent AN. With extant knowledge, such trials would be premature as the specific nutrients underlying AN-related starvation effects on brain development are unknown. We aim to close this gap by examining whether PUFAs and tyrosine mediate abnormalities in the DA system in adolescents with AN and atypical AN.


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 = $734,662 )
2026	2026	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	001	2	9/2/2026	NON-COMPETING CONTINUATION	$734,662
2026	2022	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	1	7/28/2026	NEW	$0
														Subtotal = $734,662

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2022	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	1	8/27/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	1	8/7/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	1	8/16/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $767,846 )
2022	2022	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1051 RIVERSIDE DR	NEW YORK	NY	10032	NEW YORK	USA	Mental Health Research Grants	000	1	8/19/2022	NEW	$767,846
														Subtotal = $767,846

Grand Total All Awards = $1,502,508

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Nutritional deficiency and dopamine: A neurodevelopmental study of starvation effects in adolescent anorexia nervosa

Award Number: R01MH131231

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/19/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2030

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