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The ENIGMA - Eating Disorders Initiative: A Global Neuroimaging Study of Anorexia and Factors Affecting Clinical Outcomes

Award Number: U01MH136221
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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The ENIGMA - Eating Disorders Initiative: A Global Neuroimaging Study of Anorexia and Factors Affecting Clinical Outcomes - ABSTRACT Anorexia nervosa (AN) has one of the highest mortality rates of all psychiatric conditions due to long-term physical complications and a suicide rate over 50 times higher than the general population. The mortality rate encompasses a combination of the medical sequelae of underweight and death by suicide – and increases by around 5% with each decade of illness. Around one-third of people with AN develop a chronic disorder. If AN is not treated, serious complications such as heart conditions and kidney failure can arise and eventually lead to death. Despite the severity of AN, the neurobiological mechanisms that influence risk and treatment outcomes in AN are poorly understood; AN is severely understudied compared to other psychiatric conditions. Little is known about the alterations in brain circuitry and function in AN, and which brain changes predict future remission or relapse. Findings to date often raise questions related to the acute state: What are the acute and lasting effects of starvation? Which brain differences are related to the illness rather than undernutrition, and which are reversible with treatment? Which clinical measures, risk factors, and brain abnormalities are most important in understanding risk for AN and longer-term illness courses? To address these knowledge gaps, we launch the ENIGMA Eating Disorders Initiative – a global alliance to bring together clinical and neuroimaging experts in eating disorders worldwide to address pressing questions in AN research. This new international initiative is a coordinated data analysis platform to determine multimodal neuroimaging signatures of AN from a broad range of 31 clinical datasets worldwide. We build on our promising pilot data that shows 1) one of the largest effects on brain structure ever observed among psychiatric conditions, and 2) some of the brain anomalies in AN are reversible after weight restoration treatment in a subset of patients. Identifying circuits and functions that can be restored, and in which patient subgroups, is critical. In the largest worldwide dataset ever analyzed (n~1,600 cases and ~1,700 HCs), we will identify multimodal brain biomarkers of AN, its driving mechanisms, which brain abnormalities can be reversed, and in which patients. To boost statistical rigor, reproducibility and power, our coordinated international alliance will pool a broad range of brain and clinical data internationally using harmonized analytic workflows. We build on the successful launch of our ENIGMA Eating Disorders working group, which published the most highly powered neuroimaging study of AN. Our Specific Aims are to: (1) identify multimodal brain signatures of AN, with the power and range of data to understand which brain signatures are reproducible in patients across the world; (2) disentangle undernutrition effects on the brain from the aberrant brain circuitry that drives the condition and increases risk of relapse; and (3) longitudinally assess relapse and recovery, to better predict remission and risk for AN. Our Precision Medicine approach responds to NIMH’s mission to seek more reproducible, objective biomarkers of disease for individual monitoring and management, to assist prognosis, and discover factors that influence relapse, suicidality, or recovery.


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 = $615,519 )
2026	2026	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Mental Health Research Grants	000	3	4/24/2026	NON-COMPETING CONTINUATION	$475,944
2026	2026	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Mental Health Research Grants	001	3	5/11/2026	SUPPLEMENT FOR EXPANSION	$139,575
														Subtotal = $615,519

Issue Date FY: 2025 ( Subtotal = $523,499 )
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Mental Health Research Grants	000	2	1/28/2025	NON-COMPETING CONTINUATION	$523,499
														Subtotal = $523,499

Issue Date FY: 2024 ( Subtotal = $642,093 )
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Mental Health Research Grants	001	1	5/1/2024	NEW	$61,609
2024	2024	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Mental Health Research Grants	000	1	4/9/2024	NEW	$580,484
														Subtotal = $642,093

Grand Total All Awards = $1,781,111

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The ENIGMA - Eating Disorders Initiative: A Global Neuroimaging Study of Anorexia and Factors Affecting Clinical Outcomes

Award Number: U01MH136221

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 04/15/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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