Wednesday, February 5, 2025 2/5/2025

Examining the Effects of Estradiol on Neural and Molecular Response to Rewards in Perimenopausal-Onset Anhedonia and Psychosis

Award Number: R01MH128238
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary Affective disorders are highly prevalent in women and associated with significant morbidity and mortality, particularly during times of reproductive transition, including the transition to menopause. Unraveling the pathophysiology of affective disorders is challenging because depressive syndromes are heterogeneous and have diverse etiologies. Thus, studies aimed at identifying biomarkers to improve the prediction of susceptibility and illness course as well as treatment response in affective disorders have yielded inconsistent results. We propose to address this challenge by studying symptoms that initially present during the menopause transition and thus have a common endocrine trigger. We believe that studying a relatively homogeneous group of participants with similar biological mechanisms of symptom onset will increase the likelihood of elucidating the pathogenesis of perimenopausal-onset symptoms. This proposal will use simultaneous positron emission tomography and functional magnetic resonance imaging (PET-MR) to examine relations between reward-related striatal activation measured by fMRI and tonic and phasic striatal DA activity measured by [11C]raclopride PET in a transdiagnostic sample of women with varying severities of perimenopausal-onset (PO) anhedonia and psychosis. Specific Aim 1 will examine associations between PO anhedonia and psychosis symptom severity and reward-related striatal activation measured by fMRI and tonic and phasic striatal DA activity measured by [11C]raclopride PET. Specific Aim 2 will examine relations between anhedonia reductions due to estradiol administration, relative to placebo, and changes in PET-MR metrics related to reward processing. Specific Aim 3 will examine relations between PO psychosis reductions due to estradiol, relative to placebo, and changes in PET-MR metrics related to reward processing. Our central hypotheses are that the mesolimbic dopamine system is impaired during reward processing in PO anhedonia and psychosis, that the effects of estradiol administration will be associated with normalization of neural responses to rewards measured by fMRI and striatal dopamine functioning measured by PET, and that the degree of change in striatal functioning measured by fMRI and PET will be associated with the magnitude of change in PO anhedonia and psychosis symptom severity. The results of this project will increase our understanding of anhedonia and psychosis vulnerability during the menopause transition and have the potential to deliver validated molecular imaging targets to use in future mechanistic clinical trials of novel treatments for perimenopausal-onset psychiatric disorders.


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 = $621,572 )
2025	2025	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	4	12/17/2024	NON-COMPETING CONTINUATION	$621,572
														Subtotal = $621,572

Issue Date FY: 2024 ( Subtotal = $744,931 )
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	001	3	6/5/2024	NON-COMPETING CONTINUATION	$74,493
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	3	12/18/2023	NON-COMPETING CONTINUATION	$670,438
														Subtotal = $744,931

Issue Date FY: 2023 ( Subtotal = $758,209 )
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	2	12/22/2022	NON-COMPETING CONTINUATION	$682,389
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	001	2	1/18/2023	NON-COMPETING CONTINUATION	$75,820
														Subtotal = $758,209

Issue Date FY: 2022 ( Subtotal = $771,097 )
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	003	1	9/8/2022	NEW	$0
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	000	1	12/28/2021	NEW	$771,097
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	002	1	5/6/2022	NEW	$0
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Mental Health Research Grants	001	1	1/7/2022	NEW	$0
														Subtotal = $771,097

Grand Total All Awards = $2,895,809

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Examining the Effects of Estradiol on Neural and Molecular Response to Rewards in Perimenopausal-Onset Anhedonia and Psychosis

Award Number: R01MH128238

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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