Elucidating estradiol variability's impact on dopaminergic reward circuitry in perimenopausal anhedonia

The National Institute of Mental Health awarded the University of North Carolina at Chapel Hill $163,866 on November 1, 2025, under the Mental Health Research Grants program (CFDA 93.242) to examine estradiol variability's effects on dopaminergic reward circuitry in perimenopausal anhedonia.

The recipient will conduct research examining the neurobiological mechanisms linking estradiol flux and anhedonia during perimenopause using simultaneous PET-MR imaging. The work comprises four objectives: examining estradiol flux's influence on striatal dopamine binding using [11C]raclopride PET; studying the relationship between estradiol flux and neural connectivity during reward processing via fMRI; assessing estradiol flux's influence on self-reported anhedonia symptoms; and exploring the mediating roles of dopamine binding and brain connectivity between estradiol flux and anhedonia. This study complements an ongoing NIMH project (MH128238) by focusing on estradiol variability's effects on dopamine metabolism, brain reward response, and anhedonia in perimenopausal women.

Performance occurs in Chapel Hill, North Carolina, with a period extending from November 1, 2025, through May 31, 2028. This is a Project Grant, a standard assistance mechanism under NIMH supporting specified research projects for periods not exceeding five years.

Abstract

Perimenopausal women face an increased risk of developing major depressive disorder (MDD), with anhedonia as a central symptom. Anhedonia during perimenopause is linked to fluctuations in estradiol levels ("estradiol flux"), potentially influencing reward responsiveness through dopamine modulation in the mesolimbic pathway. No research has yet explored this relationship using simultaneous pet-MR, a tool uniquely suited for its molecular specificity. This proposal aims to bridge this knowledge GAP by examining the neurobiological mechanisms connecting estradiol flux and anhedonia during perimenopause. Our objectives are 1) to examine the influence of estradiol flux on striatal dopamine binding using [11C]raclopride pet, 2) to study the relationship between estradiol flux and neural connectivity during reward processing via fmri, 3) to assess the influence of estradiol flux on self-reported anhedonia symptoms, and 4) to explore the mediating roles of dopamine binding and brain connectivity between estradiol flux and anhedonia. This study complements an ongoing nimh project (MH128238) by focusing on estradiol variability's effects on dopamine metabolism, brain reward response, and anhedonia in perimenopausal women.