Noradrenergic control of neurobehavior in human binge-eating disorder and obesity

• Applicants: Professor Dr. Swen Hesse; Professorin Dr. Anja Hilbert
• Subject Area: Biological Psychiatry
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 465782368

Binge eating disorder (BED), which leads to obesity (OB), is a relatively new clinical eating disorder of high socio-economic impact, whose neurobehavioral underpinnings are largely unknown. The proposed project is based on the conceptualization of BED as a disorder with dysfunctional emotional regulation (ER) linked with changes in central noradrenaline (NA) transmission and NA-modulated neuronal networks. To assess the involvement of NA transmission in BED, we aim to quantify changes of NA transporter (NAT) availability using the highly NAT-specific [11C]methylreboxetin (MRB) and PET-MRI technology that allows to measure molecular and functional (neuronal) changes simultaneously. Acceptance-based behavioral therapy augmented by ecological meomentary intervention via smartphone will be applied for the improvement of ER. Based on our previous work and by obtaining biological and behavioral markers, the proposed study will further disentangle the involvement of NAT and central NA system in the modulation of neuronal networks that influence eating behavior. We expect abnormalities in NA activity that have an essential role in both BED and OB as a main driver of pathological overeating, which is likely to be most pronounced in BED. We expect further that these abnormalities are reversible and/or at least modifiable through state-of-the-art ER intervention, specifically in individuals with BED. These data together will provide a molecular signature beyond functional imaging biomarkers as a marker towards precision medicine tailoring treatments for individuals with BED and OB. The primary goal of this study is to investigate NAT availability, together with behavioral assessments and neuronal network activity under rest and stimulated conditions in well-characterized group of individuals with OB and BED (OB+BED), individuals with OB without BED (OB-BED), and individuals with normal weight (NW). These measurements will be repeated in OB+BED and OB-BED in order to quantify changes in NAT availability longitudinally: after short-term ER intervention or waiting list. The work program consists of two work-packages (WP), an Experimental Imaging Study (WP1) that integrates truly simultaneous PET-MRI system (mMR) by applying [11C]MRB in N=30 OB+BED (BMI 30-45 kg/m2), N=30 OB-BED (according to DSM-5, BMI 30-45 kg/m2), and N=20 healthy NW (BMI 18.5-25 kg/m2). Behavioral assessment and ER Intervention (WP2) will include a well-established clinical interview for eating disorder diagnosis as well as self-report questionnaires and tests for eating behavior, psychopathology, ER and executive function. The ER intervention will be offered through 12 individual sessions (within 10 weeks).

• DFG Programme: Research Grants