Noradrenergic control of neurobehavior in human binge-eating disorder and obesity (NOBEAD): A smartphone-supported behavioral emotion regulation intervention study protocol integrating molecular brain imaging.

Objective: The neurobehavioral underpinnings of binge-eating disorder (BED), co-occurring with obesity (OB), are largely unknown. This research project conceptualizes BED as a disorder with dysfunctional emotion regulation (ER) linked with changes in central noradrenaline (NA) transmission and NA-modulated neuronal networks.

Methods: We expect abnormalities in NA activity in both BED and OB, but most pronounced in BED. We expect these abnormalities to be modifiable through state-of-the-art ER intervention, specifically in BED. To assess the role of NA transmission, we will quantify changes in NA transporter (NAT) availability using the highly NAT-specific [ C]methylreboxetin (MRB) and positron emission tomography-magnetic resonance imaging (PET-MRI) that allows measuring molecular and neuronal changes before and after an ER intervention. Individual 12-session smartphone-supported acceptance-based behavioral therapy will be conducted to improve ER. Thirty individuals with OB and BED (OB + BED), 30 individuals with OB without BED (OB - BED), and 20 individuals with normal weight will undergo assessments of NAT availability and neuronal network activity under rest and stimulated conditions, clinical interviews, self-report questionnaires on eating behavior, ER, mental and physical health, and quality of life, and neuropsychological tests on executive function. Afterwards, in an experimental randomized-controlled design, individuals with OB + BED and OB - BED will be allocated to smartphone-supported ER intervention versus a waitlist and re-assessed after 10 weeks.

Discussion: By obtaining biological and behavioral markers, the proposed study will disentangle the involvement of NAT and the central NA system in the modulation of emotion-supporting neuronal networks that influence eating behavior. Neurobehavioral mechanisms of change during an ER intervention will be determined.

Trial Registration: German Clinical Trials Register (DRKS): DRKS00029367.

Public Significance: This study investigates the central noradrenaline system by using hybrid brain imaging in conjunction with emotion regulation as a putative core biological mechanism in individuals with obesity with or without binge-eating disorder that is targeted by emotion regulation intervention. The results will provide a molecular signature beyond functional imaging biomarkers as a predictive biomarker toward precision medicine for tailoring treatments for individuals with binge-eating disorders and obesity.