Loss of control eating exhibits an evening diurnal shift among females with bulimia nervosa and binge-eating disorder.

Loss of control (LOC) is a hallmark feature of binge eating that is associated with significant distress and impairment. Despite the central role diurnal rhythms may play in the development and maintenance of LOC eating, diurnal patterns of LOC remain understudied and poorly characterised. We assessed the diurnal timing of LOC in a sample of females with bulimia nervosa and binge-eating disorder who participated in a study assessing the impact of bright light exposure on binge eating, hypothesising that higher ratings of LOC would be more likely to occur later in the day. Participants (N = 34) completed a 22-day protocol during which they provided LOC ratings six times daily. Kernel density estimates describing LOC ratings across times of day were compared using permutation tests of equality. Results demonstrated an evening shift in LOC, wherein higher LOC was more likely to occur later in the day and lower LOC was more likely to occur earlier in the day. This study is the first to clearly depict the phenomenon that the likelihood of experiencing higher LOC increases throughout the day, pointing to the potential role diurnal rhythms, such as disrupted appetitive rhythms or mood variations, may play in maintaining binge eating.

Course of avoidant/restrictive food intake disorder: Emergence of overvaluation of shape/weight.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) is a feeding/eating disorder characterized by avoidance/restriction of food intake by volume and/or variety. The emergence of shape/weight-related eating disorder symptoms in the longitudinal course of ARFID is an important clinical phenomenon that is neither robustly documented nor well understood. We aimed to characterize the emergence of eating disorder symptoms among adults with an initial diagnosis of ARFID who ultimately developed other eating disorders. METHOD: Thirty-five participants (94% female; Mage = 23.17 ± 5.84 years) with a history of ARFID and a later, separate eating disorder completed clinical interviews (i.e., Structured Clinical Interview for DSM-5 - Research Version and Longitudinal Interval Follow-Up Evaluation) assessing the period between ARFID and the later eating disorder. Participants used calendars to aid in recall of symptoms over time. Descriptive statistics characterized the presence, order of, and time to each symptom. Paired samples t-tests compared weeks to emergence between symptoms. RESULTS: Most participants (71%) developed restricting eating disorders; the remainder (29%) developed binge-spectrum eating disorders. Cognitive symptoms (e.g., shape/weight concerns) tended to onset initially and were followed by behavioral symptoms. Shape/weight-related food avoidance presented first, objective binge eating, fasting, and excessive exercise occurred next, followed by subjective binge eating and purging. CONCLUSIONS: Diagnostic crossover from ARFID to another (typically restricting) eating disorder following the development of shape/weight concerns may represent the natural progression of a singular clinical phenomenon. Findings identify potential pathways from ARFID to the development of another eating disorder, highlighting possible clinical targets for preventing this outcome.

Discovery of BI-9508, a Brain-Penetrant GPR88-Receptor-Agonist Tool Compound for In Vivo Mouse Studies.

Decreased activity and expression of the G-protein coupled receptor GPR88 is linked to many behavior-linked neurological disorders. Published preclinical GPR88 allosteric agonists all have in vivo pharmacokinetic properties that preclude their progression to the clinic, including high lipophilicity and poor brain penetration. Here, we describe our attempts to improve GPR88 agonists' drug-like properties and our analysis of the trade-offs required to successfully target GPR88's allosteric pocket. We discovered two new GPR88 agonists: One that reduced morphine-induced locomotor activity in a murine proof-of-concept study, and the atropoisomeric BI-9508, which is a brain penetrant and has improved pharmacokinetic properties and dosing that recommend it for future in vivo studies in rodents. BI-9508 still suffers from high lipophilicity, and research on this series was halted. Because of its utility as a tool compound, we now offer researchers access to BI-9508 and a negative control free of charge via Boehringer Ingelheim's open innovation portal opnMe.com.