189 Summary and discussion avenue for chronic, treatment-resistant AN. Through meticulous selection of stimulation targets, stringent inclusion and exclusion criteria, and rigorous oversight of safety protocols, DBS offers promise in addressing the core symptomatology of AN while concurrently expanding our understanding of its complex pathophysiological mechanisms. Prior to initiating our DBS-AN study, several case reports had alluded to the potential impact of DBS on body weight and eating behavior. In 2010, our research team disseminated a frequently cited case report describing both smoking cessation and marked weight loss in an obese patient following DBS treatment for OCD (1) . To ascertain whether this isolated observation was replicable in a broader population, we conducted an analysis of weight changes in a more expansive cohort of patients undergoing vALIC-targeted DBS for either OCD or Major Depressive Disorder (MDD) (Chapter 2). Our intention was to elucidate the global effects of DBS on weight and eating behavior. This is particularly relevant given the implicated role of the reward system in various eating behaviors and conditions, including obesity, binge eating, and AN. Our results indicated no significant alteration in aggregate body weight post-vALIC DBS treatment for either OCD or MDD. Nonetheless, we observed a trending decrease in body mass index (BMI) within the subset of patients categorized as morbidly obese. Importantly, this trend did not mirror the dramatic weight loss depicted in our prior case study. It is worth noting that weight normalization or reduction was not a primary treatment objective in these cases, and no motivational therapy targeting weight loss was administered. Part III The core of this thesis is dedicated to a pilot study we conducted, aimed at evaluating the efficacy, safety, and tolerability of DBS in AN. To the best of our knowledge, this is the first study exploring vALIC DBS in the context of AN. Through an extensive optimization period coupled with comprehensive phenotyping, we provide nuanced insights into the psychological, somatic, and functional effects of this treatment modality. In Chapter 3, we present the main results of the DBS-AN study. The average Body Mass Index (BMI) exhibited a substantial and statistically significant elevation by the conclusion of the follow-up period, increasing by 5.32 kg/m² (+42.8%, P=.017), thereby attaining the DSM-5 category of ‘mild.’ This increase was predominantly observed in two of the four participants, whereas the remaining pair manifested only modest BMI increase. A response rate of 50% on primary outcome BMI corroborates the findings of seminal works in this domain, including those by Liu et al. (2020) and Lipsman et al. (2017) (2, 3), which reported response rates of 61% and 57%, respectively. Clinically, improvements were discernible, encompassing reductions in harmful eating behaviors such as purging, obsessive caloric counting, and body checking. Psychological metrics, as assessed
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