188 Summary and discussion SUMMARY OF MAIN FINDINGS Anorexia nervosa (AN) is a severe psychiatric disorder marked by low body weight, body image abnormalities, and anxiety and shows elevated rates of morbidity, comorbidity and mortality. Given the limited availability of evidence-based treatments, it manifests as a chronic condition in a significant percentage of patients. Consequently, there is an urgent need to investigate new therapeutic options that are informed by the disorder’s underlying neurobiological mechanisms. In this thesis, we explore the potential utility of deep brain stimulation (DBS) as a last-resort treatment for individuals suffering from AN. DBS has the advantage of being both reversible and adjustable. Existing studies have demonstrated that DBS can mitigate maladaptive neural activity and connectivity within the targeted region, thereby facilitating the re-establishment of healthier brain network dynamics. Furthermore, we assess the functional effects of DBS on AN through an array of methodologies, encompassing neuroimaging, electroencephalography, as well as metabolic and endocrinological evaluations. Finally, this work will situate AN within a broader theoretical framework, specifically focusing on its manifestation as a form of self-destructive behavior. Part I Part I contains the introduction of this thesis. Part II In the first chapter of this thesis, we conducted a comprehensive literature review to identify potential neurobiological correlates of anorexia nervosa (AN). Our analysis strongly implicates the fronto-striatal circuitry in the neuropathogenesis of AN, specifically the insula, ventral striatum (VS), and an ensemble of cortical regions including the prefrontal, orbitofrontal, temporal, parietal, and anterior cingulate cortices. Given the symptomatology and neurocircuitry overlap between reward-related disorders such as obsessive-compulsive disorder (OCD) and AN, along with the proven efficacy of accumbal DBS in OCD, we postulate that DBS targeting the nucleus accumbens (NAc) and other reward-associated regions, like the anterior cingulate cortex (ACC), could potentially serve as an effective intervention for patients with chronic, treatment-resistant AN. We hypothesize that this approach could facilitate not only weight restoration but also significant, sustained amelioration in the core symptoms, associated comorbidities, and complications of AN. Suggested DBS targets for AN include the ACC, the ventral anterior limb of the internal capsule (vALIC), and the VS. Given the severity of AN and its evident neurobiological substrates, we argue that there exists a compelling rationale for considering an invasive modality such as DBS as a potential therapeutic
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