193 Summary and discussion (3) a network analysis approach. We posit that the integration of these methodological vectors will augment our understanding of the salient neurobiological determinants, thereby potentially paving the way for the genesis of innovative treatment modalities for disorders characterized by self-destructive behavior, such as AN and NSSI. In summary, we hypothesize that self-destructive behavior represents a novel, transcendent psychopathological entity, as defined beyond the confines of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Aberrant reward mechanisms ostensibly underlie this entity. Consequently, both AN and NSSI, among other manifestations, could be conceptualized as disorders inherently rooted in self-destructive tendencies. GENERAL DISCUSSION In this final chapter, we will first integrate the main findings of this thesis into a conceptual framework of AN. We will subsequently discuss methodological considerations, describe implications for clinical practice and provide recommendations for future research. This study represents the first research project within the Netherlands to assess the efficacy, safety, and tolerability of DBS in the context of AN. On a global scale, the number of analogous trials are limited. We formulated hypotheses concerning the applicability of DBS as a last-resort therapeutic intervention for patients with chronic, treatment-resistant AN, subsequently constructing a comprehensive framework to probe the neurobiological substrates underpinning this disorder. This line of inquiry guided us to target the ventral anterior limb of the internal capsule (vALIC), an integral component of the brain’s reward circuitry, for DBS intervention. Beyond evaluating the primary effects of DBS on body weight, psychological metrics, and quality of life (QoL), we undertook a multifaceted assessment of its functional effects in AN. Using a variety of modalities - including functional fMRI, EEG, as well as endocrinological and metabolic analyses - we gathered empirical evidence supporting the hypothesis that DBS could serve as an efficacious treatment modality for patients with AN, whose lives are on a scale. Furthermore, this research contributes substantively to the upcoming understanding of the neurobiological pathophysiology of AN, highlighting the brain’s reward circuitry as a crucial factor. Lastly, our findings have generated additional hypotheses concerning the conceptual framework of AN, both as a psychiatric disorder and within the broader schema of self-destructive behaviors.
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