Life on a scale:Deep brain stimulation in anorexia nervosa

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, there is an urgent need to investigate new therapeutic options that are informed by the disorder’s underlying neurobiological mechanisms. This thesis represents the first study in the Netherlands and one of a limited number globally to evaluate the efficacy, safety, and tolerability of deep brain stimulation (DBS) in the treatment of AN. DBS has the advantage of being both reversible and adjustable. Beyond assessing the primary impact of DBS on body weight, psychological parameters, and quality of life, this research is novel in its comprehensive approach. We integrated evaluations of efficacy with critical examinations of the functional impact of DBS in AN, including fMRI, electroencephalography EEG, as well as endocrinological and metabolic assessments. Furthermore, this work situates AN within a broader theoretical framework, specifically focusing on its manifestation as a form of self-destructive behavior. Finally, we reflect on the practical, ethical and philosophical aspects of conducting an experimental, invasive procedure in a vulnerable patient group. This thesis deepens our understanding of the neurobiological underpinnings of AN and paves the way for future research and potential clinical applications of DBS in the management of severe and enduring AN

Psychopathological and Neurobiological Overlap Between Anorexia Nervosa and Self-Injurious Behavior: A Narrative Review and Conceptual Hypotheses

Empirical evidence and clinical observations suggest a strong -yet under acknowledged-link between anorexia nervosa (AN) and non-suicidal self-injurious behavior (NSSI). By reviewing the literature on the psychopathology and neurobiology of AN and NSSI, we shed light on their relationship. Both AN and NSSI are characterized by disturbances in affect regulation, dysregulation of the reward circuitry and the opioid system. By formulating a reward-centered hypothesis, we explain the overlap between AN and NSSI. We propose three approaches understanding the relationship between AN and NSSI, which integrate psychopathology and neurobiology from the perspective of self-destructiveness: (1) a nosographical approach, (2) a research domain (RDoC) approach and (3) a network analysis approach. These approaches will enhance our knowledge of the underlying neurobiological substrates and may provide groundwork for the development of new treatment options for disorders of self-destructiveness, like AN and NSSI. In conclusion, we hypothesize that self-destructiveness is a new, DSM-5-transcending concept or psychopathological entity that is reward-driven, and that both AN and NSSI could be conceptualized as disorders of self-destructiveness

Efficacy and safety of deep brain stimulation for treatment-refractory anorexia nervosa: a systematic review and meta-analysis

Background: Several pioneering studies investigated deep brain stimulation (DBS) in treatment-refractory anorexia nervosa (AN) patients, but overall effects remain yet unclear. Aim of this study was to obtain estimates of efficacy of DBS in AN-patients using meta-analysis. Methods: We searched three electronic databases until 1st of November 2021, using terms related to DBS and AN. We included trials that investigated the clinical effects of DBS in AN-patients. We obtained data including psychiatric comorbidities, medication use, DBS target, and study duration. Primary outcome was Body Mass Index (BMI), secondary outcome was quality of life, and the severity of psychiatric symptoms, including eating disorder, obsessive-compulsive, depressive, and anxiety symptoms. We assessed the risk of bias using the ROBINS-I tool. Results: Four studies were included for meta-analysis, with a total of 56 patients with treatment-refractory AN. Follow-up ranged from 6–24 months. Random effects meta-analysis showed a significant increase in BMI following DBS, with a large effect size (Hedges’s g = 1 ∙ 13; 95% CI = 0 ∙ 80 to 1 ∙ 46; Z-value = 6 ∙ 75; P < 0 ∙ 001), without heterogeneity (I2= 0 ∙ 00, P = 0 ∙ 901). Random effects meta-analysis also showed a significant increase in quality of life (Hedges’s g = 0 ∙ 86; 95% CI = 0 ∙ 44 to 1 ∙ 28; Z-value = 4 ∙ 01, P < 0 ∙ 001). Furthermore, DBS decreased the severity of psychiatric symptoms (Hedges’s g = 0 ∙ 89; 95% CI = 0 ∙ 57 to 1 ∙ 21; Z-value = 5 ∙ 47; P < 0 ∙ 001, I2= 4 ∙ 29, P = 0 ∙ 371). Discussion: In this first meta-analysis, DBS showed statistically large beneficial effects on weight restoration, quality of life, and reduction of psychiatric symptoms in patients with treatment-refractory AN. These outcomes call for more extensive naturalistic studies to determine the clinical relevance for functional recovery. This study is preregistered in PROSPERO,CRD42022295712

Neural effects of deep brain stimulation on reward and loss anticipation and food viewing in anorexia nervosa: a pilot study

Background: Anorexia nervosa (AN) is a severe and life-threatening psychiatric disorder. Initial studies on deep brain stimulation (DBS) in severe, treatment-refractory AN have shown clinical effects. However, the working mechanisms of DBS in AN remain largely unknown. Here, we used a task-based functional MRI approach to understand the pathophysiology of AN.  Methods: We performed functional MRI on four AN patients that participated in a pilot study on the efficacy, safety, and functional effects of DBS targeted at the ventral limb of the capsula interna (vALIC). The patients and six gender-matched healthy controls (HC) were investigated at three different time points. We used an adapted version of the monetary incentive delay task to probe generic reward processing in patients and controls, and a food-specific task in patients only.  Results: At baseline, no significant differences for reward anticipation were found between AN and HC. Significant group (AN and HC) by time (pre- and post-DBS) interactions were found in the right precuneus, right putamen, right ventral and medial orbitofrontal cortex (mOFC). No significant interactions were found in the food viewing task, neither between the conditions high-calorie and low-calorie food images nor between the different time points. This could possibly be due to the small sample size and the lack of a control group.  Conclusion: The results showed a difference in the response of reward-related brain areas post-DBS. This supports the hypotheses that the reward circuitry is involved in the pathogenesis of AN and that DBS affects responsivity of reward-related brain areas. Trial registration Registered in the Netherlands Trial Register (https://www.trialregister.nl/trial/3322 ): NL3322 (NTR3469)

Life on a scale:Deep brain stimulation in anorexia nervosa

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, there is an urgent need to investigate new therapeutic options that are informed by the disorder’s underlying neurobiological mechanisms. This thesis represents the first study in the Netherlands and one of a limited number globally to evaluate the efficacy, safety, and tolerability of deep brain stimulation (DBS) in the treatment of AN. DBS has the advantage of being both reversible and adjustable. Beyond assessing the primary impact of DBS on body weight, psychological parameters, and quality of life, this research is novel in its comprehensive approach. We integrated evaluations of efficacy with critical examinations of the functional impact of DBS in AN, including fMRI, electroencephalography EEG, as well as endocrinological and metabolic assessments. Furthermore, this work situates AN within a broader theoretical framework, specifically focusing on its manifestation as a form of self-destructive behavior. Finally, we reflect on the practical, ethical and philosophical aspects of conducting an experimental, invasive procedure in a vulnerable patient group. This thesis deepens our understanding of the neurobiological underpinnings of AN and paves the way for future research and potential clinical applications of DBS in the management of severe and enduring AN

Life on a scale:Deep brain stimulation in anorexia nervosa

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, there is an urgent need to investigate new therapeutic options that are informed by the disorder’s underlying neurobiological mechanisms. This thesis represents the first study in the Netherlands and one of a limited number globally to evaluate the efficacy, safety, and tolerability of deep brain stimulation (DBS) in the treatment of AN. DBS has the advantage of being both reversible and adjustable. Beyond assessing the primary impact of DBS on body weight, psychological parameters, and quality of life, this research is novel in its comprehensive approach. We integrated evaluations of efficacy with critical examinations of the functional impact of DBS in AN, including fMRI, electroencephalography EEG, as well as endocrinological and metabolic assessments. Furthermore, this work situates AN within a broader theoretical framework, specifically focusing on its manifestation as a form of self-destructive behavior. Finally, we reflect on the practical, ethical and philosophical aspects of conducting an experimental, invasive procedure in a vulnerable patient group. This thesis deepens our understanding of the neurobiological underpinnings of AN and paves the way for future research and potential clinical applications of DBS in the management of severe and enduring AN

Psychopathological and Neurobiological Overlap Between Anorexia Nervosa and Self-Injurious Behavior: A Narrative Review and Conceptual Hypotheses

Empirical evidence and clinical observations suggest a strong -yet under acknowledged-link between anorexia nervosa (AN) and non-suicidal self-injurious behavior (NSSI). By reviewing the literature on the psychopathology and neurobiology of AN and NSSI, we shed light on their relationship. Both AN and NSSI are characterized by disturbances in affect regulation, dysregulation of the reward circuitry and the opioid system. By formulating a reward-centered hypothesis, we explain the overlap between AN and NSSI. We propose three approaches understanding the relationship between AN and NSSI, which integrate psychopathology and neurobiology from the perspective of self-destructiveness: (1) a nosographical approach, (2) a research domain (RDoC) approach and (3) a network analysis approach. These approaches will enhance our knowledge of the underlying neurobiological substrates and may provide groundwork for the development of new treatment options for disorders of self-destructiveness, like AN and NSSI. In conclusion, we hypothesize that self-destructiveness is a new, DSM-5-transcending concept or psychopathological entity that is reward-driven, and that both AN and NSSI could be conceptualized as disorders of self-destructiveness

Efficacy and safety of deep brain stimulation for treatment-refractory anorexia nervosa: a systematic review and meta-analysis

Background: Several pioneering studies investigated deep brain stimulation (DBS) in treatment-refractory anorexia nervosa (AN) patients, but overall effects remain yet unclear. Aim of this study was to obtain estimates of efficacy of DBS in AN-patients using meta-analysis. Methods: We searched three electronic databases until 1st of November 2021, using terms related to DBS and AN. We included trials that investigated the clinical effects of DBS in AN-patients. We obtained data including psychiatric comorbidities, medication use, DBS target, and study duration. Primary outcome was Body Mass Index (BMI), secondary outcome was quality of life, and the severity of psychiatric symptoms, including eating disorder, obsessive-compulsive, depressive, and anxiety symptoms. We assessed the risk of bias using the ROBINS-I tool. Results: Four studies were included for meta-analysis, with a total of 56 patients with treatment-refractory AN. Follow-up ranged from 6–24 months. Random effects meta-analysis showed a significant increase in BMI following DBS, with a large effect size (Hedges’s g = 1 ∙ 13; 95% CI = 0 ∙ 80 to 1 ∙ 46; Z-value = 6 ∙ 75; P < 0 ∙ 001), without heterogeneity (I2= 0 ∙ 00, P = 0 ∙ 901). Random effects meta-analysis also showed a significant increase in quality of life (Hedges’s g = 0 ∙ 86; 95% CI = 0 ∙ 44 to 1 ∙ 28; Z-value = 4 ∙ 01, P < 0 ∙ 001). Furthermore, DBS decreased the severity of psychiatric symptoms (Hedges’s g = 0 ∙ 89; 95% CI = 0 ∙ 57 to 1 ∙ 21; Z-value = 5 ∙ 47; P < 0 ∙ 001, I2= 4 ∙ 29, P = 0 ∙ 371). Discussion: In this first meta-analysis, DBS showed statistically large beneficial effects on weight restoration, quality of life, and reduction of psychiatric symptoms in patients with treatment-refractory AN. These outcomes call for more extensive naturalistic studies to determine the clinical relevance for functional recovery. This study is preregistered in PROSPERO,CRD42022295712