Anorexia Nervosa (AN) has the highest mortality rate of any psychiatric condition, and despite its recognition for centuries, remains a significant treatment challenge. Marked by firmly entrenched maladaptive beliefs about body, weight and food, as well as high rates of psychiatric comorbidity, AN is a chronic illness in a large proportion of patients. The neural substrates of AN are now beginning to emerge, and appear to be related to dysfunctional, primarily limbic, circuits driving pathological thoughts and behaviours. Deep Brain Stimulation (DBS) is a neurosurgical procedure where implanted electrodes are used to regulate activity in critical nodes comprising such aberrant circuits. The promise of DBS in motor-circuit conditions, such as Parkinson’s Disease, has driven it’s investigation in other circuit-based disorders, including some psychiatric conditions. Converging evidence from clinical and imaging literatures suggests that AN is in large part a disorder of emotional processing, wherein disordered mood, anxiety, and affective dysregulation contribute to disease maintenance and are obstacles to effective treatment. The subcallosal cingulate (SCC), a key medial frontal structure involved in affective processing, has further been directly implicated in AN relevant pathways. As such, this work had three broad objectives: i) to establish the safety and initial efficacy of SCC DBS in a group of chronic and highly-refractory AN patients; ii) to show that SCC DBS can have network wide cerebral metabolic influence, on AN-relevant circuits and structures; and, iii) to investigate whether structural brain features, including hippocampal volume changes, are correlated with clinical outcomes of DBS. Our results showed that DBS is safe in AN, and associated in some patients with significant improvements in mood, anxiety and, over time, weight and treatment-response. Imaging results further showed DBS to be associated with substantial changes in glucose utilization in disease-relevant circuits, with preliminary evidence supporting a relationship between hippocampal volume changes and clinical improvements. In the context of highly refractory disease, these promising results suggest that DBS can inform AN circuit models, and be explored as a novel therapeutic option for treatment-resistant patients.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/44120 |
| Date | 01 April 2014 |
| Creators | Lipsman, Nir |
| Contributors | Lozano, Andres |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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