26 Chapter 1 Table 1. DBS in AN Study n DBS target Result Israel (2010) 1 Subgenual cingulate cortex DBS for treatment resistant major depression. Co morbid eating disorder-NOS in lasting remission (normalisation of scores on the Eating Attitudes Test-26 and Eating Disorders Examination; normalisation of weight (BMI 19,1 kg/m2) at 2 and 3 year follow-up) McLaughlin (2012) 1 Ventral capsule/ ventral striatum DBS for treatment resistant OCD. Improvements in AN symptoms consisting of less distress about caloric intake and weight (assessment tools and length of follow-up not mentioned; BMI pre-surgery 18,5 kg/m2, post-surgery 19,6 kg/m2) Sun et al. in Wu et al. (2012) 4 Nucleus accumbens Average of 65% increase in body weight at 38-month follow-up (average baseline BMI: 11,9 kg.m2; average BMI at follow-up: 19,6 kg/2); restoration of the menstrual cycle (n = 4); regaining school functioning (n = 3); remission of AN according to the DSM-IV (n = 4) Lipsman et al. (2013) 6 Subcallosal cingulate Relatively safe (1 serious adverse event), improvement of BMI compared to historical baseline (n = 3) at 9 month follow-up (average baseline BMI: 13,7 kg/m2; average BMI pre-surgery: 16,1 kg/m2; average BMI at 9 month follow-up: 16,6 kg/m2). Improvements in mood, anxiety, affective regulation and anorexia-related obsessions and compulsions (the latter assessed with the Yale-BrownCornell eating disorder scale) at 6 month follow-up; Improvements in quality of life (n = 3) Possible DBS targets for AN As stated before, many parallels can be drawn with regard to symptoms of AN and OCD (109). Moreover, there is a considerable overlap between the neurocircuits implicated in OCD and eating disorders, suggesting a possible etiological relationship between the two disorders. Both disorders consist of repetitive thoughts and preoccupations about a feared stimulus, followed by a negative emotion, than followed by compensatory behaviours. Like OCD, AN can be considered a compulsivity disorder. Compulsivity encompasses the repetitive, irresistible urge to perform a behavior, the experience of loss of voluntary control over this intense urge, the diminished ability to delay or inhibit thoughts or behaviors, and the tendency to perform repetitive acts in a habitual or stereotyped manner (110). Research showed that AN is associated with impairments in set shifting and behavioural response shifting (82, 111). Furthermore, there is a high rate of comorbidity between eating disorders and anxiety disorders (112-114). Kaye et al. reported that 41% of AN patients have a lifetime diagnosis of OCD (113). Alterations in the activity of cortico-thalamo-striatal circuits similar to those found in OCD and other compulsivity disorders have commonly been found in AN, as described above (41, 74, 115-117). Given the similarities in symptomatology and associated neurocircuits between OCD and AN, the established efficacy of DBS in OCD (89), and the neurobiological correlates of AN as described above, we hypothesize that DBS of the NAc and other areas associated with reward, e.g. the ACC, might be effective in patients with chronic, treatment refractory AN, providing not only weight restoration,
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