title: Novel insights into maladaptive behaviours in Prader-Willi syndrome: serendipitous findings from an open trial of vagus nerve stimulation.
abstract: BACKGROUND
  We report striking and unanticipated improvements in maladaptive behaviours in Prader-Willi syndrome (PWS) during a trial of vagus nerve stimulation (VNS) initially designed to investigate effects on the overeating behaviour. PWS is a genetically determined neurodevelopmental disorder associated with mild-moderate intellectual disability (ID) and social and behavioural difficulties, alongside a characteristic and severe hyperphagia.
  
  
  METHODS
  Three individuals with PWS underwent surgery to implant the VNS device. VNS was switched on 3 months post-implantation, with an initial 0.25 mA output current incrementally increased to a maximum of 1.5 mA as tolerated by each individual. Participants were followed up monthly.
  
  
  RESULTS
  Vagal nerve stimulation in these individuals with PWS, within the stimulation parameters used here, was safe and acceptable. However, changes in eating behaviour were equivocal. Intriguingly, unanticipated, although consistent, beneficial effects were reported by two participants and their carers in maladaptive behaviour, temperament and social functioning. These improvements and associated effects on food-seeking behaviour, but not weight, indicate that VNS may have potential as a novel treatment for such behaviours.
  
  
  CONCLUSIONS
  We propose that these changes are mediated through afferent and efferent vagal projections and their effects on specific neural networks and functioning of the autonomic nervous system and provide new insights into the mechanisms that underpin what are serious and common problems affecting people with IDs more generally.
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: K E
authors.initials: KE
authors.lastname: Manning
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: McAllister
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.|National Institute for Health Research (NIHR) Collaborations for Leadership in Applied Health Research and Care (CLAHRC) East of England, Cambridge, UK.|Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.
authors.forename: H A
authors.initials: HA
authors.lastname: Ring
authors.affiliation: National Centre for Cardiovascular Prevention and Outcomes, UCL Institute of Cardiovascular Sciences, London, UK.|Addenbrooke's Hospital, Cambridge, UK.
authors.forename: N
authors.initials: N
authors.lastname: Finer
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: C L
authors.initials: CL
authors.lastname: Kelly
authors.affiliation: Addenbrooke's Hospital, Cambridge, UK.
authors.forename: K P
authors.initials: KP
authors.lastname: Sylvester
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.|Addenbrooke's Hospital, Cambridge, UK.
authors.forename: P C
authors.initials: PC
authors.lastname: Fletcher
authors.affiliation: Addenbrooke's Hospital, Cambridge, UK.|Department of Medicine, University of Cambridge, Cambridge, UK.|Papworth Hospital NHS Trust, Cambridge, UK.
authors.forename: N W
authors.initials: NW
authors.lastname: Morrell
authors.affiliation: Addenbrooke's Hospital, Cambridge, UK.
authors.forename: M R
authors.initials: MR
authors.lastname: Garnett
authors.affiliation: Addenbrooke's Hospital, Cambridge, UK.|Bedford Hospital NHS Trust, Bedford, UK.
authors.forename: M R A
authors.initials: MR
authors.lastname: Manford
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.|National Institute for Health Research (NIHR) Collaborations for Leadership in Applied Health Research and Care (CLAHRC) East of England, Cambridge, UK.|Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Holland
mesh_terms: D000328:Adult; D000374:Aggression / Q000502:physiology*; D001823:Body Composition; D001835:Body Weight; D001068:Feeding and Eating Disorders / Q000209:etiology / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D011218:Prader-Willi Syndrome / Q000150:complications / Q000628:therapy*; D012920:Social Behavior Disorders / Q000209:etiology / Q000628:therapy*; D016896:Treatment Outcome; D055536:Vagus Nerve Stimulation / Q000009:adverse effects / Q000379:methods*; D055815:Young Adult
keywords: Prader-Willi syndrome; hyperphagia; maladaptive behaviour; social functioning; vagus nerve stimulation