title: Catechol-O-methyltransferase genotype modifies executive functioning and prefrontal functional connectivity in women with anorexia nervosa.
abstract: BACKGROUND
  Anorexia nervosa is characterized by high levels of perseveration and inflexibility, which interfere with successful treatments. Dopamine (DA) signalling seems to play a key role in modulating the prefrontal cortex, since both DA deficiency and excess nega tively influence the efficiency of cognitive functions. The present study explores the effect of a functional polymorphism (Val158Met) in the catechol-O-methyltransferase (COMT) gene on the set-shifting abilities and prefrontal functional connectivity of patients with anorexia nervosa.
  
  
  METHODS
  All participants performed the Wisconsin Card Sorting Task, and a subsample underwent resting-state functional magnetic resonance imaging.
  
  
  RESULTS
  We included 166 patients with DSM-IV lifetime anorexia nervosa and 140 healthy women in our study. Both underweight and weight-recovered patients with anorexia nervosa showed high levels of perseveration, but only in the underweight group did the Val158Met polymorphism affect cognitive performance, showing the U-shaped curve characteristic of increased DA signalling in the prefrontal cortex. Underweight patients with anorexia nervosa who are Met homozygotes had significantly higher levels of perseveration and increased prefrontal functional connectivity than underweight patients in the other genotype groups, indicating abnormal regional cortical processing.
  
  
  CONCLUSIONS
  Although our data show that grey matter reduction in starving patients with anorexia nervosa did not explain our findings, the cross-sectional design of the present study did not allow us to distinguish between the effects of starvation and those of low estrogen levels.
  
  
  CONCLUSIONS
  Starvation affects DA release in the prefrontal cortex of patients with anorexia nervosa with different effects on executive functioning and prefrontal functional connectivity according to the COMT genotype. This observation has several therapeutic implications that need to be addressed by future studies.
authors.affiliation: Psychiatric Clinic, Department of Neurosciences, University of Padova, Padova, Italy. angela.favaro@unipd.it
authors.forename: Angela
authors.initials: A
authors.lastname: Favaro
authors.forename: Maurizio
authors.initials: M
authors.lastname: Clementi
authors.forename: Renzo
authors.initials: R
authors.lastname: Manara
authors.forename: Romina
authors.initials: R
authors.lastname: Bosello
authors.forename: Monica
authors.initials: M
authors.lastname: Forzan
authors.forename: Alice
authors.initials: A
authors.lastname: Bruson
authors.forename: Elena
authors.initials: E
authors.lastname: Tenconi
authors.forename: Daniela
authors.initials: D
authors.lastname: Degortes
authors.forename: Francesca
authors.initials: F
authors.lastname: Titton
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Salle
authors.forename: Paolo
authors.initials: P
authors.lastname: Santonastaso
mesh_terms: D000328:Adult; D000856:Anorexia Nervosa / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003430:Cross-Sectional Studies; D056344:Executive Function / Q000502:physiology*; D005260:Female; D059907:Functional Neuroimaging; D005838:Genotype; D006801:Humans; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017397:Prefrontal Cortex / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology
chemical_list: D002394:Catechol O-Methyltransferase