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. LIMITATIONS: 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. CONCLUSION: 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.
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 DAdeficiency 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. LIMITATIONS: 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. CONCLUSION: 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: Venkata S Mattay; Terry E Goldberg; Francesco Fera; Ahmad R Hariri; Alessandro Tessitore; Michael F Egan; Bhaskar Kolachana; Joseph H Callicott; Daniel R Weinberger Journal: Proc Natl Acad Sci U S A Date: 2003-04-25 Impact factor: 11.205
Authors: Ilka Boehm; Daniel Geisler; Friederike Tam; Joseph A King; Franziska Ritschel; Maria Seidel; Fabio Bernardoni; Julia Murr; Thomas Goschke; Vince D Calhoun; Veit Roessner; Stefan Ehrlich Journal: J Psychiatry Neurosci Date: 2016-10 Impact factor: 6.186
Authors: Julius Steding; Ilka Boehm; Joseph A King; Daniel Geisler; Franziska Ritschel; Maria Seidel; Arne Doose; Charlotte Jaite; Veit Roessner; Michael N Smolka; Stefan Ehrlich Journal: Sci Rep Date: 2019-09-19 Impact factor: 4.379
Authors: E Walton; D Hibar; Z Yilmaz; N Jahanshad; J Cheung; V-L Batury; J Seitz; C M Bulik; P M Thompson; Stefan Ehrlich Journal: Mol Neurobiol Date: 2018-12-05 Impact factor: 5.590