Catechol-O-methyltransferase genotype modifies executive functioning and prefrontal functional connectivity in women with anorexia nervosa

Catechol-O-methyltransferase genotype modifies executive functioning and prefrontal functional connectivity in women with anorexia nervosa

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J Psychiatry Neurosci 2013; 38(4): 241-248

Angela Favaro, MD, PhD; Maurizio Clementi, MD; Renzo Manara, MD; Romina Bosello, MD; Monica Forzan, PhD; Alice Bruson, PhD; Elena Tenconi, PhD; Daniela Degortes, MSc; Francesca Titton, MD; Francesco Di Salle, MD; Paolo Santonastaso, MD

Favaro, Bosello, Tenconi, Degortes, Titton, Santonastaso — Psychiatric Clinic, Department of Neurosciences, University of Padova; Clementi, Forzan, Bruson — Clinical Genetics Unit, Department of Pediatrics, University of Padova; Manara — Neuro radiologic Unit, University Hospital of Padova; Di Salle — Department of Medicine and Surgery, University of Salerno, Italy, and the Department of Cognitive Neuroscience, University of Maastricht, the Netherlands

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 under weight 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.


Submitted Mar. 31, 2012; Revised June 24, Aug. 18, 2012; Accepted Aug. 24, 2012.

Acknowledgements: This study was partially supported by Veneto Region Grant BIOVEDA.

Conflict of interest: None declared.

Contributors: A. Favaro, M. Clementi and P. Santonastaso designed the study. R. Manara, R. Bosello, M. Forzan, A. Bruson, E. Tenconi, D. Degortes and F. Titton acquired the data. A. Favaro and R. Di Salle analyzed the data. A. Favaro, R. Bosello, M. Forzan, A. Bruson, E. Tenconi, D. Degortes and F. Titton wrote the article. M. Clementi, R. Manara, R. Di Salle and P. Santonastaso reviewed the article. All authors approved its publication.

DOI: 10.1503/jpn.120068

Correspondence to: A. Favaro, Department of Neurosciences, University of Padova, Via Giustiniani 3, 35128 Padova, Italy; angela.favaro@unipd.it