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Does genetics play a role in the development of anorexia nervosa?

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  • Does genetics play a role in the development of anorexia nervosa

Anorexia nervosa (AN) is a life threatening and chronic condition characterised by body image distortion, fear of weight gain and food restriction. This disease is associated with a decreased quality of life and an increased rate of mortality and suicide.[1,2] Twin and family studies have shown a genetic contribution to the development of AN, and data has highlighted the possible dysfunction of the dopaminergic and serotonergic pathways.[2,3]

The catechol-O-methyltransferase (COMT) gene is responsible for the making of the COMT enzyme, of which two forms are made. Membrane-bound COMT (MB-COMT) is the longer form of the enzyme, mostly produced in the brain by nerve cells. The shorter form, soluble COMT (S-COMT), is produced by other tissues, including the kidneys, liver and blood. The S-COMT form of the enzyme assists in hormone level control.[4]

Neurotransmitters, such as dopamine, are broken down by the COMT enzyme. This is particularly important in the prefrontal cortex, where information is coordinated from other parts of the brain.[3,4] The prefrontal cortex is involved with short-term memory, emotion, abstract thinking, inhibition of behaviours, planning and personality. COMT assists in the maintenance of healthy neurotransmitter levels including norepinephrine and dopamine, which are required for this part of the brain to function efficiently.[4]

The COMT gene may be involved in the susceptibility of developing AN, due to its functional polymorphism valine to methionine at codon 158 (Val/Met 158), which determines low and high enzyme activity alleles and its involvement with neurotransmitter catabolism.[2]

A group of 51 Israeli female patients with AN, with an average age of 16 years old and a BMI of 14.8, were recruited from specialised eating disorder clinics. They and both of their parents were tested for the COMT polymorphism Val/Met 158 using the haplotype relative risk (HHR) and transmission disequilibrium test (TDT) methods. The genotypes were then investigated to see which alleles were passed on from parents to daughters.[2]

Structured interviews took place for patients and their parents, and AN was measured against the DSM-IV system. Exclusion criteria included delusional disorders, schizophrenia and present or past physical illness. In the group, four patients had a sister with AN, 20 patients had a lifetime co-existent mood disorder, eight patients had obsessive compulsive disorder and five patients had other anxiety disorders. Anxiety or mood disorders were identified in 17% of fathers and 22% of mothers.[2]

The HHR method showed a significant frequency of transmitted H allele from parents to AN patients, compared to non-transmitted controls. The TDT method showed that L allele was only transmitted 16 times, while the H allele was passed on 33 times, out of 49 heterozygote parents. The study suggests that the COMT gene play a role in the genetic susceptibility of developing AN and that people who are homozygous with the high activity allele (HH) have double the risk for developing AN.[2]

In this study, the association between AN and COMT has only been investigated with female patients in Israeli populations. Further study involving male patients and other populations are necessary. Genetics can certainly play a role in developing further understanding for practitioners but, despite these results, we should be mindful of the whole client picture.


  1. Andrade R, Gonçalves-Pinho M, Roma-Torres A, et al. Treatment of anorexia nervosa: The importance of disease progression in the prognosis. Acta Med Port 2017;30(7-8):517-523. [Source]
  2. Frisch A, Läufer N, Danziger Y, et al. Association of anorexia nervosa with high activity allele of the COMP gene: a family-based study in Israeli patients. Molecular Psychiatry 2001;(6):243-245. [Source]
  3. Favaro A, Clementi M, Manara R, et al. Catechol-O-methyltransferase genotype modifies executive functioning and prefrontal functional connectivity in women with anorexia nervosa. J Psychiatry Neurosci 2013;38(4):241-248. [Source]
  4. Genetics Home Reference. COMT gene. US Department of Health & Human Services 2018. [Source]



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Jaime Maguire

Jaime is a Clinical Nutritionist (BHSc) from Western Australia. Her passion is in nutrition and mental health, and she focuses a lot of her research on anxiety, depression and eating disorders. Jaime volunteers for different eating disorder programs in Vancouver, BC, including blog contributions and individual support. She loves to educate people about healthy food and lifestyle habits that last a lifetime. You can find Jaime on instagram and on her blog