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Eating Disorders, Serotonin Transporter Polymorphisms and Potential Treatment Response

  • Genomics in Health and Disease
  • Published:
American Journal of Pharmacogenomics

Abstract

Anorexia nervosa, bulimia nervosa, and binge eating disorder are eating disorders with common clinical and psychological features, potentially shared mechanisms, significant morbidity and, at least for anorexia nervosa, a high mortality rate. Among the numerous risk factors involved, the importance of a genetic vulnerability has been demonstrated, and the heritability, in the broad sense, has being estimated to be between 50 and 70%. Studies have thus focused on different candidate genes.

Serotonin transmission and regulation has been extensively studied with regard to its role in core mechanisms such as feeding and fasting, but also in different clinical characteristics of eating disorders. The serotonin transporter (5-HTT), encoded by the SLC6A4 gene, may also have an important role in eating disorders, as its availability is decreased in patients with bulimia nervosa and binge eating disorder. The promoter region contains a functional insertion/deletion polymorphism with two common alleles that have been designated the short (*S) and long (*L) alleles. The frequency of the SLC6A4*S allele has been assessed in four independent samples of patients with anorexia nervosa, but gave discrepant results. A meta-analysis was performed, which showed that the *S allele could represent a moderate but significant risk factor that increases the risk of anorexia nervosa (odds ratio [OR] = 1.38, 95% confidence interval [CI] 1.16–1.72).

Eating disorders are treated using different types of psychotherapy and pharmacotherapy with antidepressants; serotonin reuptake inhibitors being the most frequently prescribed. High doses of selective serotonin reuptake inhibitors (SSRIs) are usually prescribed in eating disorders. The prevalence of non-responders (roughly one out of two), and the presence of a functional genetic polymorphism in the promotor region of SLC6A4, emphasizes the potential utility of psychopharmacogenetics in prescribing SSRIs in the treatment of patients with weight-restored anorexia nervosa. Information about genetic variations of cytochrome P450 could also facilitate pharmacotherapy by preventing the administration of high doses in poor metabolizers and identify rapid metabolizes who may require higher doses for efficacy. SLC6A4 genotyping would allow physicians to individualize selective serotonin reuptake therapy for their patients.

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Acknowledgements

This work was supported by grants from EC Framework V (Factors in Healthy Eating) and INRA/INSERM (4M406D). ## The author has no conflict of interest directly relevant to the content of this review.

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  1. Hôpital Louis Mourier (AP-HP), Service de Psychiatrie, Colombes, France

    Philip Gorwood

  2. CNRS UMR 7593-Paris VII, Personnalité et conduites adaptatives, CHU Pitié-Salpêtrière, Paris, France

    Philip Gorwood

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Gorwood, P. Eating Disorders, Serotonin Transporter Polymorphisms and Potential Treatment Response. Am J Pharmacogenomics 4, 9–17 (2004). https://doi.org/10.2165/00129785-200404010-00002

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  • DOI: https://doi.org/10.2165/00129785-200404010-00002

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