Molecular mechanisms underlying anorexia nervosa: Focus on human gene association studies and systems controlling food intake

Mathias Rask-Andersen, Pawel K. Olszewski, Allen S Levine, Helgi B. Schiöth

Research output: Contribution to journalReview articlepeer-review

87 Scopus citations

Abstract

Anorexia nervosa (AN) is a complex multi-factorial disease with high heritability. The psychological AN symptoms are poorly connected with specific molecular mechanisms. Here we review the molecular basis of AN with the focus on human genetic association studies; we put these in the experimental biological context with emphasis on molecular systems controlling food intake and body weight in a direct or indirect manner. We systematically searched for human genetic studies related to AN and grouped data into main categories/systems reflecting their major known roles: (1) Systems related to mental disorders (serotonin, brain-derived neurotrophic factor (BDNF), norepinephrine (NE), glutamate (NMDA) receptor and SK3 channel, KCCN3). (2) Hunger regulatory systems (leptin, AGRP, MSH, melanocortin 4 receptor (MC4R), NPY, ghrelin, cholecystokinin (CCK). (3) Feeding motivation- and reward-related systems (opioids, OPRD1, cannabinoids (anandamide (AEA), THC, CBR1), dopamine, DRD2, DRD3, DRD4, catecholamine-O-methyl transferase (COMT). (4) Systems regulating energy metabolism (uncoupling proteins 2 and 3 (UCP2 and UCP3). (5) Neuroendocrine systems with emphasis on sex hormones (estrogen receptor-β (ESR2). (6) The immune system and inflammatory response (tumor necrosis factor-alpha (TNF-α). Overall, we found that in total 175 association studies have been performed on AN cohorts on 128 different polymorphisms related to 43 genes. We review the strongest associations, identify some genes that have an important role in regulating BMI whose possible relationship to AN has not been investigated and discuss the potential targets for pharmacological interventions.

Original languageEnglish (US)
Pages (from-to)147-164
Number of pages18
JournalBrain Research Reviews
Volume62
Issue number2
DOIs
StatePublished - Mar 2010

Bibliographical note

Funding Information:
The studies were supported by the Swedish Research Council (VR), Swedish Brain Research Foundation, Svenska Läkaresällskapet, Åhlens Foundation and the Novo Nordisk Foundation.

Keywords

  • Addiction
  • Bulimia nervosa
  • Depression
  • Eating disorder
  • Feeding regulatory system
  • Hedonics
  • Human genetic association study
  • Obesity
  • Pathogenesis
  • Schizophrenia
  • Serotonin
  • Twin study

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