Molecular mechanisms underlying anorexia nervosa: ... [Brain Res Rev. 2009] - PubMed result

Brain Res Rev. 2009 Nov 18. [Epub ahead of print]

Molecular mechanisms underlying anorexia nervosa: Focus on human gene association studies and systems controlling food intake.
Rask-Andersen M, Olszewski PK, Levine AS, Schiöth HB.

Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Box 593, 75124 Uppsala, Sweden.

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-beta (ESR2). (6) The immune system and inflammatory response (tumor necrosis factor-alpha (TNF-alpha)). Overall, we found that in total 174 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.

PMID: 19931559 [PubMed - as supplied by publisher]

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Molecular mechanisms underlying anorexia nervosa: ... [Brain Res Rev. 2009] - PubMed result