Association of BDNF with restricting anorexia nervosa and minimum body mass index: a family-based association study of eight European populations

Abstract

Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric disorders where different genetic and environmental factors are involved. Several lines of evidence support that brain-derived neurotrophic factor (BDNF) plays an essential role in eating behaviour and that alterations on this neurotrophic system participates in the susceptibility to both AN and BN. Accordingly, intraventricular administration of BDNF in rats determines food starvation and body weight loss, while BDNF or its specific receptor NTRK2 knockout mice develop obesity and hyperphagia. Case -control studies also suggest a BDNF contribution in the aetiology of ED: we have previously reported a strong association between the Met66 variant within the BDNF gene, restricting AN (ANR) and minimum body mass index (minBMI) in a Spanish sample, and a positive association between the Val66Met and À270C/T BDNF SNPs and ED in six different European populations. To replicate these results, avoiding population stratification effects, we recruited 453 ED trios from eight European centres and performed a family-based association study. Both haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods showed a positive association between the Met66 allele and ANR. Consistently, we also observed an effect of the Met66 variant on low minBMI and a preferential transmission of the À270C/Met66 haplotype to the affected ANR offspring. These results support the involvement of BDNF in eating behaviour and further suggest its participation in the genetic susceptibility to ED, mainly ANR and low minBMI.

Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with Anorexia nervosa: Association with subtype, body-mass index, severity and age of onset

“…On the other side, this method is much less cost-effective than a case-control design (Gorwood, 1999). Our results are obviously limited by the relatively small number of family trios and a recent european family study including 453 trios also reports the association between anorexia nervosa and the Met66 allele (Ribases et al, 2005b). Several findings suggest that BDNF and its high affinity receptor TrkB contribute to food intake and body weight control.…”

Anorexia nervosa and autism spectrum disorders: Guided investigation of social cognitive endophenotypes.

“…OCPD ϭ obsessive-compulsive personality disorder. Shafran, 2003), other research finds support for the distinction in epidemiological, genetic, and descriptive studies (e.g., Ribases et al, 2004Ribases et al, , 2005. In this review, we indicate where subtypes are differentiated and highlight future directions for research with consideration of these subtypes.…”

Relevance of animal models to human eating disorders and obesity

“…Observations of altered feeding behavior leading to increased body weight in brain-derived neurotrophic factor (BDNF) knockout mice and reports that intraventricular administration of BDNF in rats resulted in reduced feeding and weight loss prompted Ribases et al (2003) to study the BDNF gene in AN. The investigators observed a strong association between restricting AN, as well as minimum body weight, and an amino acid substitution within the BDNF precursor protein (Val66Met); they replicated the findings in an independent sample (Ribases et al 2005). Because the BNDF mutation would be expected to increase food intake, the finding appears counterintuitive.…”