Association analysis of brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism in schizophrenia and bipolar affective disorder

Abstract

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of schizophrenia and bipolar disorder. A functional polymorphism Val66Met of BDNF gene was studied in patients with schizophrenia (n=336), bipolar affective disorder (n=352) and healthy controls (n=375). Consensus diagnosis by at least two psychiatrists, according to DSM-IV and ICD-10 criteria, was made for each patient using a structured clinical interview for DSM-IV Axis I disorders (SCID). No association was found between the studied polymorphism and schizophrenia or bipolar affective disorder either for genotype or allele distribution (for genotype: p=0.210 in schizophrenia, p=0.400 in bipolar disorder; for alleles: p=0.260 in schizophrenia, p=0.406 in bipolar disorder). Results were also not significant when analysed by gender. For males genotype distribution and allele frequency were (respectively): p=0.480 and p=0.312 in schizophrenia, p=0.819 and p=0.673 in bipolar affective disorder. Genotype distribution and allele frequency observed in the female group were: p=0.258 for genotypes, p=0.482 for alleles in schizophrenia; p=0.432 for genotypes, p=0.464 for alleles in bipolar affective disorder. A subgroup of schizophrenic (n=62) and bipolar affective patients (n=28) with early age at onset (18 years or younger) was analysed (p=0.328 for genotypes, p=0.253 for alleles in schizophrenia; p=0.032 for genotypes, p=0.858 for alleles in bipolar affective disorder).

A brain-derived neurotrophic factor (BDNF) haplotype is associated with antidepressant treatment outcome in mood disorders

“…31 In spite of this evidence, other investigators have not been able to replicate these findings in case-control association studies. [32][33][34][35][36][37][38] In the case of MDD, some studies reported a negative association of the Val66Met BDNF polymorphism, 33,39,40 while other studies have found a haplotype containing this variant to be positively associated to the MDD phenotype. 41,42 Moreover, positive associations of this single SNP and a haplotype containing it have been reported to be associated to childhood-onset mood disorder 41,43 as well as geriatric depression.…”

Mutant huntingtin Impairs the Post-Golgi Trafficking of Brain-Derived Neurotrophic Factor But Not Its Val66Met Polymorphism

“…In fact, several studies have associated this polymorphism with increased susceptibility to anorexia nervosa (Ribases et al, 2003), obsessive-compulsive disorders (Hall et al, 2003), eating disorders (Friedel et al, 2005), depression (Sen et al, 2003), schizophrenia (Skibinska et al, 2004), Alzheimer's disease (Ventriglia et al, 2002), and Parkinson's disease (Momose et al, 2002).…”

Positional cloning, association analysis and expression studies provide convergent evidence that the cadherin gene FAT contains a bipolar disorder susceptibility allele

“…These include BDNF, which showed evidence for association with bipolar disorder in two cohorts of predominantly Caucasian origin, 15,16 although this has not been replicated in several other cohorts of European and Japanese origin. [17][18][19][20] Association and functional studies have also implicated the XBP1 gene in bipolar susceptibility, 21 but again, this has not been replicated in cohorts of European and Chinese origin. 22,23 Evidence has also been reported for association of the GRIN1 gene with bipolar disorder in a cohort of predominantly European Caucasian origin.…”