Association study of the brain-derived neurotrophic factor (BDNF) gene with bipolar disorder

Nakata, Kenji; Ujike, Hiroshi; Sakai, Ayumu; Uchida, Naohiko; Nomura, Akihiro; Imamura, Takaki; Katsu, Takeshi; Tanaka, Yuji; Hamamura, Takashi; Kuroda, Shigetoshi

doi:10.1016/s0304-3940(02)01292-2

Cited by 132 publications

(81 citation statements)

References 22 publications

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“…It is possible that difference in ethnicity might contribute to discrepancy between our study and other study. Frequency of A allele of 196G>A (val66met) in Japanese population (Momose et al, 2002;Nakata et al, 2003;Itoh et al, 2004; this study) is higher than that of Caucasian population (Ventriglia et al, 2002;Egan et al, 2003;Hakansson et al, 2003;Sen et al, 2003), suggesting the ethnic difference in this SNP (val66met) . First, it has been reported that the 196G>A (val66met) of the BDNF gene is associated with Parkinson's disease in Japanese subjects (Momose et al, 2002).…”

Section: Discussionmentioning

confidence: 50%

“…Second, it has been reported that the 196G>A (val66met) of the BDNF gene is associated with bipolar disorder in Caucasian (Neves-Pereira et al, 2002;Sklar et al, 2002). However, no association between 196G>A (val66met) of the BDNF gene and bipolar disorder in Japanese population was detected (Nakata et al, 2003), suggesting that the BDNF gene may confer a susceptibility to bipolar disorder in Caucasian, but not in Japanese population. Thus, it is likely that ethnic differences may contribute to inconsistent findings between Caucasian sample and Japanese sample.…”

Section: Discussionmentioning

confidence: 98%

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Association study between brain‐derived neurotrophic factor gene polymorphisms and methamphetamine abusers in Japan

Itoh

Hashimoto

Shimizu

et al. 2004

American J of Med Genetics Pt B

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Several lines of evidence suggest that genetic factors might contribute to drug abuse vulnerability. Recent genomic scans for association demonstrated that the brain-derived neurotrophic factor (BDNF) gene was associated with drug abuse vulnerability. In this study, we analyzed association of two BDNF gene single nucleotide polymorphisms (SNPs), 132C>T (C270T named formerly) in the noncoding region of exon V and 196G >A (val66met)

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 98%

Association study between brain‐derived neurotrophic factor gene polymorphisms and methamphetamine abusers in Japan

Itoh

Hashimoto

Shimizu

et al. 2004

American J of Med Genetics Pt B

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“…Stratification by ethnicity is crucial for genetic studies. The prior studies of the BDNF polymorphism with BD patients demonstrated that Caucasians showed significant associations between Val66Met polymorphism and BD (NevesPereira et al, 2002;Sklar et al, 2002) but Asians did not (Hong et al, 2003;Kunugi et al, 2004;Nakata et al, 2003). Studies with substantial number of ethnically homogeneous subjects would be required to confirm that the main results of this study still exist.…”

Section: Discussionmentioning

confidence: 61%

Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder

Matsuo

Walss‐Bass

Nery

et al. 2009

Neuropsychopharmacol

112

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The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been proposed as a possible candidate for involvement in the pathophysiology of bipolar disorder (BD). To determine whether an association exists between the BDNF Val66Met genotype and morphometric abnormalities of the brain regions involved in memory and learning in BD and healthy subjects. Forty-two BD patients and 42 healthy subjects were studied. Interactions between BDNF Val66Met genotype and diagnosis in gray (GM) volumes were analyzed using an optimized voxel-based morphometry technique. Declarative memory function was assessed with the California Verbal Learning Test II. Left and right anterior cingulate GM volumes showed a significant interaction between genotype and diagnosis such that anterior cingulate GM volumes were significantly smaller in the Val/Met BD patients compared with the Val/Val BD patients (left P ¼ 0.01, right P ¼ 0.01). Within-group comparisons revealed that the Val/Met carriers showed smaller GM volumes of the dorsolateral prefrontal cortex compared with the Val/Val subjects within the BD patient (P ¼ 0.01) and healthy groups (left P ¼ 0.03, right P ¼ 0.03). The Val/ Met healthy subjects had smaller GM volumes of the left hippocampus compared with the Val/Val healthy subjects (Po0.01). There was a significant main effect of diagnosis on memory function (P ¼ 0.04), but no interaction between diagnosis and genotype was found (P ¼ 0.48). The findings support an association between the BDNF Val66Met genotype and differential gray matter content in brain structures, and suggest that the variation in this gene may play a more prominent role in brain structure differences in subjects affected with BD.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2006

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A susceptibility locus for bipolar disorder was previously localized to chromosome 4q35 by genetic linkage analysis. We have applied a positional cloning strategy, combined with association analysis and provide evidence that a cadherin gene, FAT, confers susceptibility to bipolar disorder in four independent cohorts (allelic P-values range from 0.003 to 0.024). In two case-control cohorts, association was identified among bipolar cases with a family history of psychiatric illness, whereas in two cohorts of parent-proband trios, association was identified among bipolar cases who had exhibited psychosis. Pooled analysis of the case-control cohort data further supported association (P = 0.0002, summary odds ratio = 2.31, 95% CI: 1.49-3.59). We localized the bipolar-associated region of the FAT gene to an interval that encodes an intracellular EVH1 domain, a domain that interacts with Ena/VASP proteins, as well as putative b-catenin binding sites. Expression of Fat, Catnb (b-catenin), and the three genes (Enah, Evl and Vasp) encoding the Ena/VASP proteins, were investigated in mice following administration of the mood-stabilizing drugs, lithium and valproate. Fat was shown to be significantly downregulated (P = 0.027), and Catnb and Enah were significantly upregulated (P = 0.0003 and 0.005, respectively), in response to therapeutic doses of lithium. Using a protein interaction map, the expression of genes encoding murine homologs of the FAT (ft)-interacting proteins was investigated. Of 14 interacting molecules that showed expression following microarray analysis (including several members of the Wnt signaling pathway), eight showed significantly altered expression in response to therapeutic doses of lithium (binomial P = 0.004). Together, these data provide convergent evidence that FAT and its protein partners may be components of a molecular pathway involved in susceptibility to bipolar disorder.

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Association study of the brain-derived neurotrophic factor (BDNF) gene with bipolar disorder

Cited by 132 publications

References 22 publications

Association study between brain‐derived neurotrophic factor gene polymorphisms and methamphetamine abusers in Japan

Association study between brain‐derived neurotrophic factor gene polymorphisms and methamphetamine abusers in Japan

Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder

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

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