Association between the brain-derived neurotrophic factor Val66Met polymorphism and brain morphology in a Japanese sample of schizophrenia and healthy comparisons

Takahashi, Tsutomu; Suzuki, Michio; Tsunoda, Masahiko; Kawamura, Yukiko; Takahashi, Nagahide; Tsuneki, Hiroshi; Kawasaki, Yasuhiro; Zhou, Shiyu; Kobayashi, Soushi; Sasaoka, Toshiyasu; Seto, Hikaru; Kurachi, Masayoshi; Ozaki, Norio

doi:10.1016/j.neulet.2008.02.004

Cited by 45 publications

(41 citation statements)

References 40 publications

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“…We thus did not perform meta-regression and only visually inspected the results. The smallest effect size was found in the study with the largest proportion of Met-BDNF homozygotes (Takahashi et al 2008b) and the largest effects size was seen in the study with the smallest proportion of Met-BDNF homozygotes (Gonul et al 2011). …”

Section: Meta-regressionmentioning

confidence: 80%

“…Out of 126 studies initially found by the systematic search, 14 studies measured hippocampal volumes in healthy subjects genotyped for BDNF gene Val66Met polymorphism (Szeszko et al 2005;Agartz et al 2006;Bueller et al 2006;Frodl et al 2007;Takahashi et al 2008b;Chepenik et al 2009;Dutt et al 2009;Jessen et al 2009;Joffe et al 2009;Koolschijn et al 2010;Benjamin et al 2010;Gonul et al 2011;Haukvik et al 2010;Karnik et al 2010). The study by (Haukvik et al 2010) overlapped with the (Agartz et al 2006) study, thus yielding 13 non-overlaping datasets.…”

Section: Results Of the Systematic Searchmentioning

confidence: 99%

“…Two additional volumetric studies provided data only on a mixture of healthy controls and patients without separating the results (Szeszko et al 2005;Benjamin et al 2010). Seven of the studies thus met inclusion criteria for this meta-analysis (Bueller et al 2006;Frodl et al 2007;Takahashi et al 2008b;Dutt et al 2009;Jessen et al 2009;Koolschijn et al 2010;Gonul et al 2011). The study by (Dutt et al 2009) included four subjects with personal history of depression.…”

Section: Results Of the Systematic Searchmentioning

confidence: 99%

“…In all studies, results for carriers of at least one Met-BDNF allele -a combined group of Met-BDNF homozygotes and heterozygotes -were thus provided. In six out of seven studies included in the meta-analysis the BDNF Val66Met genotype distributions were in Hardy-Weinberg equilibrium (results directly provided: Frodl et al 2007;Takahashi et al 2008b;Dutt et al 2009;Koolschijn et al 2010), results calculated from genotype frequencies (Bueller et al 2006;Gonul et al 2011). A single study did not provide information on HWE or sufficient details to calculate it (Jessen et al 2009).…”

Section: Results Of the Systematic Searchmentioning

confidence: 99%

“…The results for either the left or the right hippocampus remained significant after exclusion of any individual study, including the first study (Bueller et al 2006), the study with the largest effect (Bueller et al 2006) or sample size (Koolschijn et al 2010) or the study of Japanese subjects (Takahashi et al 2008b). Exclusion of individual studies yielded effect sizes ranging from 0.36 to 0.48 for the left and 0.36 to 0.45 for the right hippocampus.…”

Section: Sensitivity Analysismentioning

confidence: 90%

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Reduced hippocampal volumes in healthy carriers of brain-derived neurotrophic factor Val66Met polymorphism: Meta-analysis

Hájek

Kopeček

Höschl

2011

The World Journal of Biological Psychiatry

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Objectives-Converging evidence suggests that the brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects brain structure. Yet the majority of studies have shown no effect of this polymorphism on hippocampal volumes, perhaps due to small effect size.Methods-We performed a meta-analysis of studies investigating the association between Val66Met BDNF polymorphism and hippocampal volumes in healthy subjects by combining standardized differences between means (SDM) from individual studies using random effect models. Conclusions-Healthy carriers of BDNF gene Val66Met polymorphism show bilateral hippocampal volume reduction. The effect size was small, but the same direction of effect was seen in all meta-analyzed studies. The association with the BDNF gene Val66Met polymorphism makes hippocampal volume a potential candidate for an endophenotype of disorders presenting with reduced hippocampal volumes. Results-Data

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Section: Meta-regressionmentioning

confidence: 80%

Section: Results Of the Systematic Searchmentioning

confidence: 99%

Section: Results Of the Systematic Searchmentioning

confidence: 99%

Section: Results Of the Systematic Searchmentioning

confidence: 99%

Section: Sensitivity Analysismentioning

confidence: 90%

See 3 more Smart Citations

Reduced hippocampal volumes in healthy carriers of brain-derived neurotrophic factor Val66Met polymorphism: Meta-analysis

Hájek

Kopeček

Höschl

2011

The World Journal of Biological Psychiatry

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Increased BDNF Promoter Methylation in the Wernicke Area of Suicide Subjects

Keller¹,

Sarchiapone²,

Zarrilli³

et al. 2010

Arch Gen Psychiatry

347

217

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BDNF promoter/exon IV is frequently hypermethylated in the Wernicke area of the postmortem brain of suicide subjects irrespective of genome-wide methylation levels, indicating that a gene-specific increase in DNA methylation could cause or contribute to the downregulation of BDNF expression in suicide subjects. The reported data reveal a novel link between epigenetic alteration in the brain and suicidal behavior.

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A systematic review and meta‐analysis on the association between BDNF val⁶⁶met and hippocampal volume—A genuine effect or a winners curse?

Molendijk

Bus

Spinhoven

et al. 2012

American J of Med Genetics Pt B

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Inconsistenties have been reported with regard to an association between val(66)met, a polymorphism on the BDNF gene, and hippocampal volume. We performed a systematic review and a meta-analysis to determine the magnitude and direction of this putative association and estimated the potential influence of demographic, clinical, and methodological characteristics of studies. Tests of publication bias and time-related trends were performed and statistical power of the included studies was calculated. The literature search for MRI studies on differences in total hippocampal volume as a function of BDNF val(66)met returned 25 records that fulfilled our criteria (total N = 3,620). Meta-analysis showed that carriers of a met allele had lower hippocampal volumes relative to val/val homozygotes (d = 0.13, P = 0.02). Between-study heterogeneity in effect size estimates was substantial (Q = 54.47, P < .001) and this could not be explained by demographic, clinical, and methodological differences across studies. Funnel plot inspection and trim-and-fill estimations suggested evidence for publication bias and effect sizes decreased substantially over the years (Pearson's r = -0.54, P < .01). All included studies were underpowered. This meta-analysis shows that carriers of a met allele have lower total hippocampal volumes relative to val/val homozygotes. However, effect sizes converged closer to null with virtually each attempt at replication and were based on underpowered studies. Altogether, this may call into question whether the observed effect is a genuine biological effect of the met allele or whether it is subject to a winners curse, with large effect sizes found in a few early studies and increasingly smaller effect sizes in later studies.

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Association between the brain-derived neurotrophic factor Val66Met polymorphism and brain morphology in a Japanese sample of schizophrenia and healthy comparisons

Cited by 45 publications

References 40 publications

Reduced hippocampal volumes in healthy carriers of brain-derived neurotrophic factor Val66Met polymorphism: Meta-analysis

Reduced hippocampal volumes in healthy carriers of brain-derived neurotrophic factor Val66Met polymorphism: Meta-analysis

Increased BDNF Promoter Methylation in the Wernicke Area of Suicide Subjects

A systematic review and meta‐analysis on the association between BDNF val⁶⁶met and hippocampal volume—A genuine effect or a winners curse?

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Association between the brain-derived neurotrophic factor Val66Met polymorphism and brain morphology in a Japanese sample of schizophrenia and healthy comparisons

Cited by 45 publications

References 40 publications

Reduced hippocampal volumes in healthy carriers of brain-derived neurotrophic factor Val66Met polymorphism: Meta-analysis

Reduced hippocampal volumes in healthy carriers of brain-derived neurotrophic factor Val66Met polymorphism: Meta-analysis

Increased BDNF Promoter Methylation in the Wernicke Area of Suicide Subjects

A systematic review and meta‐analysis on the association between BDNF val66met and hippocampal volume—A genuine effect or a winners curse?

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Product

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A systematic review and meta‐analysis on the association between BDNF val⁶⁶met and hippocampal volume—A genuine effect or a winners curse?