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

Hájek, Tomáš; Kopeček, Miloslav; Höschl, Cyril

doi:10.3109/15622975.2011.580005

Cited by 92 publications

(59 citation statements)

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“…In case of impaired production of the functioning neurotrophin, it is probably unable to prevent neuronal degeneration, thus either providing a site of vulnerability for the development of depressive symptoms, or enabling a higher rate of hippocampal volume reduction during depression. The findings of a recent meta-analysis (Hajek et al 2011) support this theory as they reported that even in healthy carriers of the BDNF Val66Met polymorphism hippocampal volume was reduced compared to Val/Val homozygotes, although the effect sizes in the individual studies were so small, that only the meta-analysis could show the actual difference, supposedly because participants with smaller hippocampal volumes were already excluded for being depressed. Older participants are also more likely to suffer from late-onset depression, which has been suggested to often precede the onset of demen-tia, especially Alzheimer's disease (Saczynski et al 2010;Dal Forno et al 2005), which is also associated with a more pronounced hippocampal degeneration (Laakso et al 1998;Ryu et al 2010).…”

Section: Discussionsupporting

confidence: 58%

Brain-derived neurotrophic factor gene polymorphisms, neurotransmitter levels, and depressive symptoms in an elderly population

Czira

Wersching

Baune

et al. 2011

AGE

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A large number of studies have examined associations between brain-derived neurotrophic factor (BDNF) gene polymorphisms and depressive symptoms. However, results still remain controversial. Recent studies suggested a significant age and gender effect on the heritability of depression. The potential neurobiological pathways that could possibly mediate this relationship have not been examined so far. Since BDNF is involved in the regulation of neurotransmitter production, a mediating role of neurotransmitters seems plausible. The present study aims to examine the association between three common BDNF singlenucleotid polymorphisms (SNPs; rs7103411, rs7124442, and rs6265) and depressive symptoms in a community-based elderly population taking into account the serum levels of four neurotransmitters, serotonin, dopamine, adrenalin, and noradrenalin, as potential mediating factors. We also examined whether age and gender had a modifying effect on this association. We collected and analyzed the genetic and laboratory data as well as Center for Epidemiologic Studies-Depression scores of 350 community-dwelling elderly individuals (aged 65+ years). We found that the BDNF rs6265 polymorphism was related to the severity of depressive symptoms, and that this association was independent of neurotransmitter levels. Stratified analyses showed that this association was restricted to older individuals (≥74 years) and men. The associations of SNPs rs7103411 or rs7124442 SNP with depressive symptoms were not statistically significant. This study importantly adds to the existing literature by affirming previous assumptions on an age and gender difference in the relation between BDNF genotype and depression. We moreover first-time report a missing mediating role of neurotransmitters in this association.

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Section: Discussionsupporting

confidence: 58%

Brain-derived neurotrophic factor gene polymorphisms, neurotransmitter levels, and depressive symptoms in an elderly population

Czira

Wersching

Baune

et al. 2011

AGE

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“…In volumetric studies Met-carriers were found to have a hippocampal volume reduction in both healthy cohorts and psychiatric patients with schizophrenia, bipolar disorder, major depression and anxiety disorders (Pezewas et al 2004, Szeszko et al 2005, Bueller et al 2006, Frodl et al 2007, Chepenik et al 2009, Mueller et al 2013). These observations were confirmed in three meta-analytic reviews (Hajek et al 2012, Kambeitz et al 2012, Molendijk et al 2012. However, the most recent meta-analyses showed no association between Val66Met polymorphism and hippocampal volumes neither in healthy subjects nor clinical groups (Harrisberger et al 2014(Harrisberger et al , 2015.…”

Section: Introductionmentioning

confidence: 72%

BDNF gene polymorphisms and haplotypes in relation to cognitive performance in Polish healthy subjects

Wiłkość¹,

Szałkowska²,

Skibińska³

et al. 2016

Acta Neurobiologiae Experimentalis

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The brain derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in the cell survival, axonal and dendritic growth, and synaptic plasticity. BDNF gene polymorphisms, functional Val66Met mainly, were shown to influence human brain structure and cognition.The aim of the study was to assess the relationship between twelve BDNF gene variants and their haplotypes and cognitive performance measured using the Wisconsin Card Sorting Test (WCST), the Trail Making Test (TMT), the Stroop Test which are to a large extent connected with prefrontal cortex activity. Our sample consisted of 460 healthy participants from Polish population. We detected possible association between five BDNF polymorphisms (rs11030101, rs10835210, rs2049046, rs2030324, rs2883187) and TMT_A. Additionally, one haplotype block made from eleven BDNF variants (rs2883187, rs1401635, rs2049046, rs2030324, rs11030101, rs10835210, rs1013402, rs1401635, rs1013402), as significant linkage disequilibrium appeared. We discovered possible relationships of CACCGCGTACG and CACCGCGTACG haplotypes with TMT_A and TMT_B performance respectively. Our results confirmed the involvement of BDNF in the regulation of psychomotor speed, working memory and executive function in healthy subjects measured by a task engaging visuoperceptual abilities.

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“…43 Consistent with these individual reports, two meta-analyses (n = 399 and 3620, respectively) have confirmed that 66Met allele carriers have smaller bilateral hippocampi relative to 66Val homozygote controls. 44,45 However, these meta-analyses noted that the effect size of the 66Met allele on reduced hippocampal volume is relatively small 44 and that most studies suffer from underpowered samples. 45 This small effect size, when coupled with heterogeneous sampling and nuisance variability between studies, may explain why some studies have failed to report an effect of the Val66Met polymorphism on hippocampal structure and function.…”

Section: Human Neuroscience Of the Val66met Polymorphismmentioning

confidence: 98%

The BDNF gene Val66Met polymorphism as a modifier of psychiatric disorder susceptibility: progress and controversy

2015

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Brain-derived neurotrophic factor (BDNF) has a primary role in neuronal development, differentiation and plasticity in both the developing and adult brain. A single-nucleotide polymorphism in the proregion of BDNF, termed the Val66Met polymorphism, results in deficient subcellular translocation and activity-dependent secretion of BDNF, and has been associated with impaired neurocognitive function in healthy adults and in the incidence and clinical features of several psychiatric disorders. Research investigating the Val66Met polymorphism has increased markedly in the past decade, and a gap in integration exists between and within academic subfields interested in the effects of this variant. Here we comprehensively review the role and relevance of the Val66Met polymorphism in psychiatric disorders, with emphasis on suicidal behavior and anxiety, eating, mood and psychotic disorders. The cognitive and molecular neuroscience of the Val66Met polymorphism is also concisely reviewed to illustrate the effects of this genetic variant in healthy controls, and is complemented by a commentary on the behavioral neuroscience of BDNF and the Val66Met polymorphism where relevant to specific disorders. Lastly, a number of controversies and unresolved issues, including small effect sizes, sampling of allele inheritance but not genotype and putative ethnicity-specific effects of the Val66Met polymorphism, are also discussed to direct future research.

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

Cited by 92 publications

References 50 publications

Brain-derived neurotrophic factor gene polymorphisms, neurotransmitter levels, and depressive symptoms in an elderly population

Brain-derived neurotrophic factor gene polymorphisms, neurotransmitter levels, and depressive symptoms in an elderly population

BDNF gene polymorphisms and haplotypes in relation to cognitive performance in Polish healthy subjects

The BDNF gene Val66Met polymorphism as a modifier of psychiatric disorder susceptibility: progress and controversy

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