The association of the BDNF Val66Met polymorphism and the hippocampal volumes in healthy humans: A joint meta-analysis of published and new data

Harrisberger, Fabienne; Spalek, Klara; Smieskova, Renata; Schmidt, André; Coynel, David; Milnik, Annette; Fastenrath, Matthias; Freytag, Virginie; Gschwind, Leo; Walter, Anna; Vogel, Tobias; Bendfeldt, Kerstin; Quervain, Dominique J.‐F. de; Papassotiropoulos, Andreas; Borgwardt, Stefan

doi:10.1016/j.neubiorev.2014.03.011

Cited by 61 publications

(50 citation statements)

References 96 publications

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“…The effect of BDNF on brain volume may be small or BDNF levels may vary over time, preventing us from detecting an effect of current BDNF levels on volume of the amygdala, hippocampus and ACC (Piccinni et al , 2008). We also did not see an effect of BDNF genotype on brain volume and therefore were unable to replicate initial findings of decreased hippocampus volume in carriers of the met-allele (Bueller et al , 2006; M L Molendijk et al , 2012), however recent meta-analyses suggest this effect is non-existent and is related to publication bias (Marc L Molendijk et al , 2012; Harrisberger et al , 2014). …”

Section: Discussioncontrasting

confidence: 75%

Effect of childhood maltreatment and brain-derived neurotrophic factor on brain morphology

Velzen

Schmaal

Jansen

et al. 2016

Soc Cogn Affect Neurosci

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Childhood maltreatment (CM) has been associated with altered brain morphology, which may partly be due to a direct impact on neural growth, e.g. through the brain-derived neurotrophic factor (BDNF) pathway. Findings on CM, BDNF and brain volume are inconsistent and have never accounted for the entire BDNF pathway. We examined the effects of CM, BDNF (genotype, gene expression and protein level) and their interactions on hippocampus, amygdala and anterior cingulate cortex (ACC) morphology. Data were collected from patients with depression and/or an anxiety disorder and healthy subjects within the Netherlands Study of Depression and Anxiety (NESDA) (N = 289). CM was assessed using the Childhood Trauma Interview. BDNF Val66Met genotype, gene expression and serum protein levels were determined in blood and T1 MRI scans were acquired at 3T. Regional brain morphology was assessed using FreeSurfer. Covariate-adjusted linear regression analyses were performed. Amygdala volume was lower in maltreated individuals. This was more pronounced in maltreated met-allele carriers. The expected positive relationship between BDNF gene expression and volume of the amygdala is attenuated in maltreated subjects. Finally, decreased cortical thickness of the ACC was identified in maltreated subjects with the val/val genotype. CM was associated with altered brain morphology, partly in interaction with multiple levels of the BNDF pathway. Our results suggest that CM has different effects on brain morphology in met-carriers and val-homozygotes and that CM may disrupt the neuroprotective effect of BDNF.

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Section: Discussioncontrasting

confidence: 75%

Effect of childhood maltreatment and brain-derived neurotrophic factor on brain morphology

Velzen

Schmaal

Jansen

et al. 2016

Soc Cogn Affect Neurosci

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“…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. The authors suggest that inconsistency of the results may be related to measuring techniques and sample sizes.…”

Section: Introductionmentioning

confidence: 83%

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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“…The BDNF gene (located on chromosome 11p14.1) encodes for the brain-derived neurotrophic factor, a member of the nerve growth family of proteins, and has been implicated in brain development, maturation and cognition (Alfimova et al , 2012, Bath & Lee, 2006, Dincheva et al , 2012, Egan et al , 2003, Hariri et al , 2003, Harrisberger et al , 2014, Molendijk et al , 2012, Yin et al , 2015). More specifically, BDNF influences the proliferation, differentiation and survival of neurons, neural morphology and function, synaptic changes (i.e.…”

Section: Introductionmentioning

confidence: 99%

The BDNF Val 66 Met polymorphism is associated with structural neuroanatomical differences in young children

Jasińska

Molfese

Kornilov

et al. 2017

Behavioural Brain Research

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The brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism (SNP) has been associated with individual differences in brain structure and function, and cognition. Research on BDNF’s influence on brain and cognition has largely been limited to adults, and little is known about the association of this gene, and specifically the Val66Met polymorphism, with developing brain structure and emerging cognitive functions in children. We performed a targeted genetic association analysis on cortical thickness, surface area, and subcortical volume in 78 children (ages 6–10) who were Val homozygotes (homozygous Val/Val carriers) or Met carriers (Val/Met, Met/Met) for the Val66Met locus using Atlas-based brain segmentation. We observed greater cortical thickness for Val homozygotes in regions supporting declarative memory systems (anterior temporal pole/entorhinal cortex), consistent with adult findings. Met carriers had greater surface area in the prefrontal and parietal cortices and greater cortical thickness in lateral occipital/parietal cortex in contrast to prior adult findings that may relate to performance on cognitive tasks supported by these regions in Met carriers. Finally, we found larger right hippocampal volume in Met carriers, although inconsistent with adult findings (generally reports larger volumes for Val homozygotes), is consistent with a recent finding in children. Gene expression levels vary across different brain regions and across development and our findings highlight the need to consider this developmental change in explorations of BDNF-brain relationships. The impact of the BDNF Val66Met polymorphism on the structure of the developing brain therefore reflects regionally-specific developmental changes in BDNF expression and cortical maturation trajectories.

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The association of the BDNF Val66Met polymorphism and the hippocampal volumes in healthy humans: A joint meta-analysis of published and new data

Cited by 61 publications

References 96 publications

Effect of childhood maltreatment and brain-derived neurotrophic factor on brain morphology

Effect of childhood maltreatment and brain-derived neurotrophic factor on brain morphology

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

The BDNF Val 66 Met polymorphism is associated with structural neuroanatomical differences in young children

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