BDNF polymorphism associates with decline in set shifting in Parkinson's disease

Kolk, Nicolien M. van der; Speelman, A.D.; Nimwegen, Marlies van; Kessels, Roy P. C.; IntHout, Joanna; Hakobjan, Marina; Munneke, Marten; Bloem, Bastiaan R.; Warrenburg, Bart P. van de

doi:10.1016/j.neurobiolaging.2014.08.023

Cited by 37 publications

(31 citation statements)

References 44 publications

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“…Four studies were identified investigating the effect of this polymorphism on cognition in PD. The largest of these included 392 PD patients and reported less decline in executive functioning in M‐allele carriers after 2 years’ follow‐up . This contrasted with earlier studies indicating an effect in the opposite direction , and although the authors speculate that a complex interaction with age might explain these contradictory results, the role of BDNF in PD cognition will need clarification in larger studies.…”

Section: Resultsmentioning

confidence: 71%

Genetic risk factors for cognitive decline in Parkinson's disease: a review of the literature

Fagan

Pihlstrøm

2017

Euro J of Neurology

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Parkinson's disease is a highly heterogeneous disorder, where genetic factors are likely to contribute to clinical variability, including susceptibility to cognitive impairment and dementia. Monogenic forms of parkinsonism show distinct cognitive profiles, yet less is known about the impact of common genetic variants on cognition in sporadic Parkinson's disease. In a systematic review of the literature, the current results from genetic association studies of cognitive outcomes are summarized and prospects and challenges for future studies are discussed. Literature searches of the PubMed database were performed and studies using statistical methods to assess associations between genetic variation and any cognitive outcome in Parkinson's disease patients were included. For each of the candidate loci investigated in several studies, the current evidence is summarized and discussed. Sixty-one articles meeting our inclusion criteria were identified, which were highly heterogeneous with respect to study design, size and cognitive outcome measures. GBA mutations have a negative impact on cognition, whereas LRRK2-associated disease may have a milder cognitive phenotype than idiopathic Parkinson's disease. For common variants, reported results are partly conflicting, even across the larger studies, with some evidence to suggest a potential effect of APOE, MAPT, COMT and SNCA on cognitive outcomes. Future investigations should aim to collect high-quality cognitive data in a standardized way that allows for direct comparison across studies and large-scale meta-analysis. Linking genetic profiles to cognitive outcomes may have an important clinical impact, facilitating the stratification of patients for clinical trials and, ultimately, individualized treatment in Parkinson's disease.

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Section: Resultsmentioning

confidence: 71%

Genetic risk factors for cognitive decline in Parkinson's disease: a review of the literature

Fagan

Pihlstrøm

2017

Euro J of Neurology

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“…This distribution indicates that: (i) it is unlikely that the BDNF Met genotype drives the epigenetic intersection between mice and women; (ii) the number of Het-Met women is statistically insufficient to generate a subset genotypic analysis. Further studies of genotype are needed, since the BDNF Met allele is a risk factor for several other neuropsychiatric disorders, including depression, schizophrenia, Parkinson, and Alzheimer's disease [47][48][49]. Yet, at the epigenetic level, our findings generate testable hypotheses concerning conserved, crossspecies and cross-tissues epigenetic factors underlying behavioral sensitivity to ovarian hormones and may open a window to novel targets for therapy.…”

Section: Discussionmentioning

confidence: 88%

Epigenetic intersection of BDNF Val66Met genotype with premenstrual dysphoric disorder transcriptome in a cross-species model of estradiol add-back

et al. 2018

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Premenstrual dysphoric disorder (PMDD) affects over 5% of women, with symptoms similar to anxiety and major depression, and is associated with differential sensitivity to circulating ovarian hormones. Little is known about the genetic and epigenetic factors that increase the risk to develop PMDD. We report that 17β-estradiol (E2) affects the behavior and the epigenome in a mouse model carrying a single-nucleotide polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met), in a way that recapitulates the hallmarks of PMDD. Ovariectomized mice heterozygous for the BDNF Met allele (Het-Met) and their matched wild-type (WT) mice were administered estradiol or vehicle in drinking water for 6 weeks. Using the open field and the splash test, we show that E2 add-back induces anxiety-like and depression-like behavior in Het-Met mice, but not in WT mice. RNA-seq of the ventral hippocampus (vHpc) highlights that E2-dependent gene expression is markedly different between WT mice and Het-Met mice. Through a comparative whole-genome RNAseq analysis between mouse vHpc and lymphoblastoid cell line cultures from control women and women with PMDD, we discovered common epigenetic biomarkers that transcend species and cell types. Those genes include epigenetic modifiers of the ESC/E(Z) complex, an effector of response to ovarian steroids. Although the BDNF Met genotype intersects the behavioral and transcriptional traits of women with PMDD, we suggest that these similarities speak to the epigenetic factors by which ovarian steroids produce negative behavioral effects.

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“…Supporting the view that reappraisal relies on cognitive control, recent studies have shown that reappraisal ability is positively correlated with working memory capacity and set-shifting (McRae et al 2012b). Notably, there is also evidence of a disordinal BDNF Val66Met polymrphism and child maltreatment interaction in working memory (Gatt et al 2009) and improved set-shifting performance in elderly BDNF Met carriers compared to Val homozygotes (Gajewski et al 2011;van der Kolk et al 2015). In light of this literature, future studies could investigate the pleiotropic effects of BDNF Val66Met × child maltreatment on emotion regulation and cognitive control.…”

Section: Discussionmentioning

confidence: 95%

BDNFVal66Met polymorphism moderates the link between child maltreatment and reappraisal ability

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Vulturar

et al. 2017

Genes Brain and Behavior

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Child maltreatment is associated with increased risk for virtually all common mental disorders, but it is not yet clear why. One possible mechanism is emotion regulation ability. The present study investigated for the first time the influence of a BDNF Val66Met genotype × child maltreatment interaction on emotion regulation, and compared differential susceptibility and diathesis-stress models. A sample of N = 254 healthy volunteers were genotyped for the BDNF Val66Met polymorphism and underwent an experimental assessment of reappraisal ability (i.e. the success of using reappraisal to downregulate negative affect). A self-report instrument previously validated against a clinical interview was used to investigate child maltreatment. There was a significant BDNF Val66Met genotype × child maltreatment interaction (B = -0.31, P< 0.015), with Met carriers showing both the lowest level of reappraisal ability in maltreated participants, and the highest level of reappraisal ability in non-maltreated participants. By assessing alternative models, we found that the best fitting model was in line with strong differential susceptibility. As expected, reappraisal ability was negatively correlated with depressive symptoms. Therefore, the BDNF Val66Met polymorphism moderates the link between child maltreatment and emotion regulation ability. Future studies could investigate whether improving reappraisal in maltreated BDNF Met carriers results in reduced risk for mental disorders.

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BDNF polymorphism associates with decline in set shifting in Parkinson's disease

Cited by 37 publications

References 44 publications

Genetic risk factors for cognitive decline in Parkinson's disease: a review of the literature

Genetic risk factors for cognitive decline in Parkinson's disease: a review of the literature

Epigenetic intersection of BDNF Val66Met genotype with premenstrual dysphoric disorder transcriptome in a cross-species model of estradiol add-back

BDNFVal66Met polymorphism moderates the link between child maltreatment and reappraisal ability

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