Gene‐environment interaction between the brain‐derived neurotrophic factor <scp>Val66Met</scp> polymorphism, psychosocial stress and dietary intake in early psychosis

Gattere, Giulia; Stojanovic-Pérez, Alexander; Monseny, Rosa; Martorell, Lourdes; Ortega, Laura; Montalvo, Itziar; Solé, Montse; Algora, Maria José; Cabezas, Ángel; Reynolds, Rebecca M.; Vilella, Elisabet; Labad, Javier

doi:10.1111/eip.12371

Cited by 12 publications

(5 citation statements)

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“…Previous studies have indicated that the Val66Met polymorphism of BDNF gene might play an important role in the pathophysiology of several psychotic disorders (Gattere et al 2018, Kirli et al 2018, Rybakowski 2008. The association between Val66Met and OCD susceptibility has been widely studied, although inconsistent results were obtained.…”

Section: Discussionmentioning

confidence: 99%

“…A single nucleotide polymorphism (rs6265), the substitution of valine/methionine at the 66 codon in the 5 pro-region of the human BDNF protein (Val66Met), has been found to obstruct the processing of the pro-BDNF polypeptide and thereby decrease the release of BDNF (Wang et al 2015b). Many studies have shown that the BDNF valine-to-methonine substitution at codon 66 produces functional differences (Gattere et al 2018, Notaras et al 2015, Taj et al 2018, Wang et al 2015a, Zai et al 2015. The Met allele is associated with decreased activity of the BDNF system (Rybakowski 2008).…”

Section: Introductionmentioning

confidence: 99%

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Is Brain-Derived Neurotrophic Factor (Bdnf) Val66met Polymorphism Associated With Obsessive-Compulsive Disorder? A Meta-Analysis

Wang

Xu²,

Yan³

et al. 2019

Psychiat Danub

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Background: Brain-derived neurotrophic factor (BDNF) polymorphism plays an important role in neural survival and was proposed to be related to obsessive-compulsive disorder (OCD). Genetic association studies of the BDNF Val66Met polymorphism (rs6265) in OCD have produced inconsistent results. A meta-analysis of studies was conducted to compare the frequency of the BDNF Val66Met variant between cases with OCD and age-matched controls.Subjects and methods: Electronic databases were searched for eligible articles in English and ten studies on the association of the BDNF Val66Met polymorphism with OCD were analysed.Results: A total of ten studies involving 2306 cases with OCD and 4968 healthy controls were included. Findings indicated that the BDNF Val66Met polymorphism was not associated with OCD. But there was a marginally significant effect of the BDNF Val66Met variant on OCD in different ethnicity. Conclusion:Findings from this meta-analytic investigation of published literature provide little support for the Val66Met variant of BDNF as a predictor of OCD. Future well-powered agnostic genome-wide association studies with more refined phenotype are needed to clarify genetic influences on OCD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Is Brain-Derived Neurotrophic Factor (Bdnf) Val66met Polymorphism Associated With Obsessive-Compulsive Disorder? A Meta-Analysis

Wang

Xu²,

Yan³

et al. 2019

Psychiat Danub

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“…Brain-derived neurotrophic factor (BDNF), with its associated signaling, acts as a proxy for optimal brain health and neuroplasticity [15], helping neuronal cells to cope with stress conditions, including the metabolic ones [16]. Obesity and PS both exact a heavy toll on BDNF bioavailability [[17], [18], [19]]. Of relevance, BDNF and its associated receptor Tropomyosin receptor kinase B (TrkB) are required for normal myocardial function in adulthood [20,21].…”

Section: Introductionmentioning

confidence: 99%

Obese mice exposed to psychosocial stress display cardiac and hippocampal dysfunction associated with local brain-derived neurotrophic factor depletion

et al. 2019

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IntroductionObesity and psychosocial stress (PS) co-exist in individuals of Western society. Nevertheless, how PS impacts cardiac and hippocampal phenotype in obese subjects is still unknown. Nor is it clear whether changes in local brain-derived neurotrophic factor (BDNF) account, at least in part, for myocardial and behavioral abnormalities in obese experiencing PS.MethodsIn adult male WT mice, obesity was induced via a high-fat diet (HFD). The resident-intruder paradigm was superimposed to trigger PS. In vivo left ventricular (LV) performance was evaluated by echocardiography and pressure-volume loops. Behaviour was indagated by elevated plus maze (EPM) and Y-maze. LV myocardium was assayed for apoptosis, fibrosis, vessel density and oxidative stress. Hippocampus was analyzed for volume, neurogenesis, GABAergic markers and astrogliosis. Cardiac and hippocampal BDNF and TrkB levels were measured by ELISA and WB. We investigated the pathogenetic role played by BDNF signaling in additional cardiac-selective TrkB (cTrkB) KO mice.FindingsWhen combined, obesity and PS jeopardized LV performance, causing prominent apoptosis, fibrosis, oxidative stress and remodeling of the larger coronary branches, along with lower BDNF and TrkB levels. HFD/PS weakened LV function similarly in WT and cTrkB KO mice. The latter exhibited elevated LV ROS emission already at baseline. Obesity/PS augmented anxiety-like behaviour and impaired spatial memory. These changes were coupled to reduced hippocampal volume, neurogenesis, local BDNF and TrkB content and augmented astrogliosis.InterpretationPS and obesity synergistically deteriorate myocardial structure and function by depleting cardiac BDNF/TrkB content, leading to augmented oxidative stress. This comorbidity triggers behavioral deficits and induces hippocampal remodeling, potentially via lower BDNF and TrkB levels.FundJ.A. was in part supported by Rotary Foundation Global Study Scholarship. G.K. was supported by T32 National Institute of Health (NIH) training grant under award number 1T32AG058527. S.C. was funded by (19CDA34760185). G.A.R.C. was funded by (K01HL133368-01). APB was funded by a Grant from the entitled: “Heart failure as the Alzheimer disease of the heart; therapeutic and diagnostic opportunities”. M.C. was supported by PRONAT project (). N.P. was funded by (R01 HL136918) and by the . V.L. was in part supported by institutional funds from , by the , by a research grant from and in part by ETHERNA project (Prog. n. 161/16, Fondazione Pisa, Italy). Funding source had no such involvement in study design, in the collection, analysis, interpretation of data, in the writing of the report; and in the decision to submit the paper for publication.

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“…Uncovering the ontogenesis of hemispheric asymmetries requires deeper knowledge of genes involved in their development. However, specifically investigating individual genes gives rise to different methodological difficulties: First, genes can never be interpreted on their own, but have to be regarded in the context of other genes ( Zhang et al, 2015 ) and environmental factors ( Asor and Ben-Shachar, 2016 ; Gattere et al, 2016 ). Second, another promising way to shed light on the development of hemispheric asymmetries is comparing gene expression between the left and right hemisphere.…”

Section: Introductionmentioning

confidence: 99%

The Functional Genetics of Handedness and Language Lateralization: Insights from Gene Ontology, Pathway and Disease Association Analyses

et al. 2017

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Handedness and language lateralization are partially determined by genetic influences. It has been estimated that at least 40 (and potentially more) possibly interacting genes may influence the ontogenesis of hemispheric asymmetries. Recently, it has been suggested that analyzing the genetics of hemispheric asymmetries on the level of gene ontology sets, rather than at the level of individual genes, might be more informative for understanding the underlying functional cascades. Here, we performed gene ontology, pathway and disease association analyses on genes that have previously been associated with handedness and language lateralization. Significant gene ontology sets for handedness were anatomical structure development, pattern specification (especially asymmetry formation) and biological regulation. Pathway analysis highlighted the importance of the TGF-beta signaling pathway for handedness ontogenesis. Significant gene ontology sets for language lateralization were responses to different stimuli, nervous system development, transport, signaling, and biological regulation. Despite the fact that some authors assume that handedness and language lateralization share a common ontogenetic basis, gene ontology sets barely overlap between phenotypes. Compared to genes involved in handedness, which mostly contribute to structural development, genes involved in language lateralization rather contribute to activity-dependent cognitive processes. Disease association analysis revealed associations of genes involved in handedness with diseases affecting the whole body, while genes involved in language lateralization were specifically engaged in mental and neurological diseases. These findings further support the idea that handedness and language lateralization are ontogenetically independent, complex phenotypes.

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Gene‐environment interaction between the brain‐derived neurotrophic factor Val66Met polymorphism, psychosocial stress and dietary intake in early psychosis

Abstract: This study suggests that the common Val66Met polymorphism of the BDNF gene may modulate the relationship between life stress and calorie intake in subjects at risk for psychosis.

Cited by 12 publications

References 41 publications

Is Brain-Derived Neurotrophic Factor (Bdnf) Val66met Polymorphism Associated With Obsessive-Compulsive Disorder? A Meta-Analysis

Is Brain-Derived Neurotrophic Factor (Bdnf) Val66met Polymorphism Associated With Obsessive-Compulsive Disorder? A Meta-Analysis

Obese mice exposed to psychosocial stress display cardiac and hippocampal dysfunction associated with local brain-derived neurotrophic factor depletion

The Functional Genetics of Handedness and Language Lateralization: Insights from Gene Ontology, Pathway and Disease Association Analyses

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