Childhood trauma, BDNF Val66Met and subclinical psychotic experiences. Attempt at replication in two independent samples

Castro-Català, Marta de; Nierop, Martine van; Barrantes‐Vidal, Neus; Cristóbal-Narváez, Paula; Sheinbaum, Tamara; Kwapil, Thomas Richard; Peña, Elionora; Jacobs, Nele; Derom, Cathérine; Thiery, Evert; Os, Jim van; Winkel, Ruud van; Rosa, Araceli

doi:10.1016/j.jpsychires.2016.08.014

Cited by 22 publications

(16 citation statements)

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“…According to our review, 12 studies have evaluated interactions between exposure to childhood trauma and genetic factors in schizophrenia spectrum disorders [ 21 , 22 , 31 , 33 – 36 , 38 , 41 , 42 , 45 , 123 ]. The vast majority of studies suggest significant interactions between genetic underpinnings and exposure to childhood adversities, stressful life events or recent stressors and genetic factors, with only three studies reporting negative findings [ 25 , 35 , 45 ].…”

Section: Resultsmentioning

confidence: 99%

“…In three studies [ 21 , 33 , 123 ], interactions between a history of childhood trauma and the BDNF Val66Met polymorphism were addressed, showing positive findings. Aas et al [ 33 ] found an additive effect of the BDNF 66Met allele and a history of childhood trauma on reduced levels of BDNF mRNA as well as CA2/3 and CA4 subfield volumes of dentate gyrus in the hippocampus.…”

Section: Resultsmentioning

confidence: 99%

“…Similar effects of interactions between the BDNF Val66Met polymorphism and childhood abuse, but not childhood neglect, on positive psychotic-like experiences have been found in a non-clinical study [ 123 ]. Another non-clinical study revealed that the BDNF 66Val allele, especially in male twins, was associated with higher vulnerability of the effects of childhood trauma on psychotic experiences, while in the group of female twins this association was driven by the BDNF 66Met allele [ 21 ]. There are also studies addressing the effects of interaction between variability in the FKBP5 gene and childhood trauma on psychosis phenotypes in clinical and non-clinical populations [ 22 , 31 , 34 , 38 ].…”

Section: Resultsmentioning

confidence: 99%

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Interactions Between Variation in Candidate Genes and Environmental Factors in the Etiology of Schizophrenia and Bipolar Disorder: a Systematic Review

et al. 2017

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Schizophrenia and bipolar disorder (BD) are complex and multidimensional disorders with high heritability rates. The contribution of genetic factors to the etiology of these disorders is increasingly being recognized as the action of multiple risk variants with small effect sizes, which might explain only a minor part of susceptibility. On the other site, numerous environmental factors have been found to play an important role in their causality. Therefore, in recent years, several studies focused on gene × environment interactions that are believed to bridge the gap between genetic underpinnings and environmental insults. In this article, we performed a systematic review of studies investigating gene × environment interactions in BD and schizophrenia spectrum phenotypes. In the majority of studies from this field, interacting effects of variation in genes encoding catechol-O-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF), and FK506-binding protein 5 (FKBP5) have been explored. Almost consistently, these studies revealed that polymorphisms in COMT, BDNF, and FKBP5 genes might interact with early life stress and cannabis abuse or dependence, influencing various outcomes of schizophrenia spectrum disorders and BD. Other interactions still require further replication in larger clinical and non-clinical samples. In addition, future studies should address the direction of causality and potential mechanisms of the relationship between gene × environment interactions and various categories of outcomes in schizophrenia and BD.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Interactions Between Variation in Candidate Genes and Environmental Factors in the Etiology of Schizophrenia and Bipolar Disorder: a Systematic Review

et al. 2017

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“…The BDNF Val66Met polymorphism has been reported to interact with early life stress; thus, Val carriers with childhood trauma are more susceptible to the occurrence of subclinical psychotic experiences ( de Castro-Catala et al, 2016 ). Another study in subjects with the schizophrenia spectrum or bipolar disorder demonstrated that Met carriers with high levels of childhood trauma have significantly low levels of blood BDNF mRNA and decreased CA2/3 and CA4 subfield areas in the dentate gyrus ( Aas et al, 2014 ).…”

Section: Interaction Between Bdnf Val66met Polymormentioning

confidence: 99%

Critical Issues in BDNF Val66Met Genetic Studies of Neuropsychiatric Disorders

Tsai

2018

Front. Mol. Neurosci.

117

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Neurotrophins have been implicated in the pathophysiology of many neuropsychiatric diseases. Brain-derived neurotrophic factor (BDNF) is the most abundant and widely distributed neurotrophin in the brain. Its Val66Met polymorphism (refSNP Cluster Report: rs6265) is a common and functional single-nucleotide polymorphism (SNP) affecting the activity-dependent release of BDNF. BDNF Val66Met transgenic mice have been generated, which may provide further insight into the functional impact of this polymorphism in the brain. Considering the important role of BDNF in brain function, more than 1,100 genetic studies have investigated this polymorphism in the past 15 years. Although these studies have reported some encouraging positive findings initially, most of the findings cannot be replicated in following studies. These inconsistencies in BDNF Val66Met genetic studies may be attributed to many factors such as age, sex, environmental factors, ethnicity, genetic model used for analysis, and gene–gene interaction, which are discussed in this review. We also discuss the results of recent studies that have reported the novel functions of this polymorphism. Because many BDNF polymorphisms and non-genetic factors have been implicated in the complex traits of neuropsychiatric diseases, the conventional genetic association-based method is limited to address these complex interactions. Future studies should apply data mining and machine learning techniques to determine the genetic role of BDNF in neuropsychiatric diseases.

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“…In this sense, a limited but increasing number of GxE studies have shown that certain single nucleotide polymorphisms (SNPs) interact with distal or proximal stress to heighten risk for psychotic experiences (PEs; e.g., 11). For example, it has been shown that the brain‐derived neurotrophic factor ( BDNF ) Val66Met polymorphism moderates the psychosis‐inducing effects of distal 12, 13 and momentary stress 14. However, scarce research has examined the interaction of genetic variants with both distal and proximal stress within the same study.…”

Section: Introductionmentioning

confidence: 99%

The role of stress‐regulation genes in moderating the association of stress and daily‐life psychotic experiences

Cristóbal-Narváez

Sheinbaum

Myin-Germeys

et al. 2017

Acta Psychiatr Scand

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ObjectiveThe interaction of single nucleotide polymorphisms with both distal and proximal environmental factors across the extended psychosis phenotype is understudied. This study examined (i) the interaction of relevant SNPs with both early‐life adversity and proximal (momentary) stress on psychotic experiences (PEs) in an extended psychosis sample; and (ii) differences between early‐psychosis and non‐clinical groups for these interactions.MethodsTwo hundred and forty‐two non‐clinical and 96 early‐psychosis participants were prompted randomly eight times daily for 1 week to complete assessments of current experiences, including PEs and stress. Participants also reported on childhood trauma and were genotyped for 10 SNPs on COMT, RGS4, BDNF, FKBP5, and OXTR genes.ResultsUnlike genetic variants, distal and proximal stressors were associated with PEs in both samples and were more strongly associated with PEs in the early‐psychosis than in the non‐clinical group. The RGS4 TA and FKBP5 CATT haplotypes interacted with distal stress, whereas the A allele of OXTR (rs2254298) interacted with proximal stress, increasing momentary levels of PEs in the early‐psychosis group. No interactions emerged with COMT or BDNF variants.ConclusionIndividual differences in relevant stress‐regulation systems interact with both distal and proximal psychosocial stressors in shaping the daily‐life manifestation of PEs across the psychosis continuum.

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Childhood trauma, BDNF Val66Met and subclinical psychotic experiences. Attempt at replication in two independent samples

Cited by 22 publications

References 78 publications

Interactions Between Variation in Candidate Genes and Environmental Factors in the Etiology of Schizophrenia and Bipolar Disorder: a Systematic Review

Interactions Between Variation in Candidate Genes and Environmental Factors in the Etiology of Schizophrenia and Bipolar Disorder: a Systematic Review

Critical Issues in BDNF Val66Met Genetic Studies of Neuropsychiatric Disorders

The role of stress‐regulation genes in moderating the association of stress and daily‐life psychotic experiences

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