BDNF Genetic Variant and Its Genotypic Fluctuation in Major Depressive Disorder

Siqueira, Jhon Willatan Saraiva; Gontijo, Bruna Rodrigues; Santos, Maurício de Lima; Silva, Calliandra Maria de Souza; Silva, Izabel Cristina Rodrigues da

doi:10.1155/2021/7117613

Cited by 8 publications

(3 citation statements)

References 80 publications

(161 reference statements)

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“…Especially, the single-nucleotide polymorphism BDNF Val 66 Met, which causes a valine (Val) to methionine (Met) substitution at codon 66 of the BDNF protein, is of high interest because of its known influence on hippocampal functions [ 16 ]. It has also been associated with AD and depression in the past [ 20 , 21 ]. Studies in rodents and humans suggested that carriers of the BDNF Met allele show lower hippocampal volumes [ 19 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Deciphering the Effect of Different Genetic Variants on Hippocampal Subfield Volumes in the General Population

Kirchner

Garvert

Wittfeld

et al. 2023

IJMS

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The aim of this study was to disentangle the effects of various genetic factors on hippocampal subfield volumes using three different approaches: a biologically driven candidate gene approach, a hypothesis-free GWAS approach, and a polygenic approach, where AD risk alleles are combined with a polygenic risk score (PRS). The impact of these genetic factors was investigated in a large dementia-free general population cohort from the Study of Health in Pomerania (SHIP, n = 1806). Analyses were performed using linear regression models adjusted for biological and environmental risk factors. Hippocampus subfield volume alterations were found for APOE ε4, BDNF Val, and 5-HTTLPR L allele carriers. In addition, we were able to replicate GWAS findings, especially for rs17178139 (MSRB3), rs1861979 (DPP4), rs7873551 (ASTN2), and rs572246240 (MAST4). Interaction analyses between the significant SNPs as well as the PRS for AD revealed no significant results. Our results confirm that hippocampal volume reductions are influenced by genetic variation, and that different variants reveal different association patterns that can be linked to biological processes in neurodegeneration. Thus, this study underlines the importance of specific genetic analyses in the quest for acquiring deeper insights into the biology of hippocampal volume loss, memory impairment, depression, and neurodegenerative diseases.

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Section: Introductionmentioning

confidence: 99%

Deciphering the Effect of Different Genetic Variants on Hippocampal Subfield Volumes in the General Population

Kirchner

Garvert

Wittfeld

et al. 2023

IJMS

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“…Depression rates are on the rise globally. According to the World Health Organization (WHO), the number of MDD cases grew by 18.4% from 2005 to 2015 [ 1 ], though this increase could also be attributed to population growth and/or gradually decreasing stigmatization surrounding mental illness [ 3 ]. In the first year of the COVID-19 pandemic, rates of common conditions, such as depression and anxiety, went up by more than 25% [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

BDNF rs962369 Is Associated with Major Depressive Disorder

2023

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This study enrolled 291 patients diagnosed with depression and schizophrenia (F32, F33, and F20 according to ICD-10) and 227 ethnicity-matched control subjects. We analyzed the distribution of BDNF rs6265 and BDNF rs962369 genotypes, finding no significant associations between these and schizophrenia. We revealed a significant increase in the risk of single-episode major depression disorder (MDD) for rs962369 minor allele homozygotes (CC vs. TT+TC), an association that persisted after adjusting for age and sex (OR 3.47; 95% CI 1.36–8.85; p = 0.009). Furthermore, rs962369 genotype was significantly associated with an increased risk of recurrent MDD in a log-additive model (OR per C-allele 1.65; 95% CI 1.11–2.45; p = 0.013). A comparative analysis between MDD subtypes and between MDD subtypes and schizophrenia showed no significant differences for BDNF rs6265. Notably, the frequency of minor allele C of BDNF rs962369 varied across subgroups, with the highest frequency in patients with recurrent MDD (0.32) and the lowest in schizophrenia patients (0.20). The presence of genotypes with at least one minor allele C was significantly higher in the recurrent MDD patient group compared to the schizophrenia group. In conclusion, the BDNF rs962369 variant was associated with MDD but not with schizophrenia.

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“…The most commonly examined BDNF single nucleotide polymorphism (SNP) produces a valine-to-methionine substitution at codon 66 (Val66Met; rs6265), with the Met allele associated with reduced activity-dependent secretion of BDNF (Egan et al, 2003). While hundreds of studies have examined the association between rs6265 (and other BDNF SNPs) and brain-related conditions, results have been mixed, as is observed in many complex phenotypes (Ahmed et al, 2015; Ferreira Fratelli et al, 2021; Pereira et al, 2018). Also, when examined in consortium studies with very large sample sizes, some of the BDNF associations previously seen in small candidate gene studies have not replicated (Border et al, 2019; Johnson et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor (BDNF) Epigenomic Modifications and Brain-Related Phenotypes in Humans: A Systematic Review

Treble‐Barna

Heinsberg

Stec

et al. 2022

Preprint

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Epigenomic modifications of the brain-derived neurotrophic factor (BDNF) gene have been postulated to underlie the pathogenesis of neurodevelopmental, psychiatric, and neurological conditions. This systematic review summarizes current evidence investigating the association of BDNF epigenomic modifications (DNA methylation, non-coding RNA, histone modifications) with brain-related phenotypes in humans. A novel contribution is our creation of an open access web-based application, the BDNF DNA Methylation Map, to interactively visualize specific positions of CpG sites investigated across all studies for which relevant data were available. Our literature search of four databases through September 27, 2021 returned 1,701 articles, of which 153 met inclusion criteria. Our review revealed exceptional heterogeneity in methodological approaches, hindering the identification of clear patterns of robust and/or replicated results. We summarize key findings and provide recommendations for future epigenomic research. The existing literature appears to remain in its infancy and requires additional rigorous research to fulfill its potential to explain BDNF-linked risk for brain-related conditions and improve our understanding of the molecular mechanisms underlying their pathogenesis.Highlights153 articles examined BDNF epigenomic modifications and brain-related phenotypesNovel BDNF DNA Methylation Map allows users to interactively visualize CpGsBDNF epigenomics lack robust/replicated results due to methodological heterogeneity

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BDNF Genetic Variant and Its Genotypic Fluctuation in Major Depressive Disorder

Cited by 8 publications

References 80 publications

Deciphering the Effect of Different Genetic Variants on Hippocampal Subfield Volumes in the General Population

Deciphering the Effect of Different Genetic Variants on Hippocampal Subfield Volumes in the General Population

BDNF rs962369 Is Associated with Major Depressive Disorder

Brain-Derived Neurotrophic Factor (BDNF) Epigenomic Modifications and Brain-Related Phenotypes in Humans: A Systematic Review

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