Relation of high neuroticism with increased methylation of the BDNF gene

Shirata, Toshinori; Suzuki, Akihito; Matsumoto, Yoshihiko; Takahashi, Nana; Noto, Keisuke; Goto, Kaoru; Otani, Koichi

doi:10.2147/ndt.s169787

Cited by 6 publications

(5 citation statements)

References 28 publications

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“…This is consistent with a previous study where individuals with higher neuroticism scores (or lower emotional stability) had higher levels of brain-derived neurotrophic factor gene methylation compared with those with lower neuroticism (or higher emotional stability) scores. 45 More studies are needed to examine the mechanisms linking chronic pain, epigenetics and characteristics such as personality traits in aging.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic aging is associated with clinical and experimental pain in community-dwelling older adults

et al. 2019

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Gerontological research reveals considerable interindividual variability in aging phenotypes, which has motivated research efforts to identify “aging biomarkers.” Aging biomarkers are used to calculate biological age, which are better predictors of disease risk and residual lifespan when compared to chronological age alone. Emerging evidence using the epigenetic clock as an aging biomarker supports highly reliable individualized predictions about future health. This study aimed to determine whether an epigenetic aging biomarker was associated with chronic pain in older adults (60–83 years old). A subset of participants (n = 29) in the Neuromodulatory Examination of Pain and Mobility Across the Lifespan study underwent a blood draw, demographic, psychological, cognitive, and pain assessments. We estimated Horvath’s epigenetic clock and calculated the difference between epigenetic age and chronological age that has been previously reported to predict overall mortality risk. Older individuals without chronic pain (n = 9) had significantly “younger” epigenetic age compared to those with chronic pain (n = 20, p < 0.05). Older epigenetic age was associated with greater pain during daily activities (r = 0.494, p = 0.010) and anatomical pain sites (r = 0.741, p < 0.001) but not pain frequency/duration. An older epigenetic age was also associated with higher vibratory detection thresholds (r = 0.490, p = 0.021), heat pain thresholds (r = −0.478, p = 0.028), and pressure pain thresholds at the trapezius (r = −0.571, p = 0.006) but not thermal detection, pressure pain at the quadriceps or pain inhibition (p’s > 0.05). Epigenetic aging was associated with greater emotional stability (r = −0.461, p = 0.027), conscientiousness (r = −0.549, p = 0.007), and lower extraversion (r = 0.414, p = 0.049) but not depression or affect (p’s > 0.05). Epigenetic aging was also associated with lower episodic (r = −0.698, p = 0.001) and working memory (r = −0.760, p < 0.001). Our findings suggest that chronic pain is associated with accelerated epigenetic aging in healthy, community-dwelling older individuals, and future studies with larger samples are needed to confirm our findings. An aging biomarker such as the epigenetic clock may help identify people with chronic pain at greater risk of functional decline and poorer health outcomes.

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Section: Discussionmentioning

confidence: 99%

Epigenetic aging is associated with clinical and experimental pain in community-dwelling older adults

et al. 2019

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“…BDNF is a member of the neurotrophin family, and it plays an important role in neural differentiation, neural cell survival and synaptic plasticity [ 38 ]. A close relationship is found between neuroticism and increased BDNF gene methylation, which the higher the neuroticism score is related to higher level of BDNF gene methylation [ 39 ]. Therefore, abnormal process of protease FURIN cleaves proBDNF to generate mature BDNF (mbdnf) participate in neuropsychiatric disorders including neuroticism [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Exploring the novel SNPs in neuroticism and birth weight based on GWAS datasets

2023

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Objectives Epidemiological studies have confirmed that low birth weight (BW) is related to neuroticism and they may have a common genetic mechanism based on phenotypic correlation research. We conducted our study on a European population with 159,208 neuroticism and 289,142 birth weight samples. In this study, we aimed to identify new neuroticism single nucleotide polymorphisms (SNPs) and pleiotropic SNPs associated with neuroticism and BW and to provide more theoretical basis for the pathogenesis of the disease. Methods We estimated the pleiotropic enrichment between neuroticism and BW in two independent Genome-wide association studies (GWAS) when the statistical thresholds were Conditional False Discovery Rate (cFDR) < 0.01 and Conjunctional Conditional False Discovery Rate (ccFDR) < 0.05. We performed gene annotation and gene functional analysis on the selected significant SNPs to determine the biological role of gene function and pathogenesis. Two-sample Mendelian Randomization (TSMR) analysis was performed to explore the causal relationship between the neuroticism and BW. Results The conditional quantile–quantile plots (Q-Q plot) indicated that neuroticism and BW have strong genetic pleiotropy enrichment trends. With the threshold of cFDR < 0.001, we identified 126 SNPs related to neuroticism and 172 SNPs related to BW. With the threshold of ccFDR < 0.05, we identified 62 SNPs related to both neuroticism and BW. Among these SNPs, rs8039305 and rs35755513 have eQTL (expressed quantitative trait loci) and meQTL (methylation quantitative trait loci) effects simultaneously. Through GO enrichment analysis we also found that the two pathways of positive regulation of “mesenchymal cell proliferation” and “DNA-binding transcription factor activity” were significantly enriched in neuroticism and BW. Mendelian randomization analysis results indicate that there is no obvious causal relationship between neuroticism and birth weight. Conclusion We found 126 SNPs related to neuroticism, 172 SNPs related to BW and 62 SNPs associated with both neuroticism and BW, which provided a theoretical basis for their genetic mechanism and novel potential targets for treatment/intervention development.

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“…4 In the former scenario once high sociotropy is formed, it may further increase BDNF gene methylation by creating interpersonal stresses, 41 while in the latter scenario once hypermethylation of the BDNF gene is formed, it may further increase sociotropy by producing negative self-images through the hippocampal mechanism. 37 Recently, we proposed a similar vicious cycle between high methylation of the BDNF gene and high neuroticism, 18 another personality vulnerability factor for depression.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study suggests that increased BDNF gene methylation is connected with neuroticism, 18 which is most characterized by negative emotionality. 19,20 On the other hand, the present study suggests that this epigenetic change is linked with sociotropy, which is characterized by negative cognition and problems in stress coping and interpersonal relationships.…”

Section: Discussionmentioning

confidence: 99%

“…As BDNF activity modulates various aspects of mental function including neurocognition and stress sensitivity, 2,3 it is not surprising if methylation of the BDNF gene causing altered BDNF activity 7 affects the formation of these personality vulnerabilities in cognitive theory. In fact, we recently found out that elevated BDNF gene methylation produces high neuroticism, 18 another personality vulnerability factor for depression. 19 Neuroticism is a dimension in the five-factor personality model derived from factor analysis of personality adjectives in dictionaries and questionnaires, assuming that they cover all meaningful personality descriptions.…”

Section: Introductionmentioning

confidence: 99%

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<p>Interrelation Between Increased BDNF Gene Methylation and High Sociotropy, a Personality Vulnerability Factor in Cognitive Model of Depression</p>

Shirata

Suzuki

Matsumoto

et al. 2020

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It is suggested that increased methylation of the brain-derived neurotrophic factor (BDNF) gene is involved in the pathogenesis of depression, while sociotropy and autonomy are proposed as personality vulnerability factors in cognitive model of depression. We examined the interrelation between BDNF gene methylation and sociotropy or autonomy, with taking into account the previously reported deleterious effect of parental overprotection on sociotropy. Materials and Methods: The participants consisted of 90 healthy Japanese volunteers. Methylation levels of the BDNF gene in peripheral blood were quantified by bisulfite pyrosequencing. Sociotropy and autonomy were assessed by the Sociotropy-Autonomy Scale, and perceived parental protection was evaluated by the Parental Bonding Instrument. Results: In Pearson's correlation analysis, there was a positive correlation between methylation levels of the BDNF gene and sociotropy scores (p<0.05) but not autonomy scores, and a positive correlation between maternal protection scores and sociotropy scores (p<0.05). In structural equation modeling, two models were proposed; the first one is that hypermethylation of the BDNF gene and maternal overprotection independently contribute to high sociotropy, and the second one is that maternal overprotection contributes to high sociotropy which then leads to hypermethylation of the BDNF gene. Conclusion: The present study suggests an interrelation between increased BDNF gene methylation and high sociotropy.

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Relation of high neuroticism with increased methylation of the BDNF gene

Cited by 6 publications

References 28 publications

Epigenetic aging is associated with clinical and experimental pain in community-dwelling older adults

Epigenetic aging is associated with clinical and experimental pain in community-dwelling older adults

Exploring the novel SNPs in neuroticism and birth weight based on GWAS datasets

<p>Interrelation Between Increased BDNF Gene Methylation and High Sociotropy, a Personality Vulnerability Factor in Cognitive Model of Depression</p>

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