Test of the Serotonin Transporter Gene × Early Life Stress Interaction Effect on Subjective Well‐Being and Loneliness Among Japanese Young Adults

BackgroundChildhood adverse experiences are known to induce persistent changes in the hypothalamic–pituitary–adrenal (HPA) axis reactivity to stress. However, the mechanisms by which these experiences shape the neuroendocrine response to stress remain unclear.MethodWe tested whether bullying victimization influenced serotonin transporter gene (SERT) DNA methylation using a discordant monozygotic (MZ) twin design. A subsample of 28 MZ twin pairs discordant for bullying victimization, with data on cortisol and DNA methylation, were identified in the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative 1994–1995 cohort of families with twins.ResultsBullied twins had higher SERT DNA methylation at the age of 10 years compared with their non-bullied MZ co-twins. This group difference cannot be attributed to the children's genetic makeup or their shared familial environments because of the study design. Bullied twins also showed increasing methylation levels between the age of 5 years, prior to bullying victimization, and the age of 10 years whereas no such increase was detected in non-bullied twins across time. Moreover, children with higher SERT methylation levels had blunted cortisol responses to stress.ConclusionsOur study extends findings drawn from animal models, supports the hypothesis that early-life stress modifies DNA methylation at a specific cytosine–phosphate–guanine (CpG) site in the SERT promoter and HPA functioning and suggests that these two systems may be functionally associated.

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Functional polymorphism (5-HTTLPR) in the serotonin transporter gene is associated with subjective well-being: evidence from a US nationally representative sample

Journal of Human Genetics ◽

10.1038/jhg.2011.39 ◽

2011 ◽

Vol 56 (6) ◽

pp. 456-459 ◽

Cited By ~ 54

Author(s):

Jan-Emmanuel De Neve

Keyword(s):

Serotonin Transporter ◽

Representative Sample ◽

Well Being ◽

Serotonin Transporter Gene ◽

Functional Polymorphism ◽

Subjective Well Being ◽

Transporter Gene ◽

Nationally Representative

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Three-way interaction effects of early life stress, positive parenting and FKBP5 in the development of depressive symptoms in a general population

Journal of Neural Transmission ◽

10.1007/s00702-021-02405-0 ◽

2021 ◽

Author(s):

Rebecka Keijser ◽

Susanne Olofsdotter ◽

Kent W. Nilsson ◽

Cecilia Åslund

Keyword(s):

Young Adults ◽

Depressive Symptoms ◽

Life Stress ◽

Early Life ◽

Differential Susceptibility ◽

Early Life Stress ◽

Interaction Effects ◽

Positive Parenting ◽

Depressive Symptomology ◽

Patterns Of Interaction

AbstractFKBP5 gene–environment interaction (cG × E) studies have shown diverse results, some indicating significant interaction effects between the gene and environmental stressors on depression, while others lack such results. Moreover, FKBP5 has a potential role in the diathesis stress and differential susceptibility theorem. The aim of the present study was to evaluate whether a cG × E interaction effect of FKBP5 single-nucleotide polymorphisms (SNPs) or haplotype and early life stress (ELS) on depressive symptoms among young adults was moderated by a positive parenting style (PASCQpos), through the frameworks of the diathesis stress and differential susceptibility theorem. Data were obtained from the Survey of Adolescent Life in Västmanland Cohort Study, including 1006 participants and their guardians. Data were collected during 2012, when the participants were 13 and 15 years old (Wave I: DNA), 2015, when participants were 16 and 18 years old (Wave II: PASCQpos, depressive symptomology and ELS) and 2018, when participants were 19 and 21 years old (Wave III: depressive symptomology). Significant three-way interactions were found for the FKBP5 SNPs rs1360780, rs4713916, rs7748266 and rs9394309, moderated by ELS and PASCQpos, on depressive symptoms among young adults. Diathesis stress patterns of interaction were observed for the FKBP5 SNPs rs1360780, rs4713916 and rs9394309, and differential susceptibility patterns of interaction were observed for the FKBP5 SNP rs7748266. Findings emphasize the possible role of FKBP5 in the development of depressive symptoms among young adults and contribute to the understanding of possible differential susceptibility effects of FKBP5.

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