Associations among oxytocin receptor gene (OXTR) DNA methylation in adulthood, exposure to early life adversity, and childhood trajectories of anxiousness

Abstract

Recent models propose deoxyribonucleic acid methylation of key neuro-regulatory genes as a molecular mechanism underlying the increased risk of mental disorder associated with early life adversity (ELA). The goal of this study was to examine the association of ELA with oxytocin receptor gene (OXTR) methylation among young adults. Drawing from a 21-year longitudinal cohort, we compared adulthood OXTR methylation frequency of 46 adults (23 males and 23 females) selected for high or low ELA exposure based on childhood socioeconomic status and exposure to physical and sexual abuse during childhood and adolescence. Associations between OXTR methylation and teacher-rated childhood trajectories of anxiousness were also assessed. ELA exposure was associated with one significant CpG site in the first intron among females, but not among males. Similarly, childhood trajectories of anxiousness were related to one significant CpG site within the promoter region among females, but not among males. This study suggests that females might be more sensitive to the impact of ELA on OXTR methylation than males.

Epigenetic aging in children from a small‐scale farming society in The Congo Basin: Associations with child growth and family conflict

“…In total, our results pertaining to family social stress align with some prior studies in the U.S. and Europe showing that childhood psychosocial stress and trauma were associated with greater EAA (Jovanovic et al, ; Wolf et al, ). Complementing some recent EAA work (Brody, Miller, et al, ; Brody, Yu, et al, ; Lawn et al, ) and previous epigenetics research using epigenome‐wide (Bush et al, ; Essex et al, ; McDade et al, ) and candidate‐gene approaches (Gouin et al, ; Turecki & Meaney, ), our findings indicate that parental conflict may be a component of stressful family environments that merits further study as a correlate of accelerated epigenetic aging in children.…”

“…Complementing some recent EAA work Lawn et al, 2018) and previous epigenetics research using epigenome-wide (Bush et al, 2018;Essex et al, 2013;McDade et al, 2017) and candidate-gene approaches (Gouin et al, 2017;Turecki & Meaney, 2016), our findings indicate that parental conflict may be a component of stressful family environments that merits further study as a correlate of accelerated epigenetic aging in children.…”

Targeted bisulfite sequencing: A novel tool for the assessment of DNA methylation with high sensitivity and increased coverage

“…Associations between early life adversity and altered NR3C1 DNA methylation in non-neuronal cells have been reported, with the majority of studies showing increased NR3C1 promoter DNA methylation following prenatal or postnatal stress exposure (Argentieri et al, 2017); reviewed by (Turecki and Meaney, 2016). Several other candidate genes, including the serotonin transporter gene (SLC6A4; Dammann et al, 2011;Philibert et al, 2007;van IJzendoorn et al, 2010), the FK506 binding protein 5 gene -an important regulator of glucocorticoid sensitivity (FKBP5; Hohne et al, 2015;Klengel et al, 2013;Tyrka et al, 2015;Zannas et al, 2016), and the oxytocin receptor gene (OXTR; Cecil et al, 2014;Gouin et al, 2017;Unternaehrer et al, 2012) have been investigated for differential DNA methylation, and associations with different stress-related phenotypes have been described.…”

“…To illustrate the method, we investigated 90 female individuals (45 with a diagnosis of borderline personality disorder (BPD) and 45 matched healthy controls) for their DNA methylation pattern of genomic regions typically studied in stress research. Assays were performed for the NR3C1 1F promoter fragment including 42 CpGs (McGowan et al, 2009;Moser et al, 2007;Weaver et al, 2004), for the whole SLC6A4 specific CpG island and 3 CpGs located upstream of the CpG island (84 CpGs; Alexander et al, 2014;Beach et al, 2010;Devlin et al, 2010;Kang et al, 2013;Philibert et al, 2007;Zhao et al, 2013), for five CpGs located in the genomic region coding for the FKBP5 (Hohne et al, 2015;Klengel et al, 2013;Tyrka et al, 2015;Zannas et al, 2016), and for 12CpGs located in a putative enhancer element located in intron 3 of the OXTR (Gouin et al, 2017).…”

Epigenetic modification of the oxytocin and glucocorticoid receptor genes is linked to attachment avoidance in young adults

“…During situations of threat or threat anticipation, the availability of positive social contacts (through priming, photographs, or physical presence) not only entailed diminished threat-related responses, but the extent of beneficial influence of positive social contacts on threat-related responses was modulated by the subjectively perceived degree of relationship closeness/quality or participants' attachment style (Coan, Schaefer, & Davidson, 2006;Eisenberger et al, 2011;Krahe, Drabek, Paloyelis, & Fotopoulou, 2016;Norman, Lawrence, Iles, Benattayallah, & Karl, 2015;Tops, Koole, Ijzerman, & Buisman-Pijlman, 2014;Weisman, Zagoory-Sharon, & Feldman, 2013). Concerning a gene by environment interaction in terms of epigenetic modification of the above positive social relationship formation and social stress regulation, as well as HPA axis negative feedback loop systems, accumulating evidence generally points to a role of OXTR and NR3C1 in animals as well as in humans, particularly in the context of early life adversity and stressful life experiences (Bockmuhl et al, 2015;Gouin et al, 2017;Heim & Binder, 2012;Kumsta, Hummel, Chen, & Heinrichs, 2013;Lupien, McEwen, Gunnar, & Heim, 2009;Murgatroyd, Wu, Bockmuhl, & Spengler, 2010;Puglia, Lillard, Morris, & Connelly, 2015;Tyrka et al, 2016;Ziegler et al, 2015).…”