Attachment and Epigenetics: A Scoping Review of Recent Research and Current Knowledge

Abstract

Background

Epigenetic research has pointed to that the interaction between genetics and environmental factors may play a role in making some individuals more vulnerable than others.

Aim

The aim of this article was to present a broad perspective on the current state of knowledge in a relatively new and complex field of “attachment and epigenetic processes.”

Method

We conducted a scoping review based on a systematic literature search in PsycINFO, PubMed, and Embase databases for relevant abstracts using the terms attachment and epigenet*.

Results

In total, 11 studies were included. Research predating 2009 and animal studies were excluded in order to review the current state of research in humans.

Conclusion

Overall, there seems to be a consistency in the literature, pointing to a link between early childhood adversity, attachment processes, and epigenetic changes. However, research in human subjects is still limited.

Keywords

Attachment genetics and behavior mental and physical health public health issues sociobiology

Background

Infant attachment to the caregiver is a strong and enduring bond with unique characteristics such as proximity-seeking behavior. This is to ensure the infant’s care and survival. The behavior was described and explained by the Attachment Theory presented in the 1950s by Bowlby. He postulated that infants internalize their interactions with attachment figures, and that these internalized experiences are the foundation for building internal working models as representations of both themselves and their attachment figures. Further Harry Harlow’s experiments on rhesus monkeys provided important evidence for the significance of attachment formation as a general and inborn characteristic in many species (Bowlby, 1958, 1960a, 1960b). Harlow observed and documented how the attachment to a mere blanket could make the difference between life and death for the infant monkey separated from the mother. This spurred Harlow’s research into monkeys’ emotional and social development including the study of the behavior toward a surrogate mother. As Bowlby, he proposed that the care and comfort of a mother—or surrogate mother—is crucial for the development of good mental health (Seay, Hansen, & Harlow, 1962). It is moreover well established that differences in attachment representations and the resulting inner working models are depending on the quality of maternal sensitivity (Ainsworth, Blehar, Waters, & Wall, 1978; Van Ijzendoorn & Bakermans-Kranenburg, 1997). The dyadic relationship between infant and caregiver also significantly influences emotional and cognitive development, since poor maternal caregiving has been associated with poorer outcomes in offspring (Choe, Olson, & Sameroff, 2013; Kochanska & Kim, 2013). Furthermore, secure attachment has been found to be associated with improved resiliency to overcome adversity (Darling Rasmussen et al., 2018). However, even though these inner working models are stable throughout life, they are not immune to change. Maturation processes will ensure the child optimal conditions and adaptation of the current attachment representation due to a continued need to accommodate changing environmental influences. Parental care is, therefore, an important factor in the emotional and cognitive development of the offspring.

Importantly, researchers have also documented a “transmission gap” as “maternal responsiveness” can only partly explain the intergenerational transmission of attachment (Van Ijzendoorn & Bakermans-Kranenburg, 1997). This has spurred the debate on “nature versus nurture.” In a review, Gervai (2009) states that although sensitivity on the part of parents is well demonstrated as a major factor in the development of offspring attachment representation, there is still an unexplained transmission gap challenging the notion of an exclusively environmental explanation for individual variations in patterns of early attachment. Gervai reviewed the evidence for a gene–environment interaction effect on developing early attachment relationships and concludes that children’s differential susceptibility to environmental factors in upbringing depends at least partly on genetic differences.

This raises the question of whether the interaction between genetics and environmental factors rather than one of the two may play a more significant role in making some individuals more vulnerable than others. If so, this signifies a change in our perception of factors in prevention and treatment. The apparent paradox of why identical genotypes do not necessarily result in identical phenotypes has been discussed for many years. An important aspect of this discussion is centered around the theory of epigenetic modifications. Conrad Waddington was one of the pioneering researchers to introduce the term “epigenetics” in the early 1940s. He defined this as “the branch of biology which studies the causal interactions between genes and their products which bring the phenotype into being.” American geneticist David Nanney also used the term “epigenetics” referring to aspects of biology that cannot be explained by genetics alone. He contributed to the discussion on whether phenotypes are shaped by a combination of nature (our genes) and nurture (environmental influence) by suggesting that cellular expression states can persist through cell division. For a more detailed description of the history of epigenetics, see Deans and Maggert (2015). Epigenetics is today most commonly referred to as “the study of the biological mechanisms that explain how environmental influences result in dynamic variations in physiology and adaptive behaviours without changes in the DNA sequence” (Cappi et al., 2016, 2). Epigenetic research has greatly increased our understanding of the interactions between genetics and environmental factors, resulting in different phenotypes depending on differences in environmental exposures. The smallest known epigenetic modification is called a methyl group. Methylation of DNA sections of the DNA causes silencing of the affected genes. This process is reversible under the right conditions. Hence, it is possible for environmental exposures to affect our health at any stage of life. However, the child is particularly vulnerable to epigenetic modifications, while it is developing in the womb and during the early childhood. Developmental windows of epigenetic reprogramming are known to exist, and exposures occurring during these dynamic periods are more likely to produce changes in the epigenome (Nagy & Turecki, 2012). When it comes to attachment, the formation of attachment representation is also thought to have sensitive periods and developmental periods (A. N. Schore, 2001; J. R. Schore & Schore, 2008). Hence, the investigation of epigenetic markers might be a step toward understanding the effect of events that occur during critical periods of early childhood development as well as later along the life span. Furthermore, this may subsequently add to our knowledge of the development of attachment and, to some extent, account for the “transmission gap.” The question is whether we can use the methods and results of epigenetic research to investigate the genetic influences of attachment and vice versa (Nagy & Turecki, 2012).

Objectives and focus of the review

The aim of this article is to scope the literature on the current state of knowledge in the interdisciplinary field of “attachment and epigenetics.” This summary will be based on only recently published work, to provide an overview of the most recent progress in this field.

Method

Due to the complexity of this area and the risk of overlooking pertinent literature, we chose to conduct a scoping review. A scoping review permits the use of a broad question for investigating research progress in a field, whereas a systematic review requires a highly focused objective.

Scoping reviews are described as a type of knowledge synthesis, following a systematic approach to map evidence and identify main concepts and theories on a topic (Daudt, Van Mossel, & Scott, 2013; Levac, Colquhoun, & O’Brien, 2010). Hence, we applied the methods of a systematic review in the search process with the exception of quality assessment of included studies. As explained by Peterson, Pearce, Ferguson, and Langford (2016), a scoping study is less likely to address narrow and specific research questions consequently making an assessment of the quality of included studies difficult.

Moreover, as there is no consensus on the standard structure of a scoping review, we applied the format, which is typically preferred in reviews: Introduction, Methods, Results, and Discussion.

Search process

Initially, we conducted a broad and unstructured “territory mapping” through Google Scholar on the keywords “attachment and epigenetics” to find out whether there was any relevance to the review, and further if there was more relevance to some keywords than others. This resulted in more than 26,000 hits and by doing a title browsing through the first 20 pages we realized that the term “attachment” in many papers on this topic refers to the physical attachment of centromeres in the DNA. Hence, to scope the literature further, we repeated the procedure using the search term “Psychological Attachment and Epigenetics,” which resulted in 18,900 items, half of which were from the last three years. We therefore restricted the search to material published within the last 10 years. Following these initial search procedures, we conducted our literature search systematically (for an overview of the review and selection process, see Figure 1). A literature search was conducted in the PsycINFO, PubMed, and Embase databases for relevant abstracts using the terms attachment and epigenet*. We carried out our primary literature search in November 2018, resulting in 1477 records. The reference lists of the relevant articles were scanned for additional studies. Four additional articles were found by a manual search, which was conducted in 2019. Overall, this resulted in 15 studies, of which 11 were studies of human material. These 11 studies were included. The four studies of animal material were excluded. Notably, all the included studies were published no earlier than 2010, pointing to rapid development in this area.

Figure 1.

Flowchart—review and selection process.

Eligibility and criteria for inclusion and exclusion

The studies included in this review had a focus mainly on how attachment processes and epigenetic changes may be mutually reinforcing factors. Only studies presenting empirical data and considering epigenetic processes in the attachment formation were included. We included studies on human material only. Non-English literature and papers on epigenetics that did not relate to attachment were excluded. We also excluded reports considered to be of less academic significance: mainly conference papers, editorial articles, and purely descriptive studies. Papers with a focus on “child maltreatment” were considered by both authors and included if consensus on relevance was obtained.

Results

From the included studies, bibliographic characteristics were retrieved mainly from abstract information and systemized in Table 1. This included origin, publication year, population characteristics, and the number of participants. Furthermore, measures applied to assess the attachment and epigenetic focus of each study were assembled in this table along with a short description of the main focus of each. This last information was retrieved as part of the eligibility assessment of each study.

Table 1.

Characteristics of included studies.

First author	Origin/year	N/gender/age	Measures: attachment measure (AM) and epigenetic focus (EF)	Main theme (aim(s))
Tyrka	US/2012	99/58 female/27.3 (SD = 10.4)	AM: PBIEF: NR3C1 promotor methylation	Investigation of epigenetic changes caused by early-life stress.
Haas	Athens/2016	127/72 females/21.37 (SD = 3.49)	AM: ASQEF: DNA methylation of OXT (saliva)	Association between sociability and epigenetic modifications in OXT
Jones-Mason	USA/2016	101/82 female/M = 19.8 years	AM: AAIEF: SLC6A4 methylation of a serotonin receptor gene	Epigenetic markers as the link between environment and developmental processes
Lawn	UK/2018	ASPD: 989Time point 1: 28.7 years (SD = 5.54)/femaleTime point 2: 47.3 years (SD = 4.42)/femaleNSHD: 773/53.4 years (SD = 0.16)/female	AM: SEP and Psychosocial adversity—before the age of 17 and cumulativeEF: DNA methylation age acceleration in adulthood	DNA methylation-based biomarkers as a measure of age acceleration—potential biological mechanism linking environmental exposures to later health outcomes
Ebner	USA/2019	22 young/M = 23.6, SD = 2.95/40.9%female34 older/M = 71.4, SD = 4.82/55.9% female	AM: ECREF: OXTR methylation	The role of epigenetic modification of OXTR in individual differences (age-variability) in behavioral phenotypes
Unternaehrer et al.	Switzerland/2015	89/all female/mean age 27.5 years (SD = 8.4 years)	AM: PBIEF: DNA methylation in two stress-associated genes: two target sequences in the OXTR gene, OXTR and one in the BDNF gene	Maternal caregiving during childhood and association between high versus low caregiving with DNA methylation in the BDNF and OXTR
Ein-Dor	Israel/2018	109/56 female/23.75 years (±1.56)	AM: AASEF: OXTR and NR3C1 promotor methylation	The specific role of attachment in a epigenetic model of social proximity seeking and stress regulation
Mulder	Netherlands/2017	298/43% females/14.58 M (SD = 0.87)	AM: SSPEF: Methylation of FKBP5 in cord blood. (saliva—cortisol)	Examining how parent–child dyadic regulation works in epigenetic aspects of stress regulation
Schechter	Switzerland/2016	70/35 mothers and 35 children/gender/age	AM: DAIEF: HTR3A gene methylation at CpG2_III	Methylation status in mothers linked to maternal exposure to violence, maternal neural activity, and child attachment
Bosmans	Netherlands/2017	487/56% female/11.84 years (SD = 2.4)	AM: ECR-RSEF: NR3C1 methylation	The role of epigenetic processes in development of attachment
Van Ijzendoorn	Netherlands/2010	143/50% female/mean age 39 years (SD = 7.32)	AM: AAIEF: Methylation of CpG sites at the 5HTTLPR locus	The role of epigenetic factors in individual vulnerability

Note: PBI: Parental Bonding Index; ASQ: Attachment Style Questionnaire; OCD: Obsessive Compulsive Disorder; AAS: Adult Attachment Scale; SSP: Strange Situation Procedure; DAI: Disturbance of Attachment Interview; TSA: TrichoStatin A; ECR-RS: Experiences In Close Relationships—Relationship Structures Questionnaire; MSSP: Mouse Strange Situation Procedure; AAI: Adult Attachment Interview; OXTR: Oxytocin Receptor; ASPD: Avon Longitudinal Study of Parents and Children; NSHD: National Survey of Health and Development; SEP: socioeconomic position; OXT: oxytocin; BDNF: brain-derived neurotrophic factor; FKBP5: FK506 binding protein 51; SD: standard deviation.

Synthesis of main findings

The common notion today when it comes to the quality of attachment representation is that it is the result of genetic as well as social factors (Murgatroyd & Spengler, 2011). However, research on the genetic component is limited, and neither genetics nor environmental factors does sufficiently explain the development of attachment. Moreover, how differences in attachment representations may arise is not fully explained. Epigenetic research may shed light on some of the uncertainties. The studies presented later have contributed to our knowledge in this area, since, despite differences in genetic focus, they all aim to increase knowledge of the gene–environment interaction. For a brief overview of main results, see Table 2.

Table 2.

Summary of main findings.

Author	Main findings
Tyrka et al.	Disruption or lack of adequate parental nurturing was associated with increased gene methylation, which was in turn linked to attenuated cortisol responses.
Haas et al.	Lower OXT DNA methylation (presumably linked to higher OXT expression) results in more secure attachment styles and improved ability to recognize emotional facial expressions. These findings provide a link between epigenetic modification and sociability in humans.
Jones-Mason et al.	Within the unresolved category of attachment, low-SES unresolved participants had higher levels of methylation than mid/upper-SES participants did. SES was unrelated to methylation within the secure and organized categories. This suggests that the quality of attachment relationships may impact epigenetic processes.
Lawn et al.	A cumulative score of several psychosocial adversity measures such as sexual abuse were associated with DNA methylation age acceleration in adulthood suggesting a potential for adverse outcomes.
Ebner et al.	The study assessed associations between OXTR methylation, plasma oxytocin (OT), and attachment in young and older adults and found lower methylation and higher OT to be associated with less attachment anxiety in young but not in older adults.
Unternaehrer	Low maternal caregiving in childhood was associated with greater DNA methylation in an OXTR and a BDNF target sequence in adulthood indicating components of the epiphenotype from early-life stress.
Ein-Dor et al.	This study examined relations between intraindividual differences in attachment and epigenetic modification of the OXTR and glucocorticoid receptor (NR3C1) gene promoter. Attachment avoidance was significantly and specifically associated with increased OXTR and NR3C1 promoter methylation.
Mulder et al.	A study of stress reactivity, and specifically of associations between attachment, extreme maternal insensitivity, and gene methylation, with cortisol reactivity to the Strange Situation Procedure. It was found that FKBP5 methylation seems to moderate the associations of FKBP5 genotype and resistant attachment with cortisol reactivity.
Schechter et al.	Maternal severity of interpersonal violence exposure was associated with diagnosis of maternal post-traumatic stress disorder. • This was in turn associated with disturbed child attachment.
Bosmans et al.	This study found that more stressed children who experience less maternal support reported increased anxious attachment when their NR3C1 gene was highly methylated. This effect could not be explained by the children’s level of psychopathology.These findings indicate that epigenetic processes are involved in attachment development.
Van Ijzendoorn et al.	The study found associations between 5HTTLPR polymorphisms and psychological problems to be significantly influenced by environmentally induced methylation patterns. This indicates methylation to be a mediating factor between adverse environment and developmental trajectories.

Note: SES: socioeconomic status; OXT: oxytocin; OXTR: oxytocin receptor; FKBP5: FK506 binding protein 51; BDNF: brain-derived neurotrophic factor.

The first study by Tyrka, Price, Marsit, Walters, and Carpenter (2012) aims to examine the degree of methylation of a variety of CpG sites of the promoter region, NR3CI, of the human glucocorticoid receptor (GR) gene. This was measured in leukocyte DNA from 99 healthy adults. They found parental behavior and lack of adequate nurturing caused by factors such as parental death or desertion, and childhood maltreatment to be linked with increased methylation of the CpG 1 site (r = 2.23, p = .03 and F = 5.9, p = .02, respectively) in the NR3C1 promotor region. This was in turn associated with attenuated cortisol responses in the neuroendocrine challenge test dexamethasone/corticotropin-releasing hormone (p = .05). The authors conclude that childhood adversity may cause epigenetic modifications and hence activity of the GR gene. Differences in methylation of the CR gene may, therefore, represent a link between childhood adversity and stress reactivity, which is further associated with the risk of deviant developmental trajectories including the risk of developing psychopathology.

In the next study, the neuropeptide oxytocin (OXT) is investigated. Although it is well known that oxytocin is involved in the mammalian tendency to be social, very little is currently known regarding the way the structural gene for the expression of oxytocin is involved in differences in human sociability. Haas et al. (2016) aimed therefore to investigate the association between epigenetic modification of OXT via DNA methylation social processing and behavior, and brain function and structure. Saliva samples were collected from 129 adults recruited from the University of Georgia and the surrounding community (72 females, 57 males; mean age = 21.37 years, standard deviation (SD) = 3.49 years). DNA was extracted from these samples in order to quantify methylation across the promoter region of OXT. Next, the participants were assessed using a series of sociability measures, including the self-reported measure of attachment style; Attachment Style Questionnaire designed to assess both anxious and avoidant attachment styles. Overall, they found that participants exhibiting lower OXT DNA methylation (thought to be linked to higher OXT expression) displayed a number of associated traits such as more secure attachment styles and an improved ability to recognize emotional facial expressions. Functional magnetic resonance imaging (MRI) tasks revealed greater activity in the superior temporal sulcus during the social–cognitive tasks and larger fusiform gyrus gray matter volume.

In a third study, Jones-Mason, Allen, Bush, and Hamilton (2016) conducted a pilot study to examine the potential link between socioeconomic status (SES), attachment, and methylation of the promoter region of the serotonin transporter gene (SLC6A4). The project included 101 adolescents from a large public university in the western United States. The majority were female (n = 82), and the mean age was 19.8 years. Attachment representation, including the assessment of unresolved state with respect to loss and trauma, was determined using the Adult Attachment Interview (AAI). DNA was extracted from peripheral lymphocytes, and gene methylation was measured by “sodium bisulfate methylation mapping” in which unmethylated cytosines are converted to uracil. The authors hypothesized and found SES, unresolved trauma, and methylation state to be interactive. In more detail, the results revealed lower methylation and low-SES to be associated with higher scores on unresolved loss, and higher methylation and low-SES to be associated with higher unresolved trauma. Participants in the unresolved category differentiated with respect to SES, as higher levels of methylation were associated with low-SES. Furthermore, SES was not related to methylation within the secure and organized categories of attachment representations, which may be indicative of the protective properties of secure attachment. Overall, the results indicate that the quality of attachment relationships might affect epigenetic processes.

A study by Lawn et al. (2018) did not use an attachment measure per se, but applied a wide range of measures to collect data on childhood adversity (parental physical or mental illness or death), parental separation, parental absence, suboptimal maternal bonding, sexual, emotional, and physical abuse and neglect. As psychosocial adversity in childhood and low socioeconomic position (SEP) is known to affect social and health outcomes and be correlated with attachment style (Alhusen, Hayat, & Gross, 2013), this study was included in our review. The aim was to investigate whether environmental factors may be associated with epigenetic age acceleration. DNA methylation-based biomarkers are known to be highly correlated with chronological age. However, methylation may also be useful in defining a measure of age acceleration, representing a potential biological link between environmental exposures and later health outcomes. In this study, the authors used data from two cohorts of women: Avon Longitudinal Study of Parents and Children (ALSPAC) and MRC National Survey of Health and Development (NSHD). In ALSPAC, 989 women had methylation measured during pregnancy (mean age: 29 years) and/or at a follow-up 17 years later (mean age: 47 years). In NSHD, 773 women, age 53 years, had methylation measured. Overall, the ALSPAC follow-up found that sexual abuse was strongly associated with age acceleration, presenting 3.41 years higher DNA methylation age (95% confidence interval: 1.53–5.29) even after adjusting for SEP. Data on sexual abuse were not available from the women in NSHD. Furthermore, there was no association between low SEP and other types of psychosocial adversity.

Ebner et al. (2019) aimed to investigate epigenetic mechanisms related to the oxytocin receptor gene (OXTR) in nonclinical populations. Furthermore, they included the question of age-dependent variability in the circulating plasma oxytocin. Consequently, they assessed methylation levels at OXTR CpG site-934 and plasma OT levels in 22 young (20–31 years, mean (M) = 23.6) and 34 older (63–80 years, M = 71.4) participants. They found lower levels of OXTR methylation and higher plasma OT levels to be associated with less self-reported attachment anxiety but only in the younger group. In the overall sample, lower levels of OXTR methylation were associated with higher self-reported attachment avoidance. However, the analysis showed this finding mainly to be applicable to the younger population. Furthermore, plasma OT levels were found to be unrelated to attachment avoidance. Overall, the authors conclude that their findings support that not only endogenous OT levels but also epigenetic properties of OXTR seem to be a factor in adult attachment representations.

In a cross-sectional study, Unternaehrer et al. (2015) recruited participants from a large group scoring either high (n = 47) or low (n = 42) on the maternal care subscale of the Parental Bonding Index. In total, 85 consented to give blood in order to determine DNA methylation in two stress-associated genes: two target sequences in the oxytocin receptor gene, OXTR, and one in the brain-derived neurotrophic factor gene, BDNF. Using mixed-model statistical analysis, they showed low maternal care in childhood to be associated with greater DNA methylation in the BDNF target sequence and in one of the OXTR target sequences. This study has important limitations mentioned by the authors such as the cross-sectional design and wide age range as well as the uncertain relevance of changes in blood cells for gene methylation in the brain. However, the findings may point to potential components of an “early life stress” phenotype.

Ein-Dor, Verbeke, Mokry, and Vrtička (2018) also sought to illuminate the genetic component of the environment interaction by measuring epigenetic DNA modification related to the attachment. In this study, they recruited 109 adult participants and investigated intraindividual differences in attachment representation using self-reported attachment anxiety and avoidance measures derived from the Adult Attachment Scale based on the original self-report measure of adult romantic attachment (Hazan & Shaver, 1987). The epigenetic focus was the OXTR and GR (NR3C1) gene promoter, and the results revealed attachment avoidance to be significantly associated with increased OXTR and NR3C1 promoter methylation. The authors conclude that the findings may add to the knowledge of the possible etiology of attachment avoidance as they demonstrate an epigenetic modification in genes related to both social stress regulation and hypothalamic–pituitary–adrenal (HPA) axis functioning.

Mulder et al. (2017) are also investigating the potential role of genetic and epigenetic factors in the infant stress regulation system, and how these modifications may interact with maternal sensitivity and attachment. They recruited pregnant women from the prospective population-based cohort, Generation R (Peterson et al., 2016). This later resulted in the assessment of attachment representation by the Strange Situation Procedure in 298 infants at age 14 months (M = 14.58, SD = 0.87). The genetic focus in the study was the FK506 binding protein 51 (FKBP5) genotype, and the epigenetic focus was DNA methylation, as these have been associated with activity in the HPA axis. More specifically, they studied infant cortisol reactivity to the Strange Situation Procedure in order to investigate the associations between attachment, extreme maternal insensitivity, and FKBP5 methylation. The results indicated that FKBP5 methylation moderates the associations of FKBP5 genotype and resistant attachment. Hence, the authors suggest that increased knowledge in the field of epigenetics of developmental psychopathology may lead to a more detailed knowledge of the interaction between genetics and parenting in infant stress reactivity.

According to Schechter et al., there is a link between methylation of the serotonin 3 A receptor gene (HTR3A), child maltreatment, and adult psychopathology. Hence, in this study, they are examining whether HTR3A methylation might also be associated with mothers’ lifetime exposure to interpersonal violence (IPV), IPV-related psychopathology, child disturbance of attachment, and maternal neural activity. In a sample of 35 mothers and children aged 12 to 42 months, they found maternal IPV exposure-frequency to be associated with maternal posttraumatic stress disorder (PTSD). This was in turn associated with child attachment disturbance as measured by “secure base distortion” (SBD). Regarding epigenetics, they found the degree of methylation on several CpG sites in the HTR3A gene to be associated with maternal IPV and IPV–PTSD severity and also child SBD (Schechter et al., 2017).

A prospective study by Bosmans, Young, and Hankin (2018) examined the potential interaction between methylation of the GR Gene (NR3C1), stress, and experienced maternal support. They expected insecure attachment representations (anxious and avoidant attachment) to be predicted by synergistic interaction of low maternal support and higher NR3C1 methylation. Furthermore, this effect would be reinforced in the context of exposure to stress. The study was conducted in a general population sample of 487 children and adolescents recruited from the Gene–Environment Mood study, a longitudinal study focusing on child and adolescent as well as social and emotional development; 44% were boys, and the age ranged from 7 to 16 years (M = 11.6, SD = 2.4). A longitudinal design was chosen in order to determine potential epigenetic processes in the manifestation of attachment representations when the context of stress and parental support overtime was taken into consideration. The sample was followed for a period of 18 months in which attachment style was determined at baseline and 18 months later by the self-report questionnaire, Experiences In Close Relationships—Relationship Structures Questionnaire. Methylation levels were determined using quantitative bisulfite pyrosequencing in a three-way interaction between NR3C1 methylation, stress, and attachment. This was done for each attachment dimension (secure/insecure, avoidant, and anxiety). Level of stress was established as a measure of chronic stress severity by the Youth Life Stress Interview (Rudolph & Flynn, 2007), and as longitudinal stress exposure by the Adolescent Life Events Questionnaire (Hankin & Abramson, 2002). Maternal support was reported by mother and child both to avoid “mono-informant bias” by the Network of Relationships Inventory (Buhrmester & Furman, 1985). The authors conclude that these findings point to the possibility of predicting individual differences in insecure attachment levels at 18 months from baseline by high levels of NR3C1 methylation, low maternal support, and high chronic stress.

Van IJzendoorn, Caspers, Bakermans-kranenburg, Beach, and Philibert (2010) also investigate the role of genetic and epigenetic factors in making some individuals more prone to vulnerability than others in the context of traumatic experiences. More specifically, they were interested in why the loss of attachment figures or other traumatic events seems to have greater impact on some individuals than others. The sample in this study was recruited from The Iowa Adoption Studies, which is a series of studies on children adopted in the first few months after birth into middle-class families. The current sample consisted of 143 adoptees with a mean age of 39 years, (SD = 7.32), 91% Caucasian, and 50% female. They all participated in the Berkeley AAI to establish unresolved loss or trauma. The transcribed interviews were coded “blindly” by reliable raters and intraclass correlation was r = .76. Furthermore, depressive symptoms were assessed by The Brief Symptom Instrument to determine a potential concurrent mood disturbance. Genotyping of the 5HTTLPR locus was carried out in DNA obtained from lymphoblast cell lines and rate of methylation measures for each of the CpG residues was assessed using quantitative mass spectroscopy. Overall, they found associations between 5HTTLPR polymorphisms and psychological problems to be influenced significantly by environmental factors mediated by differences in methylation patterns. They found higher levels of methylation of the 5HTT promoter-associated CpG site to be associated with increased risk of unresolved state with respect to loss or other trauma in carriers of the 5HTTLPR ll variant which is usually considered protective, whereas the ss variant of 5HTTLPR predicted more unresolved loss or trauma only in the context of lower levels of methylation.

The authors conclude that different outcomes arise from the same genotype and that methylation may serve as the link between adversity and the developmental trajectories.

Discussion

In this study, we aimed to review the latest research in order to report on the current state of knowledge in the interdisciplinary field of “attachment and epigenetic processes.” Our objective was to review the potential contribution of these studies to the current literature in the field of epigenetics and attachment, as this field uncovers the mutual interactions between genetics and environmental factors. Therefore, epigenetics may help to bridge the gap in our understanding of genetics versus environmental influences.

We chose to conduct a scoping review as it allows a broad question for investigating progress in a field. Conducting an initial and broad “territory” search on Google Scholar, we found half of the query material to originate from the past three years. Looking further back, there is not nearly the same concentration of studies. Moreover, these previous studies are primarily on animal models. This may indicate that the area is relatively new and in a significant developmental trajectory. Scoping reviews serve primarily to provide a periodic synthesis of the most recent developments in a designated area, including diverse findings and lack of consensus. Hence, we limited our study to include studies from the past 10 years. Furthermore, we excluded animal studies.

Historically different models of health have dominated the research when seeking to clarify factors leading to illness or health. For many years, there has been a debate on the importance of different explanatory models for the etiology of disease and symptom development. In 1948, the following statement was issued by the World Health Organization (Grad, 2002):

Health is a state of complete physical, social and mental well-being and not merely the absence of disease or infirmity. The enjoyment of the highest attainable standard of health is one of the fundamental rights of every human being, without distinction of race, religion, political beliefs or economic and social conditions.

The Medical Model developed during the age of enlightenment in the 18th century, when the traditional natural sciences began to dominate academia. The Medical Model has formed the basis for important breakthroughs in medical research. However, it assumes developmental trajectories in disease to be attributable to a specific organ. Further that the trajectory of disease is unrelated to factors in the life of each individual. Hence, this model has also been criticized for its failure to perceive the patient as a human being taking part in a world with many and diverse daily influences. The criticism has resulted in opposing views developed from the social model of health, which has been strongly advocated by the disability rights movement. However, the social model of health is to some degree equally reductionistic in that its principal focus is the contribution of psychosocial influences to the development of the disease.

Finally, a more balanced view was offered by the bio-psycho-social disease model moving away from the dichotomous mind-set of “either-or” and perceiving disease and/or health as a result of dynamic interactions between the factors from the two abovementioned models. That is, man can have innate biological factors representing strengths as well as weaknesses, and these are under continuous influence and contribution of psychological and social circumstances.

Epigenetics does not offer yet another model to those that exist, but it may help in the efforts to understand the mechanisms of the bio-psycho-social model. It may further serve to nuance ongoing debate on the principal causes of adverse developmental trajectories. Although there has been a rapid development in epigenetics, as a research field, it has continued to focus mainly on developmental pathways for psychopathology. It is well recognized that genetics alone cannot explain phenotypes and adverse developmental trajectories. Hence, more general development processes may also play an important role as they may serve as fundamental factors in overall prognosis. However, it is still not very well understood how environmental factors may exert effect on the resulting phenotypes. For example, the child attachment representation is known to play an important role in child development and is thought to be a result of complex genetic processes interacting with environmental factors. Studies suggest that problems in the parent–child relationship may be a contributing factor (Prevatt, 2003; Storebø, Darling Rasmussen, & Simonsen, 2013). Furthermore, a strong correlation has been found between the attachment representation of mother and offspring (Van IJzendoorn & Bakermans-Kranenburg, 1996). However, no definitive genetic or environmental factor has been implicated. As mentioned in the introduction, there is a well-known “transmission gap,” which cannot be explained solely by maternal sensitivity (Fonagy & Target, 2005). This transmission gap seems to be even greater in clinical populations (Darling Rasmussen et al., 2019), which may indicate that epigenetic modifications may play a role.

As the overarching theme in all of the included studies of this review is the importance of methylation status for selected gene sequences. However, the selection of gene-sequence varied greatly, presenting the possibility of many and diverse gene-sequences implicated in a potential “attachment-epigenetic” link. In the study by Van IJzendoorn et al. (2010), they found genetic polymorphism to be of potential importance. The findings suggest that associations between genetic polymorphisms and psychological problems are significantly altered by environmental factors resulting in diverse gene expression. Importantly, this seems to be mediated by differences in methylation patterns.

Some studies reveal emerging common themes in gene selection with, for example, three studies (Bosmans et al., 2018; Ein-Dor et al., 2018; Tyrka et al., 2012) predicting and finding NR3C1 promoter methylation to be associated with attachment-related factors (e.g., avoidance). Bosmans found children’s anxious attachment levels (but not the avoidant attachment) to be predicted from a three-way interaction between NR3C1 methylation, children’s stress exposure, and maternal support, as lower levels of maternal support were linked to higher levels of attachment anxiety. This association was significant only in the context of greater stress exposure, which may be explained by the nature of the attachment system. The attachment system is typically activated as a result of stressful events. This was further associated with levels of NR3C1 methylation underlining the complexity of this field and of human development in general. Tyrka et al. support these findings, as they found early-life stress to be associated with epigenetic changes. In this study, the epigenetic focus was also NR3C1, as they investigated the methylation of this promoter region of the GR gene. They found methylation of the promoter region to be linked to functional changes in the HPA axis linking adversity to daily health and functioning. Adverse childhood experiences, in the form of loss of a parent during childhood, maltreatment, and low parental care, were associated with increased NR3C1 promoter methylation (p = .05), which was further linked to attenuated cortisol responses. They conclude that their findings provide support for methylation as a mechanism linking environmental factors to the function of the neuroendocrine system.

Another theme emerging from the included studies is the study of oxytocin (Ebner et al., 2019; Haas et al., 2016; Unternaehrer et al., 2015). Oxytocin is a well-known neuropeptide in attachment research (Buchheima et al., 2009; Tops, Van Peer, Korf, Wijers, & Tucker, 2007). However, in these studies, the aim and focus was the interaction between adversity and modification of the structural gene by DNA methylation. Overall, the finding indicates gene expression underlying the circulating oxytocin to be influenced by environmental factors. Oxytocin is known to be important not only during birth but also in the process of attachment formation (Buchheima et al., 2009).

Some findings are particularly worthy of note. The study by Schecter et al. found the severity of IPV exposure in mothers to be associated with altered DNA methylation in selected sites in the mothers and further disturbed child attachment mediated by maternal post-traumatic stress disorder. This points to the intergenerational effects of adversity (Schechter et al., 2017). Intergenerational effects may be mediated by epigenetic modification as suggested in a study on maternal behavior (Elmadih & Abumadini, 2019).

Age-dependent variability as a factor in epigenetics is proposed by Lawn and Ebner, as their findings suggest the process of DNA methylation to be correlated with chronological age (Ebner et al., 2019; Lawn et al., 2018). This further suggests that sensitive periods should be an area of interest in future research.

The findings of the studies in this review are in line with animal studies pointing to epigenetic processes playing an essential role in the relationships between maternal care and negative outcomes in offspring. Hence, this is not unique to humans. Animal studies suggest that early developmental phases and processes are open to epigenetic programming, which may have a significant impact on life, developmental trajectories, and susceptibility to diverse negative outcomes (Weaver, 2009; Weaver, Meaney, & Szyf, 2006).

Overall, as suggested by Bossmans et al., investigation of epigenetic processes is a complex area but it may be a way to expand our understanding of core features of human development, such as attachment, and to contribute to closing some of the gaps and inconsistencies associated with attachment theory and research on gene–environment interactions.

In conclusion, it seems we may have entered a new era in which the boundaries between nature and nurture are dissolving.

Methodological considerations

When conducting a review, there are initial considerations to take before choosing the review type. Narrative overviews (NRs) are often considered one of the weakest forms of evidence. Contrary to the systematic review benefitting from the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines along with rigorous methods to identify, critically evaluate, and synthesize all relevant studies, no consensus and clear guidelines exist on publication standards for the NR. However, the systematic review (SR) may be better suited to focused clinical issues, whereas the NR primarily deals with giving an overview of broader areas (Bartolucci & Hillegass, 2010).

The NR has significant shortcomings worth mentioning. Most importantly, as it does not usually meet the stringency criteria of the method applied to systematic reviews, there is a high risk of bias (Green, Johnson, & Adams, 2006). However, since NRs and SRs are written retrospectively, they are both prone to bias (Ferrari, 2015). The NR is considered useful in keeping up-to-date on a research topic and for prompting further investigation of new and unexplored areas. Hence, the NR paper is popular among clinicians, as it provides an overview of the current state of knowledge in specific areas. A literature review in any form is often more up to date than textbooks and helps place information into perspective. Nevertheless, as NR is increasingly being rejected by peer-reviewed journals; this may overall result in loss of important research development and advances.

Consequently, as literature reviews still constitutes an important part of the literature, publication standards are needed to ensure that the reader is provided with relevant information in complex areas for evaluating the quality and relevance of the reported results.

The scoping review comprises a different type of systematic review, but as a technique to “map” relevant literature, it has not received much attention until in recent years. The main differences between a systematic review and a scoping review are primarily that the systematic approach typically focuses on a well-defined question, while the scoping review allows the researcher to address broader topics and different study designs in included studies (Peterson et al., 2016). Daudt et al. (2013) has proposed a revised definition: “scoping studies aim to map the literature on a particular topic or research area and provide an opportunity to identify key concepts, gaps in the research; and types and sources of evidence to inform practice, policymaking, and research.”

Indeed, we found it hard to get started like many other reviewers of complex research areas. Firstly, we were uncertain of which part of epigenetic research might be involved in attachment research. Secondly, as this subject combines developmental psychology with biomedicine we did not know which database was most likely to display the literature we were looking for. Accordingly, we conducted a broad “territory mapping” displaying a large body of evidence. Thirdly, during the initial search and evaluation of the studies, we realized that narrowing down our focus too much might rule out our initial scope to provide an overview of the research linking epigenetic processes to the development of attachment representation. Hence, we held on to the systematic approach known from SR, but also to the relatively broad search terms and therefore decided to name our study a narrative and theoretical review. Accordingly, the most important limitation of our study is attempting to make generalizations based on relatively scarce and diversified literature.

Implication for practice

On the cover page of Times Magazine in January 2010 it said “Why your DNA isn’t your destiny.” Epigenetic research has revealed to us that genes can be activated or silenced in response to environmental factors. This is of great importance, as it challenges the determinism that for some time has dominated the debate on genetic influence. Epigenetic modification is a process that can be activated by a variety of events and daily influences such as exposure to diet and social experiences (Tammen, Friso, & Choi, 2013). In this respect, formation of attachment bond becomes of interest as the interplay between child and caregiver represents one of the earliest environmental signals to the genome (Elmadih & Abumadini, 2019). Attachment representations are important throughout life and are known to play a vital part in, for example, regulation of stress and emotions. Hence, attachment is also suggested to be an important factor in differing health outcomes (McWilliams & Bailey, 2010; Nolte, Guiney, Fonagy, Mayes, & Luyten, 2011; Puig, Englund, Simpson, & Collins, 2013).

The aim of this article was to present a broad perspective on the state of research in a relatively recent and complex field. Knowledge synthesis is an important factor in health-care research, as it helps make sense of the massive amounts of primary research for clinical practice and practitioners. Thus, as a scoping review, this article may be useful as an educational article as it seeks to pull pieces of information together into an accessible format. However, in order to complete our understanding of the development of attachment, there is a need to further explore the role of epigenetics in different developmental trajectories.

Supplemental Material

PRX901846 Supplemental Material1 - Supplemental material for Attachment and Epigenetics: A Scoping Review of Recent Research and Current Knowledge

Supplemental material, PRX901846 Supplemental Material1 for Attachment and Epigenetics: A Scoping Review of Recent Research and Current Knowledge by Pernille Darling Rasmussen and Ole Jakob Storebø in Psychological Reports

Supplemental Material

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Supplemental material, PRX901846 Supplemental Material2 for Attachment and Epigenetics: A Scoping Review of Recent Research and Current Knowledge by Pernille Darling Rasmussen and Ole Jakob Storebø in Psychological Reports

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Supplemental material, PRX901846 Supplemental Material3 for Attachment and Epigenetics: A Scoping Review of Recent Research and Current Knowledge by Pernille Darling Rasmussen and Ole Jakob Storebø in Psychological Reports

Footnotes

Notes

ORCID iD

Pernille Darling Rasmussen

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