Associations between oxytocin receptor gene (OXTR) methylation, plasma oxytocin, and attachment across adulthood
Open accessAbstract
The neuropeptide oxytocin (OT) has been implicated in a wide range of affiliative processes. OT exerts its functions via OT receptors, which are encoded by the oxytocin receptor gene (OXTR). Epigenetic modification of OXTR through the process of DNA methylation has been associated with individual differences in behavioral phenotypes. Specifically, lower levels of OXTR methylation have been linked to better social and affective functioning. However, research on epigenetic mechanisms of OXTR is scarce in non-clinical populations, and even less is known about epigenetic variability across adulthood. The present study assessed methylation levels at OXTR CpG site -934 and plasma OT levels in 22 young (20–31 years, M = 23.6) and 34 older (63–80 years, M = 71.4) participants. Lower levels of OXTR methylation and higher plasma OT levels were associated with less self-reported attachment anxiety in young but not older participants, with largely independent contributions of OXTR methylation and plasma OT levels. In contrast, in the overall sample, lower levels of OXTR methylation were associated with higher self-reported attachment avoidance. Age analysis suggested that these results were largely driven by young adults. Plasma OT levels were unrelated to attachment avoidance. Taken together, these findings support the emerging notion in the literature that epigenetic properties of OXTR, in addition to endogenous OT levels, are related to adult attachment. Further, the age effects observed in the associations between OXTR methylation, plasma OT, and adult attachment emphasize the importance of adopting a developmental perspective when studying properties of the OT system and their relation to affiliative processes. Findings contribute to growing evidence suggesting that epigenetic modification of genes regulating OT pathways and endogenous OT levels are associated with the way people form and maintain intimate social relationships.
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Written from the paper’s full text.
TL;DR
In a cross-sectional sample of 22 young and 34 older adults, lower OXTR methylation at CpG site -934 and higher plasma oxytocin were associated with less attachment anxiety in young but not older adults. Lower OXTR methylation was also associated with greater attachment avoidance in the overall sample, contrary to the authors’ prediction, with effects largely driven by young adults.
Key findings
- In young participants, lower OXTR methylation (B = .08, β = .44, p = .03, Partial R² = .24) and higher plasma OT (B = −.006, β = −.43, p = .045, Partial R² = .23) were associated with less self-reported attachment anxiety; neither effect was significant in older participants.
- In the overall sample, lower OXTR methylation was associated with higher self-reported attachment avoidance (B = −.05, β = −.36, p = .01, Partial R² = .11), contrary to Hypothesis 3; the OXTR methylation × age interaction was significant (p = .048) but its confidence interval contained 0, and the effect was largely driven by young adults.
- Plasma OT was unrelated to attachment avoidance, and neither main effect of OXTR methylation nor plasma OT on attachment anxiety was significant before considering age interactions.
- Among young participants, 38.1% of variance in attachment anxiety was explained, with OXTR methylation uniquely accounting for 19.6%, plasma OT uniquely for 18.0%, and only 0.5% shared.
Methods
- Cross-sectional subsample of a larger project: 56 adults with blood samples, comprising 22 young (20–31 years, M = 23.6) and 34 older (63–80 years, M = 71.4) participants; only Caucasian individuals were eligible, and older participants were recruited if they scored 30 or higher on the TICS.
- Adult attachment was measured with the ECR-S; OXTR methylation was assessed at CpG site -934 using bisulfite conversion, PCR, and pyrosequencing; plasma OT was measured by EIA without extraction.
- Analyses used regression models with OXTR methylation, plasma OT, age, and their interactions as predictors of attachment anxiety and avoidance, with bootstrapping (2,000 samples), follow-up age-specific regressions, and a Pedhazur communality analysis.
Limitations
- The authors state the design was cross-sectional, so causal direction cannot be determined; individual differences in attachment may drive OT-system changes rather than the reverse.
- The authors note the small sample limited examination of age-by-sex effects and OXTR polymorphism interactions, relied on self-report attachment, held race/ethnicity constant to Caucasian participants, assumed blood OXTR methylation reflects brain methylation, and used a single blood draw.
- The text also makes evident that older adults showed numerically greater variability in OXTR methylation, which may have reduced sensitivity to detect effects in that group, and that the significant OXTR methylation × age interaction for avoidance had a confidence interval containing 0.
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Claims the paper makes
0 of 27 cited sources checked · 0 supported · 0 flagged
- Findingown data
The interaction between OXTR methylation and age on attachment avoidance was significant.
“The interaction between OXTR methylation and age on attachment avoidance was significant (B = .08, β = .24, t(50) = 1.73, p = .048, Partial R2 = .06, CI = [−.03, .14]; however, note that the estimated CI contained 0).”
Quote in the paperSubstantial claim - Findingown data
The interaction between OXTR methylation and age on attachment anxiety was significant.
“both the interaction between OXTR methylation and age (B = −.09, β = −.31, t(50) = −2.24, p = .03, Partial R2 = .09, CI = [−.20, −.03]) and the interaction between plasma OT and age (B = .01, β = .26, t(50) = 1.96, p = .05, Partial R2 = .07, CI = [.001, .01]) were significant”
Quote in the paperSubstantial claim - Findingown data
The interaction between plasma OT and age on attachment anxiety was significant.
“both the interaction between OXTR methylation and age (B = −.09, β = −.31, t(50) = −2.24, p = .03, Partial R2 = .09, CI = [−.20, −.03]) and the interaction between plasma OT and age (B = .01, β = .26, t(50) = 1.96, p = .05, Partial R2 = .07, CI = [.001, .01]) were significant”
Quote in the paperSubstantial claim - Findingown data
The main effect of OXTR methylation on attachment avoidance was significant.
“The main effect of OXTR methylation on attachment avoidance was significant (B = −.05, β = −.36, t(50) = −2.50, p = .01, Partial R2 = .11, CI = [−.08, −.01]).”
Quote in the paperSubstantial claim - Findingown data
In older participants, the effect of plasma OT on attachment anxiety was not significant.
“In contrast, neither the effect of OXTR methylation (B = −.01, β = −.11, t(19) = −.60, p = .56, Partial R2 = .01, CI = [−.06, .03]) nor the effect of plasma OT (B = .001, β = .05, t(19) = .28, p = .75, Partial R2 = .002, CI = [−.003, .004]) on attachment anxiety was significant in older participants.”
Quote in the paperSubstantial claim
- Findingown data
Among young participants, only 0.5% of the variance in attachment anxiety was commonly explained by OXTR methylation and plasma OT.
“Only 0.5% variance in attachment anxiety among young participants was commonly explained by OXTR methylation and plasma OT.”
Quote in the paperNot a substantial claim - Findingown data
Plasma OT levels were not associated with attachment avoidance in young and older participants.
“Thus, our data did not support Hypothesis 4 that plasma OT levels were associated with attachment avoidance in young and older participants (Figure 2D).”
Quote in the paperSubstantial claim - Findingown data
Lower OXTR methylation was associated with more self-reported attachment avoidance.
“However, in contrast to Hypothesis 3, lower OXTR methylation levels were associated with more self-reported attachment avoidance (Figure 1B).”
Quote in the paperSubstantial claim - Findingown data
Among young participants, plasma OT uniquely accounted for 18.0% of the variance in attachment anxiety.
“OXTR methylation uniquely accounted for 19.6% and plasma OT for 18.0%.”
Quote in the paperSubstantial claim - Findingown data
The main effect of plasma OT on attachment avoidance was not significant.
“neither the main effect of plasma OT (B = .002, β = .17, t(50) = 1.26, p = .20, Partial R2 = .03, CI = [−.001, .006]) nor its interaction with age (B = .001, β = .04, t(50) = .30, p = .77, Partial R2 = .002, CI = [−.004, −.008]) on attachment avoidance was significant.”
Quote in the paperSubstantial claim - Findingown data
In older participants, the effect of OXTR methylation on attachment anxiety was not significant.
“In contrast, neither the effect of OXTR methylation (B = −.01, β = −.11, t(19) = −.60, p = .56, Partial R2 = .01, CI = [−.06, .03]) nor the effect of plasma OT (B = .001, β = .05, t(19) = .28, p = .75, Partial R2 = .002, CI = [−.003, .004]) on attachment anxiety was significant in older participants.”
Quote in the paperSubstantial claim - Findingown data
The main effect of plasma OT on attachment anxiety was not significant.
“Neither the main effect of OXTR methylation (B = .02, β = .18, t(50) = 1.28, p = .21, Partial R2 = .03, CI = [−.01, .07], see Figure 1A) nor the main effect of plasma OT (B = −.002, β = −.18, t(50) = −1.34, p = .19, Partial R2 = .03, CI = [−.005, .001]) on attachment anxiety were significant.”
Quote in the paperNot a substantial claim - Findingown data
Among young participants, OXTR methylation uniquely accounted for 19.6% of the variance in attachment anxiety.
“OXTR methylation uniquely accounted for 19.6% and plasma OT for 18.0%.”
Quote in the paperSubstantial claim - Findingown data
The main effect of OXTR methylation on attachment anxiety was not significant.
“Neither the main effect of OXTR methylation (B = .02, β = .18, t(50) = 1.28, p = .21, Partial R2 = .03, CI = [−.01, .07], see Figure 1A) nor the main effect of plasma OT (B = −.002, β = −.18, t(50) = −1.34, p = .19, Partial R2 = .03, CI = [−.005, .001]) on attachment anxiety were significant.”
Quote in the paperNot a substantial claim - Findingown data
Young participants reported higher attachment anxiety than older participants.
“young and older participants differed in their self-reported attachment anxiety, with young participants reporting higher levels than older participants.”
Quote in the paperNot a substantial claim - Findingown data
The interaction between plasma OT and age on attachment avoidance was not significant.
“neither the main effect of plasma OT (B = .002, β = .17, t(50) = 1.26, p = .20, Partial R2 = .03, CI = [−.001, .006]) nor its interaction with age (B = .001, β = .04, t(50) = .30, p = .77, Partial R2 = .002, CI = [−.004, −.008]) on attachment avoidance was significant.”
Quote in the paperSubstantial claim - Findingown data
Reduced OXTR methylation was largely uniquely linked to lower self-reported attachment anxiety in young adults.
“Our exploration of unique vs. shared contributions of OXTR methylation and OT plasma levels on attachment anxiety and avoidance suggested that that lower levels of OXTR methylation and higher levels of plasma OT were largely uniquely associated with less self-reported attachment anxiety in young adults, thus constituting unique predictors of adult attachment anxiety in young adulthood.”
Quote in the paperSubstantial claim- The authors state this as an assumption: OXTR methylation measured in blood reflects OXTR methylation in the brain.
- Findingown data
Elevated plasma oxytocin was largely uniquely linked to lower self-reported attachment anxiety in young adults.
“Our exploration of unique vs. shared contributions of OXTR methylation and OT plasma levels on attachment anxiety and avoidance suggested that that lower levels of OXTR methylation and higher levels of plasma OT were largely uniquely associated with less self-reported attachment anxiety in young adults, thus constituting unique predictors of adult attachment anxiety in young adulthood.”
Quote in the paperSubstantial claim - Findingown data
Among young adults, reduced OXTR methylation correlated with less attachment anxiety.
“Lower levels of OXTR methylation and higher levels of plasma OT were associated with lower attachment anxiety while lower levels of OXTR methylation were associated with greater attachment avoidance in young participants.”
- Also stated in: § 4.4 Conclusion · hedged
“In line with the previous literature (Bell al., 2014; Dadds et al., 2014; Gregory et al., 2009; Jack et al., 2012; Puglia et al., 2015), our data suggests that low OXTR methylation and high plasma OT levels are associated with better social outcomes, (i.e., lower attachment anxiety) in young adults.”
Quote in the paperSubstantial claim- The authors state this as an assumption: OXTR methylation measured in blood reflects OXTR methylation in the brain.
- Also stated in: § 4.4 Conclusion · hedged
- Findingown data
Among young adults, elevated plasma oxytocin correlated with less attachment anxiety.
“Lower levels of OXTR methylation and higher levels of plasma OT were associated with lower attachment anxiety while lower levels of OXTR methylation were associated with greater attachment avoidance in young participants.”
- Also stated in: § 4.4 Conclusion · hedged
“In line with the previous literature (Bell al., 2014; Dadds et al., 2014; Gregory et al., 2009; Jack et al., 2012; Puglia et al., 2015), our data suggests that low OXTR methylation and high plasma OT levels are associated with better social outcomes, (i.e., lower attachment anxiety) in young adults.”
Quote in the paperSubstantial claim - Also stated in: § 4.4 Conclusion · hedged
- Findingown data
The attachment anxiety and avoidance subscales were not correlated in this study.
“In our study, however, the two subscales were uncorrelated, suggesting that they constituted two independent dimensions of adult attachment.”
Quote in the paperSubstantial claim - Findingown data
Among young adults, reduced OXTR methylation correlated with greater attachment avoidance.
“Lower levels of OXTR methylation and higher levels of plasma OT were associated with lower attachment anxiety while lower levels of OXTR methylation were associated with greater attachment avoidance in young participants.”
Quote in the paperSubstantial claim- The authors state this as an assumption: OXTR methylation measured in blood reflects OXTR methylation in the brain.
- Study design and conductcitation
Only Caucasian individuals were eligible because DNA methylation varies across race and ethnicity.
“Only Caucasian individuals were eligible for study participation based on evidence that DNA methylation varies across race/ethnicity (Bakermans-Kranenburg, & Van Iljezdoorn, 2014; Heyn, et al., 2013; Liu et al., 2010).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
EIA without extraction may be the most accurate assessment of OT in human blood plasma.
“This decision was based on tests for parallelism, spike-recovery, and cross-reactivity/specificity validating the present study’s EIA procedure and suggesting that EIA without extraction may constitute the most accurate assessment of OT in human blood plasma (Carter et al., 2009; MacLean et al., 2017; Lancaster et al., 2017).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Carter et al., 2009
Not checked in the free run.
- cites MacLean et al., 2017 source
Not checked in the free run.
- cites Lancaster et al., 2017
Not checked in the free run.
- Interpretationown data
The effect of OXTR methylation on attachment avoidance was largely driven by young participants.
“In particular, the effect of OXTR methylation on attachment avoidance was largely driven by young participants4 (Figure 2C).”
Quote in the paperNot a substantial claim - Premisenone given
No aging data exist on DNA methylation of OXTR and plasma OT levels in their effects on affiliative processes.
“currently, no aging data exists pertaining to DNA methylation of OXTR and plasma OT levels in their effects on affiliative processes, which is the research focus our study took.”
Quote in the paperNot a substantial claim - Premisenone given
Lower OXTR methylation has been linked to better social and affective functioning.
“Specifically, lower levels of OXTR methylation have been linked to better social and affective functioning.”
Quote in the paperSubstantial claim - Study design and conductown data
The ECR-S showed acceptable internal consistency for attachment anxiety and attachment avoidance.
“Cronbach’s alpha in the total sample for attachment anxiety was α = 0.79 (Young participants: α = 0.91; Older participants: α = 0.77) and for attachment avoidance α = 0.87 (Young participants: α = 0.88; Older participants: α = 0.87).”
Quote in the paperNot a substantial claim - Study design and conductreasoning
The findings do not directly test the production, function, or accessibility of oxytocin in the central nervous system.
“Thus, our findings do not provide a direct empirical test regarding production, function, or accessibility of OT within the central nervous system.”
Quote in the paperSubstantial claim - Interpretationown data
This study supports an association between the oxytocin system and affiliative processes in humans.
“Taken together, the current study supports the link between the OT system and affiliative processes in humans and qualifies existing work by suggesting age-differential variations in these associations.”
Quote in the paperSubstantial claim- The authors state this as an assumption: OXTR methylation measured in blood reflects OXTR methylation in the brain.
- Study design and conductown data
The small sample size prevented examination of age-by-sex variations in the effects of epigenome and plasma oxytocin on affiliative phenotypes.
“While our sample comprised men and women, the sample size was small and thus did not allow us to examine age-by-sex variations on the epigenome and plasma OT levels in their impact on affiliative phenotypes.”
Quote in the paperSubstantial claim - Interpretationown data
The findings contribute to growing evidence that epigenetic modification of genes regulating OT pathways and endogenous OT levels are associated with how people form and maintain intimate social relationships.
“Findings contribute to growing evidence suggesting that epigenetic modification of genes regulating OT pathways and endogenous OT levels are associated with the way people form and maintain intimate social relationships.”
Quote in the paperSubstantial claim - Study design and conductcitation
The study kept race/ethnicity constant by including only Caucasian participants.
“Being the first adult developmental examination into this topic, we held race/ethnicity constant to only Caucasian participants based on evidence that DNA methylation varies across race/ethnicity (Bakermans-Kranenburg & Van Iljezdoorn, 2014, Heyn, et al., 2013, Liu et al., 2010).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Dadds et al. (2014) found no link between OXTR methylation and plasma oxytocin in their full sample of young and older boys.
“Also, Dadds et al. (2014) found no associations between OXTR methylation and plasma OT in their total sample of young and older boys.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Dadds et al. (2014) source
Not checked in the free run.
- Interpretationown data
Lower OXTR methylation was associated with greater attachment avoidance, particularly in young adults.
“In contrast to our predictions, however, lower levels of OXTR methylation were associated with greater self-reported attachment avoidance, particularly in young adults.”
Quote in the paperSubstantial claim - Interpretationown data
This study indicates that the associations between OXTR methylation, plasma oxytocin, and attachment vary with age.
“Taken together, the current study supports the link between the OT system and affiliative processes in humans and qualifies existing work by suggesting age-differential variations in these associations.”
Quote in the paperSubstantial claim- The authors state this as an assumption: OXTR methylation measured in blood reflects OXTR methylation in the brain.
- Interpretationown data
The findings support the emerging notion that epigenetic properties of OXTR, in addition to endogenous OT levels, are related to adult attachment.
“Taken together, these findings support the emerging notion in the literature that epigenetic properties of OXTR, in addition to endogenous OT levels, are related to adult attachment.”
Quote in the paperSubstantial claim - Premisecitation
Rubin et al. (2016) found no link between OXTR methylation and plasma oxytocin in psychotic patients and healthy controls.
“Rubin et al. (2016) found no associations between OXTR methylation and plasma OT in their sample of psychotic patients and healthy controls.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Rubin et al. (2016)
Not checked in the free run.
- Study design and conductreasoning
Because the present study was cross-sectional, it cannot establish that lower OXTR methylation and higher plasma oxytocin cause reduced attachment anxiety in young adults.
“Importantly, the adult developmental approach taken in the present study, though highly innovative in this field of study, was cross-sectional in design. Thus, we cannot conclude from the present data that lower levels of OXTR methylation and higher levels of plasma OT cause reduction in attachment anxiety in young adults—in fact, the reverse might be true.”
Quote in the paperSubstantial claim - Premisecitation
Haas et al. found no significant effects for attachment avoidance.
“In fact, Haas et al. found no significant effects for attachment avoidance.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Haas et al., 2016 source
Not checked in the free run.
- Study design and conductown data
The small sample size prevented examination of interactions between OXTR polymorphisms, OXTR methylation, and plasma oxytocin while considering age or sex.
“Moreover, although we collected OXTR polymorphisms in the context of the present study, the small sample size did not allow us to look into interaction effects between OXTR polymorphisms and OXTR methylation and OT plasma levels, while also considering age or sex.”
Quote in the paperNot a substantial claim - Interpretationcitation
The observed age differences are in line with lifespan theory that environmental influences may be less pronounced in later life.
“The observed age differences are in line with theoretical suggestions from lifespan theory that the impact of environmental influences may be less pronounced in later years of life (Baltes, 1997).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Baltes, 1997 source
Not checked in the free run.
- Interpretationown data
The age effects observed in the associations between OXTR methylation, plasma OT, and adult attachment emphasize the importance of a developmental perspective when studying the OT system and affiliative processes.
“Further, the age effects observed in the associations between OXTR methylation, plasma OT, and adult attachment emphasize the importance of adopting a developmental perspective when studying properties of the OT system and their relation to affiliative processes.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 14
- May combine two claims. 12
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataYoung and older participants did not differ in self-reported attachment avoidance.
“The age groups did not differ in their self-reported attachment avoidance.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataYoung and older participants were comparable in OXTR methylation and plasma OT levels.
“The age groups were also comparable in their levels of OXTR methylation (in %) and plasma OT (in pg/ml) (Table 2).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThere were no sex differences in attachment anxiety, attachment avoidance, OXTR methylation, or plasma OT.
“there were no sex differences in attachment anxiety, attachment avoidance, OXTR methylation level, or plasma OT level (Table A in Supplementary Material).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataNumerically there was greater variability in OXTR methylation in older than young adults, although this was not statistically significant.
“Of note, although not statistically significant, numerically there was greater variability in OXTR methylation in older than young adults.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Premisenone givenLittle is known about adult age differences in the associations between OXTR methylation and attachment.
“Further, currently still close to nothing is known about adult age differences in these associations.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataThe plasma OT assay had inter- and intra-assay coefficients of variation below 8%.
“All samples were run at once and the inter- and intra-assay coefficients of variation were less than 8%.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S4 (based).
Premisenone givenNo previous study has examined adult age variability in the association between OXTR methylation and attachment while considering plasma OT levels.
“No previous study, however, has examined adult age variability in the association between levels of OXTR methylation and attachment, thereby also considering variations in plasma OT levels, towards improved understanding of adult developmental mechanisms in affiliative processes.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationGrowing evidence suggests developmental change and aging effects on the OT system.
“There is a growing body of evidence suggesting developmental change and effects of aging on the OT system (Arsenijevic, Dreifuss, Vallet, Marguerat, & Tribollet, 1995; Barraza et al., 2013; Campbell, Ruffman, Murray, & Glue, 2014; Ebner et al., 2013, 2015, 2016; Keck et al., 2000; Melis, Mauri, & Argiolas, 1995; Parker, Hoffman, Hyde, Cummings, & Maestripieri, 2010).”
Quote in the paperSubstantial claim0 of 3 sources checkedClassified as probably not a substantial claim.
Premisenone givenThe respective contributions of OXTR methylation and endogenous OT levels to adult attachment have not been determined.
“Finally, determination of respective contributions of OXTR methylation and endogenous OT levels in their impact on adult attachment has not been undertaken yet.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisenone givenOxytocin has been implicated in a broad range of affiliative processes.
“The neuropeptide oxytocin (OT) has been implicated in a wide range of affiliative processes.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataLower OXTR methylation and higher plasma OT were uniquely associated with less attachment anxiety in young but not older adults.
“our data showed that lower levels of OXTR methylation and higher levels of plasma OT were uniquely associated with less self-reported attachment anxiety in young but not older adults.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenOlder participants were required to score 30 or higher on the Telephone Interview for Cognitive Status.
“For older participants, only those who scored 30 or higher on the Telephone Interview for Cognitive Status (TICS; M = 35.32, SD = 2.53, range = 29–40; Brandt, Spencer, & Folstein, 1988) were recruited into the study2.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Brandt, Spencer, & Folstein, 1988
Not checked in the free run.
May combine two claims.
Study design and conductown dataThe small sample size for age-by-sex subgroups reduced power to detect interaction effects, so participant sex was not included as a factor.
“Given the small sample size for the age-by-sex subgroups in the current study, providing us with reduced power to detect significant interaction effects, we did not consider participant sex as factor in the design.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataPCR amplification was performed in triplicate and samples were randomized to account for plate and run variability.
“performed in triplicate on three identical machines (C1000 Thermal Cycler; Biorad; see also Jack et al., 2012).”
- Also stated in: § 2.3 Measures · plain
“samples during this procedure were randomized to account for plate/run variability.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Jack et al., 2012 source
Not checked in the free run.
- Also stated in: § 2.3 Measures · plain
Classified as probably not a substantial claim.
Premisenone givenSpecific associations between OXTR methylation and adult attachment have not yet been determined.
“However, specific associations between OXTR methylation and adult attachment have not been determined yet.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationThere is growing evidence that the oxytocin system is affected by age.
“This present examination of age-differential associations is particularly relevant, given growing evidence of age effects on the OT system (Campbell et al., 2014; Ebner et al., 2015, 2016).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Campbell et al., 2014 source
Not checked in the free run.
- cites Ebner et al., 2015, 2016
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Classified as probably not a substantial claim.
PremisecitationIt remains unclear how well blood-based DNA methylation reflects DNA methylation in brain loci.
“The extent to which blood-based DNA methylation levels reflect DNA methylation patterns in brain loci specifically, however, is not clear yet (van Ijzendoorn et al., 2011).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites van Ijzendoorn et al., 2011 source
Not checked in the free run.
May combine two claims.
Interpretationown dataAttachment anxiety and avoidance represent two separate dimensions of adult attachment.
“In our study, however, the two subscales were uncorrelated, suggesting that they constituted two independent dimensions of adult attachment.”
Quote in the paperSubstantial claim- The authors state this as an assumption: OXTR methylation measured in blood reflects OXTR methylation in the brain.
May combine two claims.
Study design and conductreasoningThe study used only self-report measures of adult attachment, so it cannot determine whether OXTR methylation and plasma oxytocin predict real behavioral differences across adulthood.
“Limiting the scope of our research and warranting future work is that we relied exclusively on self-report indices of adult attachment and thus cannot determine the extent to which OXTR methylation and plasma OT predict actual behavioral differences in individuals across adulthood.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn boys aged 9-16 years, higher OXTR methylation was linked to lower plasma oxytocin.
“When looking at only the older boys in their sample, however, they observed a negative relationship (i.e., higher OXTR methylation levels were associated with lower plasma OT levels in boys aged 9–16 years).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Dadds et al. (2014) source
Not checked in the free run.
May combine two claims.
Interpretationown dataThe associations between OXTR methylation and plasma OT levels and attachment phenotypes were more pronounced in young than older adults, while levels were comparable across age groups.
“That is, the associations between OXTR methylation and plasma OT levels, and attachment-related phenotypes were more pronounced in young than in older adults, while OXTR levels and plasma OT levels were comparable across these age groups.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationEpigenetic changes in genes that regulate oxytocin pathways, along with endogenous oxytocin levels, are related to how people form and maintain close social relationships.
“Our findings are in line with emerging evidence (Dadds et al., 2014; Haas et al., 2016) suggesting that epigenetic modification of genes regulating OT pathways and endogenous OT levels are associated with the way people form and maintain intimate social relationships with others.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Dadds et al., 2014 source
Not checked in the free run.
- cites Haas et al., 2016 source
Not checked in the free run.
- The authors state this as an assumption: OXTR methylation measured in blood reflects OXTR methylation in the brain.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationEnvironmental processes such as parenting styles, abuse, and chronic stress can lead to methylation of genes critical for neurodevelopment.
“Important environmental processes (e.g., parenting styles, abuse, chronic stress) can lead to methylation of genes critical for neurodevelopment (Meaney & Szyf, 2005; van Ijzendoorn, Bakermans-Kranenburg, & Ebstein, 2011).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Meaney & Szyf, 2005 source
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- cites van Ijzendoorn, Bakermans-Kranenburg, & Ebstein, 2011
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Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPeople with lower DNA methylation of the OXT gene tend to have more secure attachment, marked by less attachment anxiety.
“Our findings regarding attachment anxiety are in line with a recent study showing that individuals with lower DNA methylation levels of the structural gene for oxytocin (OXT) have more secure attachment characterized by lower levels of attachment anxiety (Haas et al., 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Haas et al., 2016 source
Not checked in the free run.
May combine two claims.
Interpretationown dataReduced OXTR methylation and elevated plasma oxytocin are distinct predictors of attachment anxiety in young adulthood.
“Our exploration of unique vs. shared contributions of OXTR methylation and OT plasma levels on attachment anxiety and avoidance suggested that that lower levels of OXTR methylation and higher levels of plasma OT were largely uniquely associated with less self-reported attachment anxiety in young adults, thus constituting unique predictors of adult attachment anxiety in young adulthood.”
Quote in the paperSubstantial claim- The authors state this as an assumption: OXTR methylation measured in blood reflects OXTR methylation in the brain.
The authors state this as an assumption.
OXTR methylation measured in blood reflects OXTR methylation in the brain.
“Further, in the current study we assumed that OXTR methylation in blood is congruent with OXTR methylation in the brain.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Decreased OXTR methylation is associated with lower ratings of self-reported attachment anxiety in young probands.
“decreased OXTR methylation to be associated with lower ratings of self-reported attachment anxiety in young probands (Ebner et al., 2019).”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Ebner et al., 2019
The Results (§3.2.1; page not available) report that lower OXTR methylation was associated with less self-reported attachment anxiety in young participants. The Methods (§2.1; page not available) describe them as healthy adult volunteers, not probands, so the claim’s description of the population is unsupported. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Statistics that don’t add up
Each reported p-value recomputed from its test statistic and degrees of freedom.
Inconsistent p-value across alpha = .05: t(50) = 1.73, p = .048
MajorThe paper reports p = .048 here; recomputing from the test statistic and its degrees of freedom gives p = .090 (two-tailed). The two fall on opposite sides of alpha = .05. The check cannot tell whether the statistic or the p-value is the misprint.
Reported p = .048 · recomputed p = .090
“t(50) = 1.73, p = .048”
Inconsistent p-value: t(19) = −2.36, p = .045
MinorThe paper reports p = .045 here; recomputing from the test statistic and its degrees of freedom gives p = .029 (two-tailed). The check cannot tell whether the statistic or the p-value is the misprint.
Reported p = .045 · recomputed p = .029
“t(19) = −2.36, p = .045”
Inconsistent p-value: t(19) = 2.46, p = .03
MinorThe paper reports p = .03 here; recomputing from the test statistic and its degrees of freedom gives p = .024 (two-tailed). The check cannot tell whether the statistic or the p-value is the misprint.
Reported p = .03 · recomputed p = .024
“t(19) = 2.46, p = .03”
Inconsistent p-value: t(19) = .28, p = .75
MinorThe paper reports p = .75 here; recomputing from the test statistic and its degrees of freedom gives p = .783 (two-tailed). The check cannot tell whether the statistic or the p-value is the misprint.
Reported p = .75 · recomputed p = .783
“t(19) = .28, p = .75”
Inconsistent p-value: t(50) = 1.26, p = .20
MinorThe paper reports p = .2 here; recomputing from the test statistic and its degrees of freedom gives p = .214 (two-tailed). The check cannot tell whether the statistic or the p-value is the misprint.
Reported p = .2 · recomputed p = .214
“t(50) = 1.26, p = .20”
Statistics recomputed
Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.
- Doesn’t add upt(50) = 1.73reported p = .048 · recomputed p = .090The two fall on opposite sides of .05
“t(50) = 1.73, p = .048”
- Doesn’t add upt(19) = 2.46reported p = .03 · recomputed p = .024
“t(19) = 2.46, p = .03”
- Doesn’t add upt(19) = -2.36reported p = .045 · recomputed p = .029
“t(19) = −2.36, p = .045”
- Doesn’t add upt(19) = 0.28reported p = .75 · recomputed p = .783
“t(19) = .28, p = .75”
- Doesn’t add upt(50) = 1.26reported p = .2 · recomputed p = .214
“t(50) = 1.26, p = .20”
- Not confirmedt(50) = -2.5reported p = .01 · recomputed p = .016
“t(50) = −2.50, p = .01”
- Consistentt(50) = 1.28reported p = .21 · recomputed p = .206
“t(50) = 1.28, p = .21”
- Consistentt(50) = -1.34reported p = .19 · recomputed p = .186
“t(50) = −1.34, p = .19”
- Consistentt(50) = -2.24reported p = .03 · recomputed p = .030
“t(50) = −2.24, p = .03”
- Consistentt(50) = 1.96reported p = .05 · recomputed p = .056
“t(50) = 1.96, p = .05”
- Consistentt(19) = -0.6reported p = .56 · recomputed p = .556
“t(19) = −.60, p = .56”
- Consistentt(50) = 0.3reported p = .77 · recomputed p = .765
“t(50) = .30, p = .77”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
An older participant scored below the stated eligibility cutoff
MinorThe paper says only older participants scoring 30 or higher were recruited, but the reported score range starts at 29.
“only those who scored 30 or higher on the Telephone Interview for Cognitive Status”
“range = 29–40”
The citation lists haven’t been fetched yet
References 121 · Cited by 79
- Authors
- Ebner, N. C., Lin, T., Muradoglu, M., Weir, D. H., Plasencia, G. M., Lillard, T. S., Pournajafi-Nazarloo, H., Cohen, R. A., Sue Carter, C., & Connelly, J. J.
- Affiliations
- University of Florida Health (US)
- University of Florida (US)
- Loyola University Chicago (US)
- University of Virginia (US)
- Corresponding author
- Ebner, Natalie C.
- ORCID
- Venue
- International Journal of Psychophysiology
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 136
- Pages
- 22-32
- ISSN
- 0167-8760 (ISSN-L)
- PMC
- PMC6072619
- OpenAlex
- W2790067418
- Semantic Scholar
- 2d73ec3fdce98e4ab430a0159f216e91a75dafa8
- Cited by
- 79
- References
- 121
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 8 · 2023: 13 · 2022: 7 · 2021: 16 · 2020: 12 · 2019: 6 · 2018: 4
- FWCI
- 12.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- International Journal of Psychophysiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Florida
- McKnight Brain Research Foundation
- University of Florida Center for Cognitive Aging and Memory
- University of Florida Clinical and Translational Science (NIH/NCATS; UL1 TR000064)
- Scientific Research Network on Decision Neuroscience and Aging (NIH/NIA, R24 AG039350)
- NIH (P30AG028740)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Social Sciences › Psychology › Social Psychology › Attachment and Relationship Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- oxytocin receptor gene, plasma oxytocin, adult attachment, attachment anxiety, attachment avoidance, epigenetics, age differences, young adults, older adults, affiliative behavior, interpersonal relationships
- MeSH terms
- Adult, Age Factors, Aged, Aged, 80 and over, Anxiety, Female, Humans, Male, Middle Aged, Object Attachment, Oxytocin, Receptors, Oxytocin, DNA Methylation, Epigenesis, Genetic, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-08.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-08.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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