These results point to independent genetic effects on maternal sensitivity of 5-HTT SLC6A4
and OXTR rs53576
polymorphisms, taking into account differences in educational level, depression and marital discord. We found lower levels of sensitive responsiveness to their toddlers in parents with the potentially less efficient variants of the serotonergic and oxytonergic system genes. The genetic effects did not interact with depression or the quality of the marital relationship and neither depression nor the marital relationship was associated with the genotypes examined in the current study. Thus, differences in sensitive parenting appear to be associated with molecular genetic differences that may implicate the production of oxytocin. Sensitive parenting is a well-documented crucial determinant of young children's socio-emotional development with long-lasting consequences (Cassidy and Shaver, 1999
; Sroufe et al
; Belsky et al
), underscoring the relevance of our findings.
Given the important role of the oxytocin system in affiliative relationships OXTR
is an excellent target in a candidate gene approach involving parental caregiving of offspring (Carter, 1998
). Oxytocin not only has a critical role in birth and lactation but also in the emergence of an intimate bond with offspring, as it may lower feelings of stress and fear (Carter, 1998
; Young, 1999
; Numan, 2006
; Emiliano et al
). Beyond the reduction of anxiety oxytocin is suggested to have specific rewarding or hedonic effects that may facilitate parenting (Numan and Insel, 2003
). Our study is one of the first suggesting functional implications for GG vs
AG and AA variants of OXTR
, although the underlying processes linking variants of the OXTR
gene to actual oxytocin levels in humans have not yet been clarified. In previous studies, variations in OXTR
have been related to autism. In a study in the Chinese Han population preferential transmission of A over G was found for rs53576
(Wu et al
), indicating genetic vulnerability to autism in carriers of the A allele—the same genotypic variant that was related to lower levels of sensitivity in our study. Replication in a Caucasian sample showed preferential transmission of G over A at rs2254298
for children with autism, but no significant association with rs53576
(Jacob et al
). These findings point to OXTR
as an excellent candidate for mediating genetic vulnerability to autism, but they also indicate its potential for studies on the association with sensitive parenting, which presupposes awareness of and empathy with children's needs and subtle emotional signals.
In contrast surprisingly little evidence supporting the significance of 5-HTT
genes for parenting has been reported (Numan and Insel, 2003
). Serotonin has been associated with negative emotions, such as anxiety or stress, although meta-analyses on linear relations between 5-HTT SLC6A4
and anxiety related traits have shown somewhat divergent results (Sen et al
; Munafo et al
). Here we suggest that 5-HTT SLC6A4
is associated with parenting through its potential influence on the oxytonergic system as we did exclude the possibility that its influence would be through its associations or interactions with maternal depression.
The influence of genetic differences in 5-HTT
(3% explained variation) and OXTR
(3% explained variation) genes on parenting is much smaller than the association between sensitive parenting and parental educational level (15% explained variation). As Kagan et al
) recently argued, most psychological traits and behaviors may be better explained by a combination of basic characteristics such as gender and socio-economic status than by genetic markers alone, although including both genetic and environmental factors might predict such outcomes in specific sub-groups with most accuracy. The findings of the current study illustrate this point in showing that lower maternal educational level is more strongly associated with less sensitive parenting than genes potentially related to less efficient oxytocin production. It should be noted that mothers’ sensitive interaction with their toddlers was observed during problem-solving tasks potentially eliciting differences in sensitive instruction, which might explain its association with educational level. Moreover, the more accurate assessments of genetic factors compared with environmental influences may lead to less comparable effect sizes.
The role of genetic factors may also be dependent on the presence or absence of stressful life circumstances, with an increasing influence of hormonal effects on parenting in deprived contexts with low social support (Repetti et al
). Numan and Insel (2003
) argue that in primates (as compared with rats) the balance between size and role of the medial pre-optical area and the neocortex has shifted in favor of the latter (Keverne, 2001). Primate parenting might therefore be under stronger cognitive than hormonal control, at least in normal circumstances (Numan and Insel, 2003
; Kagan et al
). However, the medial preoptic area (MPOA) of the hypothalamus might still be involved by signaling the level of maternal motivation to the neocortex, which uses this input in the development of complex voluntary response strategies (Numan and Insel, 2003
). Associations between serotonin and oxytocin system genes and parenting might be most pronounced but not limited to mothers in deprived settings, characterized by, for example, high degrees of stress or marital discord. The association between the 5-HTT
‘s’ allele and depression under conditions of environmental adversity (Caspi et al
) is a replicated finding (Uher and McGuffin, 2008
). The absence of a significant gene–environment (GxE) interaction in our study does not support the claim that in certain (deprived) environments the role of hormones on behavior is more pronounced, but it should be noted that our sample is rather homogeneously well-educated, and major deprivation is absent. In a previous report on the same sample we found a negative impact of daily hassles on parental sensitivity (Van IJzendoorn et al
). Including daily hassles as covariate in the current analyses did not change the results. Better assessment of the environment as well as more intense levels of environmental stress or deprivation might however uncover GxE interactions that were not apparent in the current study.
It has been noted that the influence of oxytocin might be most important immediately after birth, for establishing the bond between mother and offspring instead of maintaining this bond at a later stage (Fahrbach et al
; Feldman et al
; Insel and Harbough, 1989). In the current study sensitive parenting was measured at 23 months. In order to assess the role of hormonal mechanisms such as the oxytonergic system some time after birth, Numan and Insel (2003
) proposed to compare the sensitivity of adoptive mothers with the sensitivity of biological mothers to their offspring. Studying adoptive and non-adoptive parents from similar backgrounds, Juffer (1993
) reported the absence of large differences in sensitive parenting. The influence of oxytocin caused by parturition and lactation may, therefore, be overridden by other mechanisms of a more cognitive nature.
Although the oxytonergic system might thus not be a necessary or sufficient condition for sensitive parenting, experimental research showing that oxytocin improves ‘mind reading’ suggests that oxytocin nevertheless may facilitate parental sensitivity at any stage in parents’ lives and not only during the period around birth. In a double-blind placebo controlled study on 30 adult males, Domes and colleagues (2007
) found that after intranasal administration of a single dose of oxytocin participants were substantially better able to infer the affective mental state of others from subtle social cues from the eye region in a standard paradigm, the Reading the Mind in the Eyes Test. The authors state that reading the mind of an interactive partner is a cornerstone of all human interactions, which would also pertain to parenting. The definition of sensitive parenting explicitly includes the reading of the child's attachment needs from subtle facial or other non-verbal signals as a first and important step to responding in a prompt and adequate manner (Ainsworth et al
; Egeland et al
; Sroufe et al
Our study is limited in several ways. First, generalization of our findings may be limited to samples similar to the rather homogeneous middle-class sample included in the current study. Moreover, the families in the current study had an externalizing toddler (75th percentile or above on the CBCL), and our findings may only apply to parents who perceive their children as difficult and non-compliant, and who already at an early stage have difficulty managing their children. It is important to note, however, that the families in our study were two-parent families from predominantly well-educated background and without psychiatric disorders. Nevertheless, replication in unselected samples is needed.
Second, although our sample size is relatively large compared with other studies including observational measures of parenting, our study may nevertheless lack power to detect gene–gene or gene–environment interaction effects. Moreover, the OXTR
AA and AG genotypes were combined in the analyses, as were the 5-HTT
sl and ll genotypes (similar to, e.g. Kaufman et al
; Battaglia et al
; Hayden et al
; Young et al
; but see Hariri et al
; Caspi et al
for combined ss/sl vs
ll genotypes). In our study 5-HTT
ll did not contribute significantly to the prediction of maternal sensitivity. It should be noted that the 5-HTT SLC6A4
gene possesses several other polymorphic loci affecting its expression and function that were not included in this study (Wendland et al
Third, because 5-HTT
genes have been associated with other forms of social behavior and mental states (Uher and McGuffin, 2008
), it is unclear how specific and direct their influence is on sensitive parenting. It is possible that both genes affect interpersonal sensitivity more generally, which may in turn make parents more sensitive to their offspring. Alternatively, the genes might be associated with affective states that promote or hamper the display of sensitive parenting. Further research is needed to clarify the process underlying the association found in the current study.
Last, we did not assess oxytocin levels directly, but variants of the oxytocin receptor gene that have not yet been shown to be functional. In a promising line of research Carter and her colleagues (2007
) showed that oxytocin might be extracted from saliva samples, with detectable variations of oxytocin concentrations in saliva depending on lactation in mothers and massage in male subjects. Oxytocin levels in saliva were however low and assessments labor-intensive. In the near future it may become easier to measure salivary oxytocin as a biomarker for affiliative behavior in humans, in particular in parenting, which would enable direct tests of the association between oxytocin and sensitive parenting suggested in the current report.
In conclusion, the present study is the first to suggest independent effects on maternal sensitivity of 5-HTT and OXTR genes in humans. Taking into account differences in maternal educational level, depression and marital discord, we found that parents with the possibly less efficient variants of the serotonergic and oxytonergic system genes showed lower levels of sensitive responsiveness to their toddlers. The current study is among the first to examine the molecular genetic basis of human parenting. The findings support previous results of environmental effects on sensitive parenting, but additionally point to molecular genetic differences that may be implicated in the production of oxytocin as a factor explaining differences in sensitive parenting.