Intermediate phenotypes, such as DNA methylation, may help clarify aetiological pathways to CU, for youth with low vs. high internalizing problems. DNA methylation is an epigenetic mechanism involved in transcriptional regulation (8) that can be influenced by the social environment (9). Recently, Dadds et al (10) reported that elevated DNA methylation in the vicinity of the oxytocin receptor gene (OXTR) is associated with (i) lower levels of circulating oxytocin and (ii) higher levels of CU. This is noteworthy, given that oxytocin (a hormone and neuropeptide) is known to modulate prosocial and affiliative behaviours that are impaired in CU youth, including empathy, emotional recognition, attachment and bonding (11–13). Also of interest, Dadds et al reported no association between levels of OXTR methylation and environmental risk exposure (measured as quality of family environment). The study, however, did not assess levels of co-occurring internalizing problems. As a result, it is not known whether OXTR methylation associates with CU and/or is influenced by environmental risks similarly for youth with low vs. high internalizing problems. Moreover, because the study was cross-sectional, it was not possible to pinpoint when in development environmental risks and/or alterations in OXTR DNA methylation may contribute to CU.
