Externalizing problems are among the most common mental health problems of children. Research suggests that these problems are heritable, yet little is known about the specific genes involved in their pathophysiology. The current study examined a genotype-endophenotype-phenotype model of externalizing problems in 320 preschool-aged children. Markers of the oxytocin (OXT) and arginine vasopressin (AVP) hormone genes were selected as candidates owing to their known association with psychopathology in other domains. We tested whether OXT and AVP variants were related to children's externalizing problems, as well as two cognitive endophenotypes presumed to underlie these problems: theory of mind (ToM) and executive functioning (EF). Externalizing problems were assessed at age 4.5 using a previously-validated rating scale. ToM and EF were measured with age-appropriate tasks. Using a family-based association design and controlling for non-genomic confounds, support was found for an association between a two-marker OXT haplotype (rs2740210-rs2770378) and a two-marker AVP haplotype (rs1887854-rs3761249) and externalizing problems. Specific associations of these haplotypes with ToM and EF were also observed. Further, ToM and EF were shown to independently and jointly predict externalizing problems, and to partially mediate the effects of OXT and AVP on externalizing problems. This study provides the first evidence that genetic variation in OXT and AVP may contribute to individual differences in childhood externalizing problems, and that these effects may operate through emerging neurocognitive abilities in the preschool period.
Bibliographical noteFunding Information:
We are grateful to the families who give so generously of their time, to the Hamilton and Toronto Public Health Units for facilitating recruitment of the sample, and to Mira Boskovic for project management. The grant ‘Transactional Processes in Emotional and Behavioral Regulation: Individuals in Context’ was awarded to Jennifer M. Jenkins and Michael Boyle from the Canadian Institutes of Health Research (Funding Reference # 70334 ) and covered data collection. The study team, beyond the current authors includes: Cathy Barr, Kathy Georgiades, Greg Moran, Michal Perlman, Hildy Ross, and Louis Schmidt.
© 2016 Elsevier Inc.
- Executive functioning
- Externalizing problems
- Molecular genetic
- Theory of mind