title: Oxytocin and vasopressin hormone genes in children's externalizing problems: A cognitive endophenotype approach.
abstract: 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.
authors.affiliation: Department of Applied Psychology and Human Development, University of Toronto, Canada. Electronic address: m.wade@utoronto.ca.
authors.forename: Mark
authors.initials: M
authors.lastname: Wade
authors.affiliation: Department of Epidemiology and Biostatistics, and Institute for Human Genetics, University of California at San Francisco, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hoffmann
authors.affiliation: Department of Psychology, The Hebrew University of Jerusalem, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Knafo-Noam
authors.affiliation: Department of Psychiatry, University of Rochester, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: O'Connor
authors.affiliation: Department of Applied Psychology and Human Development, University of Toronto, Canada. Electronic address: jenny.jenkins@utoronto.ca.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Jenkins
mesh_terms: D001127:Arginine Vasopressin / Q000235:genetics; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000235:genetics; D002652:Child Behavior / Q000523:psychology; D002653:Child Behavior Disorders / Q000235:genetics* / Q000523:psychology; D002675:Child, Preschool; D003071:Cognition / Q000502:physiology; D058068:Endophenotypes; D056344:Executive Function / Q000502:physiology; D019260:Expressed Emotion / Q000502:physiology*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D010121:Oxytocin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000066553:Problem Behavior / Q000523:psychology; D014667:Vasopressins / Q000235:genetics*
chemical_list: D014667:Vasopressins; D001127:Arginine Vasopressin; D010121:Oxytocin
keywords: Endophenotype; Executive functioning; Externalizing problems; Molecular genetic; Oxytocin; Theory of mind; Vasopressin