title: Environmental risk, Oxytocin Receptor Gene (OXTR) methylation and youth callous-unemotional traits: a 13-year longitudinal study.
abstract: Youth with high callous-unemotional traits (CU) are at risk for early-onset and persistent conduct problems. Research suggests that there may be different developmental pathways to CU (genetic/constitutional vs environmental), and that the absence or presence of co-occurring internalizing problems is a key marker. However, it is unclear whether such a distinction is valid. Intermediate phenotypes such as DNA methylation, an epigenetic modification regulating gene expression, may help to clarify etiological pathways. This is the first study to examine prospective inter-relationships between environmental risk (prenatal/postnatal) and DNA methylation (birth, age 7 and 9) in the prediction of CU (age 13), for youth low vs high in internalizing problems. We focused on DNA methylation in the vicinity of the oxytocin receptor (OXTR) gene as it has been previously implicated in CU. Participants were 84 youth with early-onset and persistent conduct problems drawn from the Avon Longitudinal Study of Parents and Children. For youth with low internalizing problems (46%), we found that (i) OXTR methylation at birth associated with higher CU (age 13) as well as decreased experience of victimization during childhood (evocative epigenetic-environment correlation; birth-age 7), (ii) higher prenatal parental risks (maternal psychopathology, criminal behaviors, substance use) associated with higher OXTR methylation at birth and (iii) OXTR methylation levels were more stable across time (birth-age 9). In contrast, for youth with high internalizing problems, CU were associated with prenatal risks of an interpersonal nature (that is, intimate partner violence, family conflict) but not OXTR methylation. Findings support the existence of distinct developmental pathways to CU.
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: C A M
authors.identifier: 0000000223895922
authors.initials: CA
authors.lastname: Cecil
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Lysenko
authors.affiliation: Department of Psychology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Jaffee
authors.affiliation: 1] Institute of Psychiatry, King's College London, London, UK [2] Division of Psychology and Language Sciences, University College London, London, UK.
authors.forename: J-B
authors.initials: JB
authors.lastname: Pingault
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: R G
authors.initials: RG
authors.lastname: Smith
authors.affiliation: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors.forename: C L
authors.initials: CL
authors.lastname: Relton
authors.affiliation: Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
authors.forename: G
authors.initials: G
authors.lastname: Woodward
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: W
authors.initials: W
authors.lastname: McArdle
authors.affiliation: 1] Institute of Psychiatry, King's College London, London, UK [2] Exeter Medical School, Exeter University, Exeter, UK.
authors.forename: J
authors.initials: J
authors.lastname: Mill
authors.affiliation: Institute of Psychiatry, King's College London, London, UK.
authors.forename: E D
authors.initials: ED
authors.lastname: Barker
mesh_terms: D002648:Child; D019955:Conduct Disorder / Q000453:epidemiology* / Q000235:genetics*; D019548:Crime Victims; D019175:DNA Methylation; D005190:Family / Q000523:psychology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D011247:Pregnancy; D011446:Prospective Studies; D018045:Receptors, Oxytocin / Q000235:genetics*; D012306:Risk; D012931:Social Environment
chemical_list: C569600:OXTR protein, human; D018045:Receptors, Oxytocin