Maternal sensitivity and child internalizing and externalizing behavior: a mediating role for glucocorticoid receptor gene (NR3C1) methylation?

Development and Psychopathology, vol. 36, pp. 967–978

Abstract

Abstract The early caregiving environment can have lasting effects on child mental health. Animal models suggest that glucocorticoid receptor gene (NR3C1) DNA methylation plays a mediating role in linking more responsive caregiving to improved behavioral outcomes by its impact on the stress regulatory system. In this longitudinal study, we examined whether children’s NR3C1 methylation levels mediate an effect of maternal sensitivity in infancy on levels of child internalizing and externalizing behavior in a community sample. Maternal sensitivity of 145 mothers was rated at infant age 5 weeks, 12 months, and 30 months by observing mother–infant interactions. Buccal DNA methylation was assessed in the same children at age 6 years and maternal-reported internalizing and externalizing behavior was assessed at age 6 and 10 years. Higher sensitivity at age 5 weeks significantly predicted lower DNA methylation levels at two NR3C1 CpG loci, although methylation levels at these loci did not mediate an effect of maternal sensitivity on levels of child internalizing and externalizing behavior. Overall, the study provides evidence that maternal sensitivity in early infancy is associated with DNA methylation levels at loci involved in stress regulation, but the significance of this finding for child mental health remains unclear.

Authors 5

1. Nicole Creasey corresponding

   University of Amsterdam

   Affiliation as printed

   Preventive Youth Care, Research Institute of Child Development and Education, University of Amsterdam, the Netherlands

2. Roseriet Beijers

   Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Department of Social Development, Behavioral Science Institute, Radboud University, the Netherlands, and Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, the Netherlands

3. Kieran J. O’Donnell

   Canadian Institute for Advanced Research · Douglas Mental Health University Institute · Yale University · Ludmer Centre for Neuroinformatics and Mental Health · McGill University

   Affiliation as printed

   Ludmer Centre for Neuroinformatics and Mental Health, Douglas Hospital Research Centre, McGill University, QC, Canada; Canadian Institute for Advanced Research, Child and Brain Development Program, Canada; and Yale Child Study Center & Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, USA

   Canadian Institute for Advanced Research, Child and Brain Development Program, Canada

   Ludmer Centre for Neuroinformatics and Mental Health, Douglas Hospital Research Centre, McGill University, QC, Canada

   Yale Child Study Center & Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, USA

4. Carolina de Weerth

   Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, the Netherlands

5. Marieke S. Tollenaar Aachen Institute of Psychology and Leiden Institute for Brain and Cognition

   Leiden University

   Affiliation as printed

   Institute of Psychology and Leiden Institute for Brain and Cognition, Leiden University, the Netherlands