Development and Psychopathology

Research Article

Gene–environment interactions reexamined: Does mother's marital stability interact with the dopamine receptor D2 gene in the etiology of childhood attention-deficit/hyperactivity disorder?

Irwin D. Waldmana1 c1

a1 Emory University

Abstract

Potential candidate Gene × Environment interactions in the etiology of childhood attention-deficit/hyperactivity disorder (ADHD) are examined between the dopamine receptor D2 gene (DRD2) and putative family environmental risk factors that reflect mothers' marital stability. Specifically, interactions were tested between DRD2 and mothers' marital status, number of marriages or cohabiting relationships, and age at first marriage. Moderate relations were found among the marital stability measures, and mother's marital status and number of marriages or cohabiting relationships (but not age at first marriage) were risk factors for their children's ADHD. All three mother's marital stability variables were associated with either the child's or mother's DRD2 genotypes. Gene × Environment interactions were found for children's ADHD diagnoses between children's DRD2 genotypes and mother's marital status and number of marriages or cohabiting relationships. It is of interest that these interactions were strengthened with the progressive addition of sets of covariates intended to control for alternative causal pathways that represent background genetic and environmental context confounds. The present findings highlight the importance of considering both the nexus of putative environmental risk factors and whether their etiology and effects are truly environmental in future Gene × Environment interaction research.

Correspondence

c1 Address correspondence and reprint requests to: Irwin D. Waldman, Department of Psychology, Emory University, 532 North Kilgo Circle, Atlanta, GA 30322; E-mail: psyiw@emory.edu.

Footnotes

This work was supported partially by NIMH Grant K01 MH-01818 and partially by a sabbatical leave from Emory University. The author thanks Kelly Harrington for her assistance in finding relevant articles for the literature review, Ann Abramowitz for providing access to the clinical sample, and David Rowe for beginning the search for genes underlying attention-deficit/hyperactivity disorder with me. Some of the research presented herein was begun while the author was a Visiting Scientist at the Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, at Massachusetts General Hospital, in the Department of Psychiatry at Harvard Medical School, and at the Broad Institute of Harvard and MIT. The author thanks Pamela Sklar for sponsoring him as a Visiting Scientist at Harvard. Aspects of this work were presented at the annual meeting of the Behavior Genetics Association, June 3–8, 2007, in Amsterdam, The Netherlands.