COMT Val/Met, stressful life events and externalizing behaviors in youth: A longitudinal study from the ABCD sample
Tuana Kant,
Emiko Koyama,
Clement C. Zai,
Marcos Sanches,
Joseph H. Beitchman,
James L. Kennedy
Affiliations
Tuana Kant
Institute of Medical Science, University of Toronto, Toronto, M5S 1A8, Canada; Temerty Faculty of Medicine, University of Toronto, Toronto, M5S 1A8, Canada; Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, M6J 1H4, Canada; Corresponding author. Centre for Addiction and Mental Health, 250 College St, Toronto, ON M5T 1R8, Canada.
Emiko Koyama
Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, M6J 1H4, Canada; Laboratory for Molecular Pathology of Psychiatric Disorders, RIKEN Center for Brain Science, Saitama, 351-0198, Japan; Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Centre for Addiction and Mental Health, Toronto, M6J 1H4, Canada
Clement C. Zai
Institute of Medical Science, University of Toronto, Toronto, M5S 1A8, Canada; Temerty Faculty of Medicine, University of Toronto, Toronto, M5S 1A8, Canada; Department of Psychiatry, University of Toronto, Toronto, M5S 1A8, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, M5S 1A8, Canada
Marcos Sanches
Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, M6J 1H4, Canada
Joseph H. Beitchman
Institute of Medical Science, University of Toronto, Toronto, M5S 1A8, Canada; Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Centre for Addiction and Mental Health, Toronto, M6J 1H4, Canada; Department of Psychiatry, University of Toronto, Toronto, M5S 1A8, Canada
James L. Kennedy
Institute of Medical Science, University of Toronto, Toronto, M5S 1A8, Canada; Brain Science Department, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, M6J 1H4, Canada; Department of Psychiatry, University of Toronto, Toronto, M5S 1A8, Canada; Corresponding author. Centre for Addiction and Mental Health, 250 College St, Toronto, ON M5T 1R8, Canada.
Early adolescence is a crucial time for understanding and detecting the risk factors that may influence youth externalizing/disruptive behaviors and disorders. Previous literature reported evidence that risk factors for disruptive behaviors include catechol-O-methyltransferase (COMT) Val158Met (rs4680) polymorphism and environmental influences. An unanswered question is whether there is a change in these risk factors over stages of youth development. This longitudinal study examines the interaction effect of Val158Met and stressful life events (SLE) on youth externalizing behaviors from ages 9–11. Participants were 2363 children of European ancestry recruited as part of the Adolescent Brain Cognitive Development study. Repeated measures linear mixed models were used to examine the effect of the interaction between Val158Met and SLE (G × E) on disruptive behaviors over development. Externalizing behaviors were analyzed at both baseline and two-year follow-up. Both Val158Met genotype and SLE scores demonstrated significant main effects on disruptive behaviors in youth, and those effects were consistent at both time points. G × E was not associated with externalizing behaviors. Youth who carried the Val allele and/or were exposed to higher SLE consistently had increased externalizing behavior scores. To our knowledge, this is the first study to longitudinally examine the interaction effects of Val158Met and SLE on externalizing behaviors in youth. The results highlight the importance of understanding the genetic and environmental factors underlying externalizing behaviors for better detection of at-risk youth, helping further with early prevention efforts. The findings propose that COMT Val158Met genotype may act as a biomarker for development of novel treatment strategies for disruptive behaviors.
