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The synergistic effect of genetic and environmental factors in the development of attention-deficit/hyperactivity disorder symptoms in children and adolescents

Published online by Cambridge University Press:  24 April 2023

Douglas Teixeira Leffa
Affiliation:
ADHD Outpatient Program & Development Psychiatry Program, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Arthur Caye
Affiliation:
ADHD Outpatient Program & Development Psychiatry Program, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Sintia I. Belangero
Affiliation:
Genetics Division, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil Laboratory of Integrative Neuroscience (LiNC), Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil
Ary Gadelha
Affiliation:
Laboratory of Integrative Neuroscience (LiNC), Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil
Pedro Mario Pan
Affiliation:
National Institute of Developmental Psychiatry for Children and Adolescents, São Paulo, Brazil
Giovanni Abrahão Salum
Affiliation:
Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Section on Negative Affect and Social Processes, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
Luis Augusto Rohde*
Affiliation:
ADHD Outpatient Program & Development Psychiatry Program, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil Department of Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil Advisory council, Medical School, UNIEDUK, Indaiatuba, Brazil
*
Corresponding author: Luis Augusto Rohde, email: lrohde@terra.com.br

Abstract

Gene-environment interactions (GxE) have been increasingly explored in psychiatry but with low replication rates. Attention-deficit/hyperactivity disorder (ADHD) is a suitable candidate for studying GxE due to its high heritability and well-defined environmental risk factors. Here, we explored GxE using polygenic risk score (PRS) to represent the genetic liability to ADHD (ADHD-PRS) and environmental risk score (ERS) to represent the combined effects of environmental risk factors. We analyzed longitudinal data of 2,046 individuals (6-14 years of age at baseline and 14-23 at the last follow-up) from the Brazilian High-Risk Cohort Study for Psychiatric Disorders. Psychiatric evaluation included the Child Behavior Checklist and the Strength and Difficulties Questionnaire. Statistical analyses were performed using mixed-effects models. We observed statistically significant interactions between ADHD-PRS and ERS, suggesting that environmental and genetic factors act synergistically in the development of ADHD symptoms. These effects were not present for depression or anxiety symptoms. No evidence of GxE correlation was detected. Mechanistically, our findings suggest that environmental stressors modulate the genetic risk for ADHD. Future studies should investigate whether the reduction of environmental risks can prevent the development of symptoms of ADHD, especially in children with a family history of the disorder.

Type
Regular Article
Copyright
© The Author(s), 2023. Published by Cambridge University Press

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