Perinatal risk factors interacting with catechol O‐methyltransferase and the serotonin transporter gene predict ASD symptoms in children with ADHD |
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| Authors: | Judith S Nijmeijer Catharina A Hartman Nanda NJ Rommelse Marieke E Altink Cathelijne JM Buschgens Ellen A Fliers Barbara Franke Ruud B Minderaa Johan Ormel Joseph A Sergeant Frank C Verhulst Jan K Buitelaar Pieter J Hoekstra |
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| Affiliation: | 1. Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;2. Department of Psychiatry, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;3. Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, The Netherlands;4. Karakter, Child and Adolescent Psychiatry University Center Nijmegen, Nijmegen, The Netherlands;5. Youth Department, Lucertis, Parnassia‐Bavo‐Group, Rotterdam, The Netherlands;6. Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;7. Department of Child and Adolescent Psychiatry, Erasmus‐MC Sophia, Rotterdam, The Netherlands |
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| Abstract: | Background: Symptoms of autism spectrum disorder (ASD) and attention‐deficit/hyperactivity disorder (ADHD) often co‐occur. Given the previously found familiality of ASD symptoms in children with ADHD, addressing these symptoms may be useful for genetic association studies, especially for candidate gene findings that have not been consistently replicated for ADHD. Methods: We studied the association of the catechol O‐methyltransferase (COMT) Val158Met polymorphism and the serotonin transporter (SLC6A4/SERT/5‐HTT) 5‐HTTLPR insertion/deletion polymorphism with ASD symptoms in children with ADHD, and whether these polymorphisms would interact with pre‐ and perinatal risk factors, i.e., maternal smoking during pregnancy and low birth weight. Analyses were performed using linear regression in 207 Dutch participants with combined type ADHD of the International Multicenter ADHD Genetics (IMAGE) study, and repeated in an independent ADHD sample (n = 439) selected from the TRracking Adolescents’ Individual Lives Survey (TRAILS). Dependent variables were the total and subscale scores of the Children’s Social Behavior Questionnaire (CSBQ). Results: No significant main effects of COMT Val158Met, 5‐HTTLPR, maternal smoking during pregnancy and low birth weight on ASD symptoms were found. However, the COMT Val/Val genotype interacted with maternal smoking during pregnancy in increasing stereotyped behavior in the IMAGE sample (p = .008); this interaction reached significance in the TRAILS sample after correction for confounders (p = .02). In the IMAGE sample, the 5‐HTTLPR S/S genotype interacted with maternal smoking during pregnancy, increasing problems in social interaction (p = .02), and also interacted with low birth weight, increasing rigid behavior (p = .03). Findings for 5‐HTTLPR in the TRAILS sample were similar, albeit for related CSBQ subscales. Conclusions: These findings suggest gene–environment interaction effects on ASD symptoms in children with ADHD. |
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| Keywords: | Attention‐deficit/hyperactivity disorder autism spectrum disorder gene environment 5‐HTT COMT |
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