Perinatal risk factors interacting with catechol O‐methyltransferase and the serotonin transporter gene predict ASD symptoms in children with ADHD
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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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In children with ADHD, the 5-HTTLPR S/S genotype interacted with maternal smoking during pregnancy, increasing problems in social interaction.
“5-HTTLPR S/S genotype interacted with maternal smoking during pregnancy, increasing problems in social interaction”
From Autism risk factors: genes, environment, and gene-environment interactions (2012) · cites this paper as [111]
An association study in ADHD found GxE effects on ASD symptoms in children with ADHD.
“an encouraging result came from an association study in attention deficit with hyperactivity disorder (ADHD), which found GxE effects on ASD symptoms in children with ADHD.”
From Autism risk factors: genes, environment, and gene-environment interactions (2012) · cites this paper as [111]
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- Authors
- Nijmeijer, J. S., Hartman, C. A., Rommelse, N. N. J., Altink, M. E., Buschgens, C. J. M., Fliers, E. A., Franke, B., Minderaa, R. B., Ormel, J., Sergeant, J. A., Verhulst, F. C., Buitelaar, J. K., & Hoekstra, P. J.
- Affiliations
- University Medical Center Groningen (NL)
- Radboud University Nijmegen (NL)
- Vrije Universiteit Amsterdam (NL)
- Erasmus MC (NL)
- ORCID
- Venue
- Journal of Child Psychology and Psychiatry
- Publisher
- Wiley
- Published
- 2010-09-24
- Volume
- 51
- Issue
- 11
- Pages
- 1242-1250
- ISSN
- 0021-9630 (ISSN-L)
- 1469-7610
- PMC
- PMC2970704
- OpenAlex
- W2109309857
- Cited by
- 57
- References
- 65
- Citations by year
- 2023: 2 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 2 · 2017: 4 · 2016: 9 · 2015: 3 · 2014: 9 · 2013: 11 · 2012: 5
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Child Psychology and Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (175.010.200, 940-38-011)
- National Institute of Mental Health (R01MH062873, 1 R01 MH62873-01A1)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- autism symptoms, attention deficit hyperactivity disorder, catechol-O-methyltransferase, COMT Val158Met polymorphism, serotonin transporter, 5-HTTLPR, gene-environment interaction, perinatal risk factors, smoking during pregnancy, low birth weight, stereotypy, social interaction difficulties, children
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Birth Weight, Catechol O-Methyltransferase, Child, Child Development Disorders, Pervasive, Female, Genotype, Humans, Interpersonal Relations, Male, Maternal Behavior, Methionine, Netherlands, Pregnancy, Surveys and Questionnaires, Risk Factors, Sampling Studies, Smoking, Stereotyped Behavior, Valine, Linear Models, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Serotonin Plasma Membrane Transport Proteins, INDEL Mutation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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