Document Detail

Perinatal risk factors interacting with catechol O-methyltransferase and the serotonin transporter gene predict ASD symptoms in children with ADHD.
MedLine Citation:
PMID:  20868372     Owner:  NLM     Status:  MEDLINE    
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.
Judith S Nijmeijer; Catharina A Hartman; Nanda N J Rommelse; Marieke E Altink; Cathelijne J M Buschgens; Ellen A Fliers; Barbara Franke; Ruud B Minderaa; Johan Ormel; Joseph A Sergeant; Frank C Verhulst; Jan K Buitelaar; Pieter J Hoekstra
Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-09-24
Journal Detail:
Title:  Journal of child psychology and psychiatry, and allied disciplines     Volume:  51     ISSN:  1469-7610     ISO Abbreviation:  J Child Psychol Psychiatry     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-02     Completed Date:  2011-03-01     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  0375361     Medline TA:  J Child Psychol Psychiatry     Country:  England    
Other Details:
Languages:  eng     Pagination:  1242-50     Citation Subset:  IM    
Copyright Information:
© 2010 The Authors. Journal of Child Psychology and Psychiatry © 2010 Association for Child and Adolescent Mental Health.
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MeSH Terms
Attention Deficit Disorder with Hyperactivity / epidemiology,  genetics*,  psychology
Birth Weight
Catechol O-Methyltransferase / genetics*
Child Development Disorders, Pervasive / epidemiology,  genetics*,  psychology
Genetic Predisposition to Disease
INDEL Mutation
Interpersonal Relations*
Linear Models
Maternal Behavior
Netherlands / epidemiology
Polymorphism, Single Nucleotide
Risk Factors
Sampling Studies
Serotonin Plasma Membrane Transport Proteins / genetics*
Stereotyped Behavior*
Grant Support
1 R01 MH62873-01A1/MH/NIMH NIH HHS; R01 MH062873/MH/NIMH NIH HHS
Reg. No./Substance:
0/SLC6A4 protein, human; 0/Serotonin Plasma Membrane Transport Proteins; AE28F7PNPL/Methionine; EC O-Methyltransferase; HG18B9YRS7/Valine

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