TY - JOUR
T1 - Perinatal risk factors interacting with catechol O-methyltransferase and the serotonin transporter gene predict ASD symptoms in children with ADHD
AU - Nijmeijer, Judith S.
AU - Hartman, Catharina A.
AU - Rommelse, Nanda N. J.
AU - Altink, Marieke E.
AU - Buschgens, Cathelijne J. M.
AU - Fliers, Ellen A.
AU - Franke, Barbara
AU - Minderaa, Ruud B.
AU - Ormel, Johan
AU - Sergeant, Joseph A.
AU - Verhulst, Frank C.
AU - Buitelaar, Jan K.
AU - Hoekstra, Pieter J.
N1 - Article
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
KW - Attention-deficit
KW - hyperactivity disorder
KW - autism spectrum disorder
KW - gene environment
KW - 5-HTT
KW - COMT
KW - DEFICIT-HYPERACTIVITY DISORDER
KW - ATTENTION-DEFICIT/HYPERACTIVITY DISORDER
KW - PERVASIVE DEVELOPMENTAL DISORDERS
KW - ANTISOCIAL-BEHAVIOR
KW - BIRTH-WEIGHT
KW - AUTISTIC SYMPTOMS
KW - ASSOCIATION
KW - POLYMORPHISMS
KW - METAANALYSIS
KW - EXPRESSION
U2 - 10.1111/j.1469-7610.2010.02277.x
DO - 10.1111/j.1469-7610.2010.02277.x
M3 - Article
SN - 0021-9630
VL - 51
SP - 1242
EP - 1250
JO - Journal of Child Psychology and Psychiatry
JF - Journal of Child Psychology and Psychiatry
IS - 11
ER -