Perinatal risk factors interacting with catechol O-methyltransferase and the serotonin transporter gene predict ASD symptoms in children with ADHD.
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.
Nijmeijer
Judith S
JS
Department of Psychiatry, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, The Netherlands. j.nijmeijer@accare.nl
Hartman
Catharina A
CA
Rommelse
Nanda N J
NN
Altink
Marieke E
ME
Buschgens
Cathelijne J M
CJ
Fliers
Ellen A
EA
Franke
Barbara
B
Minderaa
Ruud B
RB
Ormel
Johan
J
Sergeant
Joseph A
JA
Verhulst
Frank C
FC
Buitelaar
Jan K
JK
Hoekstra
Pieter J
PJ
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D001724:Birth Weight; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D054643:INDEL Mutation; D007398:Interpersonal Relations; D016014:Linear Models; D008297:Male; D008425:Maternal Behavior; D008715:Methionine; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012307:Risk Factors; D012494:Sampling Studies; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012907:Smoking; D013239:Stereotyped Behavior; D011795:Surveys and Questionnaires; D014633:Valine
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine