The DRD4 gene and severity of tics and comorbid symptoms: main effects and interactions with delivery complications.

In this study, we investigated the role of the dopamine receptor D4 (DRD4) 48-base pairs (bp) variable number of tandem repeats (VNTR) and perinatal adversities regarding severity of tics and comorbid symptoms in children with tic disorders. We genotyped 110 children with tics with regard to the 48-bp VNTR and assessed presence of prenatal smoking exposure, and pregnancy and delivery complications by parent questionnaires. We examined associations between 2, 3, 4, and 7 repeat (R) alleles and severity of tics and comorbid obsessive-compulsive, depressive, anxious, and autistic symptoms. Through linear regressions, we investigated whether perinatal adversities and the 2R, 3R, 4R, and 7R alleles would interact with severity ratings of tics or comorbid symptoms as outcome. Presence of a 2R allele was related to more severe obsessive-compulsive symptoms, and presence of a 3R allele to increased severity of autistic features. Pregnancy complications were associated with decreased obsessive-compulsive symptom severity, and prenatal smoking exposure to more severe depressive and autistic symptoms. In children without a 3R allele delivery complications were associated with more severe tics, but in children with a 3R variant an inverse relation between delivery complications and tic severity was found. Moreover, the relation between delivery complications and internalizing symptom severity appeared to be most pronounced in children with a 2R allele. In conclusion, this study provides evidence for a role of the 48-bp VNTR in the etiology of tic and associated disorders, and for interactions with delivery complications regarding severity of tics and co-occurring internalizing symptoms.