Genetic Variation in the Dopamine System Influences Intervention Outcome in Children with Cerebral Palsy

BACKGROUND There is large variation in treatment responses in children with cerebral palsy. Experimental and clinical results suggest that dopamine neurotransmission and brain-derived neurotrophic factor (BDNF) signalling are involved in motor learning and plasticity, which are key factors in modern habilitation success. We examined whether naturally occurring variations in dopamine and BDNF genes influenced the treatment outcomes. METHODS Thirty-three children (18-60months of age) with spastic unilateral cerebral palsy were enrolled in the study. Each child had participated in a training programme consisting of active training of the involved hand for 2h every day during a 2-month training period. The training outcome was measured using Assisting Hand Assessment before and after the training period. Saliva was collected for genotyping of COMT, DAT, DRD1, DRD2, DRD3, and BDNF. Regression analyses were used to examine associations between genetic variation and training outcome. FINDINGS There was a statistically significant association between variation in dopamine genes and treatment outcome. Children with a high polygenic dopamine gene score including polymorphisms of five dopamine genes (COMT, DAT, DRD1, DRD2, and DRD3), and reflecting higher endogenous dopaminergic neurotransmission, had the greatest functional outcome gains after intervention. INTERPRETATION Naturally occurring genetic variation in the dopamine system can influence treatment outcomes in children with cerebral palsy. A polygenic dopamine score might be valid for treatment outcome prediction and for designing individually tailored interventions for children with cerebral palsy.