Although the clinical efficacy of dopamine D2 receptor antagonists against positive symptoms of schizophrenia supports the dopamine hypothesis of the disease, the resistance of negative and cognitive symptoms to these drugs implicates other systems in its pathophysiology.
These findings suggest that DRD2 polymorphisms are associated with the therapeutic effects of risperidone as they relate to positive symptoms and that plasma drug concentrations are associated with overall symptoms as well as excitement and cognitive symptoms.
The dopamine D2 receptor (DRD2) Ser311Cys polymorphism may also play a role in determining risperidone efficacy for positive, negative and cognitive symptoms, the DRD2 Ins-A2/Del-A1 diplotype may predict better risperidone response, and the DRD3 Ser311Cys variant may affect general treatment response of several atypical agents.