Dopaminergic genes influence early response to atypical antipsychotics in patients with first presentation of psychosis
Diana P Prata Department of Psychosis Studies
Institute of Psychiatry, King´s College London
UK
Abstract:
Background: Antipsychotic dopaminergic antagonists are the mainstay of treatment for patients with psychosis; used to treat acute psychotic episodes and reduce the risk of relapse. However, inter-patient treatment response is unpredictable and is thought to be significantly heritable. We hypothesize that this variability in treatment response (in particular, improvement in positive symptoms during the first month of treatment) is influenced by common variations in dopaminergic genes.
Methods: We analysed the impact of COMT (rs4680), the dopamine D4 receptor (DRD4 rs1800955) and the dopamine D2 receptor (DRD2 rs1800497) gene polymorphisms on the improvement of symptoms rated using the Positive and Negative Syndrome Scale (PANSS) in a cohort of first presentation, drug-naive patients (randomised to risperidone and quetiapine in a previously conducted and reported single blind control trial). A multivariate analysis of variance was undertaken using medication dose, medication type and ethnicity as covariates of no interest.
Results: Irrespective of medication, there was a main effect of COMT genotype for total-PANSS improvement (p=0.002) and for positive-PANSS improvement (p=0.011). There was also a statistically significant main effect of DRD4 genotype on total and positive symptom improvements (p=012 and p=0.002, respectively). There was also a borderline statistically significant main effect of DRD2 genotype on positive-PANSS improvement (p=0.056).
Conclusion: Common variants in dopaminergic genes affect symptom improvement in first episode psychosis patients treated with atypical antipsychotic drugs. This is particularly pronounced for positive symptoms which is consistent with previous studies of the mechanism of action of these drugs and with the revised dopamine hypothesis of psychosis. These findings will inform the development of pharmacogenetic tests for atypical antipsychotics.
