![[ Visit Client Website ]](images/banner.JPG)
Objectives: This ongoing pharmacogenetic study aims at the identification of genetic factors underlying the variability in individual response of autistic patients to risperidone therapy.
Methods: Autistic patients (N=41) initiating risperidone therapy were recruited for this study. Drug efficacy and tolerability was monitored at baseline and at specific times after risperidone introduction (one, three, six and twelve months) using the Autism Treatment Evaluation Checklist (ATEC). Safety and tolerability measures included prolactin levels, weight gain and extrapyramidal movements. The influence of genetic variation in candidate genes CYP2D6, DRD2, DRD3, HT2A, HT2C, HTR6, MDR1 and BDNF in drug efficacy and safety was analysed.
Results: ATEC scores decreased very significantly during all time intervals (P<0.0001), corresponding to an improvement that was more pronounced in the behavioural and sociability domains and generally during the first month of treatment, and significantly correlated with gender. Prolactin levels, weigh, Body Mass Index (BMI) and waist circumference increased most significantly in the first month of treatment. We found an association of MDR1 T1236C marker with improvement in the speech (P=0.007) and sensory/cognitive (P=0.006) subscales and of HTR2A C-1438A>G with speech improvement (P=0.044). BDNF genotypes were significantly associated with BMI, after adjustment for sex and age (P=0.007).
Conclusions: Our preliminary results indicate that the MDR1 and HTR2A genes influence response to risperidone, corroborating previous observations that the MDR1 T1236C and HTR2A -A1438G polymorphisms affect, respectively, the availability and binding of the risperidone. BMI variation was associated with BDNF, previously implicated in weight regulation, eating behaviour and drug related weight changes.