Association Study Between COMT Gene Polymorphism And Aripiprazole's Clinical Response In Schizophrenia

ObjectiveApplying WCST ( wisconsin card sorting test ), WMS-RC, P300, PANSS, CGI and prolactine concentration test to explore the association between COMT gene polymorphism and curative efficacy of Aripiprazole to Schizophrenia. Both WCST and WMS-RC are Psychological Testing Tools that reflect cognitive function of the brain prefrontal. Through observing and studying to improvement of aripiprazole on memory, executive function in Schizophrenic patients, deducing correlations between COMT gene and them. To explore the possibility of successful predicting to clinical efficacy by detecting genotypes of patients with Schizophrenia so as to achieve individual treatment.Methods1. According to the inclusion criteria, 78 cases outpatients and inpatients of NingBo KangNing Hospital Who treated with Aripiprazole were selected as the case group. Sbusequently, 65 healthy volunteers who match crews of the case group in gender, age, educational level were selected as the control group.2. The median cubital vein blood 5ml from every volunteer was extracted,their genome DNA would be abstracted in one week,then identified their COMT genotypes by PCR-RFLP. All subjects were genotyped into V/V,V/M and M/M.3. The WCST test and P300 examination of the control group would be fulfilled under a healthy body and Calm state. At the baseline (before treatment), 4th weekend, 8th weekend, the case group respectively accepted PANSS, CGI scale score and the WCST, WMS-RC test. Serum prolactin levels were measured and the event-related potential P300 were examined at the basebine and 8th weekend.4. In the study,statistical method of t test, chi-square test, single variance analysis was applied to all observed data. Results1. Genotypes of two groups were passed by Hard Weinberg Equilibrium test successfully. It demonstrates that there is no blood relationships within candididates. COMT M/M genotype and Met allele frequency of the case group was significantly higher than the control group.2. Analysis of demographic data of the case group suggests that V/M genotype has a delayed onset age, shorter duration.3. After aripiprazole treatment, both patients'mental symptoms, and the total score of clinical efficacy have significantly improved. But the improvement degree has no significant difference among the three genotypes.4. At the baseline, there were no significant differences on WCST scores among the three genotypes, the same result is obtained in the control group. Therefore, after treatment, patients'executive function has significantly improved. The error and perseverative error was reduced, yet the categories achieved and correct was increased obviously, compared with themselves after treatment. among three genotypes, the score of categories achieved and correct of patients with M / M-type have significantly improved than other two genotypes, but other items of executive function have no significant differences among the three genotypes.5. At the baseline, patients with V / M genotype have more scores of accumulation memory than the other two types. Additionly, in patients with M / M genotype,the improvement of accumulation lenovo, touch, and the"100-1"long memory is better than the other two genotypes.6. Before and after therapy, the P300 latency and amplitude of Patients on the whole has significantly improved. It shows that the latency is shorten, the amplitude is extended. The P300 of patients with M / M allele were significantly more improved than the other two genotypes.7. After treatment, elevated levels of prolactin secretion in patients have no significant difference , analysis among different genotypes is also in the case.Conclusion1. M/M genotype and M allele of COMT gene polymorphism maybe increase susceptibility of Schizophrenia. It might be associated with onset age and duration of schizophrenia.2. COMT gene polymorphism is not associated with the amelioration of clinical symptoms in schizophrenia. 3. New antipsychotic aripiprazole can release symptoms of schizophrenia and improves parts of cognitive function in patients with mental disorders.4. COMT gene polymorphism is associated with curative response of aripiprazole to executive function, memory function and the event-related potential P300. M/M genotype can be as a predictive factor on the improvement of cognitive function in schizophrenic patients.