Evaluation of pharmacotherapy with reference to QOL and the analysis of therapeutic drug response.

观察精神分裂症患者的临床症状和生活质量。检测白细胞mRNA，作为一个可能的状态标志物，可能预测临床反应。此外，还分析了遗传多态，以确定药物治疗反应中的个体特征差异。结果表明，自评主观生活质量和观察者客观生活质量分别与抑郁症状和阴性症状相关。家庭成员评定的生活技能与抑郁和阴性症状均相关。生活质量和生活技能与阳性症状均无相关性。提示积极治疗抑郁和阴性症状对提高患者的生活质量和生活技能具有重要意义。DNA TIP或实时聚合酶链式反应分析显示，患者白细胞中某些基因的表达水平发生了变化。正在进行进一步的研究，以测试这些变化是否会成为诊断和治疗的有用生物标记物。在基因多态性研究方面，收集了300多名精神分裂症患者的样本，这些患者有详细的临床病史，并使用简明精神病学评定量表对精神症状进行了评估。我们重点研究了脑源性神经营养因子(BDNF)Val66Met基因的多态，这种多态可以影响神经元的功能，并与一些神经和精神疾病相关。我们发现不同基因型组的平均发病年龄和简明精神病评定量表评分(BPRS)有显著差异。这些结果表明，BDNF基因Val66Met多态性与精神分裂症的发病年龄和长期抗精神病药物治疗后的临床症状水平有关。结合这些临床和分子生物学研究，一项使用3Tesla磁共振成像仪的神经成像研究已被纳入我们对精神分裂症的研究中。

We observed clinical symptoms and QOL in schizophrenic patients. Leukocyte mRNA was measured as a possible state maker that might predict the clinical response. In addition, genetic polymorphism was analyzed to identify the individual trait difference in the therapeutic response to a drug. It was revealed that self-rated subjective and observer-rated objective QOL were correlated with depressive and negative symptoms respectively. The life skill rated by the family member was correlated with both depressive and negative symptoms. Neither QOL nor the life skill correlated with positive symptoms. These results suggest the importance of active treatment of depressive and negative symptoms for the improvement of QOL and life skills of the patients. DNA tip or real time PCR analysis revealed changes in the expression levels of some genes in the leukocyte from the patients. Further studies are being conducted to test if these changes would be useful biological makers for the diagnosis and treatment. As to the genetic polymorphism study, samples have been collected from more than 300 patients with schizophrenia with a detailed clinical history and an evaluation of psychiatric symptoms using Brief Psychiatric Rating Scale. We focused on Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism which is known to affect the function of neurons, and be associated with several neurological and psychiatric disorders. We found the mean onset ages and the mean Brief Psychiatric Rating Scale scores (BPRS) were significantly different among groups with different genotypes. These results indicate that the BDNF gene Val66Met polymorphism is related to the onset age of schizophrenia and the levels of clinical symptoms that remain after long-term antipsychotic treatment. Together with these clinical and molecular biological studies, a neuroimaging study with 3 tesla magnetic resonance imaging apparatus has been incorporated into our study on schizophrenia.