Large scale prevalence study and Exploring biological marker by long-term follow-up study for PDD/ARMS

入校时怀疑PDD的儿童，阿加诺市为1.88%(9/477)，新泻市为1.19%(11/919)。作为PDD的危险因素，我们在Agano市确定了父亲的高龄，在新泻市确定了出生窒息。在我们的成像研究中，与对照组相比，PDD受试者MRI图像中的丘脑体积显著减小；与对照组相比，PDD受试者在模仿任务中表现出左右前额叶皮质活动平衡的左倾减少。在我们的分子遗传学研究中，我们观察到TPH2基因与PDD之间可能存在关联；我们未能在Micro RNA137中发现与PDD显著相关的基因多态性。在我们的中间表型研究中，5-HTTLPR基因的多态性影响了PDD受试者内侧前额叶皮质的神经发育；5-HTR1A基因的多态性与PDD的一些临床分型有关，入学时的体检很难识别高危精神状态(ARMS)症状，因此在研究期间不存在出现ARM症状的儿童。我们将在已建立的30多年研究基地的基础上，推进流行病学调查，探索生物标志物。

Rates of children with doubt of PDD, in medical examination at the time of entering school, were 1. 88%(9/477) in Agano city and 1. 19%(11/919) in Niigata city. As a risk factor of PDD, we identified an advanced father's age in Agano city and a birth asphyxia in Niigata city. In our imaging study, the thalamus volume in an MRI image is significantly smaller in PDD subjects compared with controls ; PDD subjects have shown a decrease in leftward bias of the balance between right and left prefrontal cortex activity during imitation tasks when compared with controls. In our molecular genetic study, we observed a potential association between TPH2 gene and PDD ; we failed to identify a gene polymorphism in micro RNA 137 that significantly associated PDD. In our intermediate phenotype study, the polymorphism of 5-HTTLPR gene influences the neural development of the medial prefrontal cortex among PDD subjects ; The polymorphism of 5-HTR1A gene is related to some divided clinical phenotypes of PDD.It is difficult to identify At Risk Mental State(ARMS) symptoms by a medical examination at the time of entering school, thus children who showed ARMS symptoms between this research period did not exist. We will promote the epidemiological survey and exploring biological marker based on the established research base for over 30 years.