Sensorimotor abnormalities in childhood onset psychotic disorders

描述(由申请者提供)：我们请求支持一项关于儿童期起病精神病患者大脑感觉运动异常的研究。运动障碍一直存在于精神病患者群体中，也被确认为少数几个有希望的儿童早期精神病危险因素之一。我们将使用神经行为方法与使用脑磁图(MEG)和结构磁共振成像(MRI)的非侵入性神经成像相结合。80名患有儿童期精神病双相情感障碍(N=40)或精神分裂症(N=40)的年轻参与者将与年龄和性别匹配的对照受试者(N=40)进行比较，这些对照对象没有精神病和/或双相情感障碍的个人或家族病史。我们对运动协调缺陷的总体看法是两方面的。首先，我们认为大脑半球间运动抑制的失败会导致在双手协调中正确协调时间信号的失败。其次，我们认为，从运动到躯体感觉皮层的前馈传出复制机制的失败导致了患者自身运动过程中不正确的知觉反馈。我们这项研究的长期目标是提炼精神病患者运动障碍的神经生物学，为未来基于家庭的遗传风险研究开发生物标记物，并评估精神分裂症和情绪相关精神病之间的神经生物学差异。这些生物标记物中的一些应该与精神病本身有关，而另一些生物标记物则具有更具障碍的特定临床表现。这样的知识可以a)有助于更早和更准确的诊断，b)导致在疾病开始时改进治疗计划，c)帮助更准确地估计疾病轨迹和预后，d)帮助开发可能的新的精神病的内表型标记，以及e)形成关于这些疾病的遗传和发育贡献的未来家庭研究的基础。公共卫生相关性：包括精神分裂症和具有精神病特征的双相情感障碍在内的精神疾病是重大的公共卫生问题。虽然对每种疾病的具体风险因素给予了很大的关注，但很少注意到疾病之间的共同因素(即，对风险因素采取维度方法，而不是分类方法)。运动行为受损是广泛定义的精神病患者的一个有希望的危险因素。我们这项研究的长期目标是提炼跨类别精神障碍运动缺陷的神经生物学，并为未来基于家庭的遗传风险研究开发生物标记物。其中一些生物标记物应该与精神病本身有关，而另一些生物标记物则具有更具精神障碍特异性的临床表现(例如，针对精神分裂症)。这样的知识可以a)有助于更早和更准确的诊断，b)导致在疾病开始时改进治疗计划，c)帮助更准确地估计疾病轨迹和预后，d)帮助开发可能的新的精神病的内表型标记，以及e)形成关于这些疾病的遗传和发育贡献的未来家庭研究的基础。

DESCRIPTION (provided by applicant): We are requesting support for a study of brain sensorimotor abnormalities in childhood onset psychotic illnesses. Motor deficits are consistently found in psychotic patient populations and have also been identified as among a few promising early childhood risk factors for psychosis. We will employ a combination of neurobehavioral methods with non-invasive neuroimaging using magnetoencephalography (MEG) and structural magnetic resonance imaging (MRI). Eighty young participants with either childhood onset psychotic bipolar disorder (N=40) or schizophrenia (N=40) will be compared to age and gender matched comparison subjects (N=40) without personal or family history of psychotic and/or bipolar mood disorders. Our general perspective on motor coordination deficits is two-fold. First, we propose that a failure in inter-hemispheric motor inhibition results in failures to properly coordinate timing signals in bimanual coordination. Second, we believe that a failure in feed-forward efferent copy mechanisms from motor to somatosensory cortex results in improper perceptual feedback during patient's own movements. Our long term goals for this research are to refine the neurobiology of motor deficits in psychotic disorders, develop biomarkers for future family-based studies of genetic risk and evaluate neurobiological differences between schizophreniform and mood-related psychotic illnesses. Some of these biomarkers should be associated with psychosis per se and others with more disorder specific clinical manifestations. Such knowledge could a) contribute to earlier and more accurate diagnosis, b) lead to improved treatment planning at onset of illness, c) assist with more accurate estimate of illness trajectory and prognosis, d) aid in the development of possible new endophenotypic markers for psychosis, and e) form the basis for future family studies relating to genetic vs. developmental contributions to these disorders. PUBLIC HEALTH RELEVANCE: Psychotic illnesses including schizophrenia and bipolar disorder with psychotic features are significant public health concerns. Although much focus has been given to specific risk factors for each illness, little attention has been paid to factors in common between the disorders (i.e., a dimensional approach rather than categorical approach to risk factors). Impaired motor behavior is a promising risk factor for psychoses broadly defined. Our long term goals for this research are to refine the neurobiology of motor deficits in psychotic disorders across category and develop biomarkers for future family-based studies of genetic risk. Some of these biomarkers should be associated with psychosis per se and others with more disorder specific clinical manifestations (e.g., specific to schizophrenia). Such knowledge could a) contribute to earlier and more accurate diagnosis, b) lead to improved treatment planning at onset of illness, c) assist with more accurate estimate of illness trajectory and prognosis, d) aid in the development of possible new endophenotypic markers for psychosis, and e) form the basis for future family studies relating to genetic vs. developmental contributions to these disorders.