Sensorimotor abnormalities in childhood onset psychotic disorders

描述（由申请人提供）：我们正在申请一项关于儿童期精神病发病的脑感觉运动异常的研究。运动缺陷在精神病患者群体中一直存在，并且也被确定为少数有希望的早期儿童精神病风险因素之一。我们将采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性双相情感障碍（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组（N=40）进行比较，对照组没有精神病性和/或双相情感障碍的个人或家族史。我们对运动协调缺陷的一般看法是双重的。首先，我们提出半球间运动抑制的失败导致在双手协调中无法正确协调时间信号。其次，我们认为，从运动到体感皮层的前馈传出复制机制的失败导致患者在自己的运动过程中感知反馈不正确。我们这项研究的长期目标是完善精神障碍中运动缺陷的神经生物学，为未来基于家庭的遗传风险研究开发生物标志物，并评估精神分裂症和情绪相关精神疾病之间的神经生物学差异。其中一些生物标志物应该与精神病本身有关，而另一些则与精神病的具体临床表现有关。这些知识可以a)有助于更早和更准确的诊断，b)导致疾病发作时改善治疗计划，c)有助于更准确地估计疾病轨迹和预后，d)有助于开发可能的新的精神病内表型标记物，e)为未来有关这些疾病的遗传与发育贡献的家庭研究奠定基础。公共卫生相关性：包括精神分裂症和双相情感障碍在内的精神疾病具有精神病性特征，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，但对这些疾病之间的共同因素却很少注意（即，对风险因素采取维度方法而不是分类方法）。运动行为障碍是广义精神病的一个有希望的危险因素。我们这项研究的长期目标是完善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志物。其中一些生物标志物应该与精神病本身有关，而另一些则与更特定的疾病临床表现有关（例如，特定于精神分裂症）。这些知识可以a)有助于更早和更准确的诊断，b)导致疾病发作时改善治疗计划，c)有助于更准确地估计疾病轨迹和预后，d)有助于开发可能的新的精神病内表型标记物，e)为未来有关这些疾病的遗传与发育贡献的家庭研究奠定基础。

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.