Olfactory Function in Schizophrenia: A Lifespan Analysis

描述（由申请人提供）：精神分裂症目前被认为是一种复杂的遗传性疾病，可能在生命早期发生神经元发育改变，在确定脆弱性方面很重要。神经发生和神经发育发生在成年嗅上皮，和嗅觉系统的探针可能会提供洞察这种疾病的神经发育改变的神经生物学基础。事实上，对精神分裂症患者的研究已经证明了嗅觉系统的强大行为，结构和功能障碍。我们的工作，沿着其他人的工作，已经表明嗅觉脑区域受到神经退行性和遗传介导的神经发育过程的影响。这个项目代表了唯一的系统性努力，从寿命的角度来研究这些化学感觉障碍的基础。迄今为止，我们的努力已经确定：1）精神分裂症患者在整个生命周期中存在广泛和稳定的嗅觉缺陷; 2）没有观察到显著的药物作用; 3）患者的一级亲属中存在类似的心理物理，结构和功能缺陷; 4）潜在的面部结构，如鼻和腭体积异常。在胎儿早期，脑形态发生与颅面形态发生在胚胎学上密切相关。因此，定量分析颅面和大脑畸形沿着详细的心理物理评估嗅觉系统可能提供有关精神分裂症的发展起源的重要信息。在这个应用程序中，我们提出了一个深入的评估的结构和功能异常的嗅觉系统从早期神经发育的角度。我们将研究40名精神分裂症患者，40名其他方面健康的一级家庭成员，40名无关的健康对照，以及40名出现精神病早期症状的高危受试者。新的方法将被用来检查患者的神经发育的贡献，包括鼻/腭体积，结构MRI和面部形态的定量检查化学感觉功能障碍。这些损伤的预测效用将通过检查精神病发展风险增加的受试者来探讨。我们的工作模型是，嗅觉障碍反映了神经发生和突触形成的发育障碍过程，这些措施可能代表了精神分裂症相关的胚胎畸形的特定标志物。精神分裂症目前被认为是一种复杂的遗传疾病，大脑结构和功能的早期发育异常，在确定疾病的脆弱性方面很重要。这项研究将检查精神分裂症患者嗅觉能力的变化，以及鼻腔和口腔的详细测量，以及面部和大脑结构和地形图的绘制。我们认为，在患者中看到的强大的嗅觉障碍反映了早期发育过程的障碍，这些功能和结构的分析可能提供有关精神分裂症的发展起源的重要信息。

DESCRIPTION (provided by applicant): Schizophrenia is currently thought to be a complex genetic disorder, with altered neuronal development, perhaps very early in life, important in determining vulnerability. Neurogenesis and neurodevelopment occur in the adult olfactory epithelium, and probes of the olfactory system may provide insights into the neuro-biological basis of altered neurodevelopment in this disorder. Indeed, studies of patients with schizophrenia have demonstrated robust behavioral, structural, and functional impairments of the olfactory system. Our work, along with others', has indicated that olfactory brain regions are affected by both neurodegenerative and genetically-mediated neurodevelopmental processes. This project represents the only systematic effort to examine the underpinnings of these chemosensory impairments from a life-span perspective. To date, our efforts have established that: 1)pervasive and stable olfactory deficits exist across the lifespan in schizophrenia; 2)no significant medication effects are seen; 3)similar psychophysical, structural, and functional deficits exist in first-degree relatives of patients; and 4)underlying facial structures such as nasal and palate volumes are abnormal. Over early fetal life, cerebral morphogenesis proceeds in embryological intimacy with craniofacial morphogenesis. As such, quantitative analysis of craniofacial and cerebral dysmorphology along with a detailed psychophysical assessment of the olfactory system may provide important information concerning the developmental origins of schizophrenia. In this application, we propose an in-depth assessment of the structural and functional abnormalities of the olfactory system from an early neurodevelopmental perspective. We will study 40 schizophrenia patients, 40 otherwise healthy first-degree family members, 40 unrelated healthy controls, and 40 high-risk subjects who present with early symptoms of psychosis. New methods will be utilized to examine the neurodevelopmental contributions to chemosensory dysfunction in patients including nasal/palate volume, structural MRI, and quantitative examination of facial morphology. Predictive utility of these impairments will be probed by examining subjects at increased risk for the development of psychosis. Our working model is that olfactory impairment reflects developmentally disturbed processes of neurogenesis and synapse formation and that these measures may represent specific markers of embryological dysmorphogenesis underlying schizophrenia. Schizophrenia is currently thought to be a complex genetic disorder, with early developmental abnormalities in brain structure and function, being important in determining vulnerability to illness. This study will examine changes in smell abilities in schizophrenia along with detailed measurements of the nasal and oral cavities and mapping of facial and brain structure and topography. We believe that robust olfactory impairment seen in patients reflects a disturbance of an early developmental process and that the analysis of these functions and structures may provide important information concerning the developmental origins of schizophrenia.