Olfaction in the Psychosis Prodrome: Behavioral and ERP Measures

描述（由申请人提供）：通过行为标记（嗅觉识别和气味阈值）和嗅觉事件相关电位（OERPs）来识别，精神分裂症患者的嗅觉功能受到干扰。这些障碍也存在于未受影响的家庭成员中，这使他们成为精神分裂症风险的潜在生物标志物。嗅觉识别缺陷被发现可以区分高危人群中谁会真正患上精神分裂症。然而，对于在前驱期出现的精神病的潜在病理生理学知之甚少。这个R21应用程序将从事前驱研究的临床研究人员和具有精神分裂症认知和电生理研究专业知识的研究人员聚集在一起。本研究将采用改进的ERP分析方法和识别高危年轻人的方法，以评估前驱患者嗅觉功能的横截面行为和电生理测量，以及它们与症状特征和社会认知功能测量的关联。如果发现嗅觉ERPs在前驱患者中异常，我们将申请R01来评估前驱队列中的嗅觉ERPs是否可能是转化为精神分裂症的生物标志物。在三种硫化氢浓度的检测任务中，将测量30名前驱患者和30名匹配的健康对照者的erp和行为检测反应。这将利用现有的精确控制嗅觉刺激的方法（嗅觉计）和电生理学领域的新数据分析技术。电流源密度（CSD；表面拉普拉斯）和时间主成分分析（PCA）相结合，产生与有意义的嗅觉ERP成分相对应的径向电流的无参考测量。听觉ERP也将在一个新奇古怪的检测任务中被测量，从而开始检查嗅觉ERP缺陷的模态特异性。以访谈者为基础的精神病理自评、社会功能测量、面部情绪识别和认知功能将被用于检查ERP和患者的行为嗅觉缺陷与前驱症状、社会功能和认知的关系。公共卫生相关性：从临床角度来看，前驱患者的研究不仅对发现预测转化为精神分裂症的标记物很重要，而且对潜在的治疗发展也很重要，可以在精神病发作之前进行治疗。识别风险生物标志物可以降低前驱研究中的假阳性率，并可能保护年轻人免受不必要的药物暴露。

DESCRIPTION (provided by applicant): Olfactory function is disturbed in schizophrenia, as identified by behavioral markers (smell identification and odor threshold) and olfactory event-related potentials (OERPs). These disturbances are also present in unaffected family members, which make them good candidates as potential biomarkers of schizophrenia risk. Smell identification deficits were found to discriminate who among high-risk cases will actually develop schizophrenia. Little is, however, known about the underlying pathophysiology of emerging psychosis during the prodromal period. This R21 application brings together clinical researchers doing prodromal studies and investigators with expertise in cognitive and electrophysiologic studies in schizophrenia. The proposed study will use improved methods for ERP analyses and for identifying at-risk young people so as to evaluate in cross-section behavioral and electrophysiological measures of olfactory function in prodromal patients, and their association with symptom features and measures of social and cognition function. If olfactory ERPs are found to be abnormal in prodromal patients, we will then apply for an R01 to evaluate whether olfactory ERPs in a prodromal cohort may be a biomarker of conversion to schizophrenia. ERPs and behavioral detection responses will be measured in 30 prodromal patients and 30 matched healthy controls to three concentrations of hydrogen sulfide during a detection task. This will take advantage of existing methods for precise control of olfactory stimuli (olfactometer) and also new data analytic techniques in the electrophysiologic domain. Current source density (CSD; surface Laplacian) and temporal principal components analysis (PCA) are combined to yield reference-free measures of radial current flow corresponding to meaningful olfactory ERP components. Auditory ERPs will also be measured during a novelty oddball detection task so as to begin to examine the modality specificity of olfactory ERP deficits. Interviewer-based and self-ratings of psychopathology, measures of social function, facial emotion recognition, and cognitive function will be used to examine the relation of ERP and behavioral olfactory deficits in patients to prodromal symptoms, social function, and cognition. PUBLIC HEALTH RELEVANCE: From a clinical perspective, the study of prodromal patients is of importance not only for discovering markers for predicting conversion to schizophrenia but also for the potential development of treatments that would precede the onset of psychosis. Identification of a risk biomarker could lead to a lower rate of false positives in prodromal research and perhaps protect young people against unnecessary medication exposure.