Olfaction in the Psychosis Prodrome: Behavioral and ERP Measures

描述(申请人提供)：精神分裂症患者的嗅觉功能受到干扰，通过行为标记物(嗅觉识别和嗅觉阈值)和嗅觉事件相关电位(OERPs)进行鉴定。这些干扰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记物。气味识别缺陷被发现可以在高危病例中区分谁会真正患上精神分裂症。然而，人们对先兆时期出现的精神病的潜在病理生理学知之甚少。这一R21应用程序将进行前驱研究的临床研究人员和在精神分裂症认知和电生理研究方面具有专业知识的研究人员聚集在一起。这项拟议的研究将使用改进的方法进行事件相关电位分析和识别高危青年，以横断面评估先兆患者的嗅觉功能的行为和电生理指标，以及它们与症状特征和社会和认知功能指标的关系。如果在先兆患者中发现嗅觉ERPs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。在一项检测任务中，将测量30名先兆患者和30名匹配的健康对照对三种浓度的硫化氢的事件相关电位和行为检测反应。这将利用现有的精确控制嗅觉刺激的方法(嗅觉仪)，以及电生理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，得到与有意义的嗅觉ERP成分相对应的径向电流的无参考测量。听觉事件相关电位也将在一项新奇古怪的检测任务中被测量，以便开始检查嗅觉事件相关电位缺陷的通道特异性。以面试者为基础的精神病理学和自我评分、社会功能、面部情绪识别和认知功能的测量将被用来检查患者的事件相关电位和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：从临床的角度来看，对先兆患者的研究不仅对于发现预测转化为精神分裂症的标志物具有重要意义，而且对于可能开发出在精神病发病之前的治疗方法也具有重要意义。识别风险生物标记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.