Olfaction in the Psychosis Prodrome: Behavioral and ERP Measures

精神病前驱症状中的嗅觉：行为和 ERP 测量

• 批准号: 7647847
• 负责人: GERARD E BRUDER
• 金额: $ 23.99万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-17 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7647847
• 关键词: Affective Symptoms; Age; Anxiety; Attenuated; Auditory; Award; Behavioral; Biological Markers; Chronic Disease; Clinical; Clinical Research; Cognition; Cognitive; Data; Detection; Disease; Early treatment; Emotions; Employee Strikes; Enrollment; Event-Related Potentials; Exploratory/Developmental Grant; Face; Family member; Functional disorder; Funding; Gender; Housing; Hydrogen Sulfide; Individual; Inferior; Institutes; Intervention; Interviewer; Laboratories; Lead; Measures; Medial; Memory; Memory impairment; Mentors; Methods; Modality; Morbidity - disease rate; New York; Odors; Palliative Care; Parietal; Patients; Pharmaceutical Preparations; Positioning Attribute; Predictive Value; Principal Component Analysis; Process; Psychopathology; Psychophysiology; Psychotic Disorders; Radial; Research; Research Personnel; Risk; Role; Schizophrenia; Smell Perception; Social Functioning; Source; Specificity; Surface; Symptoms; Techniques; Universities; auditory stimulus; base; cognitive function; cohort; density; disability; high risk; improved; neurophysiology; olfactory stimulus; olfactory threshold; prevent; programs; public health relevance; response; social; social cognition; therapy development

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.

描述（由申请人提供）：精神分裂症患者的嗅觉功能受到干扰，可通过行为标记（嗅觉识别和气味阈值）和嗅觉事件相关电位（OERPs）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志物的良好候选人。研究人员发现，在高风险病例中，识别缺陷可以区分哪些人实际上会患上精神分裂症。然而，鲜为人知的是，在前驱期新兴的精神病的基础病理生理学。这个R21应用程序汇集了进行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。拟议的研究将使用改进的方法进行ERP分析，并确定有风险的年轻人，以评估前驱患者的嗅觉功能的横截面行为和电生理措施，以及它们与症状特征和社会和认知功能的措施之间的关系。如果在前驱期患者中发现嗅觉ERPs异常，我们将申请R 01，以评估前驱期队列中的嗅觉ERPs是否可能是转换为精神分裂症的生物标志物。在检测任务期间，将在30名前驱患者和30名匹配的健康对照中测量三种浓度的硫化氢的ERP和行为检测反应。这将利用现有的方法来精确控制嗅觉刺激（嗅觉计），也在电生理领域的新的数据分析技术。电流源密度（CSD;表面拉普拉斯算子）和时间主成分分析（PCA）相结合，以产生对应于有意义的嗅觉ERP分量的径向电流的无参考测量。听觉ERP也将在一个新奇的古怪的检测任务，以便开始检查嗅觉ERP缺陷的通道特异性进行测量。将使用基于访谈者的精神病理学和自我评定、社会功能、面部情绪识别和认知功能的测量来检查患者的ERP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，前驱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，而且对于在精神病发作之前的治疗的潜在发展具有重要意义。风险生物标志物的识别可能会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。