EPILEPSY AS A NEUROLOGICAL MODEL OF SCHIZOPHRENIA

癫痫作为精神分裂症的神经学模型

• 批准号: 6219360
• 负责人: LAURA MARSH
• 金额: $ 0.06万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6219360
• 关键词: clinical research; electroencephalography; electrophysiology; epilepsy; frontal lobe /cortex; human subject; magnetic resonance imaging; model; neuroanatomy; pathologic process; schizophrenia; sign /symptom; temporal lobe /cortex

Neuroanatomical abnormalities reported in idiopathic schizophrenia (ISZ) include evidence for focal as well as global nonspecific neuropathology. These abnormalities are often subtle and it is uncertain which are specific to pathogenesis and clinical symptoms. Comparison of patients with epilepsy who share analogous symptoms with ISZ enables identification of converging brain abnormalities which may be specific to the schizophrenic syndrome. Though seizures are not a feature of ISZ, the two conditions have commonalities: schizophrenia-like states occur in ictal, post-ictal, or interictal phases of epilepsy and medial temporal, neurodevelopmental, and eletrophysiological abnormalities are implicated in each. While ictal and post-ictal psychosis are related to discrete eletrophysiological events, interictal schizophrenia-like illness may represent additional brain disease, i.e., structural pathology, not related to seizure generation. In particular, the associated neuropathology should be over and above that seen in epilepsy without ISZ-like symptoms. Using clinical assessments and quantitative MRI and EEG methods, the broad research objectives of this project are to identify converging clinical, neuroanatomical, and electrophysiological features, and clinicopathological relationships in ISZ as compared to epilepsy with interictal schizophrenia-like symptoms(ESZ) and localization-related epilepsy of unilateral temporal lobe origin (TLE) withour interictal psychosis. Healthy controls will provide normative MRI data. Such knowledge will help establish the location, specificity, and pathophysiological significance of abnormalities in ISZ and further direct studies of regional neuropathology and brain dysfunction in ISZ to focus on areas of etiologic significance. The specific aims are to test whether (1) ISZ and ESZ share a common profile of positive symptoms (hallucinations, delusions, and thought disorder) and negative symptoms (e.g., flat affect and amotivation); (2) ISZ and ESZ share a profile of predominant frontal and temporal lobe neocortical structural abnormalities, whereas TLE shows hippocampas and neocortical deficits predominantly in the epileptogenic temporal lobe; (3) ISZ and ESZ show more background EEG slowing, especially in frontal and temporal regions, relative to TLE in which focal slowing is concordant with the seizure focus. Epileptiform discharges (ED) are most abundant and multifocal in ESZ, less frequent and concordant with the seizure focus in TLE, and rare in ISZ; and, (4) Positive and negative symptoms are related to MRI and EEG abnormalities in neocortical temporal and frontal lobes, respectively. EEG slowing and ED are associated with tissue abnormalities in corresponding electrical fields.

特发性精神分裂症（ISZ）的神经解剖学异常包括局灶性和全局非特异性神经病理学证据。这些异常往往是微妙的，它是不确定的，具体的发病机制和临床症状。与ISZ具有相似症状的癫痫患者进行比较，可以识别可能特异于精神分裂症综合征的会聚性脑异常。虽然癫痫发作不是ISZ的特征，但这两种情况具有共性：精神分裂症样状态发生在癫痫发作期、发作后或发作间期，每种情况都涉及内侧颞叶、神经发育和电生理异常。虽然发作期和发作后精神病与离散的电生理事件有关，但发作间期精神分裂症样疾病可能代表额外的脑部疾病，即，结构病理学，与癫痫发作无关。特别是，相关的神经病理学应该超过没有ISZ样症状的癫痫。 使用临床评估和定量MRI和EEG方法，该项目的广泛研究目标是确定ISZ的临床，神经解剖学和电生理学特征，以及与癫痫发作间期精神分裂症样症状（ESZ）和单侧颞叶起源（TLE）的定位相关癫痫发作间期精神病的临床病理关系。健康对照将提供规范的MRI数据。这些知识将有助于建立的位置，特异性和病理生理学意义的异常ISZ和区域神经病理学和脑功能障碍的ISZ进一步直接研究，专注于领域的病因学意义。具体目的是测试（1）ISZ和ESZ是否具有共同的阳性症状（幻觉、妄想和思维障碍）和阴性症状（例如，平的影响和动机）;（2）ISZ和ESZ均以额叶和颞叶新皮层结构异常为主，而TLE则以致痫性颞叶为主要表现;（3）ISZ和ESZ的背景EEG减慢更明显，尤其是在额叶和颞叶，而TLE的局灶性减慢与癫痫灶一致。癫痫样放电（艾德）在ESZ最多且多灶性，在TLE较少且与癫痫灶一致，在ISZ少见;（4）阳性和阴性症状分别与新皮质颞叶和额叶的MRI和EEG异常有关。EEG减慢和艾德与相应电场中的组织异常相关。