EPILEPSY AS A NEUROLOGICAL MODEL OF SCHIZOPHRENIA

特发性精神分裂症(ISZ)的神经解剖学异常包括局灶性和全球性非特异性神经病理的证据。这些异常通常是微妙的，并不确定哪些是发病机制和临床症状的特异性。对与ISZ有相似症状的癫痫患者进行比较，可以识别可能是精神分裂症综合征特有的汇聚性脑异常。虽然癫痫发作不是ISZ的特征，但这两种情况有共同之处：类分裂状态发生在癫痫的发作期、发作后或发作间歇期，每一种状态都涉及内侧颞叶、神经发育和电生理异常。虽然发作期和发作期后的精神病与离散的电生理事件有关，但发作期的精神分裂症样疾病可能是额外的脑部疾病，即结构病理，与癫痫的产生无关。特别是，相关的神经病理应该超过在没有ISZ样症状的癫痫中看到的。利用临床评估和定量MRI和EEG方法，本项目的主要研究目标是确定ISZ的临床、神经解剖学和电生理特征以及临床病理关系，并将其与发作期精神分裂症样症状(ESZ)的癫痫和伴有发作期精神病的单侧颞叶起源的定位相关癫痫(TLE)进行比较。健康对照公司将提供标准化的MRI数据。这些知识将有助于确定ISZ异常的位置、特异性和病理生理学意义，并进一步指导ISZ的局部神经病理学和脑功能障碍的研究，以专注于病因学意义的区域。具体目的是测试(1)ISZ和ESZ是否有相同的阳性症状(幻觉、妄想和思维障碍)和阴性症状(如平淡的情感和运动)；(2)ISZ和ESZ共有主要的额叶和颞叶新皮质结构异常的概况，而TLE显示海马区和新皮质缺陷主要在致痫的颞叶；(3)ISZ和ESZ显示更多的背景脑电减慢，特别是在额叶和颞区，相对于TLE，焦点减慢与癫痫灶一致。癫痫样放电(ED)在ESZ区最为丰富且多发，在TLE区较少出现且与癫痫灶一致，在ISZ区较少见；(4)阳性症状和阴性症状分别与新皮质颞叶和额叶的MRI和EEG异常有关。脑电减慢和ED与相应电场中的组织异常有关。

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.