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[精神分裂症:神经发育障碍还是脑部退行性病变?]

[Schizophrenia: neurodevelopmental disorder or degenerative brain process?].

作者信息

Gross G, Huber G

机构信息

Universitäts-Nervenklinik, Bonn, Germany.

出版信息

Fortschr Neurol Psychiatr. 2008 May;76 Suppl 1:S57-62. doi: 10.1055/s-2008-1038153.

Abstract

In the last two decades schizophrenia is viewed increasingly as a neurodevelopmental (ND) disorder; as indicators are discussed f.e. premorbid personality, behaviour anomalies, premorbid somatic signs, deviations shown by brain imaging methods, neuropathological findings or neuropsychological deficits. Premorbid personality and behaviour anomalies have to be distinguished from precursor syndromes (prodromes and outpost syndromes), preceding the first psychotic episode many years. Moreover, only a minority of patients, later developing schizophrenia, reveal abnormal premorbid personality traits. Explanations why clinical expression of the disorder is delayed until adult life or at least adolescence, remain speculative. Findings of neocortical and limbic maldevelopment, e.g. in parahippocampal cortex, are hitherto not yet conclusive. As an argument for the ND hypothesis is claimed that ventricular enlargement already is present at the onset of positive symptoms and does not progress on follow-ups. But, if a ND disorder would have caused the ventricular enlargement, cranial volume and head size must be decreased, what is not the case in schizophrenia. Furtheron, there are findings of progressive increase in ventricular size and also of gliosis, especially in subcortical and periventricular areas. Anomalies of cerebral asymmetry; also distinct ND brain anomalies such as cavum septi pellucidi or dysgenesis of corpus callosum do not occur more frequently than expected in schizophrenia. As to the rate of obstetric complications (OCs) and viral infections sufficiently reliable data are missing; the great majority of schizophrenics have no OCs. Altogether, attempts to correlate brain findings, regarded as expression of an aberrant brain development with clinical subgroups of schizophrenia, were not very successful. This is also valid for ND concepts confined to male, early onset or sporadic schizophrenias. Only a distinct psychopathological remission type with the component of an irreversible pure dynamic-cognitive deficiency can be correlated with distinct brain imaging changes. There are associations between brain imaging and psychopathological findings and also between the progression of neuroradiological and psychopathological changes. The investigation of the long-term course of schizophrenia with progression to different residual syndromes has shown some hints that schizophrenia certainly is not a neurodegenerative process in the usual sense, but may be a special neuroregressive illness in the majority of cases. Data, relevant for this assumption are, that the disorder in 78% shows no full remitting courses; that the progression concerns only 5 until 10 years after onset; that chronic defect psychoses can remit still after decades of course to non-psychotic pure deficiency syndromes; that some cases (15%) can progress even after years and decades of remitting course and, finally, that altogether no correlation exists between the duration of course and outcome. The data prove that schizophrenia is not an illness progressing continuously over the whole lifelong course in the sense of a primary neurodegenerative process, but rather a disorder, progressing transiently in brief stages and afterwards coming to a standstill. That schizophrenia is not neurodegenerative in the traditional sense, does not mean that it is a ND disorder. This applies only to a small subgroup, while the assumption of a non-ND subgroup with an only transitory, in short periods advancing special regressive brain process seems to be plausible. There are analogies to organic brain disorders . Hence ensues the interpretation of the brain findings in a subgroup of schizophrenia as "premature, locally accentuated involution of advanced age". The argument that at time of the first psychotic episode the brain changes already have developed without progressing in the further course, can be refuted by neuropsychiatric observations in brain atrophic processes and the knowledge of the true onset of schizophrenia with prodromes and outpost syndromes several years before the first psychotic manifestation with positive symptoms.

摘要

在过去二十年中,精神分裂症越来越被视为一种神经发育障碍;例如,人们讨论了病前人格、行为异常、病前躯体体征、脑成像方法显示的偏差、神经病理学发现或神经心理学缺陷等指标。病前人格和行为异常必须与前驱综合征(前驱症状和前驱后期综合征)区分开来,前驱综合征在首次精神病发作前数年就已出现。此外,只有少数后来发展为精神分裂症的患者表现出异常的病前人格特征。关于该疾病的临床表现为何延迟至成年期或至少青春期的解释,仍属推测。新皮质和边缘系统发育异常的发现,例如海马旁回皮质的发育异常,迄今尚无定论。作为神经发育假说的一个论据,有人认为在阳性症状出现时脑室就已经扩大,且随访中并无进展。但是,如果神经发育障碍导致了脑室扩大,那么颅腔容积和头围必然会减小,而精神分裂症患者并非如此。此外,还有研究发现脑室大小逐渐增加以及胶质增生,尤其是在皮质下和脑室周围区域。大脑不对称异常;以及一些明显的神经发育性脑异常,如透明隔腔或胼胝体发育不全,在精神分裂症患者中的出现频率并不比预期更高。关于产科并发症(OCs)和病毒感染的发生率,目前缺乏足够可靠的数据;绝大多数精神分裂症患者并无产科并发症。总体而言,试图将被视为异常脑发育表现的脑影像学发现与精神分裂症的临床亚组相关联的尝试并不十分成功。这对于仅限于男性、早发型或散发性精神分裂症的神经发育概念同样适用。只有一种具有不可逆的纯动态认知缺陷成分的独特精神病理缓解类型,能够与特定的脑成像变化相关联。脑成像与精神病理学发现之间存在关联,神经放射学和精神病理学变化的进展之间也存在关联。对精神分裂症进展为不同残留综合征的长期病程研究显示,有一些线索表明,精神分裂症肯定不是通常意义上的神经退行性过程,但在大多数情况下可能是一种特殊的神经退行性疾病。支持这一假设的数据包括:78%的患者病情未完全缓解;病情进展仅发生在发病后的5至10年;慢性缺陷性精神病在病程数十年后仍可缓解为非精神病性的纯缺陷综合征;一些病例(15%)即使在缓解多年甚至数十年后仍可进展;最后,病程长短与预后之间完全不存在相关性。这些数据证明,精神分裂症并非像原发性神经退行性过程那样在整个生命过程中持续进展的疾病,而是一种在短暂阶段短暂进展、随后停止的疾病。精神分裂症并非传统意义上的神经退行性疾病,并不意味着它是一种神经发育障碍。这仅适用于一小部分亚组,而假设存在一个非神经发育亚组,其具有仅在短时间内短暂进展的特殊退行性脑过程似乎是合理的。这与器质性脑疾病存在相似之处。因此,将精神分裂症一个亚组的脑影像学发现解释为“过早出现的、局部加重的老年期脑萎缩”。关于在首次精神病发作时脑变化就已形成且在后续病程中无进展的观点,可以通过对脑萎缩过程的神经精神病学观察以及对精神分裂症真正发病时间(在首次出现阳性症状的精神病发作前数年有前驱症状和前驱后期综合征)的了解来反驳。

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