The neurodevelopmental model of schizophrenia: what can very early onset cases tell us?
The neurodevelopmental model of schizophrenia: what can very early onset cases tell us?
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DOI：
10.1007/s11920-005-0001-z
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发表时间：
2005-04-01
影响因子：
6.7
通讯作者：
Frangou, Sofia
中科院分区：
文献类型：
--
作者：
Rapoport, Judith L;Addington, Anjene;Frangou, Sofia
精神分裂症的神经发育模型能够识别疾病的纵向前兆，具有很大的启发意义，在过去的二十年中主要集中在病因学研究上。这些模型在假设的遗传和环境“打击”的特异性和时间方面存在很大差异，但主要集中在对产前大脑发育的损害上。对早发精神分裂症病例的研究非常重要，因为任何模型都必须考虑到广泛的发病年龄，并且按发病年龄进行分层对于疾病的遗传学理解已取得了丰硕的成果[1]。近年来，对健康儿童的纵向脑成像研究表明，进行性大脑变化比以前想象的更加动态，[2]其中灰质体积损失在青春期尤其明显[3]。极早发病的精神分裂症患者也表现出类似的发展模式，但更为夸张[4]。这支持了精神分裂症除了（理论上至少是继发性的）早期“病变”之外，还存在长期的异常神经发育。在精神分裂症中，许多微妙的认知、运动和行为偏差在发病前几年就已出现[5]。对早发性精神分裂症的研究表明，更显着的病前神经发育障碍表明在广泛的发育时期存在更恶性的过程 [6, 7]。最近的研究表明，成年后患精神分裂症的人在儿童时期出现短暂“阳性”（幻觉和/或妄想）症状的比例有所增加，这表明大脑功能的早期异常比以前认为的更广泛，而且精神病本身的连续性也比以前认为的更大[R. PR07-2-IC-01.15]。
Neurodevelopmental models of schizophrenia that identify longitudinal precursors of illness have been of great heuristic importance, focusing mostly on etiologic research during the past two decades. These models have varied considerably with respect to specificity and timing of hypothesized genetic and environmental “hits,” but have largely focused on insults to prenatal brain development. The study of early onset cases of schizophrenia is important as any model must also account for the wide range of age of onset and stratification by age of onset has been fruitful for genetic understanding of illness [1]. In recent years, longitudinal brain imaging studies of healthy children indicate that progressive brain changes are more dynamic than previously thought,[2] with gray matter volume loss particularly striking in adolescence [3]. Patients with very early onset schizophrenia show a similar developmental pattern, but it is more exaggerated [4]. This supports an extended period of abnormal neurodevelopment in schizophrenia in addition to (theory at least secondary) an earlier “lesion.” In schizophrenia, many subtle cognitive, motor, and behavioral deviations are seen years before illness onset [5]. Studies of early onset schizophrenia indicate more striking premorbid neurodevelopmental impairment suggesting a more malignant process across a broad developmental period [6, 7]. More recent studies suggest that there is an increased rate of brief “positive”(hallucinations and/or delusions) symptoms in childhood in those who become schizophrenic as adults, indicating more widespread earlier abnormality in brain function than was thought previously and greater continuity regarding psychosis per se than has been thought previously [R. PR07-2-IC-01.15].