Neurodevelopmental and Neurodegenerative Models of Schizophrenia: White Matter at the Center Stage
Neurodevelopmental and Neurodegenerative Models of Schizophrenia: White Matter at the Center Stage
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DOI：
10.1093/schbul/sbu070
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发表时间：
2014-07-01
影响因子：
6.6
通讯作者：
Hong, L. Elliot
中科院分区：
文献类型：
--
作者：
Kochunov, Peter;Hong, L. Elliot
精神分裂症是一种大脑失联的疾病，其一生过程被建模为神经发育和神经退行性疾病。神经发育模型将精神分裂症归因于产前到青少年早期发育的改变。神经退行性模型将进行性神经退行性作为其核心属性。从历史上看，精神分裂症的生理学、药理学和治疗靶点是根据神经元、神经递质水平和突触受体来概念化的。这两种模型的大部分证据都来自于对皮层和皮层下灰质的研究。我们认为，白质一生轨迹的动力学以及精神分裂症中连通性缺陷的一致性，支持白质完整性作为一种有希望的表型来评估支持和反对神经发育和神经退行性启发式的竞争证据。我们通过回顾白质和灰质变化的正常一生轨迹来发展这一观点。我们强调了白质发育高峰年龄与精神分裂症发病年龄之间的重叠，并回顾了精神分裂症发病前、发病时和慢性阶段白质异常的研究结果。我们强调了发病时白质完整性降低和慢性期加速下降的发现，但发病前的发育轨迹在很大程度上是未知的。我们提出了4种可能的一生白质轨迹模型，可作为区分神经发育和神经退行性病因的基础。我们认为，患者白质完整性的横断面和纵向研究的结合可以用来桥接神经发育和退化启发式，以推进精神分裂症的研究
Schizophrenia is a disorder of cerebral disconnectivity whose lifetime course is modeled as both neurodevelopmental and neurodegenerative. The neurodevelopmental models attribute schizophrenia to alterations in the prenatal-to-early adolescent development. The neurodegenerative models identify progressive neurodegeneration as its core attribute. Historically, the physiology, pharmacology, and treatment targets in schizophrenia were conceptualized in terms of neurons, neurotransmitter levels, and synaptic receptors. Much of the evidence for both models was derived from studies of cortical and subcortical gray matter. We argue that the dynamics of the lifetime trajectory of white matter, and the consistency of connectivity deficits in schizophrenia, support white matter integrity as a promising phenotype to evaluate the competing evidence for and against neurodevelopmental and neurodegenerative heuristics. We develop this perspective by reviewing normal lifetime trajectories of white and gray matter changes. We highlighted the overlap between the age of peak of white matter development and the age of onset of schizophrenia and reviewed findings of white matter abnormalities prior to, at the onset, and at chronic stages of schizophrenia. We emphasized the findings of reduced white matter integrity at the onset and findings of accelerated decline in chronic stages, but the developmental trajectory that precedes the onset is largely unknown. We propose 4 probable lifetime white matter trajectory models that can be used as the basis for separation between the neurodevelopmental and neurodegenerative etiologies. We argue that a combination of the cross-sectional and longitudinal studies of white matter integrity in patients may be used to bridge the neurodevelopment and degeneration heuristics to advance schizophrenia research