Keshavan M S, Anderson S, Pettegrew J W
Department of Psychiatry, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213.
J Psychiatr Res. 1994 May-Jun;28(3):239-65. doi: 10.1016/0022-3956(94)90009-4.
Several lines of evidence support the notion that a substantial reorganization of cortical connections, involving a programmed synaptic pruning, takes place during adolescence in humans. A review of neurobiological abnormalities in schizophrenia indicates that the neurobiological parameters that undergo peripubertal regressive changes may be abnormal in this disorder. An excessive pruning of the prefrontal corticocortical, and corticosubcortical synapses, perhaps involving the excitatory glutamatergic inputs to pyramidal neurons, may underlie schizophrenia. A reciprocal failure of pruning in certain subcortical structures, such as lenticular nuclei, may also occur. Several developmental trajectories, related to early brain insults as well as genetic factors affecting postnatal neurodevelopment, could lead to the illness. These models would have heuristic value and may be consistent with several known facts of the schizophrenic illness, such as its onset in adolescence and the gender differences in its onset and natural course. The relationship between these models and other etiological models of schizophrenia are summarized and approaches to test relevant hypotheses are discussed.
多条证据支持这样一种观点，即人类在青春期会发生涉及程序性突触修剪的皮质连接的实质性重组。对精神分裂症神经生物学异常的综述表明，在青春期前后经历退行性变化的神经生物学参数在这种疾病中可能是异常的。前额叶皮质-皮质及皮质-皮质下突触的过度修剪，可能涉及锥体细胞的兴奋性谷氨酸能输入，可能是精神分裂症的基础。在某些皮质下结构，如豆状核中，也可能发生修剪的相互失败。与早期脑损伤以及影响出生后神经发育的遗传因素相关的几种发育轨迹，可能导致该疾病。这些模型具有启发价值，并且可能与精神分裂症的几个已知事实一致，例如其在青春期的发病以及发病和自然病程中的性别差异。总结了这些模型与精神分裂症其他病因模型之间的关系，并讨论了检验相关假设的方法。
