Schizophrenia as a disorder of developmentally reduced synaptic connectivity
Schizophrenia as a disorder of developmentally reduced synaptic connectivity
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DOI：
10.1001/archpsyc.57.7.637
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发表时间：
2000-07-01
影响因子：
--
通讯作者：
Hoffman, RE
中科院分区：
文献类型：
--
作者：
McGlashan, TH;Hoffman, RE
最近的精神分裂症尸检和神经影像学研究描绘了脑结构和体积的变化，似乎是由于神经炎过程（如树突和突触）的减少，而不是神经元或神经胶质细胞体的损失。为了解释这些发现，我们提出了一个病理生理模型，减少突触连接所产生的干扰，大脑发育活跃在围产期和青少年时期，我们回顾了一个计算机模拟消除的突触连接，模型正常的认知发展和精神病症状的形成。我们描述了模型的关键参数，并讨论了它们如何解释精神分裂症的重要方面，包括其独特的症状，短期和长期病程，典型的发病年龄，神经发育缺陷，有限的神经退行性进展，性别差异等。我们讨论了一些模型的预测和问题提出的基础研究，早期发现和预防性干预。
Recent postmortem and neuroimaging studies of schizophrenia delineate changes in brain structure and volume that appear to arise from a reduction of neuritic processes (such as dendrites and synapses) rather than loss of neuronal or glial cell bodies. To account for these findings, we propose a pathophysiological model of reduced synaptic connectivity arising from disturbances of brain development active during perinatal and adolescent periods, We review a computer simulation of the elimination of the synaptic connections that models normal cognitive development and psychotic symptom formation. We describe the model's key parameters and discuss how they can account for important aspects of schizophrenia, including its unique symptoms, short- and long-term course, typical age of onset, neurodevelopmental deficits, limited neurodegenerative progression, sex differences, and more. We discuss some of the model's predictions and questions raised for basic research, early detection, and preventive intervention.