Weinberger D R, Lipska B K
Clinical Brain Disorders Branch, National Institute of Mental Health, NIH, Neurosciences Center at Saint Elizabeths, Washington, DC 20032, USA.
Schizophr Res. 1995 Aug 1;16(2):87-110. doi: 10.1016/0920-9964(95)00013-c.
Two of the favorite hypotheses of schizophrenia research-maldevelopment of cerebral cortex and malfunction of brain dopamine systems-have often seemed difficult to reconcile. This article reviews recent research that suggests a heuristically useful reconciliation centered on the functional neuroanatomical concept of prefrontal-temporolimbic cortical connectivity. Anatomical findings from postmortem studies and neuropsychological and neuroimaging studies of brain function in patients with schizophrenia have implicated a developmental 'dysconnection' of temporolimbic-prefrontal cortices. The possibility that such dysconnection can account for the principal phenomenology of the illness, including its delayed onset and its treatment, is suggested by neurologic disease analogies such as metachromatic leukodystrophy and by recent studies in animals with developmental cortical lesions. Studies mapping neuronal gene expression indicate that all antipsychotic drugs modulate DNA transcription in a region of the nucleus accumbens that receives converging inputs from prefrontal and temporolimbic cortices, suggesting that indirect compensation for dysfunctional communication between prefrontal and temporolimbic cortices is a therapeutic mechanism of these drugs. Treatments aimed at direct cortical compensation may be more effective.
精神分裂症研究中最受青睐的两个假说——大脑皮质发育异常和脑多巴胺系统功能失调——常常难以协调统一。本文回顾了近期的研究，这些研究提出了一种基于前额叶 - 颞叶边缘皮质连接的功能性神经解剖学概念且具有启发意义的协调方式。来自尸检研究的解剖学发现以及对精神分裂症患者脑功能的神经心理学和神经影像学研究表明，颞叶边缘 - 前额叶皮质存在发育性“失联”。诸如异染性脑白质营养不良等神经系统疾病的类比以及近期对有发育性皮质损伤动物的研究表明，这种失联有可能解释该疾病的主要症状表现，包括其起病延迟和治疗情况。绘制神经元基因表达图谱的研究表明，所有抗精神病药物都会调节伏隔核区域的DNA转录，该区域接收来自前额叶和颞叶边缘皮质的汇聚输入，这表明对前额叶和颞叶边缘皮质之间功能失调的通信进行间接补偿是这些药物的一种治疗机制。旨在进行直接皮质补偿的治疗可能会更有效。
