Pickar D
Psychiatr Clin North Am. 1986 Mar;9(1):35-48.
Neuroleptic drugs have provided not only the most efficacious form of treatment for schizophrenia but also a unique pharmacologic probe for discerning its pathophysiology. The link between the antipsychotic effects of neuroleptics and dopamine systems continues to be supported by current research. Recent preclinical and clinical studies suggest that time-delayed changes in DA neuronal function may more closely relate to the therapeutic effects of neuroleptics than does their relatively immediate effect of DA receptor blockade. The use of levels of plasma HVA as a noninvasive reflector of DA function provides a research strategy for longitudinal studies of neuroleptic effects in schizophrenia. Preliminary evidence suggests that neuroleptic-induced changes in levels of plasma HVA may be of value as an in vivo marker for neuroleptic antipsychotic effects. The recent identification and characterization of the mesocortical DA system, which links the midbrain to frontal areas of the cerebral cortex, represents a significant development in the neurobiology of CNS DA systems. The behavioral implications of the functional neuroanatomy of the mesocortical system, its relative unresponsiveness to neuroleptic agents, and the possibility of modulatory effects on the mesolimbic DA system render the mesocortical system a particularly important area of research with etiologic and pharmacotherapeutic implications for schizophrenia. The accumulating evidence indicating structural brain abnormalities in a significant number of schizophrenic patients has renewed interest in classical neuropathologic approaches to understanding its etiology. Although current evidence does not uniformly support the hypothesis of two schizophrenia types reflecting DA and non-DA forms of the illness, the postulate is useful as an attempt to integrate recent findings into a conceptual framework. Better understanding of the biochemical basis for heterogeneity of neuroleptic response and systematic data relating this responsivity to morphologic brain changes constitute an important direction for schizophrenia research.
抗精神病药物不仅为精神分裂症提供了最有效的治疗方式，还为洞察其病理生理学提供了独特的药理学研究手段。目前的研究继续支持抗精神病药物的抗精神病作用与多巴胺系统之间的联系。最近的临床前和临床研究表明，多巴胺神经元功能的延迟变化可能比多巴胺受体阻断的相对即时效应更密切地与抗精神病药物的治疗效果相关。使用血浆高香草酸（HVA）水平作为多巴胺功能的非侵入性反映指标，为精神分裂症患者抗精神病药物作用的纵向研究提供了一种研究策略。初步证据表明，抗精神病药物引起的血浆HVA水平变化可能作为抗精神病药物抗精神病作用的体内标志物具有价值。中脑皮质多巴胺系统（将中脑与大脑皮质额叶区域相连）的最近鉴定和表征，代表了中枢神经系统多巴胺系统神经生物学的一项重大进展。中脑皮质系统功能神经解剖学的行为学意义、其对抗精神病药物相对不敏感以及对中脑边缘多巴胺系统的调节作用可能性，使中脑皮质系统成为一个特别重要的研究领域，对精神分裂症的病因学和药物治疗具有重要意义。越来越多的证据表明，大量精神分裂症患者存在脑结构异常，这重新激发了人们对经典神经病理学方法来理解其病因的兴趣。尽管目前的证据并不一致支持两种反映多巴胺和非多巴胺形式疾病的精神分裂症类型假说，但该假说是将近期研究结果整合到一个概念框架中的有益尝试。更好地理解抗精神病药物反应异质性的生化基础以及将这种反应性与脑形态学变化相关的系统数据，构成了精神分裂症研究的一个重要方向。
