Szekeres György, Pávics László, Janka Zoltán
Szegedi Tudományegyetem, Pszichiátriai Klinika 6725 Szeged, Semmelweis u. 6.
Ideggyogy Sz. 2002 Jul 20;55(7-8):226-32.
The most elaborated biochemical concept of schizophrenia is the dopamine hypothesis. However, this classical theory is based on indirect observations. It has recently become possible to study this theory directly by means of advanced functional neuroimaging techniques, the development of specific radioligands and study protocols that are eligible to monitor dynamic changes in the neurotransmitter systems. According to the early concept, the essence of schizophrenia is the hyperactivity of the dopamine system. Nevertheless, this idea has gone through many modifications. In accordance with the modified dopamine hypothesis, the cognitive deficit and negative symptoms are related to the hypoactivity of the dorsolateral prefrontal cortex while the acute phases of the disease associates with hyperactivity of the ventral striatal elements of the dopaminergic system. Between these dysfunctions there is causality via their exuberant connections. Beyond that, the interactions between the prefrontal and striatal anomalies implicate the involvement of other neurotransmitters than dopamine. Observations from model psychosis induced by N-methyl-D-aspartate antagonists and in vivo neuroimaging investigations in humans support primarily the role of glutamatergic system. Our developing knowledge about the neurochemical mechanism of schizophrenia can significantly affect therapeutic strategies as well.
关于精神分裂症最详尽的生化概念是多巴胺假说。然而,这一经典理论是基于间接观察得出的。近来,借助先进的功能神经成像技术、特定放射性配体的开发以及适用于监测神经递质系统动态变化的研究方案,得以直接研究该理论。根据早期概念,精神分裂症的本质是多巴胺系统的功能亢进。然而,这一观点历经了诸多修正。根据修正后的多巴胺假说,认知缺陷和阴性症状与背外侧前额叶皮质的功能减退有关,而疾病的急性期与多巴胺能系统腹侧纹状体成分的功能亢进相关。在这些功能障碍之间,通过它们丰富的联系存在因果关系。除此之外,前额叶和纹状体异常之间的相互作用意味着除多巴胺之外其他神经递质也参与其中。由N - 甲基 - D - 天冬氨酸拮抗剂诱发的模型精神病观察结果以及人体的体内神经成像研究主要支持谷氨酸能系统的作用。我们对精神分裂症神经化学机制不断发展的认识也会显著影响治疗策略。