Beerpoot L J, Lipska B K, Weinberger D R
Clinical Brain Disorders Branch, Neuroscience Center at St. Elizabeths Hospital, National Institute of Mental Health, Washington, DC 20032, USA.
Eur Neuropsychopharmacol. 1996;6 Suppl 2:S27-34. doi: 10.1016/0924-977x(96)00008-9.
In an attempt to understand schizophrenia, four important fields have been implicated in the disease process and are reviewed here. Early findings that antipsychotic drugs were dopamine antagonists led to a dopaminergic theory of schizophrenia. However, it now appears that a primary dopaminergic abnormality is an unlikely explanation. The cortex has always been thought to be involved in the development of schizophrenia and recent data from neuropsychological, postmortem and imaging studies have indicated that connections between the prefrontal and temporolimbic areas within the brain may be abnormal. Traditionally, schizophrenia has been considered to be a disease with an adult onset pathology. This theory has now been challenged by data suggesting that in schizophrenia, anatomical changes in the adult brain are non-progressive and occurred prior to the onset of illness. Finally, studies on neuronal gene expression have indicated that all antipsychotic drugs modulate DNA transcription in the shell of the nucleus accumbens and that newer antipsychotics produce a quite different pattern of expression from conventional neuroleptics. These recent approaches provide new opportunities in the understanding of schizophrenia, its treatment and prevention.
为了理解精神分裂症，有四个重要领域被认为与该疾病的发病过程相关，在此进行综述。早期发现抗精神病药物是多巴胺拮抗剂，由此产生了精神分裂症的多巴胺能理论。然而，现在看来原发性多巴胺能异常不太可能是其病因。一直以来，人们都认为大脑皮层与精神分裂症的发生有关，近期神经心理学、尸检及影像学研究数据表明，大脑内前额叶和颞叶边缘区域之间的联系可能存在异常。传统上，精神分裂症被认为是一种成年起病的疾病。但现在这一理论受到了挑战，因为有数据表明，在精神分裂症患者中，成年大脑的解剖学变化是非进行性的，且在疾病发作之前就已出现。最后，对神经元基因表达的研究表明，所有抗精神病药物都会调节伏隔核壳中的DNA转录，而且新型抗精神病药物产生的表达模式与传统抗精神病药物截然不同。这些最新研究方法为理解精神分裂症及其治疗和预防提供了新的契机。
