Psychiatric Imaging Group Cyclotron Building Hammersmith Hospital, London W12 0NN, UK.
Curr Pharm Des. 2012;18(4):459-65. doi: 10.2174/138161212799316217.
Schizophrenia is a chronic psychotic disorder that remains a considerable cause of global disease burden. Cognitive impairments are common and contribute significantly to the morbidity of the disorder. Over the last two decades or so molecular imaging studies have refined understanding of the pathophysiology underlying the development of psychosis and cognitive impairments. Firstly they have consistently implicated presynaptic dopaminergic dysfunction in the disorder, finding that dopamine synthesis capacity, dopamine release and baseline dopamine levels are increased in the illness. Secondly recent findings show that dopamine synthesis capacity is elevated in those that go on to develop psychosis in the following year, but not in those that do not, and appears to increase further with the development of psychosis. Thirdly evidence links greater dopamine synthesis capacity to poorer cognitive performance and altered frontal cortical function measured using functional imaging during cognitive tasks. Finally they have provided data on the nature of other neurofunctional alterations in the disorder, in particular in the serotonergic system and neuroinflammation. We review these findings and discuss their implications for understanding the neurobiology of psychosis and cognitive impairments in schizophrenia.
精神分裂症是一种慢性精神病，仍然是全球疾病负担的重要原因。认知障碍很常见，并且对该疾病的发病率有很大影响。在过去的二十年左右，分子影像学研究深化了对精神分裂症和认知障碍发展的病理生理学的理解。首先，它们一致表明，突触前多巴胺能功能障碍与该疾病有关，发现多巴胺合成能力、多巴胺释放和基础多巴胺水平在疾病中增加。其次，最近的研究结果表明，在接下来的一年中发展为精神病的人中，多巴胺合成能力升高，但在没有发展为精神病的人中则没有升高，并且随着精神病的发展似乎进一步升高。第三，证据表明，更大的多巴胺合成能力与使用认知任务期间的功能成像测量的较差的认知表现和额叶皮质功能改变相关。最后，他们提供了有关该疾病中其他神经功能改变的性质的数据，特别是在 5-羟色胺能系统和神经炎症中。我们回顾这些发现，并讨论它们对理解精神分裂症中精神病和认知障碍的神经生物学的意义。
