Dopamine and psychosis: theory, pathomechanisms and intermediate phenotypes.

Schizophrenia is a chronic, severe, and disabling brain disorder arising from the adverse interaction of predisposing risk genes and environmental factors. The psychopathology is characterized by a wide array of disturbing cognitive, emotional, and behavioral symptoms that interfere with the individual's capacity to function in society. Contemporary pathophysiological models assume that psychotic symptoms are triggered by a dysregulation of dopaminergic activity in the brain, a theory that is tightly linked to the serendipitous discovery of the first effective antipsychotic agents in the early 1950s. In recent years, the availability of modern neuroimaging techniques has significantly expanded our understanding of the key mediator circuits that bridge the gap between genetic susceptibility and clinical phenotype. This paper discusses the pathophysiological concepts, molecular mechanisms and neuroimaging evidence that link psychosis to disturbances in dopamine neurotransmission.

精神分裂症是一种慢性、严重且致残的脑部疾病，由易感风险基因和环境因素的不良相互作用引起。其精神病理学特征是存在大量令人困扰的认知、情感和行为症状，这些症状干扰个体在社会中发挥功能的能力。当代病理生理学模型假定，精神病性症状是由大脑中多巴胺能活动的失调所引发，这一理论与20世纪50年代初偶然发现的第一种有效的抗精神病药物密切相关。近年来，现代神经影像学技术的应用极大地拓展了我们对关键介导回路的理解，这些回路在遗传易感性和临床表型之间架起了桥梁。本文讨论了将精神病与多巴胺神经传递紊乱相关联的病理生理学概念、分子机制和神经影像学证据。