Schizophrenia is a leading cause of global disability. Current pharmacotherapy for the disease predominantly uses one mechanism — dopamine D2 receptor blockade — but often shows limited efficacy and poor tolerability. These limitations highlight the need to better understand the aetiology of the disease to aid the development of alternative therapeutic approaches. Here, we review the latest meta-analyses and other findings on the neurobiology of prodromal, first-episode and chronic schizophrenia, and the link to psychotic symptoms, focusing on imaging evidence from people with the disorder. This evidence demonstrates regionally specific neurotransmitter alterations, including higher glutamate and dopamine measures in the basal ganglia, and lower glutamate, dopamine and γ-aminobutyric acid (GABA) levels in cortical regions, particularly the frontal cortex, relative to healthy individuals. We consider how dysfunction in cortico-thalamo-striatal–midbrain circuits might alter brain information processing to underlie psychotic symptoms. Finally, we discuss the implications of these findings for developing new, mechanistically based treatments and precision medicine for psychotic symptoms, as well as negative and cognitive symptoms.

精神分裂症是全球残疾的主要原因。目前针对该疾病的药物疗法主要使用一种机制——多巴胺 D2 受体阻断——但往往疗效有限且耐受性差。这些局限性凸显了需要更好地了解该疾病的病因学，以帮助开发替代治疗方法。在这里，我们回顾了关于前驱期、首发期和慢性精神分裂症的神经生物学的最新荟萃分析和其他发现，以及与精神病症状的联系，重点关注来自该疾病患者的影像学证据。这一证据表明，与健康个体相比，区域特定的神经递质发生了变化，包括基底神经节中谷氨酸和多巴胺的水平较高，而皮质区域（特别是额叶皮层）的谷氨酸、多巴胺和γ-氨基丁酸（GABA）水平较低。我们考虑皮质-丘脑-纹状体-中脑回路的功能障碍如何改变大脑信息处理，从而导致精神病症状。最后，我们讨论了这些发现对于开发新的、基于机械的治疗方法和针对精神病症状以及阴性和认知症状的精准医学的影响。