Duration of untreated psychosis (DUP) is defined as the time from the onset of psychotic symptoms until the first treatment. Studies have shown that longer DUP is associated with poorer response rates to antipsychotic medications and impaired cognition, yet the neurobiologic correlates of DUP are poorly understood. Moreover, it has been hypothesized that untreated psychosis may be neurotoxic. Here, we conducted a comprehensive review of studies that have examined the neurobiology of DUP. Specifically, we included studies that evaluated DUP using a range of neurobiologic and imaging techniques and identified 83 articles that met inclusion and exclusion criteria. Overall, 27 out of the total 83 studies (32.5%) reported a significant neurobiological correlate with DUP. These results provide evidence against the notion of psychosis as structurally or functionally neurotoxic on a global scale and suggest that specific regions of the brain, such as temporal regions, may be more vulnerable to the effects of DUP. It is also possible that current methodologies lack the resolution needed to more accurately examine the effects of DUP on the brain, such as effects on synaptic density. Newer methodologies, such as MR scanners with stronger magnets, PET imaging with newer ligands capable of measuring subcellular structures (e.g., the PET ligand [¹¹C]UCB-J) may be better able to capture these limited neuropathologic processes. Lastly, to ensure robust and replicable results, future studies of DUP should be adequately powered and specifically designed to test for the effects of DUP on localized brain structure and function with careful attention paid to potential confounds and methodological issues.

未治疗精神病持续时间 (DUP) 定义为从精神病症状发作到第一次治疗的时间。研究表明，较长的 DUP 与较差的抗精神病药物反应率和认知受损有关，但人们对 DUP 的神经生物学相关性知之甚少。此外，有人假设未经治疗的精神病可能具有神经毒性。在这里，我们对检查 DUP 神经生物学的研究进行了全面审查。具体来说，我们纳入了使用一系列神经生物学和成像技术评估 DUP 的研究，并确定了 83 篇符合纳入和排除标准的文章。总体而言，总共 83 项研究中有 27 项 (32.5%) 报告了与 DUP 的显着神经生物学相关性。这些结果提供了证据，证明精神病在全球范围内具有结构或功能上的神经毒性，并表明大脑的特定区域（例如颞区）可能更容易受到 DUP 的影响。目前的方法也可能缺乏更准确地检查 DUP 对大脑的影响所需的分辨率，例如对突触密度的影响。较新的方法，例如具有更强磁体的 MR 扫描仪、具有能够测量亚细胞结构的较新配体的 PET 成像（例如，PET 配体 [ 目前的方法也可能缺乏更准确地检查 DUP 对大脑的影响所需的分辨率，例如对突触密度的影响。较新的方法，例如具有更强磁体的 MR 扫描仪、具有能够测量亚细胞结构的较新配体的 PET 成像（例如，PET 配体 [ 目前的方法也可能缺乏更准确地检查 DUP 对大脑的影响所需的分辨率，例如对突触密度的影响。较新的方法，例如具有更强磁体的 MR 扫描仪、具有能够测量亚细胞结构的较新配体的 PET 成像（例如，PET 配体 [¹¹ C]UCB-J) 可能能够更好地捕捉这些有限的神经病理过程。最后，为了确保可靠和可复制的结果，未来对 DUP 的研究应该有足够的动力和专门设计来测试 DUP 对局部大脑结构和功能的影响，并仔细注意潜在的混淆和方法问题。