Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England.
South London & the Maudsley NHS Trust, London, England.
Neuropsychopharmacology. 2024 Nov;50(1):164-183. doi: 10.1038/s41386-024-01943-x. Epub 2024 Aug 12.
Synapses are implicated in many neuropsychiatric illnesses. Here, we provide an overview of in vivo techniques to index synaptic markers in patients. Several positron emission tomography (PET) tracers for synaptic vesicle glycoprotein 2 A (SV2A) show good reliability and selectivity. We review over 50 clinical studies including over 1700 participants, and compare findings in healthy ageing and across disorders, including addiction, schizophrenia, depression, posttraumatic stress disorder, and neurodegenerative disorders, including tauopathies, Huntington's disease and α-synucleinopathies. These show lower SV2A measures in cortical brain regions across most of these disorders relative to healthy volunteers, with the most well-replicated findings in tauopathies, whilst changes in Huntington's chorea, Parkinson's disease, corticobasal degeneration and progressive supranuclear palsy are predominantly subcortical. SV2A PET measures are correlated with functional connectivity across brain networks, and a number of other measures of brain function, including glucose metabolism. However, the majority of studies found no relationship between grey matter volume measured with magnetic resonance imaging and SV2A PET measures. Cognitive dysfunction, in domains including working memory and executive function, show replicated inverse relationships with SV2A measures across diagnoses, and initial findings also suggest transdiagnostic relationships with mood and anxiety symptoms. This suggests that synaptic abnormalities could be a common pathophysiological substrate underlying cognitive and, potentially, affective symptoms. We consider limitations of evidence and future directions; highlighting the need to develop postsynaptic imaging markers and for longitudinal studies to test causal mechanisms.
突触与许多神经精神疾病有关。在这里，我们概述了用于在患者中标记突触的体内技术。几种突触小泡糖蛋白 2A（SV2A）的正电子发射断层扫描（PET）示踪剂具有良好的可靠性和选择性。我们综述了 50 多项临床研究，包括 1700 多名参与者，并比较了健康衰老和各种疾病（包括成瘾、精神分裂症、抑郁症、创伤后应激障碍以及神经退行性疾病，包括tau 病、亨廷顿病和α-突触核蛋白病）中的发现。这些研究表明，与健康志愿者相比，大多数这些疾病的皮质脑区的 SV2A 测量值较低，tau 病的研究结果最具可重复性，而亨廷顿舞蹈病、帕金森病、皮质基底节变性和进行性核上性麻痹的变化主要是皮质下的。SV2A PET 测量值与脑网络之间的功能连接以及其他一些脑功能测量值（包括葡萄糖代谢）相关。然而，大多数研究发现，磁共振成像测量的灰质体积与 SV2A PET 测量值之间没有关系。认知功能障碍，包括工作记忆和执行功能等领域，在各种诊断中与 SV2A 测量值呈反向关系，最初的发现还表明与情绪和焦虑症状存在跨诊断关系。这表明突触异常可能是认知和潜在情感症状的共同病理生理基础。我们考虑了证据的局限性和未来的方向；强调需要开发突触后成像标记物和进行纵向研究以测试因果机制。
