ImportanceSynaptic dysfunction is involved in schizophrenia pathophysiology. However, whether in vivo synaptic density is reduced in early stages of psychosis, including its high-risk states, remains unclear.ObjectiveTo investigate whether synaptic density (synaptic vesicle glycoprotein 2A [SV2A] binding potential) is reduced in first-episode psychosis (FEP) and in clinical high risk (CHR) and investigate the effect of cannabis use on synaptic density and examine its relationship with psychotic symptoms and gray matter microstructure across groups.Design, Setting, and ParticipantsThis cross-sectional study was performed in a tertiary care psychiatric hospital from July 2021 to October 2023. Participants were patients with antipsychotic-free or minimally exposed FEP or CHR and healthy controls with a clean urine drug screen (except cannabis).Main Outcomes and MeasuresSynaptic density was quantified with dynamic 90-minute [18F]SynVesT-1 positron emission tomography (PET) scans across prioritized brain regions of interest (ROIs) delineated in individual magnetic resonance images (MRIs). Cannabis use was confirmed with urine drug screens. Gray matter microstructure was assessed using diffusion-weighted MRI to estimate neurite density.ResultsA total of 49 participants were included, including 16 patients with FEP (mean [SD] age, 26.1 [4.6] years; 9 males and 7 females), 17 patients at CHR (mean [SD] age, 21.2 [3.5] years; 8 males and 9 females), and 16 healthy controls (mean [SD] age, 23.4 [3.6] years; 7 males and 9 females). Synaptic density was significantly different between groups (F2,273 = 4.02, P = .02, Cohen F = 0.17; ROI: F5,273 = 360.18, P < .01, Cohen F = 2.55) with a group × ROI interaction (F10,273 = 2.67, P < .01, Cohen F = 0.32). Synaptic density was lower in cannabis users (F1,272 = 5.31, P = .02, Cohen F = 0.14). Lower synaptic density across groups was associated with more negative symptoms (Positive and Negative Syndrome Scale negative scores: F1,81 = 4.31, P = .04, Cohen F = 0.23; Scale of Psychosis-Risk Symptoms negative scores: F1,90 = 4.12, P = .04, Cohen F = 0.21). SV2A binding potential was significantly associated with neurite density index (F1,138 = 6.76, P = .01, Cohen F = 0.22).Conclusions and RelevanceThis study found that synaptic density reductions were present during the early stages of psychosis and its risk states and associated with negative symptoms. The implications of SV2A for negative symptoms in psychosis and CHR warrant further investigation. Future studies should investigate the impact of cannabis use on synaptic density in CHR longitudinally.

中文翻译：

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精神病早期和临床高危的突触密度


重要性突触功能障碍与精神分裂症的病理生理学有关。然而，在精神病的早期阶段，包括其高危状态，体内突触密度是否降低仍不清楚。目的探讨首发精神病 （FEP） 和临床高危 （CHR） 的突触密度 （突触小泡糖蛋白 2A [SV2A] 结合电位） 是否降低，探讨大麻使用对突触密度的影响，并检查其与精神病症状和灰质微观结构的关系跨组。设计、设置和参与者这项横断面研究于 2021 年 7 月至 2023 年 10 月在一家三级护理精神病医院进行。参与者是无抗精神病药物或最低暴露 FEP 或 CHR 的患者，以及尿液药物筛查干净的健康对照者（大麻除外）。主要结局和措施通过动态 90 分钟 [18F] SynVesT-1 正电子发射断层扫描 （PET） 扫描在单个磁共振图像 （MRI） 中描绘的优先感兴趣大脑区域 （ROI） 量化突触密度。通过尿液药物筛查证实了大麻的使用。使用弥散加权 MRI 评估灰质微观结构以估计神经突密度。结果共纳入 49 名参与者，包括 16 名 FEP 患者 （平均 [SD] 年龄，26.1 [4.6] 岁;9 名男性和 7 名女性），17 名 CHR 患者 （平均 [SD] 年龄，21.2 [3.5] 岁;8 名男性和 9 名女性）和 16 名健康对照者 （平均 [SD] 年龄，23.4 [3.6] 岁;7 名男性和 9 名女性）。各组突触密度差异显著 （F2,273 = 4.02，P = .02，Cohen F = 0.17;ROI：F5,273 = 360.18，P < .01，Cohen F = 2.55），一组 × ROI 交互作用 （F10,273 = 2.67，P < .01，Cohen F = 0.32）。 大麻使用者的突触密度较低 （F1,272 = 5.31，P = .02，Cohen F = 0.14）。各组较低的突触密度与较多的阴性症状相关（阳性和阴性症状量表阴性评分：F1,81 = 4.31，P = .04，Cohen F = 0.23;精神病风险症状量表负分：F1,90 = 4.12，P = .04，Cohen F = 0.21）。SV2A 结合电位与神经突密度指数显著相关 （F1,138 = 6.76，P = .01，Cohen F = 0.22）。结论和相关性本研究发现，突触密度降低存在于精神病的早期阶段及其风险状态，并与阴性症状相关。SV2A 对精神病和 CHR 阴性症状的影响值得进一步研究。未来的研究应纵向调查大麻使用对 CHR 突触密度的影响。