Despite longstanding interest in the central cholinergic system in schizophrenia (SCZ), cholinergic imaging studies with patients have been limited to receptors. Here, we conducted a proof-of-concept positron emission tomography study using [F]-VAT, a new radiotracer that targets the vesicular acetylcholine transporter as a proxy measure of acetylcholine transmission capacity, in patients with SCZ and explored relationships of vesicular acetylcholine transporter with clinical symptoms and cognition. A total of 18 adult patients with SCZ or schizoaffective disorder (the SCZ group) and 14 healthy control participants underwent a positron emission tomography scan with [F]-VAT. Distribution volume (V) for [F]-VAT was derived for each region of interest, and group differences in V were assessed with 2-sample tests. Functional significance was explored through correlations between V and scores on the Positive and Negative Syndrome Scale and a computerized neurocognitive battery (PennCNB). No group differences in [F]-VAT V were observed. However, within the SCZ group, psychosis symptom severity was positively associated with V in multiple regions of interest, with the strongest effects in the hippocampus, thalamus, midbrain, cerebellum, and cortex. In addition, in the SCZ group, working memory performance was negatively associated with V in the substantia innominata and several cortical regions of interest including the dorsolateral prefrontal cortex. In this initial study, the severity of 2 important features of SCZ—psychosis and working memory deficit—was strongly associated with [F]-VAT V in several cortical and subcortical regions. These correlations provide preliminary evidence of cholinergic activity involvement in SCZ and, if replicated in larger samples, could lead to a more complete mechanistic understanding of psychosis and cognitive deficits in SCZ and the development of therapeutic targets.

中文翻译：

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精神分裂症中的囊泡乙酰胆碱转运蛋白成像：使用 [18F]-VAT 的正电子发射断层扫描研究

尽管人们长期以来对精神分裂症（SCZ）的中枢胆碱能系统感兴趣，但对患者的胆碱能成像研究仅限于受体。在这里，我们使用[F]-VAT（一种新型放射性示踪剂，以囊泡乙酰胆碱转运蛋白为目标，作为乙酰胆碱传输能力的替代指标）在 SCZ 患者中进行了概念验证正电子发射断层扫描研究，并探讨了囊泡乙酰胆碱转运蛋白的关系具有临床症状和认知能力。总共 18 名患有 SCZ 或分裂情感障碍的成年患者（SCZ 组）和 14 名健康对照参与者接受了 [F]-VAT 正电子发射断层扫描。 [F]-VAT 的分布体积 (V) 是针对每个感兴趣区域得出的，并且 V 的组间差异通过 2 样本测试进行评估。通过 V 与阳性和阴性综合症量表分数以及计算机化神经认知电池 (PennCNB) 之间的相关性来探索功能意义。没有观察到 [F]-VAT V 的组间差异。然而，在 SCZ 组中，精神病症状的严重程度与多个感兴趣区域的 V 呈正相关，其中海马、丘脑、中脑、小脑和皮质的影响最强。此外，在 SCZ 组中，工作记忆表现与无名质和几个感兴趣的皮质区域（包括背外侧前额叶皮质）中的 V 呈负相关。在这项初步研究中，SCZ 的 2 个重要特征（精神病和工作记忆缺陷）的严重程度与几个皮质和皮质下区域的 [F]-VAT V 密切相关。这些相关性提供了 SCZ 中胆碱能活动参与的初步证据，如果在更大的样本中复制，可能会导致对 SCZ 中的精神病和认知缺陷以及治疗靶点的开发有更完整的机制理解。