We would like to address the results of two recent positron emission tomography (PET) imaging studies and discuss them in relation to our own findings [1]. The first study we would like to refer to is an [¹⁸F]FDOPA PET investigation performed in two independent cohorts of drug-free patients with schizophrenia [2]. [¹⁸F]FDOPA is a direct precursor of dopamine, and its uptake is generally assumed to reflect presynaptic dopamine synthesis and storage capacity. In contrast to earlier [¹⁸F]FDOPA PET studies, Eisenberg et al. failed to find elevated [¹⁸F]FDOPA uptake in patients with schizophrenia. However, the study observed inverse correlations between [¹⁸F]FDOPA uptake rates into the putamen and severity of negative symptoms in both cohorts. Thus, the Eisenberg et al. findings indicate that reduced dopamine transmission in the putamen may be an important element in the formation of negative symptoms of schizophrenia.

The second study we would like to address [3] presents the results of a PET study on the effects of oral methylphenidate (MPH) administration on non-displaceable binding potential (BP_ND) values of the dopamine D_2/3 receptor agonist radioligand [¹¹C]-(+)-PHNO in individuals at clinical high-risk (CHR) for psychosis. Changes in radioligand binding to dopamine D_2/3 receptors after a pharmacological or behavioral challenge provide an indirect measure for the fluctuations in extracellular dopamine levels. The authors aimed to replicate and extend findings on alterations in subcortical availability of dopamine in CHR individuals, as previous studies have shown that subcortical dopamine functioning is elevated in full-blown psychosis, and that enhanced dopamine transmission might be present even before psychosis onset [4, 5]. This, however, was questioned by a more recent meta-analysis [6]. The main finding of the study by Girgis et al. [3] was that, compared to non-CHR controls, CHR subjects showed greater changes in [¹¹C]-(+)-PHNO BP_ND values (∆BP_ND) in response to the MPH challenge. This conforms well with results from earlier challenge-studies in patients with schizophrenia [1, 4, 7,8,9,10,11] and extends the use of this method towards prodromal stages of psychosis (which, of course, can only be termed as such in retrospect). In addition, the study by Girgis et al. observed an inverse relationship between the expression of negative symptoms and [¹¹C]-(+)-PHNO ∆BP_ND in the ventral striatum of CHR subjects.

我们想谈谈最近两项正电子发射断层扫描 （PET） 成像研究的结果，并结合我们自己的发现来讨论它们 [1]。我们想提到的第一项研究是在两个独立的无药物精神分裂症患者队列中进行的 [¹⁸F]FDOPA PET 调查 [2]。[¹⁸个地址]FDOPA 是多巴胺的直接前体，通常假设其摄取反映了突触前多巴胺的合成和储存能力。与早期的 [¹⁸F]FDOPA PET 研究相比，Eisenberg 等人未能发现精神分裂症患者的 [¹⁸F]FDOPA 摄取升高。然而，该研究观察到 [¹⁸F]FDOPA 对壳核的摄取率与两个队列中阴性症状的严重程度之间存在负相关。因此，Eisenberg 等人的研究结果表明，壳核中多巴胺传递的减少可能是形成精神分裂症阴性症状的重要因素。

我们要讨论的第二项研究 [3] 介绍了口服哌醋甲酯 （MPH） 给药对临床高危 （CHR） 精神病个体中多巴胺 D_2/3 受体激动剂放射性配体 [¹¹C]-（+）-PHNO 的不可置换结合电位 （BP_ND） 值的影响的 PET 研究结果。药理学或行为激发后放射性配体与多巴胺 D_2/3 受体结合的变化为细胞外多巴胺水平的波动提供了间接测量。作者旨在复制和扩展 CHR 个体皮层下多巴胺可用性改变的发现，因为先前的研究表明，皮层下多巴胺功能在全面精神病中升高，并且甚至在精神病发作之前就可能存在增强的多巴胺传递 [4， 5]。然而，最近的一项荟萃分析对此提出了质疑 [6]。Girgis 等人 [3] 的研究主要发现是，与非 CHR 对照相比，CHR 受试者在响应 MPH 攻击时表现出 [¹¹C]-（+）-PHNO BP_ND 值 （∆BP_ND） 的更大变化。这与早期精神分裂症患者挑战研究的结果非常吻合 [1， 4， 7,8,9,10,11]，并将这种方法的使用扩展到精神病的前驱阶段（当然，这只能在回顾中这样称呼）。此外，Girgis 等人的研究观察到 CHR 受试者腹侧纹状体中阴性症状的表达与 [¹¹C]-（+）-PHNO ∆BP_ND 呈负相关。