Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom; Psychiatric Imaging Group, Medical Research Council, London Institute of Medical Sciences, Hammersmith Hospital, London, United Kingdom; Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Centre for Psychiatry and Mental Health, Wolfson Institute of Population Health, Queen Mary University of London, London, United Kingdom.
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom; Psychiatric Imaging Group, Medical Research Council, London Institute of Medical Sciences, Hammersmith Hospital, London, United Kingdom; Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
Biol Psychiatry. 2024 Apr 1;95(7):639-646. doi: 10.1016/j.biopsych.2023.05.022. Epub 2023 Jun 15.
The synaptic hypothesis is an influential theory of the pathoetiology of schizophrenia (SCZ), which is supported by the finding that there is lower uptake of the synaptic terminal density marker [C]UCB-J in patients with chronic SCZ than in control participants. However, it is unclear whether these differences are present early in the illness. To address this, we investigated [C]UCB-J volume of distribution (V) in antipsychotic-naïve/free patients with SCZ who were recruited from first-episode services compared with healthy volunteers.
Forty-two volunteers (SCZ n = 21, healthy volunteers n = 21) underwent [C]UCB-J positron emission tomography to index [C]UCB-J V and distribution volume ratio in the anterior cingulate, frontal, and dorsolateral prefrontal cortices; the temporal, parietal and occipital lobes; and the hippocampus, thalamus, and amygdala. Symptom severity was assessed in the SCZ group using the Positive and Negative Syndrome Scale.
We found no significant effects of group on [C]UCB-J V or distribution volume ratio in most regions of interest (effect sizes from d = 0.0-0.7, p > .05), with two exceptions: we found lower distribution volume ratio in the temporal lobe (d = 0.7, uncorrected p < .05) and lower V/f in the anterior cingulate cortex in patients (d = 0.7, uncorrected p < .05). The Positive and Negative Syndrome Scale total score was negatively associated with [C]UCB-J V in the hippocampus in the SCZ group (r = -0.48, p = .03).
These findings indicate that large differences in synaptic terminal density are not present early in SCZ, although there may be more subtle effects. When taken together with previous evidence of lower [C]UCB-J V in patients with chronic illness, this may indicate synaptic density changes during the course of SCZ.
突触假说（synaptic hypothesis）是精神分裂症（schizophrenia，SCZ）病理生理学的一个有影响力的理论，该理论得到了这样的发现的支持，即与对照组参与者相比，患有慢性 SCZ 的患者突触末梢密度标志物[C]UCB-J 的摄取较低。然而，目前尚不清楚这些差异是否在疾病早期存在。为了解决这个问题，我们调查了来自首发服务的抗精神病药物初治/无药物治疗的 SCZ 患者与健康志愿者相比，[C]UCB-J 分布容积（V）。
42 名志愿者（SCZ n=21，健康志愿者 n=21）接受[C]UCB-J 正电子发射断层扫描，以标记前扣带回、额和背外侧前额皮质、颞叶、顶叶和枕叶以及海马体、丘脑和杏仁核中的[C]UCB-J V 和分布容积比。SCZ 组的症状严重程度使用阳性和阴性综合征量表进行评估。
我们发现，在大多数感兴趣的区域（效应大小从 d=0.0-0.7，p>.05），组间对[C]UCB-J V 或分布容积比没有显著影响，只有两个例外：我们发现颞叶的分布容积比（d=0.7，未校正 p<0.05）和前扣带回皮质的 V/f 较低（未校正 p<0.05）。SCZ 组的正、阴性综合征量表总分与海马体中的[C]UCB-J V 呈负相关（r=-0.48，p=0.03）。
这些发现表明，在 SCZ 早期，突触末梢密度的差异并不明显，尽管可能存在更微妙的影响。当与先前慢性疾病患者[C]UCB-J V 较低的证据结合起来时，这可能表明在 SCZ 过程中突触密度发生了变化。
