Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, De Crespigny Park, London, SE5 8AF, UK.
Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, London, W12 0NN, UK.
Transl Psychiatry. 2021 Aug 12;11(1):425. doi: 10.1038/s41398-021-01540-2.
N-methyl-D-aspartate receptor (NMDAR) hypofunction is hypothesised to underlie psychosis but this has not been tested early in illness. To address this, we studied 40 volunteers (21 patients with first-episode psychosis and 19 matched healthy controls) using PET imaging with an NMDAR selective ligand, [F]GE-179, that binds to the ketamine binding site to index its distribution volume ratio (DVR) and volume of distribution (V). Hippocampal DVR, but not V, was significantly lower in patients relative to controls (p = 0.02, Cohen's d = 0.81; p = 0.15, Cohen's d = 0.49), and negatively associated with total (rho = -0.47, p = 0.04), depressive (rho = -0.67, p = 0.002), and general symptom severity (rho = -0.74, p < 0.001). Exploratory analyses found no significant differences in other brain regions (anterior cingulate cortex, thalamus, striatum and temporal cortex). These findings are consistent with the NMDAR hypofunction hypothesis and identify the hippocampus as a key locus for relative NMDAR hypofunction, although further studies should test specificity and causality.
N-甲基-D-天冬氨酸受体（NMDAR）功能低下被认为是精神病的基础，但这在疾病早期尚未得到验证。为了解决这个问题，我们使用 NMDAR 选择性配体 [F]GE-179 通过 PET 成像研究了 40 名志愿者（21 名首发精神病患者和 19 名匹配的健康对照者），该配体与氯胺酮结合部位结合，以指示其分布容积比（DVR）和分布容积（V）。与对照组相比，患者的海马体 DVR 明显降低（p=0.02，Cohen's d=0.81;p=0.15，Cohen's d=0.49），与总症状严重程度（rho=-0.47，p=0.04）、抑郁症状严重程度（rho=-0.67，p=0.002）和一般症状严重程度（rho=-0.74，p<0.001）呈负相关。探索性分析未发现其他脑区（前扣带回皮质、丘脑、纹状体和颞叶皮质）存在显著差异。这些发现与 NMDAR 功能低下假说一致，并确定海马体为相对 NMDAR 功能低下的关键部位，尽管进一步的研究应该检验特异性和因果关系。
Zotero 插件
