N-Methyl-D-Aspartate Receptor availability in First-Episode Psychosis: a multi-modal PET-MR brain imaging study
N-Methyl-D-Aspartate Receptor availability in First-Episode Psychosis: a multi-modal PET-MR brain imaging study
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DOI：
10.1192/j.eurpsy.2022.238
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发表时间：
2022-09-01
影响因子：
7.8
通讯作者：
Howes, O.
中科院分区：
文献类型：
--
作者：
Beck, K.;Arumuham, A.;Brugger, S.;Mccutcheon, R.;Veronese, M.;Kaar, S.;Pillinger, T.;Stone, J.;Howes, O.
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，但这在疾病的早期还没有得到测试。我们的目的是确定与健康对照组相比，首发精神病患者的NMDAR可用性是否更低。为了解决这个问题，我们研究了40名志愿者(21名首发精神病患者和19名匹配的健康对照)，使用带有NMDAR选择性配体[18F]GE179的PET成像，该配体与氯胺酮结合部位结合，以指数其分布体积比(DVR)和分布体积(VT)。用磁共振波谱成像(1H-MRS)同时测定纹状体谷氨酸和谷氨酸能指标。与对照组相比，海马区DVR显著降低(P=0.02，Cohen‘s d=0.81；P=0.15，Cohen’s d=0.49)，且与总分(Rho=-0.47，p=0.04)、抑郁(Rho=-0.67，p=0.002)、一般症状严重程度(Rho=-0.74，p<；0.001)呈负相关。探索性分析发现，其他大脑区域(前扣带回皮质、丘脑、纹状体和颞叶皮质)没有显著差异。我们发现，在首发精神病患者中，海马区NMDAR的可获得性与纹状体谷氨酸水平呈负相关(Rho=-0.74，p<；0.001)，但在健康对照组中没有(Rho=-0.22，p=0.44)。这些发现与NMDAR功能低下的假说是一致的，并将海马体确定为相对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。没有重要的关系。
N-Methyl-D-Aspartate Receptor (NMDAR) hypofunction is hypothesised to underlie psychosis but this has not been tested early in illness. Our aim was to determine if NMDAR availability was lower in patients with first episode psychosis compared to healthy controls. 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, [18F]GE179, that binds to the ketamine binding site to index its distribution volume ratio (DVR) and volume of distribution (VT). Striatal glutamatergic indices (glutamate and Glx) were measured simultaneously using magnetic resonance spectroscopy imaging (1H-MRS). Hippocampal DVR, but not VT, 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). We found an inverse relationship between hippocampal NMDAR availability and striatal glutamate levels in people with first-episode psychosis (rho = -0.74, p <0.001) but not in healthy controls (rho = -0.22, p = 0.44). 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. No significant relationships.