谷氨酸水平与高危和首发精神分裂症的症状负担：前扣带回皮层的双体素研究。
Glutamate levels and symptom burden in high-risk and first-episode schizophrenia: a dual-voxel study of the anterior cingulate cortex.
机构信息
From the Department of Psychiatry and Psychology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China (Fan); the Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China (Fan, Zhang, Ma, Wang, Yuan, Ouyang, He, Li, Chen); the Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, Que. (Fan, Palaniyappan); the Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ont. (Liang, Palaniyappan).
From the Department of Psychiatry and Psychology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China (Fan); the Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, China (Fan, Zhang, Ma, Wang, Yuan, Ouyang, He, Li, Chen); the Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montréal, Que. (Fan, Palaniyappan); the Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ont. (Liang, Palaniyappan)
出版信息
J Psychiatry Neurosci. 2024 Nov 14;49(6):E367-E376. doi: 10.1503/jpn.240094. Print 2024 Nov-Dec.
BACKGROUND
Reduced glutamatergic excitability of the anterior cingulate cortex (ACC) has been long suspected in schizophrenia; recent observations support low glutamatergic tone as the primary pathophysiology contributing to subtle early features of this illness, with a secondary disinhibition (higher glutamate tone) resulting in more prominent clinical symptoms later in its course. We sought to investigate whether people with genetic high risk (GHR) for schizophrenia have lower glutamate levels in the ACC than those at later stages of clinical high risk (CHR) and those with first-episode schizophrenia (FES), among whom symptoms are already prominent.
METHODS
We recruited people with CHR, GHR, or FES, as well as healthy controls. Using proton magnetic resonance spectroscopy, we determined glutamate levels in the perigenual ACC (pACC) and dorsal ACC (dACC) using a 3 T scanner.
RESULTS
We recruited 302 people across multiple stages of psychosis, including 63 with CHR, 76 with GHR, and 96 with FES, as well as 67 healthy controls. Those with GHR had lower glutamate levels in the dACC than those with CHR, while those with CHR had higher glutamate levels in the pACC than those with FES. Higher disorganization, but not any other symptom domain, was associated with lower levels of glutamate in the GHR group (dACC and pACC) and in the CHR group (pACC).
LIMITATIONS
The cross-sectional design precluded inferences regarding individual clinical trajectory and resolution at 3 T was insufficient to separate spectra of glutamine from glutamate.
CONCLUSION
Reduced glutamatergic tone among people genetically predisposed to schizophrenia supports diminished excitability as an early feature of schizophrenia, contributing to the subtle symptom of disorganization across high-risk states. Higher glutamate levels become apparent when psychotic symptoms become prominent, possibly as a disinhibitory effect and, at the full-blown stage of psychosis, the relationship between glutamate concentrations and symptoms ceases to be simply linear.
背景
人们早就怀疑精神分裂症患者的前扣带回皮质（ACC）谷氨酸能兴奋性降低；最近的观察结果支持低谷氨酸能状态是导致该病早期细微特征的主要病理生理学机制，随后的二次抑制（谷氨酸能增加）导致疾病过程后期更明显的临床症状。我们试图研究与处于临床高风险后期（CHR）和首发精神分裂症（FES）阶段的患者相比，遗传高风险（GHR）的个体是否在前扣带回皮质（ACC）中的谷氨酸水平更低，而后者的症状已经很明显。
方法
我们招募了 CHR、GHR 和 FES 患者以及健康对照者。使用质子磁共振波谱，我们在 3 T 扫描仪上确定了边缘 ACC（pACC）和背侧 ACC（dACC）中的谷氨酸水平。
结果
我们招募了处于精神病多个阶段的 302 人，包括 63 名 CHR 患者、76 名 GHR 患者和 96 名 FES 患者，以及 67 名健康对照者。与 CHR 患者相比，GHR 患者的 dACC 中的谷氨酸水平较低，而 CHR 患者的 pACC 中的谷氨酸水平高于 FES 患者。较高的紊乱程度，而不是其他任何症状领域，与 GHR 组（dACC 和 pACC）和 CHR 组（pACC）中的谷氨酸水平降低相关。
局限性
横断面设计排除了关于个体临床轨迹的推论，而在 3 T 时分辨率不足，无法将谷氨酰胺的光谱与谷氨酸分离。
结论
遗传易感性精神分裂症患者的谷氨酸能张力降低支持兴奋性降低是精神分裂症的早期特征，导致高风险状态下紊乱这一细微症状。当精神病症状变得明显时，谷氨酸水平会升高，可能是一种去抑制作用，而在精神病的全面发作阶段，谷氨酸浓度与症状之间的关系不再是简单的线性关系。
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