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Prefrontal glutamate neurotransmission in PTSD: A novel approach to estimate synaptic strength in vivo in humans
medRxiv - Psychiatry and Clinical Psychology Pub Date : 2022-01-10 , DOI: 10.1101/2021.04.09.21255211
Lynnette Averill , Lihong Jiang , Prerana Purohit , Anastasia Coppoli , Christopher Averill , Jeremy Roscoe , Benjamin Kelmendi , Henk De Feyter , Robin de Graaf , Ralitza Gueorguieva , Gerard Sanacora , John Krystal , Douglas Rothman , Graeme Mason , Chadi Abdallah

Trauma and chronic stress are believed to induce and exacerbate psychopathology by disrupting glutamate synaptic strength. However, in vivo in human methods to estimate synaptic strength are limited. In this study, we established a novel putative biomarker of glutamatergic synaptic strength, termed energy-per-cycle (EPC). Then, we used EPC to investigate the role of prefrontal neurotransmission in trauma psychopathology. Healthy control (n=18) and patients with posttraumatic stress (PTSD; n=16) completed 13C-acetate magnetic resonance spectroscopy scans to estimate prefrontal EPC, which is the ratio of neuronal energetic needs per glutamate neurotransmission cycle (VTCA/VCycle). Patients with PTSD were found to have 28% reduction in prefrontal EPC (t=3.0; df=32, p=0.005). There was no effect of sex on EPC, but age was negatively associated with prefrontal EPC across groups (r=–0.46, n=34, p=0.006). Controlling for age did not affect the study results. The feasibility and utility of EPC were established. Patients with PTSD were found to have reduced prefrontal glutamatergic synaptic strength. These findings suggest that reduced glutamatergic synaptic strength may contribute to the pathophysiology of PTSD and could be targeted by new treatments.

中文翻译:

创伤后应激障碍中的前额谷氨酸神经传递:一种估计人类体内突触强度的新方法

创伤和慢性压力被认为通过破坏谷氨酸突触强度来诱发和加剧精神病理学。然而,人体中估计突触强度的方法是有限的。在这项研究中,我们建立了一种新的假定的谷氨酸能突触强度生物标志物,称为每周期能量 (EPC)。然后,我们使用 EPC 来研究前额神经传递在创伤精神病理学中的作用。健康对照组 (n=18) 和有创伤后应激障碍的患者 (PTSD; n=16) 完成了13 C-乙酸磁共振波谱扫描以估计前额叶 EPC,即每个谷氨酸神经传递周期的神经元能量需求的比率 (V TCA /V循环)。发现 PTSD 患者的前额叶 EPC 降低了 28%(t =3.0;df =32,p =0.005)。性别对 EPC 没有影响,但年龄与各组前额叶 EPC 呈负相关(r =–0.46,n=34,p =0.006)。控制年龄不影响研究结果。确立了EPC的可行性和实用性。发现 PTSD 患者的前额叶谷氨酸能突触强度降低。这些发现表明,谷氨酸能突触强度的降低可能有助于 PTSD 的病理生理学,并且可能是新治疗的目标。
更新日期:2022-01-12
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