Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans.
Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans.
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DOI：
10.1177/24705470221092734
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发表时间：
2022-01
期刊：
影响因子：
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通讯作者：
Abdallah, Chadi G
中科院分区：
文献类型：
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作者：
Averill, Lynnette A;Jiang, Lihong;Purohit, Prerana;Coppoli, Anastasia;Averill, Christopher L;Roscoe, Jeremy;Kelmendi, Benjamin;De Feyter, Henk M;de Graaf, Robin A;Gueorguieva, Ralitza;Sanacora, Gerard;Krystal, John H;Rothman, Douglas L;Mason, Graeme F;Abdallah, Chadi G
创伤和慢性应激被认为通过破坏谷氨酸突触强度而诱发和加剧精神病理。然而，在人体内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突触强度生物标志物，称为能量周期（EPC）。然后，我们使用EPC来研究前额叶神经传递在创伤相关精神病理中的作用。健康对照（n = 18）和创伤后应激（PTSD; n = 16）患者完成13c -乙酸酯磁共振波谱（MRS）扫描，以估计前额叶EPC，即每个谷氨酸神经传递周期（VTCA/VCycle）神经元能量需求的比率。PTSD患者前额叶EPC减少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）。控制年龄对研究结果没有影响。验证了13c -乙酸酯MRS法估算前额叶EPC的可行性和实用性。发现PTSD患者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，并可能成为新的治疗目标。
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-related psychopathology. Healthy controls (n = 18) and patients with posttraumatic stress (PTSD; n = 16) completed 13C-acetate magnetic resonance spectroscopy (MRS) 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 = .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 = .006). Controlling for age did not affect the study results. The feasibility and utility of estimating prefrontal EPC using 13C-acetate MRS 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.