Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.
Neuropsychopharmacology. 2013 Aug;38(9):1648-54. doi: 10.1038/npp.2013.61. Epub 2013 Mar 5.
According to preclinical studies, glutamate has been implicated in the pathogenesis of anxiety. In order to elucidate the role of glutamate in anxiety and panic in humans, brain glutamate+glutamine (Glx) levels were measured during cholecystokinin-tetrapeptide (CCK-4)-induced panic using magnetic resonance spectroscopy (MRS). Eighteen healthy subjects underwent a CCK-4 challenge. MR spectra were obtained from the anterior cingulate cortex (ACC) using a single voxel point-resolved spectroscopy method and analyzed using LCModel. A combined fitting of Glx was performed. Panic was assessed using the Acute Panic Inventory (API) and Panic Symptom Scale (PSS) scores. Moreover, hypothalamic-pituitary-adrenal axis stimulation was monitored throughout the challenge. There was a significant panic response following CCK-4 as revealed by a marked increase in both the panic scores (API: F(1,17)=149.41; p<0.0001; PSS: F(1,17)=88.03; p<0.0001) and heart rate (HR: F(1,17)=72.79; p<0.0001). MRS measures showed a significant increase of brain Glx/creatine (Glx/Cr) levels peaking at 2-10 min after challenge (F(1,17)=15.94; p=0.001). There was also a significant increase in CCK-4-related cortisol release (F(6,11)=8.68; p=0.002). Finally, significant positive correlations were found between baseline Glx/Cr and both APImax (r=0.598; p=0.009) and maximum heart rate (HR(max)) during challenge (r=0.519; p=0.027). Our results suggest that CCK-4-induced panic is accompanied by a significant glutamate increase in the bilateral ACC. The results add to the hypothesis of a disturbance of the inhibitory-excitatory equilibrium and suggest that apart from static alterations rapid and dynamic neurochemical changes might also be relevant for the neural control of panic attacks.
根据临床前研究，谷氨酸已被牵连到焦虑症的发病机制中。为了阐明谷氨酸在人类焦虑和恐慌中的作用，使用磁共振波谱（MRS）测量胆囊收缩素-四肽（CCK-4）诱导的恐慌期间的脑谷氨酸+谷氨酰胺（Glx）水平。18 名健康受试者接受了 CCK-4 挑战。使用单体点分辨光谱法从前扣带皮层（ACC）获得 MR 光谱，并使用 LCModel 进行分析。进行了 Glx 的联合拟合。使用急性恐慌量表（API）和恐慌症状量表（PSS）评分评估恐慌。此外，在整个挑战过程中监测了下丘脑-垂体-肾上腺轴的刺激。CCK-4 后出现明显的恐慌反应，这表现为恐慌评分（API：F（1,17）=149.41；p<0.0001；PSS：F（1,17）=88.03；p<0.0001）和心率（HR：F（1,17）=72.79；p<0.0001）明显增加。MRS 测量显示，脑 Glx/肌酸（Glx/Cr）水平在挑战后 2-10 分钟显着增加（F（1,17）=15.94；p=0.001）。CCK-4 相关皮质醇释放也显着增加（F（6,11）=8.68；p=0.002）。最后，发现基线 Glx/Cr 与 API 最大值（r=0.598；p=0.009）和挑战期间最大心率（HR（max））之间存在显著正相关（r=0.519；p=0.027）。我们的结果表明，CCK-4 诱导的恐慌伴随着双侧 ACC 中谷氨酸的显着增加。这些结果增加了抑制-兴奋平衡紊乱的假说，并表明除了静态改变外，快速和动态神经化学变化也可能与恐慌发作的神经控制有关。
