Acute Shift in Glutamate Concentrations Following Experimentally Induced Panic with Cholecystokinin Tetrapeptide—A 3T-MRS Study in Healthy Subjects

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 38; no. 9; pp. 1648 - 1654
• Main Authors: Zwanzger, Peter, Zavorotnyy, Maxim, Gencheva, Elena, Diemer, Julia, Kugel, Harald, Heindel, Walter, Ruland, Tillmann, Ohrmann, Patricia, Arolt, Volker, Domschke, Katharina, Pfleiderer, Bettina
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.08.2013
• Subjects: Adrenocorticotropic Hormone - blood; Adult; Adult and adolescent clinical studies; Anxiety disorders; Anxiety disorders. Neuroses; Benzodiazepines; Biological and medical sciences; Brain research; Creatine - metabolism; Functional Neuroimaging; Glutamic Acid - metabolism; Glutamine - metabolism; Gyrus Cinguli - metabolism; Heart Rate; Hormones; Humans; Hydrocortisone - blood; Hypothalamo-Hypophyseal System - metabolism; Male; Medical sciences; Neurobiology; Original; Panic attacks; Panic disorder; Panic Disorder - blood; Panic Disorder - chemically induced; Panic Disorder - metabolism; Pathogenesis; Pituitary-Adrenal System - metabolism; Psychiatric Status Rating Scales; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychotherapy; Signal transduction; Spectrum analysis; Tetragastrin; Germany; Human; panic attacks; Panic; Healthy subject; Induction; Central nervous system; Anxiety disorder; magnetic resonance spectroscopy; Experimental study; Glutamate; Neuropeptide; Encephalon; Cingulate cortex; Panic attack; Excitatory aminoacid; Neurotransmitter; Anxiety; Cholecystokinin; CCK-4; anterior cingulate cortex
• DOI: 10.1038/npp.2013.61
• ISSN: 0893-133X; 1740-634X

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.