title: Acute shift in glutamate concentrations following experimentally induced panic with cholecystokinin tetrapeptide--a 3T-MRS study in healthy subjects.
abstract: 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.
authors: Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany. zwanzger@ukmuenster.de
authors: Peter
authors: P
authors: Zwanzger
authors: Maxim
authors: M
authors: Zavorotnyy
authors: Elena
authors: E
authors: Gencheva
authors: Julia
authors: J
authors: Diemer
authors: Harald
authors: H
authors: Kugel
authors: Walter
authors: W
authors: Heindel
authors: Tillmann
authors: T
authors: Ruland
authors: Patricia
authors: P
authors: Ohrmann
authors: Volker
authors: V
authors: Arolt
authors: Katharina
authors: K
authors: Domschke
authors: Bettina
authors: B
authors: Pfleiderer
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D003401:Creatine / Q000378:metabolism; D059907:Functional Neuroimaging; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism; D006339:Heart Rate; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D016584:Panic Disorder / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000378:metabolism; D011569:Psychiatric Status Rating Scales; D013758:Tetragastrin
chemical_list: D013758:Tetragastrin; D005973:Glutamine; D018698:Glutamic Acid; D000324:Adrenocorticotropic Hormone; D003401:Creatine; D006854:Hydrocortisone