Functional neuroanatomy of CCK-4-induced panic attacks in healthy volunteers.
Experimental panic induction with cholecystokinin tetrapeptide (CCK-4) is considered as a suitable model to investigate the pathophysiology of panic attacks. While only a few studies investigated the brain activation patterns following CCK-4, no data are available on the putative involvement of the amygdala in the CCK-4 elicited anxiety response. We studied the functional correlates of CCK-4-induced anxiety in healthy volunteers by means of functional magnetic resonance imaging (fMRI) and region of interest (ROI) analysis of the amygdala. Sixteen healthy volunteers underwent challenge with CCK-4 compared with placebo in a single-blind design. Functional brain activation patterns were determined for the CCK-4-challenge, the placebo response and anticipatory anxiety (AA). CCK-4-induced anxiety was accompanied by a strong and robust activation (random effects analysis, P < 0.00001, uncorrected for multiple testing) in the ventral anterior cingulate cortex (ACC), middle and superior frontal gyrus, precuneus, middle and superior temporal gyrus, occipital lobe, sublobar areas, cerebellum, and brainstem. In contrast, random effects group analysis for placebo and AA using the same level of significance generated no significant results. Using a more liberal level of significance, activations could be observed in some brain regions such as the dorsal part of the ACC during AA (random effects analysis, P < 0.005). Overall functional responses did not differ between panickers and nonpanickers. Only 5 of 11 subjects showed strong amygdala activation. However, ROI analysis pointed towards higher scores in fear items in these subjects. In conclusion, while overall brain activation patterns are not related to the subjective anxiety response to CCK-4, amygdala activation may be involved in the subjective perception of CCK-4-induced fear.
Eser
Daniela
D
Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany. daniela.eser@med.uni-muenchen.de
Leicht
Gregor
G
Lutz
Jürgen
J
Wenninger
Stephan
S
Kirsch
Valerie
V
Schüle
Cornelius
C
Karch
Susanne
S
Baghai
Thomas
T
Pogarell
Oliver
O
Born
Christine
C
Rupprecht
Rainer
R
Mulert
Christoph
C
D000328:Adult; D000679:Amygdala / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology; D001007:Anxiety / Q000139:chemically induced / Q000503:physiopathology; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology*; D001931:Brain Mapping; D005239:Fear / Q000187:drug effects / Q000502:physiology; D006179:Gyrus Cinguli / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008032:Limbic System / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology*; D016584:Panic Disorder / Q000139:chemically induced / Q000503:physiopathology*; D013758:Tetragastrin / Q000494:pharmacology; D055815:Young Adult
D013758:Tetragastrin