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Am J Psychiatry 1995; 152:1180-1184
Copyright © 1995 by American Psychiatric Association
Functional neuroanatomy of CCK4-induced anxiety in normal healthy volunteers
C Benkelfat, J Bradwejn, E Meyer, M Ellenbogen, S Milot, A Gjedde and A Evans
McConnell Brain Imaging Center, Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
OBJECTIVE: The authors tested the prediction of temporal cortex activation
during experimentally induced anxiety by using positron emission tomography
and the [15O]H2O bolus-subtraction method to determine regional cerebral
blood flow (CBF) changes in normal volunteers challenged with a bolus
injection of cholecystokinin tetrapeptide (CCK4). METHOD: Eight
right-handed healthy subjects (five male, three female; mean age, 26.4
years) underwent four 60-second [15O]H2O scans separated by 15-minute
intervals; each scan followed an intravenous bolus injection of either
saline (placebo) or CCK4 (50 micrograms). Each subject received CCK4 once,
as the first or second bolus, in a random-order, placebo-controlled,
double-blind fashion. Two of the three placebo conditions were nominally
identical, and the remaining placebo was used to control for anticipatory
anxiety. Magnetic resonance imaging scans were obtained for subsequent
anatomical correlation of blood flow changes. RESULTS: CCK4, but not
placebo, elicited a marked anxiogenic response, reflected by robust
increases in subjective anxiety ratings and heart rate. CCK4-induced
anxiety was associated with 1) robust and bilateral increases in
extracerebral blood flow in the vicinity of the superficial temporal artery
territory and 2) CBF increases in the anterior cingulate gyrus, the
claustrum-insular-amygdala region, and the cerebellar vermis. CONCLUSIONS:
Some of the temporopolar cortex CBF activation peaks previously reported in
humans in association with drug- and non-drug- induced anxiety, as well as
the increase in regional CBF in the claustrum-insular-amygdala region, may
be of vascular and/or muscular origin.
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