Dose-dependent decrease of activation in bilateral amygdala and insula by lorazepam during emotion processing

• Published in: Archives of general psychiatry Vol. 62; no. 3; p. 282
• Main Authors: Paulus, Martin P, Feinstein, Justin S, Castillo, Gabriel, Simmons, Alan N, Stein, Murray B
• Format: Journal Article
• Language: English
• Published: United States 01.03.2005
• Subjects: Adolescent; Adult; Amygdala - drug effects; Amygdala - physiology; Anti-Anxiety Agents - pharmacology; Anti-Anxiety Agents - therapeutic use; Anxiety Disorders - drug therapy; Anxiety Disorders - psychology; Cerebral Cortex - drug effects; Cerebral Cortex - physiology; Dose-Response Relationship, Drug; Emotions - drug effects; Emotions - physiology; Facial Expression; Female; Functional Laterality - drug effects; Functional Laterality - physiology; Humans; Lorazepam - pharmacology; Magnetic Resonance Imaging - methods; Magnetic Resonance Imaging - statistics & numerical data; Male; Oxygen - blood; Prefrontal Cortex - drug effects; Prefrontal Cortex - physiology; Visual Perception - drug effects; Visual Perception - physiology
• ISSN: 0003-990X
• DOI: 10.1001/archpsyc.62.3.282

Functional neuroimaging may elucidate the pathophysiologic features of anxiety disorders and the site of action of anxiolytic drugs. A large body of evidence suggests that the amygdala and associated limbic structures play a critical role in the expression of anxiety and may be treatment targets for anxiolytic drugs. To determine whether lorazepam dose-dependently attenuates blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) activation in the amygdala and associated limbic structures during an emotion face assessment task. Fifteen healthy volunteers participated in a double-blind, placebo-controlled, randomized dose-response study. Subjects underwent imaging 3 times (at least a week apart) and were given either a single-dose placebo or 0.25 mg or 1.0 mg of lorazepam 1 hour prior to an MRI session. During fMRI, subjects completed an emotion face assessment task, which has been shown to elicit amygdala activation. The BOLD-fMRI activation in amygdala, insula, and medial prefrontal cortex during the emotion face assessment task. Lorazepam significantly attenuated the BOLD-fMRI signal in a dose-dependent manner in bilateral amygdala and insula but not in the medial prefrontal cortex. Lorazepam did not affect the BOLD-fMRI signal in the primary visual cortex. The current finding provides the first neuroimaging evidence of a dose-dependent change induced by an established therapeutic agent in brain regions known to be critical for the mediation of anxiety. This investigation may help to support the use of BOLD-fMRI with pharmacological probes to investigate the neural circuits underlying anxiety and the use of fMRI as a tool in the development of new anxiolytic agents.