title: Temporal profile of brain response to alprazolam in patients with generalized anxiety disorder.
abstract: This study investigated the temporal pattern of brain response to emotional stimuli during 28 days of alprazolam treatment among patients with generalized anxiety disorder (GAD) randomized 2:1 to drug or placebo in a double-blind design. Functional magnetic resonance imaging scans obtained during an emotion face matching task (EFMT) and an affective stimulus expectancy task (STIMEX) were performed at baseline, one hour after initial drug administration and 28 days later. Alprazolam significantly reduced scores on the Hamilton Anxiety Scale and the Penn State Worry Questionnaire after one week and 28 days of treatment. Brain activation in the amygdala during the EFMT and in the insula during the STIMEX was reduced one hour after alprazolam administration but returned to baseline levels at Day 28. Exploratory analyses revealed significant treatment differences in brain activity during the STIMEX on Day 28 in frontal lobe, caudate nucleus, middle temporal gyrus, secondary visual cortex, and supramarginal gyrus. These results are consistent with the notion that the neural mechanisms supporting sustained treatment effects of benzodiazepines in GAD differ from those underlying their acute effects.
authors.affiliation: Department of Psychiatry, University of California San Diego, San Diego, CA, USA. Electronic address: gbrown@ucsd.edu.
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Brown
authors.affiliation: Neuroscience, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Ostrowitzki
authors.affiliation: Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
authors.forename: Murray B
authors.initials: MB
authors.lastname: Stein
authors.affiliation: Neuroscience, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: von Kienlin
authors.affiliation: Department of Radiology, University of California San Diego, San Diego, CA, USA.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Simmons
authors.affiliation: Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Wierenga
authors.affiliation: Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
authors.forename: Orah Y
authors.initials: OY
authors.lastname: Stein
authors.affiliation: Neuroscience, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bruns
authors.affiliation: Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Bischoff-Grethe
authors.affiliation: Department of Psychiatry, University of California San Diego, San Diego, CA, USA; Laureate Institute for Brain Research, Tulsa, OK, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Paulus
mesh_terms: D000328:Adult; D000525:Alprazolam / Q000494:pharmacology / Q000627:therapeutic use*; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000639:trends; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D055815:Young Adult
chemical_list: D014151:Anti-Anxiety Agents; D000525:Alprazolam
keywords: Affective anticipation; Alprazolam; Double-blind placebo-controlled trial; Emotional faces; Functional magnetic resonance imaging; Generalized anxiety disorder