Traolach S. Brugha, MD(NUI), FRCPsych; Sally McManus, MSc; John Bankart, MSc, PhD; et al.
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Arch Gen Psychiatry. 2011;68(5):459-465. doi:10.1001/archgenpsychiatry.2011.38
Heather Cody Hazlett, PhD; Michele D. Poe, PhD; Guido Gerig, PhD; et al.
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Arch Gen Psychiatry. 2011;68(5):467-476. doi:10.1001/archgenpsychiatry.2011.39
Melanie Föcking, MSc, PhD; Patrick Dicker, BA, MA, MSc; Jane A. English, MSc, PhD; et al.
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Arch Gen Psychiatry. 2011;68(5):477-488. doi:10.1001/archgenpsychiatry.2011.43
Andrea Mechelli, PhD; Anita Riecher-Rössler, MD; Eva M. Meisenzahl, MD; et al.
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Arch Gen Psychiatry. 2011;68(5):489-495. doi:10.1001/archgenpsychiatry.2011.42
Donald A. Sandweiss, MD, MPH; Donald J. Slymen, PhD; Cynthia A. LeardMann, MPH; et al.
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Arch Gen Psychiatry. 2011;68(5):496-504. doi:10.1001/archgenpsychiatry.2011.44
Christopher S. Culbertson, PhD; Jennifer Bramen, PhD; Mark S. Cohen, PhD; et al.
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Arch Gen Psychiatry. 2011;68(5):505-515. doi:10.1001/archgenpsychiatry.2010.193
ContextNicotine-dependent smokers exhibit craving and brain activation in the prefrontal and limbic regions when presented with cigarette-related cues. Bupropion hydrochloride treatment reduces cue-induced craving in cigarette smokers; however, the mechanism by which bupropion exerts this effect has not yet been described.ObjectiveTo assess changes in regional brain activation in response to cigarette-related cues from before to after treatment with bupropion (vs placebo).DesignRandomized, double-blind, before-after controlled trial.SettingAcademic brain imaging center.ParticipantsThirty nicotine-dependent smokers (paid volunteers).InterventionsParticipants were randomly assigned to receive 8 weeks of treatment with either bupropion or a matching placebo pill (double-blind).Main Outcome MeasuresSubjective cigarette craving ratings and regional brain activations (blood oxygen level-dependent response) in response to viewing cue videos.ResultsBupropion-treated participants reported less craving and exhibited reduced activation in the left ventral striatum, right medial orbitofrontal cortex, and bilateral anterior cingulate cortex from before to after treatment when actively resisting craving compared with placebo-treated participants. When resisting craving, reduction in self-reported craving correlated with reduced regional brain activation in the bilateral medial orbitofrontal and left anterior cingulate cortices in all participants.ConclusionsTreatment with bupropion is associated with improved ability to resist cue-induced craving and a reduction in cue-induced activation of limbic and prefrontal brain regions, while a reduction in craving, regardless of treatment type, is associated with reduced activation in prefrontal brain regions.
Teresa Franklin, PhD; Ze Wang, PhD; Jesse J. Suh, PsyD; et al.
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Arch Gen Psychiatry. 2011;68(5):516-526. doi:10.1001/archgenpsychiatry.2010.190
ContextVarenicline, an effective smoking cessation medication, functions as an 伪4尾2 nicotinic acetylcholine receptor partial agonist. It indirectly affects the dopaminergic reward system by reducing withdrawal symptoms during abstinence and by decreasing the reinforcement received from nicotine while smoking. We hypothesize that varenicline would have a third mechanism to blunt responses to smoking cues in the reward-related ventral striatum and medial orbitofrontal cortex and would be associated with a reduction in smoking cue鈥揺licited craving.DesignA laboratory model of conditioned responding and arterial spin-labeled perfusion functional magnetic resonance imaging, a biomarker of regional brain activity, was used to test our hypothesis. Perfusion functional magnetic resonance imaging is quantitative and stable across time, facilitating the measurement of medication-induced neural modifications in the brain in response to a challenge (smoking cue exposure) and in the brain in the resting condition (without provocation). Smokers were imaged during rest and during smoking cue exposure before and after a 3-week randomized placebo-controlled medication regimen. Subjects were nonabstinent to explicitly examine the effects of varenicline on cue reactivity independent of withdrawal.SettingCenter for the Study of Addictions, University of Pennsylvania, Philadelphia.SubjectsSubjects were nicotine-dependent smokers who responded to advertisements placed on local radio and Listservs to participate in a medication-related research study that specifically stated 鈥渢his is not a Quit Smoking Study鈥� and 鈥渟mokers may be contemplating but not currently considering quitting.鈥�ResultsPrerandomization smoking cues vs nonsmoking cues activated the ventral striatum and medial orbitofrontal cortex (t聽=聽3.77) and elicited subjective reports of craving (P聽=聽.006). Craving reports correlated with increased activity in the posterior cingulate (t聽=聽4.11). Administration of varenicline diminished smoking cue鈥揺licited ventral striatum and medial orbitofrontal cortex responses (t values from 鈭�3.75 to 鈭�5.63) and reduced self-reported smoking cue鈥揺licited craving, whereas placebo-treated subjects exhibited responses similar to those observed prior to randomization. Varenicline-induced activation of lateral orbitofrontal cortex in the brain at rest (t聽=聽5.63) predicted blunting of smoking cue responses in the medial orbitofrontal cortex (r听=听鈭�0.74).ConclusionsVarenicline's reciprocal actions in the reward-activated medial orbitofrontal cortex and in the reward-evaluating lateral orbitofrontal cortex underlie a diminished smoking cue response, revealing a distinctive new action that likely contributes to its clinical efficacy.
Erin Fallucca, MD; Frank P. MacMaster, PhD; Joseph Haddad, BS; et al.
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Arch Gen Psychiatry. 2011;68(5):527-533. doi:10.1001/archgenpsychiatry.2011.36