This population epidemiology study of patients with schizophrenia uses Medicaid data to compare overall and cause-specific mortality rates for adults with schizophrenia vs the US general population between 2001 and 2007.
This prospective cohort and risk score development study determines that risk prediction models for cardiovascular disease using body mass index and lipid levels perform better in people with severe mental illness compared with models that include only established risk factors.
This experimental study in humans and rats reports that organisms have diminished ability to modulate behavior as a function of reward during withdrawal of nicotine.
Holz and coauthors clarify the influence of maternal smoking during pregnancy on the neural circuitry of response inhibition and its association with related behavioral phenotypes such as attention-deficit/hyperactivity disorder and novelty seeking in the mother’s offspring.
Brody et al determine whether the degree of nicotinic acetylcholine receptor upregulation in smokers predicts quitting with a standard course of treatment.
Lerman et al examine alterations underlying nicotine dependence with the hypothesis that the salience, executive control, and default mode networks will reflect nicotine withdrawal and predict abstinence-induced craving and cognitive defects. See also the editorial by London and Ghahremani.
Müller et al assess whether adolescents with prenatal exposure to maternal cigarette smoking differ from their nonexposed peers in the response of the ventral striatum to the anticipation or the receipt of a reward.
Varenicline, an effective smoking cessation medication, functions as an α4β2 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–elicited craving.
A 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.
Center for the Study of Addictions, University of Pennsylvania, Philadelphia.
Subjects 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 “this is not a Quit Smoking Study” and “smokers may be contemplating but not currently considering quitting.”
Prerandomization smoking cues vs nonsmoking cues activated the ventral striatum and medial orbitofrontal cortex (t = 3.77) and elicited subjective reports of craving (P = .006). Craving reports correlated with increased activity in the posterior cingulate (t = 4.11). Administration of varenicline diminished smoking cue–elicited ventral striatum and medial orbitofrontal cortex responses (t values from −3.75 to −5.63) and reduced self-reported smoking cue–elicited 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 = 5.63) predicted blunting of smoking cue responses in the medial orbitofrontal cortex (r = −0.74).
Varenicline'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.
Nicotine-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.
To assess changes in regional brain activation in response to cigarette-related cues from before to after treatment with bupropion (vs placebo).
Randomized, double-blind, before-after controlled trial.
Academic brain imaging center.
Thirty nicotine-dependent smokers (paid volunteers).
Participants were randomly assigned to receive 8 weeks of treatment with either bupropion or a matching placebo pill (double-blind).
Subjective cigarette craving ratings and regional brain activations (blood oxygen level-dependent response) in response to viewing cue videos.
Bupropion-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.
Treatment 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.