ArticleBiological psychiatry2017
CYP2A6 Genetic Variation Alters Striatal-Cingulate Circuits, Network Hubs, and Executive Processing in Smokers.
Article in Biological psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- Reduced executive and reward connectivity is associated with smoking cessation response to repetitive transcranial magnetic stimulation: A double-blind, randomized, sham-controlled trial.Brain imaging and behavior · 2024Trial
- Combining neuroimaging and brain stimulation to test alternative causal pathways for nicotine addiction in schizophrenia.Brain stimulationTrial
- Tobacco Smoking Functional Networks: A Whole-Brain Connectome Analysis in 24 539 Individuals.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2025Article
- Nicotine dependence and insula subregions: functional connectivity and cue-induced activation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Not all smokers are alike: the hidden cost of sustained attention during nicotine abstinence.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Cingulate circuits are associated with escalation of heroin use and naloxone-induced increases in heroin self-administration.Addiction neuroscience · 2022Article
- Adolescent nicotine administration increases nicotinic acetylcholine receptor binding and functional connectivity in specific cortico-striatal-thalamic circuits.Brain communications · 2022Article
- Genetics of substance use disorders in the era of big data.Nature reviews. Genetics · 2021Review
- Intrinsic differences in insular circuits moderate the negative association between nicotine dependence and cingulate-striatal connectivity strength.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Article
- The Use of the Nicotine Metabolite Ratio as a Biomarker to Personalize Smoking Cessation Treatment: Current Evidence and Future Directions.Cancer prevention research (Philadelphia, Pa.) · 2020Review
- Altered functional connectivity of the nucleus accumbens subdivisions in amphetamine-type stimulant abusers: a resting-state fMRI study.BMC neuroscience · 2019Article
- Habenular and striatal activity during performance feedback are differentially linked with state-like and trait-like aspects of tobacco use disorder.Science advances · 2019Article
- Classifying and characterizing nicotine use disorder with high accuracy using machine learning and resting-state fMRI.Addiction biology · 2019Article
- Intrinsic Insular-Frontal Networks Predict Future Nicotine Dependence Severity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- The Effects of Nicotine and Tobacco Use on Brain Reward Function: Interaction With Nicotine Dependence Severity.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2019Article
- Compulsive drug use is associated with imbalance of orbitofrontal- and prelimbic-striatal circuits in punishment-resistant individuals.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Alterations in resting-state functional connectivity in substance use disorders and treatment implications.Progress in neuro-psychopharmacology & biological psychiatry · 2019Review
- Brain Gray Matter Volume and Functional Connectivity Are Associated With Smoking Cessation Outcomes.Frontiers in human neuroscience · 2019Article
- The Insula: A Brain Stimulation Target for the Treatment of Addiction.Frontiers in pharmacology · 2019Review
- Cigarette smoking is associated with cortical thinning in anterior frontal regions, insula and regions showing atrophy in early Alzheimer's Disease.Drug and alcohol dependence · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundVariation in the CYP2A6 gene alters the rate of nicotine metabolic inactivation and is associated with smoking behaviors and cessation success rates. The underlying neurobiological mechanisms of this genetic influence are unknown.
methodsIntrinsic functional connectivity strength, a whole-brain, data-driven, graph theory-based method, was applied to resting-state functional magnetic resonance imaging data in 66 smokers and 92 nonsmokers. A subset of subjects (n = 23/20; smokers/nonsmokers) performed the monetary incentive delay task, probing reward anticipation, and a go/no-go task, probing response inhibition, on two occasions, in the presence and absence of a nicotine patch.
resultsA significant CYP2A6 genotype × smoking effect was found in the dorsal anterior cingulate cortex and ventral striatum, such that the normal (vs. slow) genotype individuals showed greater functional connectivity strength among smokers but not nonsmokers. Functional connectivity strength was negatively associated with severity of nicotine dependence in slow metabolizers. Both hubs were biased by inputs from the insula identified from seed-based connectivity. Similar gene × environment interactions were seen in ventral striatum during smoking abstinence when subjects performed the monetary incentive delay task and in dorsal anterior cingulate cortex when they performed the go/no-go task; both reductions were "normalized" in smokers (and increased in nonsmokers) after acute nicotine administration.
conclusionsBecause the CYP2A6 effect was seen only in smokers, these data suggest that the rate of nicotine metabolism-and thus the concentration of nicotine presented to the brain over the course of nicotine addiction-shapes brain circuits that, among other functions, compute reward and impulsivity processes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.