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Background: Substance use disorders (SUDs) are heterogeneous across multiple functional domains. Various frameworks posit that domains (e.g., executive function) contribute to the persistence of SUDs; however, the domains identified in different studies vary.Objectives: We used factor analysis to identify the underlying latent domains present in a large sample (N = 5,244, 55.8% male) with a variety of SUDs to yield findings more generalizable than studies with a narrower focus.Method: Participants (1,384 controls and 3,860 participants with one or more SUDs including alcohol, cocaine, cannabis, and/or opioid use disorders) completed the Semi-Structured Assessment for Drug Dependence and Alcoholism, the NEO Personality Inventory, and the Wisconsin Card Sorting Test. Exploratory factor analysis (EFA) and fit indices (root mean-squared error of approximation (RMSEA), Comparative Fit Index (CFI), and Tucker-Lewis Index (TLI)) were used to examine different latent variable models. A multiple indicators, multiple causes (MIMIC) approach-tested associations of the latent variables with sociodemographics, substance use, and a history of abuse/neglect.Results: A six-factor model (predominant alcohol, predominant cocaine, predominant opioid, externalizing, personality, and executive function) provided the best fit [RMSEA = 0.063 (90% CI 0.060, 0.066), CFI = 0.98, TLI = 0.96]. All factors were moderately correlated (coefficient = 0.25-0.55, p < .05) with the exception of executive function. MIMIC analysis revealed different patterns of associations (all p < .0001) with sociodemographics, substance use, and a history of abuse/neglect among the factors.Conclusions: The domains identified, particularly executive function, were parallel to those observed previously. These factors underscore the heterogeneous nature of SUDs and may be useful in developing more targeted clinical interventions.
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BACKGROUND: Although alcohol breath testing devices that pair with smartphones are promoted for the prevention of alcohol-impaired driving, their accuracy has not been established. METHODS: In a within-subjects laboratory study, we administered weight-based doses of ethanol to two groups of 10 healthy, moderate drinkers aiming to achieve a target peak blood alcohol concentration (BAC) of 0.10%. We obtained a peak phlebotomy BAC and measured breath alcohol concentration (BrAC) with a police-grade device (Intoxilyzer 240) and two randomly ordered series of 3 consumer smartphone-paired devices (6 total devices) with measurements every 20 min until the BrAC reached <0.02% on the police device. Ten participants tested the first 3 devices, and the other 10 participants tested the other 3 devices. We measured mean paired differences in BrAC with 95% confidence intervals between the police-grade device and consumer devices. RESULTS: The enrolled sample (N = 20) included 11 females; 15 white, 3 Asian, and 2 Black participants; with a mean age of 27 and mean BMI of 24.6. Peak BACs ranged from 0.06-0.14%. All 7 devices underestimated BAC by >0.01%, though the BACtrack Mobile Pro and police-grade device were consistently more accurate than the Drinkmate and Evoc. Compared with the police-grade device measurements, the BACtrack Mobile Pro readings were consistently higher, the BACtrack Vio and Alcohoot measurements similar, and the Floome, Drinkmake, and Evoc consistently lower. The BACtrack Mobile Pro and Alcohoot were most sensitive in detecting BAC driving limit thresholds, while the Drinkmate and Evoc devices failed to detect BAC limit thresholds more than 50% of the time relative to the police-grade device. CONCLUSIONS: The accuracy of smartphone-paired devices varied widely in this laboratory study of healthy participants. Although some devices are suitable for clinical and research purposes, others underestimated BAC, creating the potential to mislead intoxicated users into thinking that they are fit to drive.
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Nivel de Alcohol en Sangre , Pruebas Respiratorias/instrumentación , Pruebas Dirigidas al Consumidor , Teléfono Inteligente , Adulto , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
A threefold increase in fatal cocaine overdoses during the past decade highlights the critical lack of medications for cocaine use disorders. The brain response to drug cues can predict future drug use; however, results have been mixed. We present preliminary evidence that a sustained response to repeated cocaine cues within a single task is a significant predictor of drug-use outcomes. Seventy-three cocaine inpatients were administered a passive-viewing fMRI task, featuring 500 ms novel evocative (cocaine, sexual, aversive) and neutral comparator cues in the first half (Half1), which were then repeated in the second half (Half2). After the baseline scan, patients received eight outpatient treatment weeks with twice-weekly drug screens. Drug-use outcome groups were empirically defined based on cocaine-positive or missing urines averaged across the outpatient phase: GOOD (<40%), POOR (>85%), and Intermediate (INT, between 40% and 85%) outcomes. Differences of response to initial (Half1) and repeated (Half2) cues in a priori (cue-reactive) regions were tested between outcome groups (3 [Group] × 2 [Halves] ANOVA). An interaction was found in the brain response to drug (but not sex or aversive) cues, with a significant difference between the GOOD and POOR outcome groups in Half2, driven by a significant decrease in brain response by the GOOD outcome group and a sustained brain response by the POOR outcome group, to repeated cocaine cues. The brain response to repeated drug cues may be a useful predictor of future drug use, encouraging future intervention studies to restore a "healthy" (decreasing) response to the repeated presentation of drug cues.
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Encéfalo/diagnóstico por imagen , Trastornos Relacionados con Cocaína/diagnóstico por imagen , Señales (Psicología) , Adulto , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
The Balloon Analogue Risk Task (BART) provides a reliable and ecologically valid model for the assessment of individual risk-taking propensity and is frequently used in neuroimaging and developmental research. Although the test-retest reliability of risk-taking behavior during the BART is well established, the reliability of brain activation patterns in response to risk-taking during the BART remains elusive. In this study, we used functional magnetic resonance imaging (fMRI) and evaluated the test-retest reliability of brain responses in 34 healthy adults during a modified BART by calculating the intraclass correlation coefficients (ICC) and Dice's similarity coefficients (DSC). Analyses revealed that risk-induced brain activation patterns showed good test-retest reliability (median ICC â= â0.62) and moderate to high spatial consistency, while brain activation patterns associated with win or loss outcomes only had poor to fair reliability (median ICC â= â0.33 for win and 0.42 for loss). These findings have important implications for future utility of the BART in fMRI to examine brain responses to risk-taking and decision-making.
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Mapeo Encefálico/normas , Encéfalo/fisiología , Toma de Decisiones/fisiología , Imagen por Resonancia Magnética/normas , Pruebas Neuropsicológicas/normas , Asunción de Riesgos , Adulto , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Obesity and cigarette smoking are two of the leading preventable causes of death in the United States. Research suggests that overlapping pathophysiology may contribute to obesity and nicotine use disorder (NUD), yet no studies have investigated the effect of obesity on neural response to reward stimuli in NUD. This study used arterial spin-labeled perfusion functional magnetic resonance imaging (fMRI) to examine neural responses during exposure to smoking versus nonsmoking cues in 79 treatment-seeking participants with NUD, 26 with normal weight, 28 with overweight, and 25 with obesity. Given that deficits in behavioral inhibitory control have been associated with both obesity and NUD, participants completed an affect-congruent Go/NoGo task to assess the effect of body mass index (BMI) on this construct in NUD. Analyses revealed that BMI was negatively associated with activation in the right dorsolateral prefrontal cortex (dlPFC) in response to smoking cues, with significantly reduced response in smokers with overweight and smokers with obesity compared with normal-weight smokers. In addition, greater commission errors on the Go/NoGo task were correlated with reduced neural response to smoking cues in the right dlPFC only among those with obesity. Together, these findings provide evidence that obesity in treatment-seeking NUDs is related to neurobiological alterations in inhibitory control over cue-potentiated behaviors, suggesting that smoking cessation may be more difficult in individuals with comorbid NUD and obesity than in those without, requiring treatment strategies tailored to meet their unique needs.
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Señales (Psicología) , Inhibición Psicológica , Obesidad/complicaciones , Corteza Prefrontal/fisiopatología , Tabaquismo/complicaciones , Adulto , Fumar Cigarrillos/fisiopatología , Fumar Cigarrillos/psicología , Comorbilidad , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Obesidad/fisiopatología , Obesidad/psicología , Corteza Prefrontal/diagnóstico por imagen , Recompensa , Tabaquismo/fisiopatología , Tabaquismo/psicologíaRESUMEN
INTRODUCTION: Evidence continues to mount indicating that endogenous sex hormones (eg, progesterone and estradiol) play a significant role in smoking-related outcomes. Although approximately one out of four premenopausal smokers use oral contraceptives (OCs), which significantly alter progesterone and estradiol levels, relatively little is known about how OCs may influence smoking-related outcomes. Thus, the goal of this review article is to describe the state of the literature and offer recommendations for future directions. METHODS: In March 2017, we searched seven databases, with a restriction to articles written in English, using the following keywords: nicotine, smoker(s), smoking, tobacco, cigarettes, abstinence, withdrawal, and craving(s). We did not restrict on the publication date, type, or study design. RESULTS: A total of 13 studies were identified. Three studies indicated faster nicotine metabolism in OC users compared to nonusers. Five of six laboratory studies that examined physiological stress response noted heightened response in OC users compared to nonusers. Three studies examined cessation-related symptomatology (eg, craving) with mixed results. One cross-sectional study observed greater odds of current smoking among OC users, and no studies have explored the relationship between OC use and cessation outcomes. CONCLUSIONS: Relatively few studies were identified on the role of OCs in smoking-related outcomes. Future work could explore the relationship between OC use and mood, stress, weight gain, and brain function/connectivity, as well as cessation outcomes. Understanding the role of OC use in these areas may lead to the development of novel smoking cessation interventions for premenopausal women. IMPLICATIONS: This is the first review of the relationship between oral contraceptives (OCs) and smoking-related outcomes. The existing literature suggests that the use of OCs is related to increased nicotine metabolism and physiological stress response. However, the relationship between OC use and smoking-related symptoms (eg, craving) is mixed. Further, no published data were available on OC use and smoking cessation outcomes. Therefore, we recommend additional research be conducted to characterize the relationship between OC use and smoking cessation outcomes, perhaps as a function of the effect of OC use on mood, stress, weight gain, and brain function/connectivity.
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Afecto/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Fumar Cigarrillos/metabolismo , Anticonceptivos Orales/administración & dosificación , Anticonceptivos Orales/metabolismo , Afecto/fisiología , Fumar Cigarrillos/psicología , Anticonceptivos Orales/efectos adversos , Estudios Transversales , Femenino , Predicción , Humanos , Cese del Hábito de Fumar/psicologíaRESUMEN
Cigarette smoking continues to be a leading cause of preventable morbidity and mortality. Although the majority of smokers report making a quit attempt in the past year, smoking cessation rates remain modest. Thus, developing accurate, data-driven methods that can classify and characterize the neural features of nicotine use disorder (NUD) would be a powerful clinical tool that could aid in optimizing treatment development and guide treatment modifications. This investigation applied support vector machine-based classification to resting-state functional connectivity (rsFC) data from individuals diagnosed with NUD (n = 108; 63 male) and matched nonsmoking controls (n = 108; 63 male) and multi-dimensional scaling to visualize the heterogeneity of NUD in individual smokers based on rsFC measures. Machine-based learning models identified five resting-state networks that played a role in distinguishing smokers from controls: the posterior and anterior default mode networks, the sensorimotor network, the salience network and the right executive control network. The classification method constructed classifiers with an average correct classification rate of 88.1 percent and an average area under the curve of 0.93. Compared with controls, individuals with NUD had weaker functional connectivity measures within these networks (P < 0.05, false discovery rate corrected). Further, multi-dimensional scaling visualization demonstrated that controls were similar to each other whereas individuals with NUD had less similarity to controls and to other individuals with NUD. Our findings build upon previous literature demonstrating that machine learning-based approaches to classifying rsFC data offer a valuable technique to understanding network-level differences in nicotine-related neurobiology and extend previous findings by improving classification accuracy and demonstrating the heterogeneity in resting-state networks of individuals with NUD.
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Encéfalo/diagnóstico por imagen , Tabaquismo/diagnóstico por imagen , Adulto , Encéfalo/fisiopatología , Estudios de Casos y Controles , Femenino , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas , Descanso , Máquina de Vectores de Soporte , Tabaquismo/clasificación , Tabaquismo/fisiopatología , Adulto JovenRESUMEN
PURPOSE OF REVIEW: Tobacco use, sex differences, and psychiatric disorders are associated with altered immune function. There are also sex differences in tobacco use and psychiatric disorders. This review summarizes findings from the small, but growing literature examining sex differences in the effects of tobacco use on inflammation and the implications for psychiatric disorders. RECENT FINDINGS: We identified four studies that tested the interaction between sex and tobacco/nicotine on inflammation. Although males and females generally exhibited differential tobacco-induced immune responses, the pattern varied depending on the sample (rodents vs. humans) and the method to evaluate inflammation. Evidence suggests that sex modulates the effects of tobacco smoke on inflammation. Many inflammation markers associated with sex differences and tobacco use are related to psychiatric disorders. We propose a model in which sex, tobacco use, and inflammation interact to increase risk for psychiatric disorders. Future studies are needed to examine the mechanisms that explain this relationship.
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Inflamación/inducido químicamente , Trastornos Mentales/etiología , Caracteres Sexuales , Uso de Tabaco , Animales , Femenino , Humanos , Inflamación/patología , Masculino , Trastornos Mentales/epidemiología , Trastornos Mentales/inmunología , Trastornos Mentales/patología , Nicotina/farmacología , Fumar/inmunología , Fumar/patología , Fumar/psicología , Uso de Tabaco/epidemiología , Uso de Tabaco/inmunología , Uso de Tabaco/patología , Uso de Tabaco/psicologíaRESUMEN
Drug-reward cues trigger motivational circuitry, a response linked to drug-seeking in animals and in humans. Adverse life events have been reported to increase sensitivity to drug rewards and to bolster drug reward signaling. Therefore, we hypothesized that cocaine-dependent individuals with prior emotional, physical and sexual abuse might have a heightened mesolimbic brain response to cues for drug reward in a new brief-cue probe. Cocaine-dependent human individuals (N = 68) were stabilized in an inpatient setting and then completed an event-related blood-oxygen-level dependent functional magnetic resonance imaging task featuring 500-ms evocative (cocaine, sexual, aversive) and comparator (neutral) cues. Responses to three questions about emotional, physical and sexual abuse from the Addiction Severity Index were used to divide the patients into subgroups (history of Abuse [n = 40] versus No Abuse [n = 28]). When subjects were grouped by the historical presence or absence of emotional, physical or sexual abuse, the Abuse group showed a heightened midbrain, thalamic, caudate, and caudal orbitofrontal cortex response to cocaine cues; a similar result was found in other evocative cues, as well. These findings are the first reported for a 500-ms cocaine-cue probe, and they highlight the ability of very brief evocative cues to activate the brain's motivational circuitry. Although all participants had severe cocaine use disorders, individuals reporting prior abuse had a heightened mesolimbic response to evocative cues. To our knowledge, this is the first study in humans linking a history of abuse to a brain vulnerability (heightened mesolimbic response to drug cues) previously shown to contribute to drug-seeking.
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Trastornos Relacionados con Cocaína/fisiopatología , Señales (Psicología) , Emociones/fisiología , Sistema Límbico/fisiopatología , Abuso Físico/psicología , Delitos Sexuales/psicología , Adulto , Cocaína/farmacología , Trastornos Relacionados con Cocaína/psicología , Inhibidores de Captación de Dopamina/farmacología , Humanos , Sistema Límbico/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , RecompensaRESUMEN
BACKGROUND: Alcohol-induced blackouts, or memory loss for all or portions of events that occurred during a drinking episode, are reported by approximately 50% of drinkers and are associated with a wide range of negative consequences, including injury and death. As such, identifying the factors that contribute to and result from alcohol-induced blackouts is critical in developing effective prevention programs. Here, we provide an updated review (2010 to 2015) of clinical research focused on alcohol-induced blackouts, outline practical and clinical implications, and provide recommendations for future research. METHODS: A comprehensive, systematic literature review was conducted to examine all articles published between January 2010 through August 2015 that focused on vulnerabilities, consequences, and possible mechanisms for alcohol-induced blackouts. RESULTS: Twenty-six studies reported on alcohol-induced blackouts. Fifteen studies examined prevalence and/or predictors of alcohol-induced blackouts. Six publications described the consequences of alcohol-induced blackouts, and 5 studies explored potential cognitive and neurobiological mechanisms underlying alcohol-induced blackouts. CONCLUSIONS: Recent research on alcohol-induced blackouts suggests that individual differences, not just alcohol consumption, increase the likelihood of experiencing an alcohol-induced blackout, and the consequences of alcohol-induced blackouts extend beyond the consequences related to the drinking episode to include psychiatric symptoms and neurobiological abnormalities. Prospective studies and a standardized assessment of alcohol-induced blackouts are needed to fully characterize factors associated with alcohol-induced blackouts and to improve prevention strategies.
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Consumo de Bebidas Alcohólicas/efectos adversos , Amnesia/inducido químicamente , HumanosRESUMEN
Previous studies indicate that topiramate reduces alcohol use among problem drinkers, with one study showing that the effect was moderated by a polymorphism (rs2832407) in GRIK1, the gene encoding the GluK1 kainate subunit. We examined whether the interactive effect of medication and genotype (1) altered the association between daily self-efficacy and later-day drinking; and (2) had an indirect effect on drinking via self-efficacy. In a 12-week, placebo-controlled trial of topiramate, we used daily interactive voice response technology to measure self-efficacy (i.e. confidence in avoiding heavy drinking later in the day) and drinking behavior in 122 European-American heavy drinkers. Topiramate's effects on both self-efficacy and drinking level were moderated by rs2832407. C-allele homozygotes treated with topiramate showed higher levels of self-efficacy and lower levels of nighttime drinking across the 12-week trial. Further, the interactive effect of topiramate and genotype on mean nighttime drinking levels was mediated by mean levels of self-efficacy. By modeling topiramate's effects on nighttime drinking across multiple levels of analysis, we found that self-efficacy, a key psychologic construct, mediated the effect of topiramate, which was moderated by rs2832407 genotype. Thus, it may be possible to use an individualized assessment (i.e. genotype) to select treatment to optimize the reduction in heavy drinking and thereby provide a personalized treatment approach.
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Consumo de Bebidas Alcohólicas/genética , Fructosa/análogos & derivados , Fármacos Neuroprotectores/uso terapéutico , Receptores de Ácido Kaínico/genética , Autoeficacia , Adolescente , Adulto , Anciano , Alelos , Femenino , Fructosa/uso terapéutico , Heterocigoto , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Topiramato , Adulto JovenRESUMEN
Relapse is a widely recognized and difficult to treat feature of the addictions. Substantial evidence implicates cue-triggered activation of the mesolimbic dopamine system as an important contributing factor. Even drug cues presented outside of conscious awareness (i.e., subliminally) produce robust activation within this circuitry, indicating the sensitivity and vulnerability of the brain to potentially problematic reward signals. Because pharmacological agents that prevent these early cue-induced responses could play an important role in relapse prevention, we examined whether baclofen-a GABAB receptor agonist that reduces mesolimbic dopamine release and conditioned drug responses in laboratory animals-could inhibit mesolimbic activation elicited by subliminal cocaine cues in cocaine-dependent individuals. Twenty cocaine-dependent participants were randomized to receive baclofen (60 mg/d; 20 mg t.i.d.) or placebo. Event-related BOLD fMRI and a backward-masking paradigm were used to examine the effects of baclofen on subliminal cocaine (vs neutral) cues. Sexual and aversive cues were included to examine specificity. We observed that baclofen-treated participants displayed significantly less activation in response to subliminal cocaine (vs neutral) cues, but not sexual or aversive (vs neutral) cues, than placebo-treated participants in a large interconnected bilateral cluster spanning the ventral striatum, ventral pallidum, amygdala, midbrain, and orbitofrontal cortex (voxel threshold p < 0.005; cluster corrected at p < 0.05). These results suggest that baclofen may inhibit the earliest type of drug cue-induced motivational processing-that which occurs outside of awareness-before it evolves into a less manageable state.
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Baclofeno/uso terapéutico , Trastornos Relacionados con Cocaína/prevención & control , Señales (Psicología) , Agonistas de Receptores GABA-B/uso terapéutico , Sistema Límbico/efectos de los fármacos , Adolescente , Adulto , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Sistema Límbico/irrigación sanguínea , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Enmascaramiento Perceptual , Estimulación Luminosa , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Structural magnetic resonance imaging techniques are powerful tools for examining the effects of drug use on the brain. The nicotine and cannabis literature has demonstrated differences between nicotine cigarette smokers and cannabis users compared to controls in brain structure; however, less is known about the effects of co-occurring cannabis and tobacco use. METHODS: We used voxel-based morphometry to examine gray matter volume differences between four groups: (1) cannabis-dependent individuals who do not smoke tobacco (Cs); (2) cannabis-dependent individuals who smoke tobacco (CTs); (3) cannabis-naïve, nicotine-dependent individuals who smoke tobacco (Ts); and (4) healthy controls (HCs). We also explored associations between gray matter volume and measures of cannabis and tobacco use. RESULTS: A significant group effect was observed in the left putamen, thalamus, right precentral gyrus, and left cerebellum. Compared to HCs, the Cs, CTs, and Ts exhibited larger gray matter volumes in the left putamen. Cs also had larger gray matter volume than HCs in the right precentral gyrus. Cs and CTs exhibited smaller gray matter volume than HCs in the thalamus, and CTs and Ts had smaller left cerebellar gray matter volume than HCs. CONCLUSIONS: This study extends previous research that independently examined the effects of cannabis or tobacco use on brain structure by including an examination of co-occurring cannabis and tobacco use, and provides evidence that cannabis and tobacco exposure are associated with alterations in brain regions associated with addiction.
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Encéfalo/patología , Abuso de Marihuana/complicaciones , Abuso de Marihuana/patología , Tabaquismo/complicaciones , Tabaquismo/patología , Adulto , Cannabis , Femenino , Sustancia Gris , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Tamaño de los Órganos , Fumar/epidemiología , Fumar/patologíaRESUMEN
INTRODUCTION: Functional magnetic resonance imaging (fMRI) has been used extensively in an attempt to understand brain vulnerabilities that mediate maladaptive responses to drug cues. Using perfusion fMRI, we have consistently shown reward-related activation (medial orbitofrontal cortex/ventral striatum) to smoking cues (SCs). Because preclinical and clinical studies generally show that progesterone may reduce reward and craving, we hypothesized that females in the follicular phase of the cycle (FPs; when progesterone levels are low) would have greater reward-related neural responses to SCs compared with females in the luteal phase (LPs). METHODS: Sated cigarette-dependent premenopausal naturally cycling females underwent pseudo-continuous arterial spin-labeled perfusion fMRI during exposure to 10-min audio visual clips of appetitive SCs and non-SCs. Brain responses to SCs relative to non-SCs were examined among females grouped according to menstrual cycle (MC) phase at the time of scanning (22 FPs, 15 LPs). Craving scores were acquired pre- and post-SC exposure. RESULTS: FPs showed increased neural responses to SCs compared with non-SCs in the medial orbitofrontal cortex (p ≤ .05 corrected), whereas LPs did not. FPs reported SC-elicited craving (p ≤ .005), whereas LPs did not. Within FPs, SC-induced craving correlated with increased neural responses in the anterior insula (r = 0.73, p < .0001). CONCLUSIONS: FPs may be more vulnerable to relapse during appetitive SC exposure than LPs. Because the influence of MC phase on drug cue neural activity has not been examined, these results contribute to our knowledge of the neurobiological underpinnings of responses to drug cues, and they highlight the importance of monitoring menstrual cycle phase in all areas of addiction research.
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Señales (Psicología) , Lóbulo Frontal/patología , Ciclo Menstrual , Fumar/fisiopatología , Adulto , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Persona de Mediana EdadRESUMEN
BACKGROUND: We examined whether the effects of topiramate and a single nucleotide polymorphism (rs2832407) in GRIK1, which encodes a kainate receptor subunit, persisted following a 12-week, placebo-controlled trial in 138 heavy drinkers with a treatment goal of reduced drinking. During treatment, topiramate 200 mg/d significantly reduced heavy drinking days and increased the frequency of abstinent days (Am J Psychiatry, 2014, 171:445). In the European-American (EA) subsample (n = 122), rs2832407 moderated the treatment effect on heavy drinking. METHODS: Patients were re-interviewed 3 and 6 months after the end of treatment. During treatment, we obtained 92.4% of drinking data, with 89.1 and 85.5% complete data at the 3- and 6-month follow-up visits, respectively. We examined 4 outcomes over time in the overall sample and the EA subsample: percent heavy drinking days (PHDD), percent days abstinent (PDA), serum γ-glutamyl transpeptidase (GGTP) concentration, and a measure of alcohol-related problems. RESULTS: In the full sample, the lower PHDD and higher PDA seen with topiramate treatment were no longer significant during follow-up. Nonetheless, the topiramate-treated patients had lower alcohol-related problem scores during treatment and both follow-up periods. Further, in the EA subsample, the greater reduction in PHDD seen with topiramate treatment in rs2832407*C-allele homozygotes persisted throughout follow-up, with no significant effects in A-allele carriers. A reduction in GGTP concentration was consistent with the reduction in heavy drinking, but did not reach statistical significance. CONCLUSIONS: There are persistent therapeutic effects of topiramate in heavy drinkers, principally in rs2832407*C-allele homozygotes.
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Abstinencia de Alcohol , Consumo de Bebidas Alcohólicas/tratamiento farmacológico , Consumo de Bebidas Alcohólicas/genética , Intoxicación Alcohólica/tratamiento farmacológico , Intoxicación Alcohólica/genética , Receptores de Ácido Kaínico/genética , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Intoxicación Alcohólica/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Factores de Tiempo , Resultado del TratamientoRESUMEN
Cigarette-dependent smokers automatically and involuntarily orient attention toward smoking cues (SCs). This attentional bias is clinically significant, as it may contribute to relapse. Thus, identifying neural and genetic correlates of attentional bias is critical for improving interventions. Our previous studies show that the dopamine transporter (DAT) SLC6A3 genotype exerts profound effects on limbic responses to SCs. One potential mechanism underlying these effects is greater attentional bias for SCs. Here, we explored associations between attentional bias for SCs and neural responses to SCs among 'sated' smokers genotyped for the SLC6A3 polymorphism. Pseudo-continuous arterial spin-labeled perfusion functional magnetic resonance imaging images were acquired during SC exposure in 35 smokers genotyped for the SLC6A3 variable number of tandem repeats polymorphism (n = 16, 9-repeats; n = 19, 10/10-repeats). Participants completed a visual dot-probe attentional bias task, which contained pictures of smoking and non-smoking pictures, to examine whether genetic variation in DAT influences attentional bias and to investigate relationships between attentional bias and neural responses to SCs. Although attentional bias to smoking pictures was not significantly different between 9-repeats and 10/10-repeats, 9-repeats showed a positive correlation between attentional bias and increased SC-induced brain activity in the amygdala, whereas 10/10-repeats showed an inverse correlation in the medial orbitofrontal cortex (mOFC). In group comparisons, 9-repeats exhibited positive correlations between attentional bias and SCs in the mOFC and amygdala, relative to 10/10-repeats. Findings suggest that genetic variation in the DAT gene influences brain responses associated with attentional bias; thus, providing additional support for a SC-vulnerable endophenotype.
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Amígdala del Cerebelo/fisiopatología , Atención/fisiología , Señales (Psicología) , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Fumar/fisiopatología , Adolescente , Adulto , Alelos , Corteza Cerebral/fisiopatología , Circulación Cerebrovascular/fisiología , Femenino , Predisposición Genética a la Enfermedad/genética , Hipocampo/fisiopatología , Humanos , Procesamiento de Imagen Asistido por Computador/estadística & datos numéricos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estimulación Luminosa/métodos , Polimorfismo Genético/genética , Tiempo de Reacción/fisiología , Recurrencia , Fumar/genética , Fumar/psicología , Secuencias Repetidas en Tándem/genética , Adulto JovenRESUMEN
Cigarette smoking and obesity are the leading causes of premature morbidity and mortality and increase the risk of all-cause mortality four-fold when comorbid. Individuals with these conditions demonstrate neurobiological and behavioral differences regarding how they respond to rewarding stimuli or engage in inhibitory control. This narrative review examines the role of reward and inhibition in cigarette smoking and obesity independently, as well as recent research demonstrating an effect of increased body mass index (BMI) on neurocognitive function in individuals who smoke. It is possible that chronic smoking and overeating of highly palatable food, contributing to obesity, dysregulates reward neurocircuitry, subsequently leading to hypofunction of brain networks associated with inhibitory control. These brain changes do not appear to be specific to food or nicotine and, as a result, can potentiate continued cross-use. Changes to reward and inhibitory function due to increased BMI may also make cessation more difficult for those comorbid for obesity and smoking.
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Fumar Cigarrillos , Humanos , Obesidad/psicología , Recompensa , Encéfalo , NicotinaRESUMEN
The brain's immune system plays a critical role in responding to immune challenges and maintaining homeostasis. However, dysregulated neuroimmune function contributes to neurodegenerative disease and neuropsychiatric conditions. In vivo positron emission tomography (PET) imaging of the neuroimmune system has facilitated a greater understanding of its physiology and the pathology of some neuropsychiatric conditions. This review presents an in-depth look at PET findings from human neuroimmune function studies, highlighting their importance in current neuropsychiatric research. Although the majority of human PET studies feature radiotracers targeting the translocator protein 18 kDa (TSPO), this review also considers studies with other neuroimmune targets, including monoamine oxidase B, cyclooxygenase-1 and cyclooxygenase-2, nitric oxide synthase, and the purinergic P2X7 receptor. Promising new targets, such as colony-stimulating factor 1, Sphingosine-1-phosphate receptor 1, and the purinergic P2Y12 receptor, are also discussed. The significance of validating neuroimmune targets and understanding their function and expression is emphasized in this review to better identify and interpret PET results.
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Enfermedades Neurodegenerativas , Humanos , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patología , Receptores de GABA/metabolismo , Tomografía de Emisión de Positrones/métodos , Radiofármacos/metabolismo , Encéfalo/metabolismoRESUMEN
Despite increased rates of cannabis use among patients with cancer, there are gaps in our understanding of barriers to accessing cannabis. Social determinants of health (SDoH) are associated with access to healthcare, but few studies have evaluated how SDoH relate to cannabis access and use among cancer patients. We examined whether access to and modes of cannabis use differed across indicators of SDoH among patients receiving treatment from a large National Cancer Institute (NCI) designated cancer center. This anonymous cross-sectional survey was developed in collaboration with the NCI Cannabis Supplement consortium, which funded 12 supplements to NCI Center Core Grants across the United States. We evaluated the association of race, gender, income, and age with mode of cannabis use, source of obtaining cannabis, what influences their purchase, and medical cannabis certification status. Overall, 1,053 patients receiving treatment for cancer in Pennsylvania completed the survey and 352 (33.4%) reported using cannabis since their cancer diagnosis. Patients who identified as Black/African-American were less likely to have medical cannabis certifications (p=0.04). Males and Black/African-Americans were more likely to report smoking cannabis (vs other forms, ps<0.01) and to purchase cannabis from an unlicensed dealer/seller (p<0.01). Lower-income patients were more likely to be influenced by price and ease of access (ps<0.05). Although cannabis users were younger than non-users, age was not associated with any outcomes. The current data shed light on how critical drivers of health disparities (such as race, gender, and income) are associated with where patients with cancer obtain cannabis, what forms they use, and what may influence their purchase decisions.
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Electronic cigarette (EC) use has increased dramatically, particularly among adolescents and young adults, and, like cigarette use, can cause pulmonary inflammation and increase the risk of lung disease. Methods: This preliminary study used PET with 18F-6-(1/2)(2-fluoro-propyl)-4-methylpyridin-2-amine (18F-NOS) to quantify inducible nitric oxide synthase expression to characterize oxidative stress and inflammation in the lungs in vivo in 3 age- and sex-matched groups: 5 EC users, 5 cigarette smokers, and 5 controls who had never smoked or vaped. Results: EC users showed greater 18F-NOS nondisplaceable binding potential (BPND) than cigarette smokers (P = 0.03) and controls (P = 0.01), whereas BPND in cigarette smokers did not differ from that in controls (P > 0.1). 18F-NOS lung tissue delivery and inducible nitric oxide synthase distribution volume did not significantly differ among groups. Although there were no group differences in peripheral inflammatory biomarker concentrations, 18F-NOS BPND correlated with the proinflammatory cytokine tumor necrosis factor-α concentrations (rs = 0.87, P = 0.05) in EC users. Additionally, when EC users and cigarette smokers were pooled together, number of vaping episodes or cigarettes per day correlated with interleukin-6 levels (rs = 0.86, P = 0.006). Conclusion: This is the first PET imaging study to compare lung inflammation between EC and cigarette users in vivo. We found preliminary evidence that EC users have greater pulmonary inflammation than cigarette smokers and controls, with a positive association between pulmonary and peripheral measures of inflammation.