RESUMO
AIMS: Sleep problems are common among individuals with alcohol use disorder (AUD) and is often associated with a heightened relapse risk. The present study examines the relationship between sleep and alcohol use among individuals with current AUD during a 6-day quit attempt as part of a medication study. METHODS: The current study is a secondary analysis of a medication trial for individuals with AUD. Individuals with AUD (N = 53, 26 females) were randomized to active medication or matched placebo. Randomized participants completed a week-long medication titration (Days 1-7). Following the titration period, participants attended an in-person visit (Day 8) to begin a 6-day quit attempt. During the quit attempt, participants completed daily diary assessments to report on previous day alcohol consumption, sleep quality, and alcohol craving. In the present study, medication condition was controlled for in all models. RESULTS: Baseline global sleep quality was not a significant predictor of drinks per drinking day (P = 0.72) or percent days abstinent (P = 0.16) during the 6-day practice quit attempt. Daily diary analyses found that greater sleep quality was associated with higher next-day drinks per drinking day (b = 0.198, P = 0.029). In contrast, participants reported worse sleep quality following nights of greater alcohol intake, albeit at a trend-level (b = -0.12, P = 0.053). CONCLUSIONS: These results suggest that better sleep quality was a risk factor for drinking during the 6-day quit period, such that better sleep may be associated with increased craving for alcohol and alcohol use the next day. These findings are limited to the early abstinence period and should be considered in studies exploring longer periods of abstinence.
Assuntos
Alcoolismo , Qualidade do Sono , Feminino , Humanos , Alcoolismo/complicações , Alcoolismo/epidemiologia , Alcoolismo/tratamento farmacológico , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Fissura , Doença CrônicaRESUMO
INTRODUCTION: This study aims to clarify differences in mood, craving, and treatment response between reward and relief/habit individuals in a study of naltrexone, varenicline, and placebo. We hypothesized that relief/habit individuals would have a poorer mood during early abstinence and higher levels of alcohol craving than reward individuals. We hypothesized that reward individuals would demonstrate better drinking outcomes on naltrexone versus placebo. METHODS: Data were culled from a randomized, double-blind, placebo-controlled human trial of 53 individuals (18F/16M) with alcohol use disorder randomized to varenicline (n = 19), naltrexone (n = 15), or matched placebo (n = 19). In this 6-day practice quit trial, participants attempted to abstain from drinking and completed daily diaries. Participants were classified into reward or relief/habit subgroups based on self-reported motivation for drinking. Multilinear models tested differences in mood and alcohol craving between reward and relief/habit individuals. General linear models tested differences between reward and relief/habit individuals' drinking outcomes on each medication versus placebo. RESULTS: Relief/habit individuals showed decreases in positive mood and increases in negative mood over the quit attempt across medications, compared to reward individuals (P's < .05). Reward individuals' tension decreased on naltrexone, while relief/habit individuals' tension remained stable (F = 3.64, P = .03). Reward individuals in the placebo group had higher percent days abstinent than relief individuals in the placebo group (P < .001). DISCUSSION: This study suggests relief/habit individuals' mood worsens during early abstinence. Our finding that reward individuals' tension decreased on naltrexone and increased on placebo may suggest a clinical response to the medication.
Assuntos
Afeto , Alcoolismo , Fissura , Naltrexona , Recompensa , Vareniclina , Humanos , Naltrexona/uso terapêutico , Masculino , Vareniclina/uso terapêutico , Feminino , Método Duplo-Cego , Adulto , Alcoolismo/tratamento farmacológico , Alcoolismo/psicologia , Fissura/efeitos dos fármacos , Pessoa de Meia-Idade , Afeto/efeitos dos fármacos , Antagonistas de Entorpecentes/uso terapêutico , Consumo de Bebidas Alcoólicas/psicologia , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Resultado do TratamentoRESUMO
AIMS: This study aimed to compare reward, relief, and habit treatment-seeking individuals on recent drinking, alcohol use disorder (AUD) phenomenology, and mood. The second aim of the study was to evaluate the predictive validity of reward, relief, and habit profiles. METHOD: Treatment-seeking individuals with an AUD (n = 169) were recruited to participate in a medication trial for AUD (NCT03594435). Reward, relief, and habit drinking groups were assessed using the UCLA Reward Relief Habit Drinking Scale. Group differences at baseline were evaluated using univariate analyses of variance. A subset of participants were enrolled in a 12-week, double-blind, placebo-controlled medication trial (n = 102), and provided longitudinal drinking and phenomenology data. The predictive validity of group membership was assessed using linear regression analyses. RESULTS: At baseline, individuals who drink primarily for relief had higher craving and negative mood than those who drink for reward and habit. Prospectively, membership in the relief drinking group predicted greater alcohol use, greater heavy drinking, and fewer days abstinent compared to those in the reward drinking group. Membership in the relief drinking group also predicted greater alcohol craving, more alcohol-related consequences, and more anxiety symptoms over 12 weeks compared to those in the reward drinking group. CONCLUSIONS: This study provides support for reward and relief drinking motive profiles in treatment-seeking individuals with an AUD. Membership in the relief drinking motive group was predictive of poorer drinking outcomes and more negative symptomology over 12 weeks, indicating that individuals who drink for relief may be a particularly vulnerable sub-population of individuals with AUD.
Assuntos
Consumo de Bebidas Alcoólicas , Alcoolismo , Hábitos , Recompensa , Humanos , Masculino , Feminino , Alcoolismo/terapia , Alcoolismo/psicologia , Consumo de Bebidas Alcoólicas/psicologia , Consumo de Bebidas Alcoólicas/terapia , Adulto , Pessoa de Meia-Idade , Método Duplo-Cego , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Afeto , FissuraRESUMO
Inflammation appears to be a critical mechanism in the development of alcohol use disorder (AUD) and a consequence of chronic alcohol use. The potential anti-inflammatory properties of cannabis may modulate the proinflammatory effects of alcohol. This study sought to extend previous work investigating the relationship between alcohol consumption, cannabis use and circulating interleukin (IL)-6 levels in a sample with AUD. One hundred and thirty-three individuals with an AUD provided blood samples to assess IL-6 and answered questions regarding alcohol and cannabis use. An ordinary least squares multiple regression analysis was conducted to assess the effect of alcohol and cannabis use on IL-6. A moderation analysis examined cannabis use as a potential moderator of the relationship between alcohol use and circulating IL-6 levels. Alcohol use was predictive of higher log IL-6 levels (standardized ß = 0.16, p = 0.03), while cannabis use was not predictive of log IL-6 levels (p = 0.36). Days of cannabis use moderated the relationship between alcohol use and IL-6 levels, such that the relationship between alcohol use and IL-6 levels was only significant in individuals with AUD without recent cannabis use. This study extends previous work to a clinical sample with an AUD and underscores the importance of considering cannabis use in studies on alcohol use and inflammation. This study also indicates the need for in-depth analyses on cannabinoids and inflammation and the interaction between cannabinoids and alcohol use on inflammation.
Assuntos
Consumo de Bebidas Alcoólicas , Alcoolismo , Inflamação , Interleucina-6 , Uso da Maconha , Humanos , Masculino , Feminino , Interleucina-6/sangue , Inflamação/sangue , Adulto , Uso da Maconha/sangue , Pessoa de Meia-IdadeRESUMO
AIMS: Magnetic resonance spectroscopy (MRS) has been used to probe inflammation in the brain. While altered MRS metabolite levels have previously been found in individuals with alcohol use disorder (AUD), the relationship between potential metabolite markers of inflammation and the clinical correlates of AUD remains understudied. Therefore, this exploratory study sought to elucidate the clinical significance of inflammation in AUD by examining relationships between metabolites, AUD severity, alcohol consumption, and craving in individuals with AUD. METHODS: Data for this secondary analysis are derived from a two-week clinical trial of ibudilast to treat AUD. Forty-three non-treatment-seeking individuals with an AUD (26M/17F) completed an MRS scan and alcohol-related questionnaires. MRS was performed using a multi-voxel array placed above the corpus callosum, extending from the pregnenual anterior cingulate to premotor cortex. The dorsal anterior cingulate was selected as the volume of interest. Metabolite levels of choline-compounds (Cho), myo-inositol (mI), and creatine+phosphocreatine (Cr) were quantified. Separate hierarchical regression models were used to evaluate the independent effects of metabolite levels on alcohol craving, alcohol problem severity, and alcohol consumption. RESULTS: Dorsal anterior cingulate Cho predicted alcohol craving and alcohol problem severity over and above demographics, medication, and alcohol consumption measures. mI and Cr did not predict alcohol craving or alcohol problem severity. Metabolite markers were not predictive of alcohol consumption. CONCLUSIONS: This preliminary study indicates that dACC Cho is sensitive to clinical characteristics of AUD. This is a further step in advancing neurometabolites, particularly Cho, as potential biomarkers and treatment targets for AUD.
Assuntos
Transtornos Relacionados ao Uso de Álcool , Alcoolismo , Humanos , Alcoolismo/metabolismo , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/metabolismo , Fissura , Colina/metabolismo , Consumo de Bebidas Alcoólicas/metabolismo , Etanol/metabolismo , Inositol/metabolismoRESUMO
Background: Inflammation is implicated in alcohol use disorder (AUD). Ibudilast, a neuroimmune modulator, shows promise for the treatment of AUD. Elevated inflammation, indicated by high levels of C-reactive protein (CRP), represents a possible subtype of AUD, which may be associated with treatment response to ibudilast.Objectives: The current study evaluated CRP as a predictor of treatment response to ibudilast; hypothesizing that ibudilast would be more effective at reducing drinking and alcohol cue-reactivity in individuals with higher CRP levels.Methods: This is a secondary analysis of a clinical trial of ibudilast for AUD, which found that ibudilast reduced heavy drinking in individuals with AUD. Fifty-one individuals were randomized to receive ibudilast (n = 24 [16 M/8F]) or placebo (n = 27 [18 M/9F]) for two weeks. Participants provided blood samples at baseline to assess CRP levels, completed daily assessments of alcohol use, and an fMRI alcohol cue-reactivity task at study mid-point. Models tested the effects of medication, CRP levels, and their interaction on drinks per drinking day and alcohol cue-reactivity.Results: There was a significant interaction between medication and CRP (F = 3.80, p = .03), such that the ibudilast high CRP group had fewer drinks per drinking day compared to the ibudilast low CRP group. CRP moderated the effect of medication on brain activation in a cluster extending from the left inferior frontal gyrus to the right-dorsal striatum (Z = 4.55, p < .001). This interaction was driven by attenuated cue-reactivity in the ibudilast high CRP group relative to the ibudilast low CRP and placebo high CRP groups.Conclusions: This study serves as an initial investigation into predictors of clinical response to ibudilast treatment and suggests that a baseline proinflammatory profile may enhance clinical efficacy.
Assuntos
Alcoolismo , Proteína C-Reativa , Humanos , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Alcoolismo/tratamento farmacológico , Proteína C-Reativa/metabolismo , Etanol , InflamaçãoRESUMO
BACKGROUND: Subjective response (SR) to alcohol represents a biobehavioral risk factor for heavy drinking and for developing alcohol use disorder (AUD). Identifying moderators of SR have been hindered by small sample sizes that are often used in alcohol administration studies. METHODS: This study combined data from multiple alcohol administration trials to test whether sex, family history of alcohol problems, and impulsivity (via delay discounting) predict SR to alcohol, comprised of four domains: stimulation, sedation, negative affect, and craving. Non-treatment-seeking heavy drinkers (N = 250) completed a battery of self-report scales and behavioral measures of alcohol use and problems, mood, and impulsivity. All participants completed an intravenous alcohol administration session wherein SR domains were measured at baseline, 20, 40, and 60 mg%. RESULTS: Analyses using multilevel modeling showed that male sex independently predicted higher alcohol-induced stimulation and alcohol craving, after controlling for other moderators. A family history of alcohol problems also independently predicted alcohol craving after controlling for other moderators. CONCLUSIONS: Using a large sample and advanced data analytic methods, this study extends the literature on alcohol administration by identifying important moderators of SR in heavy drinkers: namely, male sex and family history of alcohol problems. These findings consolidate and extend a growing body of research aimed at differentiating individuals most likely to report the SR features that confer risk for AUD.
Assuntos
Transtornos Relacionados ao Uso de Álcool , Alcoolismo , Consumo de Bebidas Alcoólicas , Fissura , Etanol/efeitos adversos , Humanos , MasculinoRESUMO
BACKGROUND: Despite the promising implications for novel immune therapeutics, few clinical trials have tested these therapies to date. An understanding of how immune pharmacotherapies influence complex alcohol use disorder (AUD) profiles, including subjective response to alcohol, is very limited. Initial findings show that ibudilast, a neuroimmune modulator, reduces rates of heavy drinking and measures of alcohol craving. METHODS: This study is a secondary analysis of a 2-week clinical trial of ibudilast that enrolled a nontreatment-seeking sample with AUD. Eligible participants (N = 52) were randomized to receive ibudilast or matched placebo and completed daily diary assessments (DDAs) during the 2-week period. Each morning, participants reported on their mood and craving levels both before and during the previous day's drinking episode, as well as stimulation and sedation levels during the previous day's drinking episode. Multilevel models were used to compare the effects of ibudilast and placebo on subjective alcohol response. Exploratory analyses tested whether ibudilast moderated the relationship between daily stimulation/sedation and alcohol intake and whether withdrawal-related dysphoria moderated ibudilast's effects on subjective response. RESULTS: Ibudilast did not significantly alter mean levels of stimulation or sedation (p's > 0.05). It did, however, moderate the effect of daily stimulation on drinking (p = 0.045). Ibudilast attenuated alcohol-induced increases in craving compared with placebo (p = 0.047), but not other subjective response measures. Ibudilast significantly tempered daily alcohol-induced changes in urge to drink and positive mood only among individuals without withdrawal-related dysphoria. CONCLUSIONS: Ibudilast's effects on subjective alcohol responses appear to be nuanced and perhaps most salient for individuals drinking for positive reinforcement as distinguished from those who drink to feel normal. Consistent with previous findings, reductions in alcohol craving may represent a primary mechanism of ibudilast's effects on drinking. The ecologically valid nature of DDAs provide a clinically useful window into how individuals experience alcohol's effects while taking ibudilast.
Assuntos
Alcoolismo , Afeto , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Alcoolismo/tratamento farmacológico , Fissura , Etanol , HumanosRESUMO
AIMS: The current study examined the association between pain catastrophizing and alcohol cue-elicited brain activation in individuals with alcohol use disorder (AUD). METHODS: Non-treatment seeking heavy drinkers with AUD (n = 45; 28 males) completed self-report measures of pain catastrophizing and alcohol use/problems as part of a clinical trial of the neuroimmune modulator ibudilast. Participants were randomized to either placebo (n = 25) or ibudilast (n = 20) and completed an functional magnetic resonance imaging (fMRI) scan to assess neural activation to alcohol cues 1 week into the medication trial. Multiple linear regression examined whether pain catastrophizing predicted cue-induced activation in a priori regions of interest, namely the dorsal and ventral striatum (VS). An exploratory whole-brain analysis was conducted to assess the relationship between pain catastrophizing and neural alcohol cue reactivity. RESULTS: Pain catastrophizing predicted greater cue-induced activation in the dorsal (b = 0.006; P = 0.03) but not VS controlling for medication. Pain catastrophizing was positively associated with neural activation to alcohol cues in regions including the bilateral thalamus, left precuneus and left frontal pole. CONCLUSION: Greater pain catastrophizing is associated with greater cue-induced neural activation in brain regions sub-serving habits and compulsive alcohol use. These findings provide initial support for a neural mechanism by which pain catastrophizing may drive alcohol craving among individuals with AUD.
Assuntos
Alcoolismo , Masculino , Humanos , Alcoolismo/tratamento farmacológico , Sinais (Psicologia) , Catastrofização , Consumo de Bebidas Alcoólicas , Fissura/fisiologia , Imageamento por Ressonância Magnética/métodos , Encéfalo/fisiologia , EtanolRESUMO
AIMS: To test whether two critical design features, inclusion criteria of required pre-trial abstinence and pre-trial alcohol use disorder (AUD) diagnosis, predict the likelihood of detecting treatment effects in AUD pharmacotherapy trials. METHODS: This secondary data analysis used data collected from a literature review to identify randomized controlled pharmacotherapy trials for AUD. Treatment outcomes were selected into abstinence and no heavy drinking. Target effect sizes were calculated for each outcome and a meta-regression was conducted to test the effects of required pre-trial abstinence, required pre-trial AUD diagnosis, and their interaction on effect sizes. A sub-analysis was conducted on trials, which included FDA-approved medications for AUD. RESULTS: In total, 118 studies testing 19 medications representing 21,032 treated participants were included in the meta-regression analysis. There was no significant effect of either predictor on abstinence or no heavy drinking outcomes in the full analysis or in the sub-study of FDA-approved medications. CONCLUSION: By examining these design features in a quantitative, rather than qualitative, fashion the present study advances the literature and shows that requiring AUD diagnosis or requiring pre-trial abstinence do not impact the likelihood of a significant medication effect in the trial.
Assuntos
Alcoolismo , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Alcoolismo/diagnóstico , Alcoolismo/tratamento farmacológico , Análise de Dados , Humanos , Resultado do TratamentoRESUMO
Ibudilast, a neuroimmune modulator, shows promise as a pharmacotherapy for alcohol use disorder (AUD). In vivo administration of ibudilast reduces the expression of pro-inflammatory cytokines in animal models, but its effects on markers of inflammation in humans are unknown. This preliminary study examined the effect of ibudilast on peripheral and potential central markers of inflammation in individuals with AUD. This study also explored the predictive relationship of neurometabolite markers with subsequent drinking in the trial. Non-treatment-seeking individuals with an AUD (n = 52) were randomized to receive oral ibudilast (n = 24) or placebo (n = 28) for 2 weeks. Plasma levels of peripheral inflammatory markers were measured at baseline and after 1 and 2 weeks of medication. At study mid-point, proton magnetic resonance spectroscopy was performed to measure potential neurometabolite markers of inflammation: choline-compounds (Cho), myo-inositol (MI) and creatine + phosphocreatine (Cr) in frontal and cingulate cortices from 43 participants (ibudilast: n = 20; placebo: n = 23). The treatment groups were compared on peripheral and central markers. Ibudilast-treated participants had lower Cho in superior frontal white matter and nominally lower MI in pregenual anterior cingulate cortex. Ibudilast-treated participants had nominally lower C-reactive protein levels at visit 2 and nominally lower TNF-α/IL-10 ratios, relative to placebo. C-reactive protein and Cho levels were correlated, controlling for medication. Superior frontal white matter Cho predicted drinking in the following week. Micro-longitudinal ibudilast treatment may induce peripheral and putative central anti-inflammatory responses in patients with AUD. The neurometabolite responses may be associated with reduction in drinking, suggesting an anti-inflammatory component to the therapeutic action of ibudilast.
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Alcoolismo , Consumo de Bebidas Alcoólicas/metabolismo , Alcoolismo/tratamento farmacológico , Alcoolismo/metabolismo , Animais , Ácido Aspártico , Proteína C-Reativa , Colina/metabolismo , Creatina/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inositol/metabolismo , PiridinasRESUMO
While the immune system is essential for survival, an excessive or prolonged inflammatory response, such as that resulting from sustained heavy alcohol use, can damage the host and contribute to psychiatric disorders. A growing body of literature indicates that the immune system plays a critical role in the development and maintenance of alcohol use disorder (AUD). As such, there is enthusiasm for treatments that can restore healthy levels of inflammation as a mechanism to reduce drinking and promote recovery. In this qualitative literature review, we provide a conceptual rationale for immune therapies and discuss progress in medications development for AUD focused on the immune system as a treatment target. This review is organized into sections based on primary signaling pathways targeted by the candidate therapies, namely: (a) toll-like receptors, (b) phosphodiesterase inhibitors, (c) peroxisome proliferator-activated receptors, (d) microglia and astrocytes, (e) other immune pharmacotherapies, and (f) behavioral therapies. As relevant within each section, we examine the basic biological mechanisms of each class of therapy and evaluate preclinical research testing the role of the therapy on mitigating alcohol-related behaviors in animal models. To the extent available, translational findings are reviewed with discussion of completed and ongoing randomized clinical trials and their findings to date. An applied and clinically focused approach is taken to identify the potential clinical applications of the various treatments reviewed. We conclude by delineating the most promising candidate treatments and discussing future directions by considering opportunities for immune treatment development and personalized medicine for AUD.
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Alcoolismo , Alcoolismo/terapia , Animais , Etanol , Humanos , Inflamação , Receptores Toll-LikeRESUMO
BACKGROUND: Ibudilast, a novel neuroimmune modulator being studied to treat alcohol use disorder (AUD), was shown in a randomized controlled trial (NCT03489850) to reduce ventral striatum (VS) activation in response to visual alcohol cues. The present study extended this finding by probing the effects of ibudilast on alcohol cue-elicited functional connectivity (i.e., temporally correlated activation) with the VS seed. The study also tests the association between functional connectivity and alcohol use during the trial. METHODS: Non-treatment-seeking participants (n = 45) with current alcohol use disorder were randomized to receive twice-daily dosing with either ibudilast (50 mg; n = 20) or placebo (n = 25). Upon reaching the target dosagee of the medication or placebo, participants completed a functional neuroimaging alcohol cue reactivity paradigm. Drinks per drinking day were assessed at baseline and daily during the 2-week trial. RESULTS: Ibudilast reduced alcohol cue-elicited functional connectivity between the VS seed and reward-processing regions including the orbitofrontal and anterior cingulate cortices compared with placebo (p < 0.05). Cue-elicited functional connectivity was correlated with drinks per drinking day (R2 = 0.5351, p < 0.001), and ibudilast reduced this association in similar reward-processing regions compared with placebo. CONCLUSIONS: Ibudilast's effects on drinking outcomes may be related to the attenuation of functional connectivity in frontostriatal circuits related to reward processing. These results provide an important proof of concept for this novel pharmacotherapy and support the clinical utility of incorporating neuroimaging-and especially functional connectivity-analyses into medication development.
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Alcoolismo/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Inibidores de Fosfodiesterase/uso terapêutico , Piridinas/uso terapêutico , Adulto , Encéfalo/diagnóstico por imagem , Conectoma , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Inibidores de Fosfodiesterase/farmacologia , Piridinas/farmacologia , Adulto JovemRESUMO
BACKGROUND: Alcohol use disorder (AUD) is heterogenous. One approach to parsing this heterogeneity is to phenotype individuals by their underlying motivation to drink, specifically drinking for reward (i.e., positive reinforcement) or for relief (i.e., negative reinforcement/normalizing). Reward- versus relief-motivated behavior is thought to be associated with a shift from ventral to dorsal striatal (DS) signaling. The present study examined whether reward and relief drinking were differentially associated with other clinical characteristics and with alcohol cue-elicited activation of the ventral and dorsal striatum. METHODS: Non-treatment-seeking heavy drinkers (N = 184; 61 female, 123 male) completed the UCLA Reward, Relief, Habit Drinking Scale (RRHDS) and the Reasons for Heavy Drinking Questionnaire (RHDQ), to categorize drinking motivation. Measures of alcohol use, alcohol problems, mood, and craving were also collected. A subset of participants (N = 45; 17 female, 28 male) also completed a functional neuroimaging alcohol cue reactivity task. RESULTS: RRHDS-designated relief/habit drinkers scored lower than reward drinkers on the RHDQ Reinforcement subscale (p = 0.04) and higher on the RHDQ Normalizing subscale (p = 0.004). Relief/habit drinkers also demonstrated greater AUD severity on a host of clinical measures. Relief/habit drinkers displayed higher cue-elicited DS activation compared with reward drinkers (p = 0.04), while ventral striatal cue-elicited activation did not significantly differ between groups. CONCLUSIONS: Our findings support and extend the differentiation of reward from relief/habit-motivated drinking and suggest that differences in DS response to conditioned alcohol cues may underlie this distinction. Elucidating neurobiological and clinical differences between these subtypes may facilitate treatment matching and precision medicine for AUD.
Assuntos
Alcoolismo/psicologia , Motivação/fisiologia , Recompensa , Estriado Ventral/fisiopatologia , Adulto , Alcoolismo/diagnóstico por imagem , Alcoolismo/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Estriado Ventral/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: Alterations in white matter microstructure associated with chronic alcohol use have been demonstrated in previous diffusion tensor imaging (DTI) research. However, there is conflicting evidence as to whether such differences are influenced by an individual's biological sex. The purpose of the present study was to investigate the prevalence of sex differences in the white matter microstructure of the brains of individuals with alcohol use disorder (AUD) and healthy controls. METHODS: One hundred participants with AUD (38 female, aged 21 to 68) participating in the National Institute on Alcohol Abuse and Alcoholism's inpatient treatment program and 98 healthy control participants (52 female) underwent a diffusion-weighted scan. Images collected were processed for each subject individually, and voxelwise, tract-based spatial statistics analysis was conducted to test for differences in the DTI measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD). RESULTS: A 2-way, between-subjects ANCOVA that tested for differences by group and sex revealed widespread differences between AUD and control subjects, but no interaction between group and sex. Additional analyses exploring demographic and alcohol use variables showed significant impacts of age on white matter microstructure that were more pronounced in individuals with AUD. Plots of FA by age, sex, and group in major white matter tracts suggest a need to explore higher order interactions in larger samples. CONCLUSIONS: These results bolster recent findings of similar microstructural properties in men and women with AUD but provide a rationale for the consideration of age when investigating the impacts of chronic alcohol use on the brain's white matter.
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Alcoolismo/patologia , Substância Branca/patologia , Adulto , Idoso , Envelhecimento/patologia , Consumo de Bebidas Alcoólicas , Análise de Variância , Anisotropia , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Caracteres Sexuais , Adulto JovemRESUMO
BACKGROUND: Alcohol administration paradigms have been used for early efficacy testing of novel compounds for alcohol use disorder (AUD). There has been an ongoing debate about sample characteristics and methodological features that affect the likelihood of detecting an early efficacy signal for AUD medications. We conducted a meta-regression to test whether the drinking level of the study sample and the peak breath alcohol concentration (BrAC) in the alcohol administration study predict the efficacy of AUD pharmacotherapies on the subjective responses to alcohol. METHODS: We computed the effects of 21 medications on alcohol-induced stimulation, sedation, negative mood, and craving during alcohol administration in 49 studies. RESULTS: Meta-regression analyses indicated a significant and positive effect of pre-study drinks per month on alcohol-induced stimulation (ß = 0.142, p < 0.0001), such that as drinking increases, the benefit of medication over placebo decreases. There was an effect of drinks per month on negative mood (ß = -0.164, p = 0.0248), such that at higher levels of drinks per month, the effects of medications on negative mood are stronger. For sedation, there was an effect of peak BrAC (ß = 0.119, p = 0.0002), such that at low levels of peak BrAC, the effects of medication on sedation were null. For craving, there was a peak BrAC × drinks per month interaction such that at low levels of BrAC, a heavier drinking sample is required to detect the effects of medication on craving. Sensitivity analyses comparing naltrexone studies and non-naltrexone studies suggested that naltrexone was less sensitive to drinks per month across subjective response domains. CONCLUSIONS: These analyses show that design features are critical in studies that test the effects of medications on the subjective responses to alcohol. By specifying the significance and directionality of these effects, as well as the specific points in BrAC or drinks per month at which medication effects are detectable, the study offers recommendations for design features of alcohol administration studies that aim to inform AUD medication development.
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Alcoolismo/tratamento farmacológico , Comportamento/efeitos dos fármacos , Resultado do Tratamento , Adolescente , Adulto , Afeto/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Testes Respiratórios , Criança , Fissura/efeitos dos fármacos , Relação Dose-Resposta a Droga , Etanol/administração & dosagem , Etanol/análise , Humanos , Hipnóticos e Sedativos , Pessoa de Meia-Idade , Naltrexona/uso terapêutico , Adulto JovemRESUMO
Studies of inflammation in alcohol use disorder (AUD) are overwhelmingly preclinical, and translation to clinical samples is necessary. Endotoxin administration has been used successfully in humans to study mood disorders, offering a translational, reliable and safe model that may be validated in AUD research. We argue for the use of endotoxin challenge to elucidate the interplay between AUD and inflammation.
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Alcoolismo/patologia , Inflamação/patologia , Lipopolissacarídeos/administração & dosagem , Pesquisa Biomédica , Endotoxinas/administração & dosagem , Humanos , Pesquisa Translacional BiomédicaRESUMO
AIMS: Natural processes of change have been documented in treatment-seekers who begin to reduce their drinking in anticipation of treatment. The study examined whether non-treatment-seeking problem drinkers would engage in drinking reduction in anticipation of participating in a research study. METHODS: Non-treatment-seeking problem drinkers (n = 935) were culled from five behavioral pharmacology studies. Participants reported on their alcohol use during the past 30 days using the Timeline Followback. Cluster analysis identified distinct groups/clusters based on drinking patterns over the 30-day pre-visit period. The identified clusters were compared on demographic and clinical measures. RESULTS: Three distinct clusters were identified (a) heavy-decreasing drinking group (n = 255, 27.27%); (b) a moderate-stable drinking group (n = 353, 37.75%) and (c) low-stable drinking group (n = 327, 34.97%). The three clusters differed significantly on a host of measures including pre-visit drinking (age at first drink, drinking days, drinks per week, drinks per drinking day), alcohol use severity, alcohol craving, readiness for change, depression and anxiety levels. These differences were alcohol dose-dependent such that the heavier drinking group reported the highest levels on all constructs, followed by the moderate group, and the low drinking group last. CONCLUSIONS: Baseline drinking patterns of non-treatment-seekers were generally stable and pre-visit reductions were only observed among the heavy drinking group. This generally stable pattern stands in contrast to previous reports for treatment-seeking samples. Nevertheless, the heavier drinking group, which is most similar to treatment-seekers, displayed pre-study drinking reduction. Overall, naturalistic processes of change may pose less of a threat to randomization and testing in this population.
Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/psicologia , Ansiedade/psicologia , Fissura , Depressão/psicologia , Adulto , Consumo de Bebidas Alcoólicas/fisiopatologia , Alcoolismo/fisiopatologia , Análise por Conglomerados , Feminino , Humanos , Masculino , Aceitação pelo Paciente de Cuidados de Saúde , Adulto JovemRESUMO
The last three decades in psychological research have been marked by interdisciplinary science. Addiction represents a prime example of a disorder marked by a complex interaction among psychosocial and biological factors. This review highlights critical findings in the basic neuroscience of addiction and translates them into clinical language that can inform clinical psychologists in their research, teaching, and practice. From mechanisms of reward processing, learning and memory, allostasis, incentive-sensitization, withdrawal, tolerance, goal-directed decision making, habit learning, genetics, inflammation, and the microbiome, the common theme of this review is to illustrate the clinical utility of basic neuroscience research and to identify opportunities for clinical science. The thoughtful integration of basic and clinical science provides a powerful tool to fulfill the scientific mission of improving health care. Clinical psychologists have a crucial role to play in the translational science of addiction.
Assuntos
Comportamento Aditivo , Neurociências , Comportamento Aditivo/terapia , Encéfalo , Humanos , Aprendizagem , RecompensaRESUMO
Given the significant cost of alcohol use disorder (AUD), identifying risk factors for alcohol seeking represents a research priority. Prominent addiction theories emphasize the role of motivation in the alcohol seeking process, which has largely been studied using preclinical models. In order to bridge the gap between preclinical and clinical studies, this study examined predictors of motivation for alcohol self-administration using a novel paradigm. Heavy drinkers (n = 67) completed an alcohol infusion consisting of an alcohol challenge (target breath alcohol = 60 mg%) and a progressive-ratio alcohol self-administration paradigm (maximum breath alcohol 120 mg%; ratio requirements range = 20-3 139 response). Growth curve modeling was used to predict breath alcohol trajectories during alcohol self-administration. K-means clustering was used to identify motivated (n = 41) and unmotivated (n = 26) self-administration trajectories. The data were analyzed using two approaches: a theory-driven test of a-priori predictors and a data-driven, machine learning model. In both approaches, steeper delay discounting, indicating a preference for smaller, sooner rewards, predicted motivated alcohol seeking. The data-driven approach further identified phasic alcohol craving as a predictor of motivated alcohol self-administration. Additional application of this model to AUD translational science and treatment development appear warranted.