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1.
Yi Chuan ; 42(1): 112-125, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31956101

RESUMO

Alcohol abuse causes tissue and organ damage, and may participate neuropsychiatric diseases. Studies have shown that DNA methylation plays an important role in gene expression and behavioral changes induced by alcohol, however the causative neurobiological mechanisms have not been clarified. In this study, 32 healthy adult male SD rats were randomly divided into a drinking water control group (n=16) and a chronic alcohol exposure group (n=16). The alcohol preference and locomotor activity of rats were evaluated by two-bottle choice test (TBCT) and open-field test (OFT). DNA methylation in the medial prefrontal cortex (mPFC) tissue was detected by the reduced representative bisulfite sequencing (RRBS) technology. The methylation differential genes closely related to alcohol abuse were screened. qRT-PCR was used to verify the mRNA expression patterns of differential genes. qRT-PCR and Western blot were used to detect the expression of DNA methyltransferases (DNMTs) and methyl CpG binding protein 2 (MeCP2). Furthermore, the effect of short-term alcohol exposure (7 days) on DNMTs and MeCP2 in the mPFC of rats was tested (n=8/group). The results indicated that the methylation level of promoter region in the mPFC of rats exposed to chronic alcohol was significantly increased. In addition, the increased methylation levels in the promoter of Ntf3 and Ppm1G were accompanied by down-regulated mRNA levels in the chronic alcohol exposure group. The decreased methylation levels in the promoter of Hap1 and DUSP1 were accompanied by up-regulated mRNA levels. Furthermore, chronic alcohol exposure increased the mRNA and protein levels of DNMT3B and MeCP2. However, short term alcohol exposure did not affect their expression. This present study provides evidence that DNA methylation is associated with the development of alcohol abuse, which may be regulated by DNMT3B and MeCP2. The target genes Ntf3, Ppm1G, Hap1, and DUSP1 related to alcohol abuse were discovered as well, providing new insights into the neurobiological mechanism of alcohol abuse and the potential pharmacological targets for the treatment of alcohol abuse.


Assuntos
Alcoolismo/fisiopatologia , Comportamento Animal , Metilação de DNA , Córtex Pré-Frontal/fisiopatologia , Animais , DNA (Citosina-5-)-Metiltransferases/genética , Locomoção , Masculino , Proteína 2 de Ligação a Metil-CpG/genética , Regiões Promotoras Genéticas , Ratos , Ratos Sprague-Dawley
2.
PLoS One ; 15(1): e0220232, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31986142

RESUMO

(A) OBJECTIVE: This study aimed to identify trajectories of alcohol use (AU) and their associations with the development of alcohol use disorder (AUD) among young men with different weekly drinking patterns. (B) METHOD: A longitudinal latent class analysis integrating several aspects of AU, such as drinking quantity and frequency on weekends vs workweek days, involving 4719 young Swiss men at ages 20, 21, and 25, and collected by the Cohort Study on Substance Use Risk Factors, was used to identify different AU trajectories over time. The development of AUD scores in these trajectories was investigated using generalized linear mixed models. (C) RESULTS: Six AU trajectory classes, similar to those described in the literature, were identified: 'abstainers-light drinkers', 'light workweek increasers', 'light decreasers', 'moderate weekend decreasers', 'moderate workweek increasers', and 'heavy drinkers'. Only 12% of participants were assigned to a trajectory class with decreasing AU associated with a decline in their AUD score. AUD scores increased in trajectory classes exhibiting increasing AU on workweek days, despite low and moderate general AU. Finally, more than 59% of participants were on an AU trajectory presenting no change in their mean AUD score over time. (D) CONCLUSIONS: Maturing out of problematic AU in emerging adulthood is not the norm in Switzerland, and the AUD score developed in late adolescence remains until at least emerging adulthood. AU on workweek days is a more practical marker of potentially problematic AU. This calls for timely interventions in adolescence and concerning regular drinking on workweek days in emerging adulthood.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Intoxicação Alcoólica/epidemiologia , Alcoolismo/epidemiologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/fisiopatologia , Intoxicação Alcoólica/fisiopatologia , Alcoolismo/fisiopatologia , Grupos Étnicos , Humanos , Masculino , Fatores de Risco , Inquéritos e Questionários , Suíça/epidemiologia , Adulto Jovem
3.
Psychol Addict Behav ; 33(8): 659-668, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31738072

RESUMO

The cardiovascular system is disrupted by chronic excessive alcohol use and often impaired in individuals with an alcohol use disorder (AUD). Less is known about cardiovascular recovery when an individual receives treatment for AUD. This observational study aimed to extend the growing body of evidence for cardiovascular biomarkers and intervention targets in the treatment of AUD. We examined cardiovascular function in 92 women before and after 12 weeks of cognitive-behavioral therapy (CBT) for AUD. Participants were recruited exclusively from a randomized clinical trial comparing group versus individual CBT treatment strategies (parent study); no control group of untreated, but treatment-seeking women was available. Demographic and drinking data were obtained from the parent study. Cardiovascular data were collected as part of this separate study, prior to and following the clinical trial. Mixed-model analyses revealed multiple within-person cardiovascular changes indicative of improving health from pre- to posttreatment, including reduced heart rate and vessel stiffness as well as increased heart rate variability and baroreflex sensitivity. These significant improvements remained when extent of drinking during treatment was included in the models, suggesting that active ingredients of AUD treatment may serve to benefit physical health over and above drinking reductions. Future studies should assess the time course of cardiovascular recovery during addiction treatment and the mechanisms by which evidence-based AUD treatments may benefit physical as well as mental health. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Alcoolismo/terapia , Barorreflexo/fisiologia , Sistema Cardiovascular/fisiopatologia , Terapia Cognitivo-Comportamental , Frequência Cardíaca/fisiologia , Adulto , Alcoolismo/fisiopatologia , Alcoolismo/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
4.
Neurology ; 93(21): e1944-e1954, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31653706

RESUMO

OBJECTIVE: To determine the association between alcohol abuse (AA) and alcohol withdrawal (AW) with acute ischemic stroke (AIS) outcomes. METHODS: All adult AIS admissions in the United States from 2004 to 2014 were identified from the National Inpatient Sample (weighted n = 4,438,968). Multivariable-adjusted models were used to evaluate the association of AW with in-hospital medical complications, mortality, cost, and length of stay in patients with AIS. RESULTS: Of the AA admissions, 10.6% of patients, representing 0.4% of all AIS, developed AW. The prevalence of AA and AW in AIS increased by 45.2% and 40.0%, respectively, over time (p for trend <0.001). Patients with AA were predominantly men (80.2%), white (65.9%), and in the 40- to 59-year (44.6%) and 60- to 79-year (45.6%) age groups. After multivariable adjustment, AIS admissions with AW had >50% increased odds of urinary tract infection, pneumonia, sepsis, gastrointestinal bleeding, deep venous thrombosis, and acute renal failure compared to those without AW. Patients with AW were also 32% more likely to die during their AIS hospitalization compared to those without AW (odds ratio 1.32, 95% confidence interval 1.11-1.58). AW was associated with ≈15-day increase in length of stay and ≈$5,000 increase in hospitalization cost (p < 0.001). CONCLUSION: AW is associated with increased cost, longer hospitalizations, and higher odds of medical complications and in-hospital mortality after AIS. Proactive surveillance and management of AW may be important in improving outcomes in these patients.


Assuntos
Alcoolismo/epidemiologia , Isquemia Encefálica/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Síndrome de Abstinência a Substâncias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alcoolismo/economia , Alcoolismo/fisiopatologia , Isquemia Encefálica/economia , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/terapia , Depressores do Sistema Nervoso Central/efeitos adversos , Etanol/efeitos adversos , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Mortalidade Hospitalar , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Respiração Artificial/estatística & dados numéricos , Acidente Vascular Cerebral/economia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Síndrome de Abstinência a Substâncias/economia , Síndrome de Abstinência a Substâncias/fisiopatologia , Síndrome de Abstinência a Substâncias/terapia , Terapia Trombolítica , Estados Unidos/epidemiologia , Adulto Jovem
5.
Int J Mol Sci ; 20(18)2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31540133

RESUMO

Alcoholic liver disease (ALD), a disorder caused by excessive alcohol intake represents a global health care burden. ALD encompasses a broad spectrum of hepatic injuries including asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The susceptibility of alcoholic patients to develop ALD is highly variable and its progression to more advanced stages is strongly influenced by several hits (i.e., amount and duration of alcohol abuse). Among them, the intestinal microbiota and its metabolites have been recently identified as paramount in ALD pathophysiology. Ethanol abuse triggers qualitative and quantitative modifications in intestinal flora taxonomic composition, mucosal inflammation, and intestinal barrier derangement. Intestinal hypermeability results in the translocation of viable pathogenic bacteria, Gram-negative microbial products, and pro-inflammatory luminal metabolites into the bloodstream, further corroborating the alcohol-induced liver damage. Thus, the premise of this review is to discuss the beneficial effect of gut microbiota modulation as a novel therapeutic approach in ALD management.


Assuntos
Alcoolismo/microbiologia , Microbioma Gastrointestinal/fisiologia , Hepatopatias Alcoólicas/microbiologia , Alcoolismo/genética , Alcoolismo/imunologia , Alcoolismo/fisiopatologia , Animais , Antibacterianos/efeitos adversos , Ácidos e Sais Biliares/metabolismo , Dieta , Suplementos Nutricionais/microbiologia , Disbiose/imunologia , Disbiose/metabolismo , Transplante de Microbiota Fecal , Hepatócitos/metabolismo , Humanos , Intestinos/microbiologia , Fígado/metabolismo , Fígado/fisiopatologia , Hepatopatias Alcoólicas/imunologia , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/fisiopatologia
6.
Nat Commun ; 10(1): 3934, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477694

RESUMO

Drug addiction is a chronic relapsing disorder of compulsive drug use. Studies of the neurobehavioral factors that promote drug relapse have yet to produce an effective treatment. Here we take a different approach and examine the factors that suppress-rather than promote-relapse. Adapting Pavlovian procedures to suppress operant drug response, we determined the anti-relapse action of environmental cues that signal drug omission (unavailability) in rats. Under laboratory conditions linked to compulsive drug use and heightened relapse risk, drug omission cues suppressed three major modes of relapse-promotion (drug-predictive cues, stress, and drug exposure) for cocaine and alcohol. This relapse-suppression is, in part, driven by omission cue-reactive neurons, which constitute small subsets of glutamatergic and GABAergic cells, in the infralimbic cortex. Future studies of such neural activity-based cellular units (neuronal ensembles/memory engram cells) for relapse-suppression can be used to identify alternate targets for addiction medicine through functional characterization of anti-relapse mechanisms.


Assuntos
Cocaína/farmacologia , Condicionamento Operante/efeitos dos fármacos , Sinais (Psicologia) , Neurônios/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Alcoolismo/fisiopatologia , Alcoolismo/prevenção & controle , Animais , Cocaína/administração & dosagem , Comportamento Compulsivo/fisiopatologia , Comportamento Compulsivo/prevenção & controle , Condicionamento Operante/fisiologia , Inibidores da Captação de Dopamina/farmacologia , Masculino , Córtex Pré-Frontal/fisiopatologia , Ratos Long-Evans , Ratos Sprague-Dawley , Ratos Transgênicos , Recidiva , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle
7.
Eur J Clin Microbiol Infect Dis ; 38(11): 2171-2176, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31392446

RESUMO

The aim of the study was to determine the effect of chronic alcohol abuse on the course and outcome of bacterial meningitis (BM). We analyzed records of patients with BM who were hospitalized between January 2010 and December 2017 in the largest neuroinfection center in Poland. Out of 340 analyzed patients, 45 (13.2%) were alcoholics. Compared with non-alcoholics, alcoholics were more likely to present with seizures (p < 0.001), scored higher on the Sequential Organ Failure Assessment (SOFA) (p = 0.002) and lower on the Glasgow Coma Scale (GCS) (p < 0.001), and had worse outcome as measured by the Glasgow Outcome Score (GOS) (p < 0.001). Furthermore, alcoholics were less likely to complain of headache (p < 0.001) and nausea/vomiting (p = 0.005) and had lower concentration of glucose in cerebrospinal fluid (CSF) (p = 0.025). In the multiple logistic regression analysis, alcoholism was associated with lower GCS (p = 0.036), presence of seizures (p = 0.041), male gender (p = 0.042), and absence of nausea/vomiting (p = 0.040). Furthermore, alcoholism (p = 0.031), lower GCS score (p = 0.001), and higher blood urea concentration (p = 0.018) were independently associated with worse outcome measured by GOS. Compared with non-alcoholics, chronic alcohol abusers are more likely to present with seizures, altered mental status, and higher SOFA score and have an increased risk of unfavorable outcome. In multivariate analysis, seizures and low GCS were independently associated with alcoholism, while alcoholism was independently associated with worse outcome.


Assuntos
Alcoolismo/epidemiologia , Meningites Bacterianas/epidemiologia , Adulto , Idoso , Alcoolismo/tratamento farmacológico , Alcoolismo/patologia , Alcoolismo/fisiopatologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/patologia , Infecções Comunitárias Adquiridas/fisiopatologia , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Meningites Bacterianas/tratamento farmacológico , Meningites Bacterianas/patologia , Meningites Bacterianas/fisiopatologia , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Polônia/epidemiologia , Prognóstico , Risco
8.
Alcohol Alcohol ; 54(5): 503-509, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31403690

RESUMO

BACKGROUND: The aim of this study was to assess the predictive value of thrombocytopenia (TP) in alcohol withdrawal syndrome (AWS) as a marker of evolution of non-complicated AWS (nAWS) to severe, complicated AWS (cAWS): delirium tremens (DTs) and withdrawal seizures (wS), and to broaden knowledge about differences between nAWS and cAWS groups in relation to severity of TP. METHODS: This study involved 300 people (236 males and 64 females), aged 19-65 years (M = 44.64, SD = 11.32), hospitalized in the detoxification ward with ICD-10 diagnosis of F10.3 (AWS) or F10.4 (DTs), divided into nAWS and cAWS groups, 150 cases each. AWS severity was measured by CIWA-Ar. Available clinical and laboratory data were analyzed. RESULTS: TP was found in 139 (46%) of all subjects (nAWS = 32, cAWS = 107). nAWS and cAWS did not differ according to age, gender, length and severity of the last binge. A relationship between the occurrence of TP and cAWS was found (P < 0.001). The lower was the number of PLT, the more AWS incidence was observed. In CIWA-Ar, TP subjects had at least moderate AWS (P < 0.001). nAWS had higher PLT values than cAWS cases (Mrang = 195.96 vs. 105.04, P < 0.001). The predictive value of TP in cAWS was confirmed. CONCLUSIONS: The study demonstrates that patients with AWS and TP (in particular <119k/mL) are at higher risk of developing cAWS.


Assuntos
Alcoolismo/diagnóstico , Alcoolismo/epidemiologia , Síndrome de Abstinência a Substâncias/diagnóstico , Síndrome de Abstinência a Substâncias/epidemiologia , Trombocitopenia/diagnóstico , Trombocitopenia/epidemiologia , Adulto , Idoso , Alcoolismo/fisiopatologia , Feminino , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Síndrome de Abstinência a Substâncias/fisiopatologia , Trombocitopenia/fisiopatologia
9.
Neuropsychology ; 33(6): 757-759, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31448944

RESUMO

OBJECTIVE: Cognitive, behavioral, emotional, and neural dysfunction have been associated with misuse of alcohol for centuries. METHOD: Multidisciplinary research efforts have shed much light on the profile of impaired and spared functions associated with excessive heavy drinking, with heterogeneity noted among alcoholic individuals. RESULTS: Myriad factors may moderate or mediate the untoward effects of misuse of alcohol and an individual's likelihood of initiation and maintenance of abstinence. CONCLUSIONS: In this special section, a number of leading experts in the field of alcohol and alcoholism provide systematic and critical reviews of published research pertaining to specific topics of interest spanning from brain-behavior relations to the latest theories on cognitive training and the bidirectional influences of social and emotional deficits and chronic pain to the initiation and maintenance of alcoholism. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Abstinência de Álcool/psicologia , Alcoolismo/psicologia , Disfunção Cognitiva/psicologia , Alcoolismo/fisiopatologia , Alcoolismo/reabilitação , Encéfalo/fisiopatologia , Cognição , Disfunção Cognitiva/fisiopatologia , Emoções , Humanos , Testes Neuropsicológicos
10.
Neuropsychology ; 33(6): 760-780, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31448945

RESUMO

OBJECTIVE: Alcohol use disorder (AUD) is a complex, dynamic condition that waxes and wanes with unhealthy drinking episodes and varies in drinking patterns and effects on brain structure and function with age. Its excessive use renders chronically heavy drinkers vulnerable to direct alcohol toxicity and a variety of comorbidities attributable to nonalcohol drug misuse, viral infections, and accelerated or premature aging. AUD affects widespread brain systems, commonly, frontolimbic, frontostriatal, and frontocerebellar networks. METHOD AND RESULTS: Multimodal assessment using selective neuropsychological testing and whole-brain neuroimaging provides evidence for AUD-related specific brain structure-function relations established with double dissociations. Longitudinal study using noninvasive imaging provides evidence for brain structural and functional improvement with sustained sobriety and further decline with relapse. Functional imaging suggests the possibility that some alcoholics in recovery can compensate for impairment by invoking brain systems typically not used for a target task but that can enable normal-level performance. CONCLUSIONS: Evidence for AUD-aging interactions, indicative of accelerated aging, together with increasing alcohol consumption in middle-age and older adults, put aging drinkers at special risk for developing cognitive decline and possibly dementia. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Envelhecimento/psicologia , Alcoolismo/psicologia , Encéfalo/diagnóstico por imagem , Alcoolismo/diagnóstico por imagem , Alcoolismo/epidemiologia , Alcoolismo/fisiopatologia , Encéfalo/fisiopatologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/psicologia , Comorbidade , Demência/epidemiologia , Neuroimagem Funcional , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Testes Neuropsicológicos
11.
Neuropsychology ; 33(6): 795-807, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31448947

RESUMO

OBJECTIVE: Alcohol use disorder (AUD) and chronic pain are widespread conditions with extensive public health burden. This review seeks to describe neuroanatomical links and major mediating influences between AUD and chronic pain, in the service of identifying factors that predict the risk of chronic pain in precipitating or facilitating AUD. METHOD: We review the neural bases of pain and the influence of AUD on processes involved in pain perception. We propose potential mechanisms involved in the development of chronic pain in AUD, and we consider implications for pain management in recovery from AUD. RESULTS: Pain is a multidimensional and subjective experience that, in its acute form, is essential for survival, but in chronic form, pain is a disorder that negatively impacts quality of life. Neural substrates involved in initiating and maintaining chronic pain include dysfunction in descending pain pathways and reward network circuitry. AUD involves preoccupation or craving, intoxication, withdrawal, and negative affect. Neural substrates of AUD involve widespread mesocorticolimbic and cerebrocerebellar networks. Both conditions involve dysfunction of extended reward and oversight circuitry, particularly prefrontal cortex. CONCLUSIONS: The interrelationship between chronic pain and AUD resides in the intersection of etiological influences, mental experiences, and neurobiological processes. Characterization of the connection between brain and behavioral abnormalities in AUD's precipitation of chronic pain-and vice versa-allows for early detection and treatment of patients at risk for developing either or both of these conditions and for preemptive interventional approaches to reduce the risk of consequent vulnerabilities and harm. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Alcoolismo/fisiopatologia , Encéfalo/fisiopatologia , Dor Crônica/fisiopatologia , Alcoolismo/reabilitação , Córtex Cerebral/fisiopatologia , Dor Crônica/terapia , Fissura , Giro do Cíngulo/fisiopatologia , Humanos , Vias Neurais , Manejo da Dor , Córtex Pré-Frontal/fisiopatologia , Qualidade de Vida , Recompensa
12.
Toxicol Lett ; 315: 87-95, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31425726

RESUMO

Prenatal alcohol exposure (PAE) is often associated with congenital heart defects, most commonly septal, valvular, and great vessel defects. However, there have been no known studies on whether PAE affects the resulting fibroblast population after development, and whether this has any consequences in the postnatal period. Our previous study focused on the effects of PAE on the postnatal fibroblast population, which translated into changes in cardiac extracellular matrix (ECM) composition and cardiac function in the neonatal heart. Moreover, our lab has previously demonstrated that alcohol-induced fibrosis is mediated by oxidative stress mechanisms in adult rat hearts following chronic alcohol exposure. Thus, we hypothesize that PAE alters cardiac ECM composition that persists into the postnatal period, leading to cardiac dysfunction, and these effects are prevented by antioxidant treatment. To investigate these effects, pregnant mice were intraperitoneally injected with 2.9 g EtOH/kg body weight on gestation days 6.75 and 7.25. Controls were injected with vehicle saline. Randomly selected dams in both groups were then treated with 100 mg/kg body weight of the antioxidant N-acetylcysteine (NAC) immediately after EtOH or vehicle administration. Left ventricular (LV) chamber dimension and function were assessed in sedated animals on neonatal day 5 using echocardiography. Ejection fraction decreased in the PAE group. NAC treatment prevented this depression of systolic function in PAE neonates. Hearts were analyzed for expression of fibroblast activation markers. Alpha smooth muscle actin (α-SMA) increased in PAE neonatal hearts, and this increase was prevented by NAC treatment. In PAE pups, collagen I decreased, but collagen III expression increased compared to saline animals; the overall collagen I/III ratio significantly decreased. When PAE mice were treated with NAC, collagen I/III ratio did not change. Overall, our data demonstrate that prenatal alcohol exposure produces changes in collagen subtype in neonatal cardiac ECM and a decline in systolic function, and these adverse effects were prevented by NAC treatment.


Assuntos
Acetilcisteína/farmacologia , Alcoolismo/fisiopatologia , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Vasos Coronários/química , Etanol/toxicidade , Fibroblastos/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Animais , Animais Recém-Nascidos , Modelos Animais de Doenças , Feminino , Camundongos , Gravidez
13.
Psychol Addict Behav ; 33(5): 431-441, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31294578

RESUMO

Hazardous alcohol use remains a significant global public health problem. A better understanding of relapse may assist the development of new interventions. Low levels of dispositional mindfulness may be a risk factor for craving and alcohol use, but few studies have examined these associations prospectively in an alcohol-dependent sample. In an ecological momentary assessment (EMA) study, Dutch alcohol dependent patients (N = 43) carried around a personal digital assistant for 4 weeks while trying to maintain abstinence. Participants completed assessments at random times 3 times per day, and when they felt a strong urge to drink or came to the brink of drinking without doing so. At each assessment, stress, negative affect, craving, recent drinking, and attentional or approach bias were assessed. Dispositional mindfulness was assessed at baseline with the Mindful Attention Awareness Scale (MAAS). More mindful individuals (higher MAAS scores) reported lower craving than less mindful individuals. There was no evidence that stress, negative affect, attentional bias, or approach bias mediated the association between MAAS and craving. However, there was evidence for an indirect path from MAAS to drinking such that higher mindfulness was associated with lower craving ratings that in turn were associated with less drinking. There was no evidence that MAAS significantly moderated associations between stress/negative affect/cognitive biases and craving, or between craving and drinking. In sum, more mindful recovering alcohol dependent patients reported lower craving ratings than less mindful patients, and this association appeared to be independent of stress/negative affect and cognitive biases. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Alcoolismo/fisiopatologia , Fissura/fisiologia , Avaliação Momentânea Ecológica , Atenção Plena , Adulto , Computadores de Mão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Trials ; 20(1): 402, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277683

RESUMO

BACKGROUND: Alcohol use disorder (AUD) leads to a significant individual and societal burden. To achieve higher therapy success rates, therapeutic interventions still need to be improved. Most current neuroscientific conceptualizations of AUD focus on the imbalance between an enhanced automatic reaction to alcohol cues and impaired inhibition. Complementary to traditional relapse prevention strategies, novel computerized training interventions aim to directly alter these processes. This study tests a computerized alcohol-specific inhibition training in a large clinical sample and investigates its effects on behavioral, experimental and neurophysiological outcomes. It also analyzes whether variations in inhibition difficulty and/or endogenous cortisol levels during training impact these effects. METHODS: This is a double-blind, randomized controlled trial (RCT) with 246 inpatients with AUD participating. After baseline assessment, participants are randomly assigned to one of three computerized Go-NoGo-based inhibition training interventions (two alcohol-specific versions with different Go/NoGo ratios, or neutral control training) and one of two intervention times (morning/afternoon), resulting in six study arms. All patients perform six training sessions within 2 weeks. Endogenous cortisol is measured in 80 patients before and after the first training session. Inhibitory control and implicit associations towards alcohol are assessed pre and post training, at which point electroencephalography (EEG) is additionally measured in 60 patients. Patients' alcohol consumption and relevant psychological constructs (e.g., craving, self-efficacy, treatment motivation) are measured at discharge and at 3-, 6- and 12-month follow-ups. Fifty healthy participants are assessed (20 with EEG) at one time point as a healthy control group. DISCUSSION: This study investigates the effects of a computerized, alcohol-specific inhibition training for the first time in patients with AUD. Results should give insight into the effectiveness of this potential add-on to standard AUD treatment, including proximal and distal measures and effects on behavioral, experimental and neurophysiological measures. Information about working mechanisms and potential optimizations of this training are gathered through variations regarding difficulty of inhibition training and training time. This study may thus contribute to a deepened understanding of AUD and the improvement of its evidence-based treatment. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02968537 . Registered on 18 November 2016.


Assuntos
Abstinência de Álcool/psicologia , Consumo de Bebidas Alcoólicas/prevenção & controle , Alcoólicos/psicologia , Alcoolismo/terapia , Aprendizagem , Motivação , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/fisiopatologia , Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/sangue , Alcoolismo/fisiopatologia , Alcoolismo/psicologia , Biomarcadores/sangue , Encéfalo/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Suíça , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
15.
Adv Exp Med Biol ; 1162: 89-127, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31332736

RESUMO

Δ9-tetrahydrocannabinol (Δ9-THC), the primary active component in Cannabis sativa preparations such as hashish and marijuana, signals by binding to cell surface receptors. Two types of receptors have been cloned and characterized as cannabinoid (CB) receptors. CB1 receptors (CB1R) are ubiquitously present in the central nervous system (CNS) and are present in both inhibitory interneurons and excitatory neurons at the presynaptic terminal. CB2 receptors (CB2R) are demonstrated in microglial cells, astrocytes, and several neuron subpopulations and are present in both pre- and postsynaptic terminals. The majority of studies on these receptors have been conducted in the past two and half decades after the identification of the molecular constituents of the endocannabinoid (eCB) system that started with the characterization of CB1R. Subsequently, the seminal discovery was made, which suggested that alcohol (ethanol) alters the eCB system, thus establishing the contribution of the eCB system in the motivation to consume ethanol. Several preclinical studies have provided evidence that CB1R significantly contributes to the motivational and reinforcing properties of ethanol and that the chronic consumption of ethanol alters eCB transmitters and CB1R expression in the brain nuclei associated with addiction pathways. Additionally, recent seminal studies have further established the role of the eCB system in the development of ethanol-induced developmental disorders, such as fetal alcohol spectrum disorders (FASD). These results are augmented by in vitro and ex vivo studies, showing that acute and chronic treatment with ethanol produces physiologically relevant alterations in the function of the eCB system during development and in the adult stage. This chapter provides a current and comprehensive review of the literature concerning the role of the eCB system in alcohol abuse disorders (AUD).


Assuntos
Alcoolismo/fisiopatologia , Endocanabinoides/fisiologia , Receptor CB1 de Canabinoide/fisiologia , Etanol , Humanos , Sinapses
16.
Elife ; 82019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31262402

RESUMO

Adolescence is a common time for initiation of alcohol use and development of alcohol use disorders. The present study investigates neuroanatomical predictors for trajectories of future alcohol use based on a novel voxel-wise whole-brain structural equation modeling framework. In 1814 healthy adolescents of the IMAGEN sample, the Alcohol Use Disorder Identification Test (AUDIT) was acquired at three measurement occasions across five years. Based on a two-part latent growth curve model, we conducted whole-brain analyses on structural MRI data at age 14, predicting change in alcohol use score over time. Higher grey-matter volumes in the caudate nucleus and the left cerebellum at age 14 years were predictive of stronger increase in alcohol use score over 5 years. The study is the first to demonstrate the feasibility of running separate voxel-wise structural equation models thereby opening new avenues for data analysis in brain imaging.


Assuntos
Alcoolismo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Núcleo Caudado/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Adolescente , Alcoolismo/fisiopatologia , Álcoois/toxicidade , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Mapeamento Encefálico , Núcleo Caudado/efeitos dos fármacos , Núcleo Caudado/fisiopatologia , Cerebelo/efeitos dos fármacos , Cerebelo/fisiopatologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Consumo de Álcool por Menores/prevenção & controle
17.
Rev Med Liege ; 74(5-6): 274-280, 2019 05.
Artigo em Francês | MEDLINE | ID: mdl-31206266

RESUMO

Alcohol dependence is a chronic and multifactorial disease with well-identified neurobiological substrates and a high relapse rate. In interaction with the environment, personal genetic vulnerability may influence the course of the disease.


Assuntos
Alcoolismo , Alcoolismo/fisiopatologia , Doença Crônica , Humanos , Recidiva
18.
Rev Med Liege ; 74(5-6): 310-313, 2019 May.
Artigo em Francês | MEDLINE | ID: mdl-31206272

RESUMO

Chronic alcohol consumption results in multiple peripheral and central nervous system dysfunctions. Some are due to the direct action of alcohol or its derivatives, others are induced by the vitamin deficiencies associated with alcoholism, others are eventually related to the failure of other vital organs, such as the liver. In this short review, we describe alcohol-induced neuropathy, Gayet-Wernicke syndrome, Korsakoff syndrome, alcoholic dementia, Marchiafava-Bignami syndrome, hepatic encephalopathy, alcoholic epilepsy and manifestations of alcohol withdrawal.


Assuntos
Alcoolismo , Demência , Encefalopatia Hepática , Encefalopatia de Wernicke , Alcoolismo/complicações , Alcoolismo/fisiopatologia , Demência/complicações , Encefalopatia Hepática/complicações , Humanos , Encefalopatia de Wernicke/complicações
19.
J Abnorm Psychol ; 128(5): 473-486, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31192638

RESUMO

Increasingly, the structure of mental disorders has been studied in the form of a network, characterizing how symptoms or criteria interact with and influence each other. Many studies of psychiatric symptoms and diagnostic criteria employ community or population-based surveys using co-occurrence of the symptoms/criteria to form the networks. However, given the overall low prevalence rates of mental disorders and their symptoms in the general population, most of those surveyed may not exhibit or endorse any symptoms and yet are often included in network analyses. Consequently, because network models are built on associations between symptoms/criteria, much of the observed variability is driven by individuals who are asymptomatic. Using data from the National Epidemiological Survey of Alcohol and Related Conditions (NESARC) Wave 2 and NESARC-III, we explore the effect of these "asymptomatic" observations on the estimated relations among diagnostic criteria of alcohol use disorder to determine the effects of such observations on estimated networks. We do so using the eLasso tool, as well as with traditional measures of correlation between binary variables (the Φ coefficient and odds ratio). We find that when the proportion of asymptomatic individuals are systematically culled from the sample, the estimated pairwise relations are often significantly affected, even changing signs in some cases. Our findings indicate that researchers should carefully consider the population(s) included in their sample and the implications it has on their interpretations of pairwise similarity estimates and resulting generalizability and reproducibility of estimates of network structures. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Alcoolismo , Manual Diagnóstico e Estatístico de Transtornos Mentais , Projetos de Pesquisa , Adulto , Idoso , Alcoolismo/classificação , Alcoolismo/diagnóstico , Alcoolismo/fisiopatologia , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Reprodutibilidade dos Testes
20.
Brain Struct Funct ; 224(6): 2087-2101, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31161472

RESUMO

Despite the common co-occurrence of cognitive impairment and brain structural deficits in alcoholism, demonstration of relations between regional gray matter volumes and cognitive and motor processes have been relatively elusive. In pursuit of identifying brain structural substrates of impairment in alcoholism, we assessed executive functions (EF), episodic memory (MEM), and static postural balance (BAL) and measured regional brain gray matter volumes of cortical, subcortical, and cerebellar structures commonly affected in individuals with alcohol dependence (ALC) compared with healthy controls (CTRL). ALC scored lower than CTRL on all composite scores (EF, MEM, and BAL) and had smaller frontal, cingulate, insular, parietal, and hippocampal volumes. Within the ALC group, poorer EF scores correlated with smaller frontal and temporal volumes; MEM scores correlated with frontal volume; and BAL scores correlated with frontal, caudate, and pontine volumes. Exploratory analyses investigating relations between subregional frontal volumes and composite scores in ALC yielded different patterns of associations, suggesting that different neural substrates underlie these functional deficits. Of note, orbitofrontal volume was a significant predictor of memory scores, accounting for almost 15% of the variance; however, this relation was evident only in ALC with a history of a non-alcohol substance diagnosis and not in ALC without a non-alcohol substance diagnosis. The brain-behavior relations observed provide evidence that the cognitive and motor deficits in alcoholism are likely a result of different neural systems and support the hypothesis that a number of identifiable neural systems rather than a common or diffuse neural pathway underlies cognitive and motor deficits observed in chronic alcoholism.


Assuntos
Alcoolismo , Cognição/fisiologia , Substância Cinzenta/patologia , Córtex Motor/patologia , Vias Neurais/patologia , Adulto , Idoso , Alcoolismo/patologia , Alcoolismo/fisiopatologia , Cerebelo/patologia , Cerebelo/fisiopatologia , Função Executiva/fisiologia , Feminino , Substância Cinzenta/fisiopatologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Memória Episódica , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia , Vias Neurais/fisiopatologia
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