The alcohol use disorders identification test (AUDIT), a screening instrument to identify individuals at risk of alcohol use-related problems, has not been validated in a Russian primary care population. We assessed the reliability, factor structure, sensitivity, and specificity of AUDIT scores among 254 subjects initiating tuberculosis treatment from 2005 to 2007 in Tomsk City. Our findings support the use of the AUDIT as a screening instrument among Russian individuals seeking primary care. We discuss implications, limitations, and future research.

The effects of alcohol abuse are multi-dimensional since alcohol is widely known to affect both the innate and adaptive immune systems. Recently, epigenetics has come into focus and has been implicated in many diseases as well as substance abuse disorders. Therefore, research efforts of understanding the epigenetic mechanisms underlying substance abuse effects including alcohol abuse have become more predominant. In our laboratory, we have studied different epigenetic changes induced by alcohol exposure including regulation of histone deacetylases (HDACs), histone quantity, and histone modifications such as acetylation and deacetylation. We have observed differential effects of acute and chronic alcohol exposure in human monocyte-derived dendritic cells (MDDCs) wherein our laboratory previously found that HDACs were modulated in MDDCs treated acutely with alcohol in vitro, and in MDDCs from alcohol users. Our previous work has also demonstrated that alcohol consumption affects the dendritic cell function by modulating inflammatory markers and cannabinoid receptors such as CB2 and GPR55 through epigenetic modifications. For instance, chronic alcohol exposure upregulates histone (H) 4 acetylation at lysine 12 (H4k12ac) and acute alcohol effects on histone acetylation are associated with an increase in GPR55 expression. The hypothesis of the study is that chronic alcohol modulates human MDDC function through epigenetic mechanisms. Therefore, the primary objective of this research project is to elucidate novel pathways involving histone post-translational modifications due to chronic alcohol exposure in human dendritic cells. For this study, monocytes isolated from commercially available human buffy coats were differentiated into MDDCs, which were treated with chronic alcohol levels of 0.1 % (100mg/dL) and 0.2 % (200mg/dL) for 5 days in the presence or absence of the histone acetyltransferase inhibitor NU9056 (50nM) or the GPR55 antagonist CID16020046 (5µM). Results showed that chronic alcohol levels upregulated H4K12ac in MDDCs and this was associated with a concomitant increase in GPR55 gene and protein expression. Further, NU9056 and CID16020046 were able to reduce alcohol-induced inflammatory chemokine MCP-2 and reactive oxygen species production indicating that H4K12ac may be an inflammation and oxidative stress regulator. Additionally, NU9056 and CID16020046 could potentially reduce alcohol-induced inflammation and serve as potential therapeutic targets for alcohol use disorders.

Underage drinking has featured prominently in both scholarly and conventional literature in recent decades as a major health and socio-economic concern in the United States. As new evidence emerges associating underage drinking with a host of negative outcomes for both the youth who drinks and society in general, a closer examination of the long-term effects of underage drinking is critical. This exploratory study was designed to examine predictor variables and their ramifications (1) using logistic regression to identify a model for underage drinking history (UDHISTORY) as a predictor of concomitant alcohol dependence and poor educational attainment (CADAPEA) among individuals aged 25 and above, and (2) obtain a better understanding of how demographic variables (age, gender, race/ethnicity) influence the prediction. The nature and strength of the effect(s) of these demographic variables on the prediction were also investigated. The 2010 National Survey on Drug Use and Health data set ICPSR 32722-0001 which is previously unexploited for this purpose is utilized in this study. The data analysis tool, SDA on SAMHSA's website and IBM SPSS were used for correlation analysis and logistic regression to test the hypothesis that currently legal age drinkers 25 years and older with UDHISTORY are more likely to experience CADAPEA than their counterparts without UDHISTORY. When considered alone, UDHISTORY was a strong and statistically significant predictor of CADAPEA. The identified bivariate logistic regression model was statistically significant, &chi2 (1, n = 60) = 13.39, Adjusted Wald F1, 60 = 13.39, p = 0.001 < .05, accounting for 1.26% (Cox and Snell R square), 1.3% (Log Likelihood Pseudo R square), to 7.9% (Nagelkerke R square) of the variance in CADAPEA. However, adding demographic variables to the model made UDHISTORY a much stronger and more statistically significant predictor. The identified final multivariable logistic regression model was statistically significant, &chi2 (6, n = 55) = 170.43, Adjusted Wald F6, 55 = 26.04, p = 0.00 < .001, accounting for 1.8% (Cox and Snell R square), 7.2% (Log Likelihood Pseudo R square) to 7.9% (Nagelkerke R square) of the variance in CADAPEA. The model also correctly classified 99.1% of cases.

Objectives: Concurrent substance use disorder (SUD) and posttraumatic stress disorder (PTSD) occur at high rates and are typically associated with poor treatment outcomes in both sexes. However, women have a propensity to cope with increased negative affect via substance use in comparison to men; thus, it is important to elucidate the sex-specific bidirectional relationships between SUD and PTSD to improve our understanding of concurrent SUD/PTSD in men and women. Methods: Using data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-Wave 3; n = 36,309), the present study evaluated the impact of sex on the relationship between past-year SUDs (new, remitted, ongoing), including alcohol and drug use, and retrospective transitions in new vs. absent and ongoing vs. remitted diagnoses of PTSD. Additionally, the impact of sex was explored in models examining past year PTSD (new, remitted, ongoing) and retrospective transitions in new vs. absent and ongoing vs. remitted diagnosis of SUDs. Diagnostic transitions were based on retrospective reporting. Results: Results indicated that new, remitted, and ongoing SUDs increase the likelihood of new PTSD diagnoses (OR range = 2.53–8.11; p < 0.05). Among individuals with ongoing drug use disorders (DUD), there were greater odds of ongoing PTSD (OR = 2.10, p < 0.01). When examining the relationship reciprocally, new, remitted, and ongoing PTSD increased the likelihood of new SUDs (OR range = 2.50–8.22; p < 0.05), and ongoing PTSD increased the likelihood of ongoing SUD and DUD (OR = 1.40, 1.70, respectively; p < 0.05). Sex-specific analyses revealed that the relationship between PTSD and SUDs varies between sexes, particularly among women. For instance, women with new PTSD had higher odds of SUDs, and women with ongoing PTSD were almost 2.5 times more likely to have an ongoing DUD. Women with a new PTSD diagnosis were more likely to be diagnosed with a new SUD (OR = 3.27) and an ongoing DUD (OR = 3.08). Conclusions: Results indicate a bidirectional relationship between PTSD and SUD that is in many instances larger in women. Thus, illustrating potential sex-specific differences in underlying mechanisms implicated in SUD/PTSD, warranting additional research.

Alcohol abuse is one of the costliest human health problems in the United States. Studies assessing the etiology of alcohol use disorders (AUDs) in adulthood suggest that these disorders are predicted by trait-like differences, such as low or impaired central serotonin or temperamental anxiety. Few studies, however, have assessed neonatal, infant, and adolescent characteristics that lead to alcohol abuse in adolescence. Given that the expression of AUDs is rooted in biological processes, the set of studies presented in this work investigate the early origins of excessive alcohol use in adolescence, with an overall goal of identifying risk factors that may aid in prevention or intervention efforts to deter future alcohol abuse. Due to their evolutionary similarities, as well as similarities in their patterns of alcohol consumption, these studies utilize a nonhuman primate model (Macaca mulatta). A series of three studies investigating neonatal, infant, and adolescent predictors of adolescent alcohol intake were conducted. In study one, we assessed the relationship between neurobehavioral measures at two weeks of life and voluntary alcohol intake in adolescence. In study two, we assessed the relationship between behaviors that reflect an anxiety-like temperament in the first six months of life and excessive alcohol intake in adolescence. In study three, we investigated the relationship between infant and adolescent trait-like stress-induced cortisol and adolescent anxiety-like behaviors and alcohol intake in adolescence. The findings from this set of studies lends itself to an increased understanding of early-life, biologically-based predictors of excessive alcohol intake in adolescence and provides critical information to establishing early interventions for individuals at risk for the development of later AUDs.

No description available.

[EN] Alcohol abuse is one of the most alarming issues for the health authorities. It is estimated that at least 23 million of European citizens are affected by alcoholism causing a cost around 270 million euros. Excessive alcohol consumption is related with physical harm and, although it damages the most of body organs, liver, pancreas, and brain are more severally affected. Not only physical harm is associated to alcohol-related disorders, but also other psychiatric disorders such as depression are often comorbiding. As well, alcohol is present in many of violent behaviors and traffic injures. Altogether reflects the high complexity of alcohol-related disorders suggesting the involvement of multiple brain systems. With the emergence of non-invasive diagnosis techniques such as neuroimaging or EEG, many neurobiological factors have been evidenced to be fundamental in the acquisition and maintenance of addictive behaviors, relapsing risk, and validity of available treatment alternatives. Alterations in brain structure and function reflected in non-invasive imaging studies have been repeatedly investigated. However, the extent to which imaging measures may precisely characterize and differentiate pathological stages of the disease often accompanied by other pathologies is not clear. The use of animal models has elucidated the role of neurobiological mechanisms paralleling alcohol misuses. Thus, combining animal research with non-invasive neuroimaging studies is a key tool in the advance of the disorder understanding. As the volume of data from very diverse nature available in clinical and research settings increases, an integration of data sets and methodologies is required to explore multidimensional aspects of psychiatric disorders. Complementing conventional mass-variate statistics, interests in predictive power of statistical machine learning to neuroimaging data is currently growing among scientific community. This doctoral thesis has covered most of the aspects mentioned above. Starting from a well-established animal model in alcohol research, Marchigian Sardinian rats, we have performed multimodal neuroimaging studies at several stages of alcohol-experimental design including the etiological mechanisms modulating high alcohol consumption (in comparison to Wistar control rats), alcohol consumption, and treatment with the opioid antagonist Naltrexone, a well-established drug in clinics but with heterogeneous response. Multimodal magnetic resonance imaging acquisition included Diffusion Tensor Imaging, structural imaging, and the calculation of magnetic-derived relaxometry maps. We have designed an analytical framework based on widely used algorithms in neuroimaging field, Random Forest and Support Vector Machine, combined in a wrapping fashion. Designed approach was applied on the same dataset with two different aims: exploring the validity of the approach to discriminate experimental stages running at subject-level and establishing predictive models at voxel-level to identify key anatomical regions modified during the experiment course. As expected, combination of multiple magnetic resonance imaging modalities resulted in an enhanced predictive power (between 3 and 16%) with heterogeneous modality contribution. Surprisingly, we have identified some inborn alterations correlating high alcohol preference and thalamic neuroadaptations related to Naltrexone efficacy. As well, reproducible contribution of DTI and relaxometry -related biomarkers has been repeatedly identified guiding further studies in alcohol research. In summary, along this research we demonstrate the feasibility of incorporating multimodal neuroimaging, machine learning algorithms, and animal research in the advance of the understanding alcohol-related disorders. / [ES] El abuso de alcohol es una de las mayores preocupaciones de las autoridades sanitarias en la Unión Europea. El consumo de alcohol en exceso afecta en mayor o menor medida la totalidad del organismo siendo el páncreas e hígado los más severamente afectados. Además de estos, el sistema nervioso central sufre deterioros relacionados con el alcohol y con frecuencia se presenta en paralelo con otras patologías psiquiátricas como la depresión u otras adicciones como la ludopatía. La presencia de estas comorbidades demuestra la complejidad de la patología en la que multitud de sistemas neuronales interaccionan entre sí. El uso imágenes de resonancia magnética (RM) han ayudado en el estudio de enfermedades psiquiátricas facilitando el descubrimiento de mecanismos neurológicos fundamentales en el desarrollo y mantenimiento de la adicción al alcohol, recaídas y el efecto de los tratamientos disponibles. A pesar de los avances, todavía se necesita investigar más para identificar las bases biológicas que contribuyen a la enfermedad. En este sentido, los modelos animales sirven, por lo tanto, a discriminar aquellos factores únicamente relacionados con el alcohol controlando otros factores que facilitan el desarrollo del alcoholismo. Estudios de resonancia magnética en animales de laboratorio y su posterior evaluación en humanos juegan un papel fundamental en el entendimiento de las patologías psiquatricas como la addicción al alcohol. La imagen por resonancia magnética se ha integrado en entornos clínicos como prueba diagnósticas no invasivas. A medida que el volumen de datos se va incrementando, se necesitan herramientas y metodologías capaces de fusionar información de muy distinta naturaleza y así establecer criterios diagnósticos cada vez más exactos. El poder predictivo de herramientas derivadas de la inteligencia artificial como el aprendizaje automático sirven de complemento a tradicionales métodos estadísticos. En este trabajo se han abordado la mayoría de estos aspectos. Se han obtenido datos multimodales de resonancia magnética de un modelo validado en la investigación de patologías derivadas del consumo del alcohol, las ratas Marchigian-Sardinian desarrolladas en la Universidad de Camerino (Italia) y con consumos de alcohol comparables a los humanos. Para cada animal se han adquirido datos antes y después del consumo de alcohol y bajo dos condiciones de abstinencia (con y sin tratamiento de Naltrexona, una medicaciones anti-recaídas usada como farmacoterapia en el alcoholismo). Los datos de resonancia magnética multimodal consistentes en imágenes de difusión, de relaxometría y estructurales se han fusionado en un esquema analítico multivariable incorporando dos herramientas generalmente usadas en datos derivados de neuroimagen, Random Forest y Support Vector Machine. Nuestro esquema fue aplicado con dos objetivos diferenciados. Por un lado, determinar en qué fase experimental se encuentra el sujeto a partir de biomarcadores y por el otro, identificar sistemas cerebrales susceptibles de alterarse debido a una importante ingesta de alcohol y su evolución durante la abstinencia. Nuestros resultados demostraron que cuando biomarcadores derivados de múltiples modalidades de neuroimagen se fusionan en un único análisis producen diagnósticos más exactos que los derivados de una única modalidad (hasta un 16% de mejora). Biomarcadores derivados de imágenes de difusión y relaxometría discriminan estados experimentales. También se han identificado algunos aspectos innatos que están relacionados con posteriores comportamientos con el consumo de alcohol o la relación entre la respuesta al tratamiento y los datos de resonancia magnética. Resumiendo, a lo largo de esta tesis, se demuestra que el uso de datos de resonancia magnética multimodales en modelos animales combinados en esquemas analíticos multivariados es una herramienta válida en el entendimiento de patologías / [CAT] L'abús de alcohol es una de les majors preocupacions per part de les autoritats sanitàries de la Unió Europea. Malgrat la dificultat de establir xifres exactes, se estima que uns 23 milions de europeus actualment sofreixen de malalties derivades del alcoholisme amb un cost que supera els 150.000 milions de euros per a la societat. Un consum de alcohol en excés afecta en major o menor mesura el cos humà sent el pàncreas i el fetge el més afectats. A més, el cervell sofreix de deterioraments produïts per l'alcohol i amb freqüència coexisteixen amb altres patologies com depressió o altres addiccions com la ludopatia. Tot aquest demostra la complexitat de la malaltia en la que múltiple sistemes neuronals interactuen entre si. Tècniques no invasives com el encefalograma (EEG) o imatges de ressonància magnètica (RM) han ajudat en l'estudi de malalties psiquiàtriques facilitant el descobriment de mecanismes neurològics fonamentals en el desenvolupament i manteniment de la addició, recaiguda i la efectivitat dels tractaments disponibles. Tot i els avanços, encara es necessiten més investigacions per identificar les bases biològiques que contribueixen a la malaltia. En aquesta direcció, el models animals serveixen per a identificar únicament dependents del abús del alcohol. Estudis de ressonància magnètica en animals de laboratori i posterior avaluació en humans jugarien un paper fonamental en l' enteniment de l'ús del alcohol. L'ús de probes diagnostiques no invasives en entorns clínics has sigut integrades. A mesura que el volum de dades es incrementa, eines i metodologies per a la fusió d' informació de molt distinta natura i per tant, establir criteris diagnòstics cada vegada més exactes. La predictibilitat de eines desenvolupades en el camp de la intel·ligència artificial com la aprenentatge automàtic serveixen de complement a mètodes estadístics tradicionals. En aquesta investigació se han abordat tots aquestes aspectes. Dades multimodals de ressonància magnètica se han obtingut de un model animal validat en l'estudi de patologies relacionades amb el consum d'alcohol, les rates Marchigian-Sardinian desenvolupades en la Universitat de Camerino (Italià) i amb consums d'alcohol comparables als humans. Per a cada animal es van adquirir dades previs i després al consum de alcohol i dos condicions diferents de abstinència (amb i sense tractament anti-recaiguda). Dades de ressonància magnètica multimodal constituides per imatges de difusió, de relaxometria magnètica i estructurals van ser fusionades en esquemes analítics multivariats incorporant dues metodologies validades en el camp de neuroimatge, Random Forest i Support Vector Machine. Nostre esquema ha sigut aplicat amb dos objectius diferenciats. El primer objectiu es determinar en quina fase experimental es troba el subjecte a partir de biomarcadors obtinguts per neuroimatge. Per l'altra banda, el segon objectiu es identificar el sistemes cerebrals susceptibles de ser alterats durant una important ingesta de alcohol i la seua evolució durant la fase del tractament. El nostres resultats demostraren que l'ús de biomarcadors derivats de varies modalitats de neuroimatge fusionades en un anàlisis multivariat produeixen diagnòstics més exactes que els derivats de una única modalitat (fins un 16% de millora). Biomarcadors derivats de imatges de difusió i relaxometria van contribuir de distints estats experimentals. També s'han identificat aspectes innats que estan relacionades amb posterior preferències d'alcohol o la relació entre la resposta al tractament anti-recaiguda i les dades de ressonància magnètica. En resum, al llarg de aquest treball, es demostra que l'ús de dades de ressonància magnètica multimodal en models animals combinats en esquemes analítics multivariats són una eina molt valida en l'enteniment i avanç de patologies psiquiàtriques com l'alcoholisme. / Cosa Liñán, A. (2017). Analytical fusion of multimodal magnetic resonance imaging to identify pathological states in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/90523

Despite over 30 years of research investigating alcohol expectancies, they have never been examined in terms of the anticipated pharmacological versus social rewards resulting from alcohol consumption, and both appear to play a central role in drinking motivation and behavior. The purpose of this study was to develop a two-dimensional instrument designed to assess both the pharmacological alcohol expectancies of pleasurable, internal states that result from alcohol consumption, as well as the social expectancies that drinking alcohol will result in higher social status and increased effectiveness in social situations. This measure, called the Pharmacological and Social Alcohol Expectancy Scale (PSAES), was developed and validated in a college sample using a two-phase design with three separate samples. Phase I results demonstrated that a respecified model of the PSAES adequately fit the proposed two-dimensional factor structure and provided justification for the items representing two distinguishable domains: social and pharmacological. The measure was then used to 1) assess patterns of drinking expectancies at various drinker levels and 2) investigate whether known risk factors for alcohol use disorders differentiate scores on the two factors. Phase II results indicated that pharmacological and social expectancies are both significantly positively associated with drinking behavior, and that sensation-seeking is significantly associated with pharmacological expectancies. The PSAES represents the first alcohol expectancy instrument to provide adequate coverage of pharmacological expectancies. Implications and limitations are discussed.

Syftet med detta examensarbete är att genom en litteraturstudie vidare utforska området kontrollerat drickande. Olika behandlingsmetoder för alkoholberoende kräver olika behandlingsmål. Ett vanligt behandlingsmål är helnykterhet. Ett antagande bland många är att helnykterhet är det enda tänkbara målet för alkoholberoende personer. Ett antagande som är utbrett än idag. Bakgrunden till detta resonemang är att alkoholberoende ses som en livslång och kronisk sjukdom. Kontrollerat drickande har varit och är ett kontroversiellt ämne. Tidigare forskning har identifierat faktorer eller prediktorer kopplade till utfallet av kontrollerat drickande. En framträdande prediktor har exempelvis varit alkoholberoendets svårighetsgrad. Senare forskning verkar också ge stöd till att beroendegraden har betydelse för möjligheten att uppnå ett kontrollerat drickande. Dock så har två presenterade studier med uppföljningsperioder under ett år inte hittat detta samband. Andra prediktorer är en hög alkoholkonsumtion innan behandling och alkoholism inom familjen. Det verkar dock som att vissa alkoholberoende personer kan reducera sin alkoholkonsumtion och uppnå ett kontrollerat drickande. Dessutom kan en kontrollerad konsumtion upprätthållas vid uppföljningsperioder på ett år eller mer. Dessa resulta diskuteras vidare i detta examensarbete. / The aim of this thesis is to research and explore the subject of controlled drinking further through a literature review. Different treatments for alcohol use disorders require different treatment goals. Some dictate that abstinence is the only feasible goal among people suffering from alcohol use disorders. This assumption appears to be prevalent still today. Behind this reasoning is the assumption that alcoholism is a lifelong and chronic disease. Controlled drinking sparked a lot of controversy during early research on the subject. Past research has identified factors, or predictors, associated with controlled drinking outcome. One emerging predictor has been the severity of dependence. According to subsequent research, the severity of dependence appears to be a predictor of success with controlled drinking. On the other hand, two studies obtained, with shorter follow up periods during one year, did not find this association. Other predictors that have been identified are past alcohol use and a family history of alcoholism. It still appears that some individuals suffering from alcohol use disorders can reduce their drinking to moderate drinking and maintain it through follow up through one year and more. These findings are further discussed in this thesis.

No description available.