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Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
Positive genetic correlation was observed between MD and AD (rgMD-AD = + 0.47, P = 6.6 × 10-10). AC-quantity showed positive genetic correlation with both AD (rgAD-AC quantity = + 0.75, P = 1.8 × 10-14) and MD (rgMD-AC quantity = + 0.14, P = 2.9 × 10-7), while there was negative correlation of AC-frequency with MD (rgMD-AC frequency = -0.17, P = 1.5 × 10-10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10-6). There was no evidence for reverse causation.
This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.
Journal Article
Supporting people with alcohol and drug problems : making a difference
This addresses the gap in social work education by providing a combination of research evidence, policy frameworks and practical hints and tips for good social work practice for all those in children's and adults' social work and social care settings who are working with people who use alcohol or other dr.
Book
Alcohol use disorders
Alcohol use disorders consist of disorders characterised by compulsive heavy alcohol use and loss of control over alcohol intake. Alcohol use disorders are some of the most prevalent mental disorders globally, especially in high-income and upper-middle-income countries; and are associated with high mortality and burden of disease, mainly due to medical consequences, such as liver cirrhosis or injury. Despite their high prevalence, alcohol use disorders are undertreated partly because of the high stigma associated with them, but also because of insufficient systematic screening in primary health care, although effective and cost-effective psychosocial and pharmacological interventions do exist. Primary health care should be responsible for most treatment, with routine screening for alcohol use, and the provision of a staggered treatment response, from brief advice to pharmacological treatment. Clinical interventions for these disorders should be embedded in a supportive environment, which can be bolstered by the creation of alcohol control policies aimed at reducing the overall level of consumption.
Journal Article
Under the volcano
It is the Day of the Dead in Mexico and Geoffrey Firmin-ex-consul, ex-husband, an alcoholic and a ruined man-is living out the last day of his life, watched by his former wife and half-brother.
Captain Billy's troopers : a writer's life
\"In this audacious memoir, William Cobb reveals the tumultuous creative life of a distinguished practitioner of southern and Alabama storytelling. As poignant and inspiring as his own fiction, Captain Billy's Troopers traces Cobb's early life, education, and struggles with alcohol and the debilitating condition normal pressure hydrocephalus (NPH). Like a curving river, the broad sweep of Cobb's turbulent life includes both startling cataracts and desultory eddies, leading sometimes into shadows or opening into unexpected sunlight. With unsentimental clarity, Cobb recounts coming of age in his native Demopolis in the churning middle years of the twentieth century. It's there he has his first tantalizing tastes of alcohol and begins to drink habitually. Readers then travel with Cobb to Livingston University (now the University of West Alabama) and then on to Vanderbilt University. Along the way, readers relish his first experiences of love and success as a writer, leading to a career as a professor of writing at Alabama College (now the University of Montevallo) in 1963. From there Cobb's struggles with alcohol and depression lead to elongated years of tumbling creative output and the collapse of his marriage. The summer of 1984 found Cobb in rehab, the first step in his path to recovery. His unflinching memoir narrates both the milestones and telling details of his intense therapy and years in Alcoholics Anonymous (AA). In the sober thirty years since, Cobb has published a string of critically praised novels and a prize-winning collection of short stories. The capstone of his comeback was winning the Harper Lee Award in 2007 for distinguished fiction writing. In 2000, shortly after retiring, Cobb developed NPH, which upset his sense of balance and triggered dementia symptoms and other maladies. Nine years later in 2009, brain surgery brought Cobb a dramatic recovery, which began the third act in his writing career. Vital, honest, and entertaining, Captain Billy's Troopers captures the life of an Alabama original. \"-- Provided by publisher.
Book
Precision Medicine in Alcohol Dependence: A Controlled Trial Testing Pharmacotherapy Response Among Reward and Relief Drinking Phenotypes
Randomized trials of medications for alcohol dependence (AD) often report no differences between active medications. Few studies in AD have tested hypotheses regarding which medication will work best for which patients (ie, precision medicine). The PREDICT study tested acamprosate and naltrexone vs placebo in 426 randomly assigned AD patients in a 3-month treatment. PREDICT proposed individuals whose drinking was driven by positive reinforcement (ie, reward drinkers) would have a better treatment response to naltrexone, whereas individuals whose drinking was driven by negative reinforcement (ie, relief drinkers) would have a better treatment response to acamprosate. The goal of the current analysis was to test this precision medicine hypothesis of the PREDICT study via analyses of subgroups. Results indicated that four phenotypes could be derived using the Inventory of Drinking Situations, a 30-item self-report questionnaire. These were high reward/high relief, high reward/low relief, low reward/high relief, and low reward/low relief phenotypes. Construct validation analyses provided strong support for the validity of these phenotypes. The subgroup of individuals who were predominantly reward drinkers and received naltrexone vs placebo had an 83% reduction in the likelihood of any heavy drinking (large effect size). Cutoff analyses were done for clinical applicability: individuals are reward drinkers and respond to naltrexone if their reward score was higher than their relief score AND their reward score was between 12 and 31. Using naltrexone with individuals who are predominantly reward drinkers produces significantly higher effect sizes than prescribing the medication to a more heterogeneous sample.
Journal Article
Educating desire : autobiographical impressions of addiction in alcoholics anonymous
This impressionistic autobiographical inquiry is an attempt to connect the personal with the socio-historical?addiction with Addiction; it is also an attempt to demonstrate that knowledge production can be generated through radically non-traditional means. Narrative serves as method and methodology in a mostly first person account of a fictional open AA meeting. A suspicious hermeneutics is applied to addiction, to AA, and to the phenomenon of total medicalization, which the author and narrative finally succumb to, in the interest of questioning common sense assumptions about these themes, and as jumping off points for literary and philosophical exploration. Highlighted is the semi-fictionalized storied nature of reflected upon lived experience?the personal telephone game of (Paul Ricoeur?s) narrative identity?and the role of institutions like AA in grafting onto lived experience new narrative forms that allow for new ways of structuring self and identity. All the made-up aspects of the narrative?the multi-tracked narrator?s voice, shifts in point-of-view, and the semi and sometimes totally imagined characters encountered at the meeting and elsewhere?are the fiction the author makes of his personal history as an addict and newcomer in AA, which complicates the relation between knower and known (author and reader) while enriching and enlivening the narrative, drawing the reader into a literary representation of imagined and lived experience.
Book
The CRF1 Antagonist Verucerfont in Anxious Alcohol-Dependent Women: Translation of Neuroendocrine, But not of Anti-Craving Effects
Blockade of corticotropin-releasing factor receptor 1 (CRF1) suppresses stress-induced alcohol seeking in rodents, but clinical translation remains. Here, we first showed that the CRF1 antagonist verucerfont potently blocks hypothalamic-pituitary adrenal (HPA) axis activation in adrenalectomized rats. We then evaluated verucerfont for its ability to block HPA axis activation and reduce stress-induced alcohol craving in alcohol-dependent patients. Anxious, alcohol-dependent women (age 21-65 years, n=39) were admitted to the NIH Clinical Center and completed withdrawal treatment before enrollment if needed. One-week single-blind placebo was followed by randomized double-blind verucerfont (350 mg per day) or placebo for 3 weeks. Verucerfont effects on the HPA axis were evaluated using the dexamethasone-CRF test. Craving was evaluated using two established protocols, one that combines a social stressor with physical alcohol cue exposure, and one that uses guided imagery to present personalized stress, alcohol, or neutral stimuli. An fMRI session examined brain responses to negative affective stimuli and alcohol cues. In contrast to our recent observations with another CRF1 antagonist, pexacerfont, verucerfont potently blocked the HPA axis response to the dexamethasone-CRF test, but left alcohol craving unaffected. Right amygdala responses to negative affective stimuli were significantly attenuated by verucerfont, but responses to alcohol-associated stimuli were increased in some brain regions, including left insula. Discontinuation rates were significantly higher in the verucerfont group. Our findings provide the first translational evidence that CRF1 antagonists with slow receptor dissociation kinetics may have increased efficacy to dampen HPA axis responses. The findings do not support a clinical efficacy of CRF1 blockade in stress-induced alcohol craving and relapse.
Journal Article