酒依赖综合征的危险因素调查研究

目的探讨中山市个体惠酒依赖综合征的危险因素,并探讨个体饮酒损害发生的相关因素。方法采用《饮酒情况筛选表》和自制的《酒依赖综合征危险因素评定问卷》进行问卷调查并与正常饮酒组比较。结果《饮酒情况筛选表》两组比较存在显著性差异;《酒依赖综合征危险因素评定问卷》两组比较在文化程度、婚姻、职业、父母亲文化、生活规律性及家族史等项存在显著性差异。采用Logis—tic回归分析,饮酒量、饮酒频度是对饮酒结果影响最大的因素。结论社会文化因素、个人生活规律性、家族吏、饮酒量、饮酒频度是中山市酒依赖综合征成因的主要危险因素,只有将认知、行为和文化等因素有机地结合起来进行干预才能减少该病造成的损害。     

A three-axes approach of subtyping the alcohol dependence syndrome

Subtyping of alcoholics according to specific characteristics has a long tradition in alcoholism research with a number of different typologies that emerged in the literature. The goal of the present study was to test a multidimensional approach of subtyping with characteristics from different axes. Therefore, male inpatients meeting ICD-10 criteria for alcohol dependence were rated on three axes by assessing their degree of sensation seeking (personality axis), age of alcoholism onset (clinical axis) and level of dopamine activity (neurobiological axis). By using a configuration frequency analysis, we identified a subtype that was characterized by high sensation seeking early age of alcoholism onset and high dopamine activity. This subtype, which is in accordance with clinical experience and cannot be explained by antisocial personality disorder, embodied a significantly greater proportion of alcoholics than expected. The result emphasizes the usefulness of multidimensional approaches integrating personality, clinical and neurobiological characteristics.     

Old wine, new bottle. The alcohol dependence syndrome

The alcohol dependence syndrome is at once a fresh approach and a restatement of established clinical lore. It is, perhaps, old wine in a new bottle. Nonetheless, behavioral researchers in this field have needed some clinically sound criteria to differentiate between subjects to account for the variability of behavioral and psychophysiologic responses to alcohol in the laboratory. Cross-cultural researchers, and those interested in the genetics of alcoholism, have needed culture-free criteria for the diagnosis of alcoholism that might help them to separate aspects of the disorder that are genetically determined from those that are influenced by culture, immediate environment, and psychopathology. The beauty of the alcohol-dependence syndrome construct is its apparent specificity and its potential clinical usefulness. The difficulty with the concept is that no questionnaire has proven entirely satisfactory in defining the severity of alcohol dependence nor have biologic variables been identified that can provide valid and reliable indicators of severity. Nonetheless, advances in biomedical research frequently await the development of a nomenclature that will permit replicable scientific investigation. The evolving definition of the alcohol dependence syndrome is consistent with this tradition.     

Genetics of alcohol dependence

Twin, family, and adoption studies have consistently shown that genetic factors play an important role in the pathogenesis of alcohol dependence. Numerous studies have aimed to identify genes that contribute to susceptibility to alcohol dependence. Whole-genome linkage studies have identified several chromosomal regions that are linked with alcohol dependence. Association studies have also identified genes associated with alcohol dependence. Alcohol-metabolizing enzymes, such as alcohol dehydrogenase-1B and aldehyde dehydrogenase-2, are the most well-established genes that have polymorphisms associated with the risk for alcohol dependence. Polymorphisms in gamma-aminobutyric acid receptor genes are also reported to be associated with alcohol dependence. The polymorphism of opioid receptor mu 1 gene is of interest because it alters the treatment effects of naltrexone. Several genes related to neural transmission have been reported to be associated with alcohol dependence, but results are inconsistent among studies. One reason for these inconsistent results is the great heterogeneity of alcohol dependence. Classifying alcohol dependence into homogeneous phenotypes is a good strategy to solve this problem. Recently, several genome-wide association studies have been reported. Genome-wide association studies enable hypothesis-free genome mapping of vulnerability-contributing genes and are expected to add data to identify genes associated with the susceptibility to alcohol dependence. Knowledge of the genetic basis of alcohol dependence is growing and leads to a better understanding of the biological mechanisms of addiction, which can help with strategies to prevent and treat this disease.     

Family history and diagnosis of alcohol dependence in cocaine dependence

Genetic research in alcoholism has made major advances in recent decades. Twin, adoption, high-risk, and familial studies have demonstrated an inheritance factor in alcoholism. No studies have demonstrated a genetic or familial disposition to cocaine and marijuana dependence. Two hundred sixty-three inpatients were given a structured psychiatric interview retrospectively (150) and prospectively (113) to obtain a DSM-III-R diagnosis of substance dependence disorders in the probands and of alcohol dependence in family members. Our study reveals a large number of probands with cocaine dependence with a positive family history for alcohol dependence. Approximately 50% of probands with cocaine dependence had at least a first or second degree relative with a diagnosis of alcohol dependence when studied by the family history and study methods. As many as 89% of probands who met DSM-III-R criteria for cocaine dependence qualified for other substance dependence diagnoses. Our study finds a high prevalence of alcohol (68% and 89%) and cannabis dependence (53% and 46%) in patients with cocaine dependence. Furthermore, the age of onset of alcohol and other drug dependence is early for those with cocaine dependence and precedes the onset of cocaine dependence. The diagnoses of other alcohol and drug dependence in cocaine dependence and in family members of probands with cocaine dependence have important implications for etiology, prognosis, and treatment.     

The genetics of alcohol dependence

Alcohol dependence is a common, complex disorder, which affects millions of people worldwide and causes considerable burden in terms of interpersonal and societal costs. Family, twin, and adoption studies have convincingly demonstrated that genes play an important role in the development of alcohol dependence, with heritability estimates in the range of 50% to 60% for both men and women. A number of studies are under way to identify specific genes involved in the predisposition toward alcohol dependence, and there is reason to be enthusiastic about recent progress. Several associated susceptibility genes are reviewed here, including genes involved in alcohol metabolism, as well as genes involved in GABAergic, endogenous opioid, dopaminergic, cholinergic, and serotonergic transmission. The next challenge will be to further characterize the risk associated with these susceptibility genes, examining how they may be related to comorbid disorders, developmental trajectories of risk, and potential moderation by environmental factors.     

The treatment of alcohol dependence

PURPOSE OF REVIEW: The present review summarizes current research on the management of alcohol dependence, including pharmacotherapy, psychosocial interventions and treatment of alcohol dependence with comorbid psychiatric disorders. RECENT FINDINGS: Among recent studies, naltrexone has demonstrated the most consistent effect in reducing alcohol consumption in the context of behavioral therapy. In contrast to most previous studies, acamprosate did not show significant benefits on treatment outcomes relative to placebo. The combined use of naltrexone and acamprosate appeared to be safe and well tolerated but there was no additional therapeutic benefit. With the exception of topiramate, there are currently no new, effective medications for alcohol dependence. Of the psychosocial interventions, such as social behavior and network therapy, cognitive behavioral therapy, and motivational enhancement therapy, no one appears to be superior to another. Psychiatric comorbidity is common in alcohol-dependent patients; however, there are too few studies to effectively guide treatment practice. SUMMARY: Progress has been made with pharmacotherapy and psychosocial interventions for alcohol-dependent individuals. More research is needed, however, in developing newer medications and psychosocial interventions in alcohol-dependent populations and in those with comorbid psychiatric conditions, and to improve the strategies to engage patients in continuing care.     

Role of GABAB receptor in alcohol dependence: Reducing effect of baclofen on alcohol intake and alcohol motivational properties in rats and amelioration of alcohol withdrawal syndrome and alcohol craving in human alcoholics

The present paper describes the results of recent preclinical and clinical studies conducted in this laboratory in order to characterize the anti-alcohol properties of the GABA(B) receptor agonist, baclofen. At a preclinical level, the repeated administration of non-sedative doses of baclofen dose-dependently suppressed the acquisition and maintenance of alcohol drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats tested under the homecage, 2-bottle "alcohol vs water" choice regimen. Acute injection of baclofen completely blocked the temporary increase in voluntary alcohol intake occurring after a period of alcohol abstinence (the so-called alcohol deprivation effect, which models alcohol relapses in human alcoholics). Acute treatment with baclofen also dose-dependently suppressed extinction responding for alcohol (an index of motivation to consume alcohol) in sP rats trained to lever-press for oral alcohol self-administration. Taken together, these results suggest the involvement of the GABA(B) receptor in the neural substrate mediating alcohol intake and alcohol motivational properties in an animal model of excessive alcohol consumption. Further, acutely administered baclofen dose-dependently reduced the severity of alcohol withdrawal signs in Wistar rats made physically dependent upon alcohol. Preliminary clinical surveys suggest that the anti-alcohol properties of baclofen observed in rats may generalize to human alcoholics. Indeed, a double-blind survey demonstrated that repeated daily treatment with baclofen was associated, when compared to placebo, with a higher percentage of subjects totally abstinent from alcohol and a higher number of days of total abstinence. Treatment with baclofen also suppressed the number of daily drinks and decreased the obsessive and compulsive components of alcohol craving. Finally, a single non-sedative dose of baclofen resulted in the rapid disappearance of alcohol withdrawal symptomatology, including delirium tremens, in alcohol-dependent patients. In both clinical studies, baclofen was well tolerated with minimal side effects. These results suggest that baclofen may represent a potentially effective medication in the treatment of alcohol-dependent patients.     

The role of genetics in alcohol dependence

In this article we examined the heritability of alcohol dependence. A review of family, twin and adoption studies, allowed us to support the thesis of an important genetic component in this dependence. The transmission of this heritability occurs through a biological vulnerability associated to environmental factors, in a model called epigenetic. We also discussed the relationship between biological vulnerability and high-risk phenotypes for alcohol dependence. In the end, we briefly comment on the molecular genetic studies associated with this disorder.     

小胶质细胞在酒精依赖中的研究进展

近年来,神经炎症在成瘾行为中的细胞和分子机制逐渐凸显,酒精滥用直接或间接与神 经免疫系统相互作用,产生中枢免疫信号,改变神经免疫基因表达和信号转导,进而导致成瘾。小胶质 细胞是中枢神经系统（CNS）中神经免疫应答和炎症的主要调节剂,现回顾有关长期酒精暴露与小胶质 细胞激活的研究,突出小胶质细胞在CNS 酒精反应中起到的关键监管作用,对于开发更好的治疗酒精 依赖的方案至关重要。     

Preadolescent alcohol abuse and dependence

The authors document 10 cases of children who met the criteria for a DSM-III axis I diagnosis of alcohol abuse or dependence by the age of 13. They present one case report to demonstrate the family history of affective disorder, especially bipolar disorder, and alcoholism that characterized these 10 patients. Most of the children with bipolar disorder responded well to psychotropics. The authors suggest that there may be a relationship between early-onset alcohol abuse and the development of major affective disorders in adolescence.     

Medical comorbidity and alcohol dependence

Alcohol dependence (AD) and, more generally, alcohol use disorders (AUDs) predispose individuals to adverse consequences that extend beyond the expected damage from alcohol-direct toxicity. Research has shown that the relationship of alcohol use to health outcomes is complex, as is the etiology of AD, and that the individual and social costs of alcohol-related problems are increasing. We review advances in alcohol science that explore the role of alcohol consumption and patterns of drinking in a range of medically comorbid conditions. Although new knowledge can assist in the development of appropriate medical management strategies, AUDs account for an important percentage of the global burden of disease and require approaches that are not uniquely focused on the identification and treatment of AD.