酒依赖的遗传学研究进展

酒依赖是一种慢性、复发性并受遗传因素影响的复杂疾病，也是重大的公共卫生问题。根据WHO的统计，全球估计有20亿饮酒者，13亿吸烟者，1．85亿非法物质使用者［1］。因而酒精是全球使用最为广泛的成瘾性物质。目前已有大量的动物实验和人类研究的结果表明，遗传学影响在物质滥用和依赖形成过程中起重要作用［2］。     

酒依赖攻击行为的分子遗传学研究进展

<正>近年来,中国酒产量大幅度增长,酒的消费量也不断攀升[1-2];在饮酒人群中,相当一部分人形成了酒依赖。酒依赖引起的社会问题,包括公共卫生问题、公共安全问题、家庭冲突问题和个人健康问题等也越来越严重。据估计,截止2005年我国酒依赖人     

酒依赖治疗药物研究进展

酒精是成瘾性或依赖性物质之一。酒精成瘾特征表现为对获得酒精的强迫性渴望,无节制地饮酒,并且发展为酒精耐受和酒依赖。     

酒依赖和烟草依赖共病的研究进展

酒精和烟草在大多数国家是不受管制的精神活性物质,与阿片类和可卡因等"硬"毒品不同,它们仅被限制使用(成年人才有资格得到它)而并未被社会禁止.因此,它们被不同国家、不同文化背景的人群广泛使用,酒依赖和烟草依赖也就成了最常见的物质使用障碍并导致了大量的医学和社会问题.许多研究显示,一种成瘾物质的使用会增加其他成瘾物质的使用风险,更有许多研究显示,吸烟和饮酒之间有阳性关联.本文就酒依赖和烟草依赖之间的关联特征和可能机制作一综述.     

药物依赖者复吸的遗传学研究进展

药物依赖是一种以强制性寻求和使用成瘾性药物为特征的慢性复发性脑病[1].大量研究证实,遗传因素在药物依赖中起着重要作用(遗传度在30%-60%之间),但其遗传方式不符合孟德尔单基因遗传规律[2],而是符合多因素疾病的模式[3].     

药物依赖的遗传学及神经生物学研究进展

1 概述遗传因素在药物依赖(包括酒依赖)的形成过程中起着重要的作用。对药物依赖的易感性个体差异相当明显。虽然每个人都在一定程度上接触到各种成瘾物质(如烟草、酒、镇痛药物、毒品等),但并非每个人都会尝试使用,即使使用,真正成瘾的人仍只是少数。流行病学研究早就证明,酒依赖具有很强的家族性。一般估计,酒依赖的危险因素中至少有40%～60%为遗传因素决定[1～3]。而另一些研究同样提示,阿片类依赖及可卡因依赖也同样具有很强的遗传基础[1,4,5]。到目前为止,人们就药物依赖与遗传的关系已经进行了诸多探索,其中包括传统的家系研究、双生…     

尼古丁依赖与酒依赖共病机制的研究进展

尼古丁依赖和酒依赖是导致发病及死亡的两大主要因素[1],并且有较高的共患率[2].虽然尼古丁和酒精较少有相似的药理学特性.例如,尼古丁有专门的受体并且可以提高警觉、促进肌肉收缩;而酒精可以作用于多种类型的受体、降低警戒以及使肌肉松弛.但是,尼古丁和酒精都可以产生耐受和依赖,有很多研究显示一种成瘾性物质的使用会增加其他成瘾性物质的使用风险;更有许多研究显示,吸烟和饮酒之间存在一些关联.本文主要阐述酒依赖和尼古丁依赖共病的可能机制.     

停止信号任务在酒依赖中的研究进展

<正>目前,频繁的使用酒精或成瘾药物所导致的负面效果已得到全球的广泛关注和重视~([1])。在2012年,全球约有330万人因使用酒精而导致死亡,占全球死亡人数的5.9%。过度使用酒精对个人、家庭及社会产生大量的健康和经济负担,因酒精使用而     

阿坎酸在酒依赖治疗中的研究进展

近年来,酒依赖对个人和社会的影响越来越大,业已成为一个严重的公共卫生问题.2001年美国药物滥用的家庭调查显示,在调查前12个月内,年龄在12 a或以上的人群中有超过1/10的人有酒精使用史.美国卫生及公共服务部2000年调查显示,美国每年用于酒精滥用的医疗费用超过260亿美元[1].Walker等[2]发现,酒依赖及其并发症与其他非物质依赖疾病相比,住院率更高、住院时间更长.     

Molecular genetics of alcohol dependence]

Predisposition to alcohol dependence is affected by multiple environmental and genetic factors in complicated way. Family and twin studies estimated about 60% of hereditary rate for alcoholism. Many lines of evidence by divergent methods, e.g. gene-manipulated animals, linkage of human genome and genetic association studies, are accumulating for molecular genetic components involved in alcoholism. These studies have shown that genetic polymorphisms of the genes encoding alcohol metabolism enzymes and neurotransmitter signaling molecules in dopamine, GABA, opioid and serotonin systems, were substantially involved in individual variation of susceptibility to alcohol dependence. Recent whole-genome association examination using 500K gene-chip revealed that a set of genes of adhesion and cytoarchitecture molecules were also involved in the disorder. These unexpected new findings by gene-chip technology, which need to be confirmed by case-control association one by one, must bring about breakthrough in investigation of neural mechanisms of alcohol dependence and innovative therapy.     

The genetics of alcohol dependence: Advancing towards systems-based approaches

BACKGROUND: Personalized treatment for psychopathologies, in particular alcoholism, is highly dependent upon our ability to identify patterns of genetic and environmental effects that influence a person's risk. Unfortunately, array-based whole genome investigations into heritable factors that explain why one person becomes dependent upon alcohol and another does not, have indicated that alcohol's genetic architecture is highly complex. That said, uncovering and interpreting the missing heritability in alcohol genetics research has become all the more important, especially since the problem may extend to our inability to model the cumulative and combinatorial relationships between common and rare genetic variants. As numerous studies begin to illustrate the dependency of alcohol pharmacotherapies on an individual's genotype, the field is further challenged to identify new ways to transcend agnostic genomewide association approaches. We discuss insights from genetic studies of alcohol related diseases, as well as issues surrounding alcohol's genetic complexity and etiological heterogeneity. Finally, we describe the need for innovative systems-based approaches (Systems Genetics) that can provide additional statistical power that can enhance future gene-finding strategies and help to identify heretofore-unrealized mechanisms that may provide new targets for prevention/treatments efforts. Emerging evidence from early studies suggest that Systems Genetics has the potential to organize our neurological, pharmacological, and genetic understanding of alcohol dependence into a biologically plausible framework that represents how perturbations across evolutionarily robust biological systems determine susceptibility to alcohol dependence.     

The structure of alcohol dependence in the community

BACKGROUND: Although dependence on alcohol appears to be a reliable unitary construct, abuse has not found a similar level of support as a separate construct. This paper describes a confirmatory factor analysis of the DSM-IV alcohol abuse and dependence criteria in a general population sample. METHODS: Data from alcohol drinkers (n = 7746) were obtained from a cross-sectional study of a large, representative sample of the Australian general population. One- and two-factor solutions for the DSM-IV criteria for abuse and dependence (assessed by CIDI-Auto) were compared using confirmatory factor analysis. RESULTS: Approximately 74% of Australians had used alcohol 12 or more times in the past year and 19% met at least one DSM-IV alcohol abuse or dependence criterion. Overall 6% met criteria for an alcohol use disorder (1.9% abuse, 4.1% dependence). More men than women met criteria for an alcohol use disorder and the prevalence of alcohol use disorders decreased with increasing age. Both one- and two-factor solutions from the confirmatory factor analyses provided an adequate fit to the data for the overall sample. The correlation between the abuse and dependence factors in the two-factor model was extremely high (0.95). CONCLUSION: Alcohol abuse and dependence criteria were most parsimoniously described by a single continuous construct incorporating all eleven abuse and dependence criteria.     

The genetics of human alcohol metabolism

1. The custom of drinking alcoholic beverages is a human behavior with serious social and medical consequences for a surprisingly large fraction of drinkers. 2. This review describes recent advances in our understanding of the genetic loci that control enzyme systems involved in the metabolism of alcohol. 3. These advances make possible new experimental programs that may lead to simple diagnostic tests for patients at risk of developing alcohol abuse behaviour.     

The position of psychiatry in alcohol dependence

It is important to discriminate psychiatric syndromes from transient psychiatric symptoms in alcohol dependent persons in order to reduce their morbidity. This can be difficult because of ambiguous criteria used for assessment. Accurate diagnosis is important because of the inherent dangers in a population at high risk of abusing psychotropic medication if incorrectly prescribed. The converse problem is present when alcohol use is symptomatic of an untreated psychiatric condition. A technique for more incisive clinical evaluation is outlined. Contemporary treatment units are often overspecialized; potential demarcation disputes must be guarded against in treatment of patients with double pathology and provision must be made for their management. Explanations for the relationship of the two conditions are advanced. Psychiatric disorder can co-exist with alcoholism either by chance, or because a family history of alcoholism increases the risk of its occurrence in the psychiatrically ill as in this sample. In addition, a skewed sample of the more severely ill person presents for treatment and creates an illusion of frequency.     

Acamprosate in the treatment of alcohol dependence

Acamprosate is indicated for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation in combination with psychosocial support. Acamprosate is a synthetic taurine analogue that seems to act centrally to restore the normal activity of glutamatergic neurotransmission altered by chronic alcohol exposure. Over the past 15 years, the safety and efficacy of acamprosate for alcohol dependence have been well established in multiple double-blind, placebo-controlled trials. Overall, acamprosate has been consistently associated with greater beneficial effects on measures of alcohol abstinence compared with placebo. Specifically, patients treated with acamprosate achieve greater rates of complete abstinence, longer times to first drink and/or increased duration of cumulative abstinence when compared with placebo. Acamprosate received approval by the US FDA for the treatment of alcohol dependence in July 2004 and is currently prescribed in 28 countries.     

Acamprosate in the treatment of alcohol dependence

Acamprosate is indicated for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation in combination with psychosocial support. Acamprosate is a synthetic taurine analogue that seems to act centrally to restore the normal activity of glutamatergic neurotransmission altered by chronic alcohol exposure. Over the past 15 years, the safety and efficacy of acamprosate for alcohol dependence have been well established in multiple double-blind, placebo-controlled trials. Overall, acamprosate has been consistently associated with greater beneficial effects on measures of alcohol abstinence compared with placebo. Specifically, patients treated with acamprosate achieve greater rates of complete abstinence, longer times to first drink and/or increased duration of cumulative abstinence when compared with placebo. Acamprosate received approval by the US FDA for the treatment of alcohol dependence in July 2004 and is currently prescribed in 28 countries.     

Recent advances in the genetics of phaeochromocytoma and functional paraganglioma

1. Recent clinical and fundamental research studies have revolutionized our understanding of the genetics of phaeochromocytoma (PH) and functional paraganglioma (FPGL). It was widely thought that only 10% of PH patients had familial disease and that the malignant phenotype of PH could not be diagnosed before occurrence of the first metastasis. 2. Human genetic studies have now shown that 25-30% of patients have hereditary PH due to a germline mutation in the SDHB, SDHD, VHL, RET or NF1 gene and that the identification of a germline SDHB mutation is associated with a high risk of malignancy and a poor prognosis in PH/PGL patients. 3. Fundamental research studies have shown that SDH genes are tumour suppressor genes and that succinate dehydrogenase inactivation induces abnormal stimulation of the hypoxia-angiogenesis pathway. 4. Finally various fundamental research studies, conducted through the Cortico and Medullo-surrenale: les Tumeurs Endocrines (COMETE) network in France and by other groups worldwide, have produced new recommendations for genetic counselling and testing and for the management of PH patients. They have also improved our understanding of the molecular mechanisms involved in PH tumorigenesis.