Alcohol and alcoholism (Oxford, Oxfordshire). Supplement最新文献

In recent years, the term 'chronic alcoholism' has had a meaning that is more descriptive than diagnostic. Several subtypes of alcoholism have been established and are now a necessary tool for studying therapy outcome. Alcohol-dependent patients can be subtyped based on clearly assigned dimensions (e.g. biological, sociological and psychological disturbances). Craving and the underlying disturbance must be treated. The number of pharmacological agents that may reduce alcohol intake has increased recently. We conducted a prospective long-term study based on four subtypes of alcohol-dependent patients to assess the efficacy of acamprosate. Our findings demonstrate that these patient subtypes are relevant to outcome in trials of pharmacological agents. We strongly recommend subtyping alcohol-dependent subjects in future trials, because the usefulness of effective drugs could be overlooked when they are tested in a heterogeneous population.

Standard treatment for alcohol abuse may include pharmacotherapy to alleviate withdrawal symptoms followed by psychotherapy in inpatient and/or outpatient settings. Treatment goals include abstinence and reduced alcohol consumption. Standard treatment for alcoholism has a high rate of success in Germany; however, for various reasons, only a small percentage of alcoholic patients are admitted to alcoholism treatment programmes. A new drug, acamprosate, could benefit many more alcoholic patients. Several studies indicate that acamprosate reduces the craving for alcohol and enhances abstinence. Acamprosate's effect is dose-dependent and it has a few minor side-effects. In addition, the availability of acamprosate may enable family practitioners to play an increasingly important role in the treatment of alcoholic patients, thus allowing more patients to receive treatment.

Results from studies of pharmacotherapies for primary alcoholism are reviewed, including selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (e.g. fluoxetine), opiate antagonists (e.g. naltrexone) and dopamine agonists (e.g. bromocriptine). Because there is considerable co-morbidity between alcohol dependence, anxiety, and affective disorders, results from studies of medications used to treat these psychiatric disorders are also reviewed, including the 5-HT agonist buspirone and the noradrenergic agent desipramine. The neurobehavioural model of alcohol dependence implies that combinations of medications may lead to more effective treatment; thus, identifying subtypes of alcoholic patients will be important in determining which therapies or combinations of therapy will be most effective in treating alcohol dependence. For example, in an ongoing study, we are attempting to subtype an alcoholic population for treatment selection by measuring endogenous opioid activity. Because endogenous opioids are involved in analgesia, we exposed male and female subjects with alcoholism [some of whom had post-traumatic stress disorder (PTSD)] to cold-induced pain and measured their response before and after administration of naloxone or placebo. The naloxone injection reduced pain response. In addition, women who have PTSD are much more sensitive to stress, which may be related to levels of brain opioid activity.

It has been known for many years that alcohol can alter both endocrine and immune function in the adult organism. Acting directly on the endocrine glands themselves, and/or at the level of the pituitary or brain, alcohol has been shown to alter secretory activity of most of the endocrine systems that have been studied. Similarly, the association between alcoholism and infections and between alcoholism and certain forms of cancer has long been recognized by clinicians. While for many years there was uncertainty about the extent to which the alterations in immune function were a direct result of alcohol consumption or a consequence of the medical complications of alcoholism, recent research on the effects of alcohol on cell-mediated and humoral immunity have demonstrated that alcohol consumption may indeed be associated with immune impairment, independent of nutritional deficiencies, liver disease, or general poor health that may occur. However, it is only recently, as our knowledge of the teratogenic effects of alcohol on the developing organism has expanded, that the effects of fetal alcohol exposure on endocrine and immune function of the offspring have begun to receive considerable attention. This review will discuss recent clinical and experimental literature on the effects of fetal alcohol exposure on offspring endocrine and immune development.

The interrelationship between alcohol dependence and schizophrenia is very complex. On the one hand, chronic alcoholism alone can result in a chronic, schizophrenia-like psychosis (alcoholic hallucinosis) which cannot be distinguished from schizophrenia on the basis of psychopathological or clinical symptoms. On the other hand, recent clinical and epidemiological studies point at a significantly increased prevalence for substance abuse and dependence in schizophrenia, especially of alcohol. Pathophysiological mechanisms possibly involved in the onset of hallucinations in alcoholics and recent studies on the comorbidity of alcohol dependence and schizophrenia are discussed.

Current understanding of the pathology of chronic pancreatitis secondary to chronic alcoholism is exclusively based on surgical biopsies or autopsy studies of the pancreatic gland from far-advanced stages of the disease. Biopsy of the pancreas is dangerous, and good experimental models for alcoholic pancreatitis are not available to evaluate the chronology of events in the pancreas. A classification system was proposed many years ago with various hypotheses on the pathogenesis of chronic pancreatitis. These hypotheses will be examined in relation to the empirical evidence.

The expression of the proteins (C-FOS and C-JUN) encoded by the immediate early genes c-fos and c-jun was investigated in the brains of rats undergoing ethanol withdrawal. Both proteins were induced in the cerebral cortex, the piriform cortex, the olfactory bulb, the inferior colliculus, the granular cell layer of the cerebellum and in the brain stem, but only C-JUN was induced in the hippocampus of animals undergoing withdrawal without overt seizures. C-FOS was detected in the hippocampus only in animals with overt seizures. Maximal C-FOS expression occurred 15 hr after withdrawal while C-JUN was maximal at 24 hr. Gel-shift assays indicated the formation of AP-1 binding factors in nuclear extracts of the cerebral cortex, hippocampus and cerebellum 15 and 17 hr after withdrawal. These data reveal a complex pattern of immediate early gene expression during ethanol withdrawal, which may be associated with changes in neuronal plasticity underlying phenomena such as withdrawal kindling.

This paper reviews some recent developments concerning the role of genetic factors in alcoholism. The accumulated evidence suggests that genetic factors do play an important role in determining the alcoholism risk. However, the search for the specific genetic influences operating in this disorder is complicated by the existence of genetic heterogeneity, the absence of simple Mendelian models, and the impact of environmental factors in producing the final level of risk. After reviewing the complexities existing in this area, the author describes the efforts of his own research group to investigate the biological and genetically controlled risk factors at work in alcoholism. Through an ongoing longitudinal evaluation of sons of alcoholics and controls, the author's group has identified the potentially genetically influenced attribute of relatively low levels of sensitivity to an alcohol challenge as an important risk factor for the subsequent development of alcoholism.

Chronic alcoholics without complicating disease showed greater densities of GABA agonist sites (labelled with the selective ligand [3H]muscimol) on the GABAA receptor in the superior frontal gyrus, in comparison with both precentral gyrus in the same cases, and with superior frontal gyrus in matched controls. Whereas cases with concomitant Wernicke encephalopathy may also have had greater numbers of superior frontal [3H]muscimol binding sites than controls, alcoholics with cirrhosis of the liver showed more muted differences. Since the GABAA receptor is a multimeric complex which also possesses binding sites for "central-type" benzodiazepine ligands, it would be expected that data obtained with these compounds should mimic that obtained with [3H]muscimol. This was not so. [3H]Flunitrazepam binding sites showed little variation between case groups, although they showed clear regional differences. [3H]Diazepam sites followed those for [3H]muscimol in uncomplicated alcoholics and alcoholics with cirrhosis of the liver, but were at lower density in superior frontal gyrus in Wernicke cases. Differential expression of GABAA receptor subunit isoform genes may give rise to these disparities.