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PubMed2006

[Drugs, a current problem. Alcohol dependency].

Alcohol is a socially accepted drug which is commercialized in multiple products including wine, cognac, gin, beer, anisette, vermouth, rum, etc. and which can be consumed in small quantities without producing harmful effects on one's health; nonetheless, women are more susceptible to alcohol's damages and an abusive consumption of alcohol creates dependence and chronic diseases. Ten percent of those people who consume alcohol develop dependency and comprise the leading group of drug addicts in many countries.

Alcoholism↗
PubMed2000

Opioid antagonists for alcohol dependence.

BACKGROUND: The benefits of selective serotonin reuptake inhibitors, disulfiram, and lithium have not been clear for people with alcohol dependence. While the results of many studies have suggested that opioid agonists increase alcohol consumption, others have shown that mu-opioid antagonists and partial agonists reduce alcohol consumption. The results from animal studies suggest that these agents may prevent the reinforcing effects of alcohol consumption. Based on the results of those animal studies, some opioid antagonists, such as, naltrexone, nalmefene, have been studied for their benefits in treating alcohol dependence. OBJECTIVES: To determine the effectiveness of opioid antagonists in attenuating or preventing the recommencement of alcohol consumption in patients with alcohol dependence in comparison to placebo, other medications and psychosocial treatments. In addition, discontinuation rate, death, patient satisfaction, functioning, health-related quality of life and economic outcomes were also evaluated. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE, CINAHL and Cochrane Controlled Trials Register were undertaken. Du Pont Pharmaceutical and Ivax Corporation were contacted for information regarding unpublished trials. The reference lists of the obtained papers were also examined. SELECTION CRITERIA: All relevant randomised controlled trials (RCTs) and clinical control trials (CCTs) were included. Participants were people with alcohol dependence, diagnosed by any set of criteria, except alcohol dependence who were currently abstinent. Naltrexone (NTX), nalmefene (NMF) and other opioid antagonists with/without other biological or psychosocial treatments were examined. A variety of clinical outcomes, for example alcohol consumption, duration of abstinence, were considered. DATA COLLECTION AND ANALYSIS: Two reviewers evaluated and extracted the data independently. The dichotomous data were extracted on an intention-to-treat basis in which the dropouts were assigned as participants with the worst outcomes. The Peto Odds Ratio with the 95% confidence interval was used to assess the dichotomous data. Weighted Mean Difference with 95% confidence interval was used to assess the continuous data. MAIN RESULTS: The short-term (< 3 months) benefits of NTX were shown in three respects, which were number of patients who return to drinking, percentage or number of drinking days and the number of standard drinks of alcohol. However, 6 months after the completion of 12-week NTX treatment, the benefit of decreasing the number of patients who return to drinking were lost. The short-term evidence from a small sample-size study suggested that disulfiram was more effective than NTX in the respects of number of abstinent days, percentage or number of drinking days and number of standard drinks of alcohol. The evidence from another small sample-size study also suggested that NTX plus an aversive agent was superior to an aversive agent alone in the respect of number of patients who return to drinking in short-, medium-, and long-term treatment. From two short-term and small sample-size studies, the benefit of NMF was shown only in the respect of number of patients who return to drinking. REVIEWER'S CONCLUSIONS: Due to the limited evidence, the following conclusions should be viewed as tentative. NTX has some benefits for patients with alcohol dependence, but patients' adherence to treatment should be of concern. Psychosocial treatments should be concurrently given with NTX. The optimal duration of NTX treatment is not yet known. Although NTX is available for treating alcohol dependence in many countries, in the respect of cost-effectiveness, disulfiram should still remain as an alternative. Due to the dearth of evidence, at present, the combination of NTX and disulfiram or NMF alone should not be used in everyday clinical practice. Randomised, double-blind, placebo-controlled trials of NTX treatment in patients with alcohol dependence

Alcoholism↗
PubMed2001

Long-term follow-up of patients diagnosed with alcohol dependence or alcohol abuse who were evaluated for liver transplantation.

The selection of patients with cirrhosis and the diagnosis of alcohol dependence or abuse who have a long-term high probability of abstinence after orthotopic liver transplantation (OLT) may enhance patient survival and outcomes. The aim of this study is to identify factors that would predict which patients would consume alcohol after OLT. Sixty-one patients with a history of alcohol dependence or abuse underwent OLT from June 1989 to June 1994 and were followed up monthly for a median of 6.9 years after OLT (range, 2.5 to 9.3 years). Survival analysis techniques (Cox proportional hazard model) were used to identify patients at high risk for recidivism. Recidivism occurred in 12 of 61 patients (20%) after OLT during follow-up. Noncompliance, with a relative hazard of 20.9 (95% confidence interval [CI], 5.6 to 78.3; P <.001), and personality disorder, with a relative hazard of 6.0 (95% CI, 1.9 to 18.7; P =.002), independently predicted recidivism among patients who underwent OLT. These data indicate that specific behaviors and psychiatric diagnoses can be used to select patients at high risk for drinking alcohol before and after OLT.

Adult↗
PubMed2004

Polymorphisms in the NMDA subunit 2B are not associated with alcohol dependence and alcohol withdrawal-induced seizures and delirium tremens.

OBJECTIVE: Ethanol-inhibited glutamatergic neurotransmission has been shown to mediate pathophysiological mechanisms in the development of alcoholism, including withdrawal symptoms. NMDA-receptor 2B (NR2B) is a subunit that confers a high sensitivity to ethanol-induced inhibition. Previously we had reported a lack of association between the single nucleotide polymorphism (SNP) rs1806201 in the NR2B gene (GRIN2B) and alcoholism. Shortly thereafter, an association between the polymorphism and early-onset alcoholism has been reported. One aim of the present study was to test whether the association between the GRIN2B polymorphism rs1806201 and early-onset alcoholism can be replicated in a larger sample. Moreover, we hypothesized that another genetic variation within GRIN2B (rs1806191) may have an effect in the etiology of alcoholism or withdrawal-related traits. METHODS: We extended our original study sample to a size of 377 patients and 464 healthy volunteers and performed a replication study, including the second GRIN2B SNP. Associations between allele, genotype and haplotype frequencies of the two polymorphisms and alcoholism as well as with patients' phenotypes were investigated. RESULTS: No associations were found between any of the two polymorphisms, tested individually or as haplotypes, and alcoholism, respectively withdrawal-related traits. CONCLUSION: Neither the analyzed SNPs nor any of their haplotypes likely modify susceptibility to alcohol dependence or withdrawal-related phenotypes.

Adult↗
PubMed2005

Cortical gamma-aminobutyric acid type A-benzodiazepine receptors in recovery from alcohol dependence: relationship to features of alcohol dependence and cigarette smoking.

CONTEXT: Adaptations in gamma-aminobutyric acid type A (GABA(A))-benzodiazepine receptors contribute to the neurobiology of human alcohol dependence and withdrawal. OBJECTIVE: To study GABA(A)-benzodiazepine receptor adaptations in subjects with alcohol dependence over the first month of sobriety. DESIGN: Inpatients who were not receiving medication, were either smokers or nonsmokers, and had alcohol dependence completed 2 iodine I 123-labeled iomazenil single-photon emission computed tomographic scans: 1 scan at a mean +/- SD of 4.9 +/- 2.5 days of sobriety (n = 23) and 1 scan at a mean +/- SD of 29.8 +/- 7.6 days of sobriety (n = 20). Participants in a matched group of healthy subjects (n = 15) completed 1 single-photon emission computed tomographic scan. PARTICIPANTS: Men with alcohol dependence (n = 27) and a matched healthy comparison group (n = 15). MAIN OUTCOME MEASURES: (123)I-iomazenil single-photon emission computed tomographic images were converted to units of distribution volume (regional activity/free (123)I-iomazenil) and were analyzed using voxel-based statistical parametric mapping and regions of interest analyses. The relationships between (123)I-iomazenil distribution volume, clinical features of alcohol dependence, and smoking status were evaluated. RESULTS: (123)I-iomazenil uptake was elevated in several cortical regions, with a more prominent increase in nonsmokers with alcohol dependence as compared with smokers with alcohol dependence at 1 week of abstinence from alcohol. No significant differences were observed at 4 weeks of abstinence. At 1 week of abstinence, frontal (123)I-iomazenil uptake correlated with the severity of alcohol withdrawal and the number of days since the last alcoholic drink was consumed. No significant associations were observed for smokers with alcohol dependence. CONCLUSIONS: These data demonstrate time-dependent regulation of cortical GABA(A)-benzodiazepine receptors associated with the recovery from alcohol dependence. Higher GABA(A)-benzodiazepine receptor levels during acute withdrawal may reflect a compensation for reduced receptor function, which is thought to contribute to alcohol tolerance and withdrawal. The subsequent decline may reflect "normalization" of GABA(A) receptor function with sobriety. Smoking may attenuate GABA(A) receptor adaptations associated with alcohol dependence and may contribute to the comorbidity between alcoholism and smoking.

Adult↗
PubMed1993

Contemporary issues in the treatment of alcohol dependence.

Alcoholism treatment has certainly come of age since its inception with the founding of Alcoholics Anonymous in 1935. Although AA is a "fellowship" and is not considered "treatment" per se, the growth and proliferation of professional treatment programs has spawned a significant new sector in the health care industry, with a corresponding rise in health care cost. Because the social cost due to the destructiveness of alcoholism is enormous, however, treatment appears to be a cost beneficial investment for society, both in terms of dollars expended and in terms of the lessening of human misery. Inpatient and outpatient programs appear to be effective, but simplistic comparisons are to be avoided because their populations are frequently much different, with patients with poor prognosis indicators showing up more frequently in inpatient settings. Although outpatient treatment is undeniably cheaper initially, appreciable long-term savings may not be realized because of the greater tendency for recidivism in outpatient-treated groups. Taken as a whole, studies of treatment outcome and cost effectiveness support the view that contemporary alcoholism treatment should provide multiple levels of care, with appropriate matching of patients, depending on severity and various demographic factors. This matching may be difficult to realize in actual practice because of the wide variability among alcoholic patients. Although some patient-treatment matching criteria are now in use by insurance carriers and treatment providers, the long-term efficacy of these criteria have not been tested adequately. In the end, it may evolve that the best determinant of assignment to a particular treatment level or modality might best be done by a responsible clinician exercising good judgment based on experience and training. Appropriate legal and financial accountability for this decision should be based on standards of reasonableness, consistent with criteria used in the treatment of other medical and surgical conditions. The alcoholism clinician is performing a valuable service to humanity and to society. Social policies should support this effort by making available appropriate facilities and programs for treatment, and by promoting access through destigmatization and favorable payment and reimbursement systems.

Aftercare↗
PubMed2003

Nutritional intake of hazardous drinkers and dependent alcoholics in the UK.

There are no recent assessments of nutritional intake in alcohol misusers in the United Kingdom. The purpose of this study was to measure nutritional intake in alcoholics attending an Alcohol Misuse outpatient clinic in an inner city general hospital in the United Kingdom and relating this to various measures of alcohol dependence. All patients (n = 30; 27 male, 3 female) consumed at least 100 g ethanol per day (mean 162 g/day) for at least 5 years and completed questionnaires on socio-demographics, alcohol dependency and psychosocial problems and had assays of biochemical and haematological indices. The data were analysed first with respect to the entire patient population and then according to the degree of alcohol dependency (mild, moderate or severe). The results showed that with respect to the entire patient group, one-third were below normal body weights, but one-quarter was overweight. The total energy intake (kJ/day) including alcohol was apparently adequate with respect to recommended levels in most patients. On average, approx. 60% of energy intake came from alcohol. The whole patient population had a low intake of one or more macro- and micro-nutrient compared to the dietary reference requirements. All patients had intakes of vitamin E and folate below UK recommended standards, while 85 - 95% of patients had low intakes of selenium and Vitamin D. Between 50 and 85% of all patents had intakes below UK recommended standards in calcium and zinc and Vitamins A, B(1), B(2), B(6) and C. There were significant correlations between calorie intake (when alcohol was excluded) and vitamins B(1), B(2), B(6) and C, and Ca, Mg, Fe and Zn intake. There were no correlations between alcohol intake with any of the nutritional and anthropometric variables or between the three subgroups with respect to daily energy, micro- and macro-nutrient intakes. In conclusion, malnutrition was common in this patient group: all subjects had intakes below UK recommended standards in one or more micro- or macro-nutrient. However, there was no difference in the degree of malnutrition between the harmful drinkers (mild dependency) and heavily dependent subgroups.

Adult↗
PubMed2003

A new measure of the alcohol dependence syndrome: the severity scale of alcohol dependence.

The purpose was to develop a diagnostic instrument of the Alcohol Dependence Syndrome defined by Edwards and Gross (1976) since comparable scales show some limitations. The methods include three studies carried out in order to develop the SEverity Scale of Alcohol dependence (SESA; total n = 774 alcohol-dependent patients), and three further studies served for validation (total n = 603 alcohol dependents). The findings reveal that the SESA, a 33-item questionnaire including 7 subscales which cover the criteria of the Alcohol Dependence Syndrome, proved to be internally consistent. The subscales are correlated with respective information from internationally validated interview instruments for the diagnosis of alcohol dependence according to DSM and ICD (CIDI, SCAN): six subscales are correlated with six of eight CIDI items and with eight of nine SCAN items selected for the purpose of validation. In addition, there are positive correlations with the Munich Alcoholism Test, the Michigan Alcoholism Test as well as single items of the WHO Alcohol Use Disorders Identification Test. It is concluded from the results that the SESA shows good validity.

Adult↗
PubMed1994

A comparison of the Alcohol Dependence Scale and clinical diagnosis of alcohol dependence in male medical outpatients.

The Alcohol Dependence Scale (ADS) is a brief self-report instrument designed to assess the alcohol dependence syndrome. Although previous studies have reported its validity, it has only been studied in populations who were presenting for assessment or treatment of alcohol problems, and recent studies have shown lower mean scores than would be expected. To assess its utility in a primary medical setting, we retrospectively examined our experience in two groups of medical outpatients: an early intervention group and a group of medically ill alcoholics. We administered the ADS to 61 male veterans being referred to a special clinic for alcohol-related medical problems. Subjects were also assessed for alcohol dependence by experienced clinicians using a DSM-III-R checklist. ADS scores overall were much lower than would be expected, especially in the medically ill alcoholics. When subjects were dichotomized into dependent or nondependent, there was poor agreement between the two methods. The correlation between the scores was significant, however, and lowering the cut-point on the ADS from 13/14 to 2/3 improved agreement. Medically ill alcoholics who are not presenting for assessment or treatment of alcohol problems may either lack insight into their drinking habits or may be reluctant to disclose them. Although conclusions from this study are tentative until more formal studies are done, it may be most prudent to use other instruments, such as the Michigan Alcoholism Screening Test, in medical outpatients. If the ADS is used, lowering the cut-score to 2/3 may reduce false negatives. Further research on the use of the ADS in different settings and with different populations is clearly needed.

Adult↗
PubMed2004

A family study of alcohol dependence: coaggregation of multiple disorders in relatives of alcohol-dependent probands.

BACKGROUND: Alcohol dependence tends to aggregate within families. We analyzed data from the family collection of the Collaborative Study on the Genetics of Alcoholism to quantify familial aggregation using several different criterion sets. We also assessed the aggregation of other psychiatric disorders in the same sample to identify areas of possible shared genetic vulnerability. DESIGN: Age-corrected lifetime morbid risk was estimated in adult first-degree relatives of affected probands and control subjects for selected disorders. Diagnostic data were gathered by semistructured interview (the Semi-Structured Assessment for the Genetics of Alcoholism), family history, and medical records. Rates of illness were corrected by validating interview and family history reports against senior clinicians' all sources best estimate diagnoses. Sex, ethnicity, comorbidity, cohort effects, and site of ascertainment were also taken into account. RESULTS: Including data from 8296 relatives of alcoholic probands and 1654 controls, we report lifetime risk rates of 28.8% and 14.4% for DSM-IV alcohol dependence in relatives of probands and controls, respectively; respective rates were 37.0% and 20.5% for the less stringent DSM-III-R alcohol dependence, 20.9% and 9.7% for any DSM-III-R diagnosis of nonalcohol nonnicotine substance dependence, and 8.1% and 5.2% for antisocial personality disorder. Rates of specific substance dependence were markedly increased in relatives of alcohol-dependent probands for cocaine, marijuana, opiates, sedatives, stimulants, and tobacco. Aggregation was also seen for panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, and major depression. CONCLUSIONS: The risk of alcohol dependence in relatives of probands compared with controls is increased about 2-fold. The aggregation of antisocial personality disorder, drug dependence, anxiety disorders, and mood disorders suggests common mechanisms for these disorders and alcohol dependence within some families. These data suggest new phenotypes for molecular genetic studies and alternative strategies for studying the heterogeneity of alcohol dependence.

Adult↗
PubMed2006

CSF monoamine metabolites and lethality of suicide attempts in depressed patients with alcohol dependence.

BACKGROUND: Alcohol dependence (alcoholism) and major depressive disorder are frequently comorbid and are risk factors for suicidal behavior. Monoaminergic abnormalities have been implicated in the pathophysiology of depression, alcohol dependence, and suicidal behavior. Lower cerebrospinal fluid (CSF) 5-hydroxyindolacetic acid (5-HIAA) levels are associated with higher lethality of suicide attempts in major depression and predict a higher rate of future suicide. We sought to study the relationship of CSF monoamine metabolites to lethality of suicidal acts in depressed subjects with comorbid alcoholism. METHODS: We compared 16 high- and 16 low-lethality drug-free depressed suicide attempters with comorbid alcoholism. Subjects were free from any substance use disorder for at least two months. Demographic and clinical parameters, and CSF 5-HIAA, homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels were examined. RESULTS: The two groups did not differ with regard to the demographic characteristics. CSF 5-HIAA levels were lower in high-lethality attempters compared to low-lethality attempters. There were no group difference in CSF HVA or MHPG levels. CONCLUSION: Higher lethality of suicidal behavior in depressed patients with alcoholism is related to lower serotonergic activity.

Adult↗
PubMed1990

The relationship between alcohol dependence and alcohol-related problems in a clinical population.

The relationship between alcohol dependence and alcohol-related problems was studied in a group of 103 problem drinkers. Responses to a 46-item Alcohol Problems Questionnaire (APQ) were compared with the Severity of Alcohol Dependence Questionnaire (SADQ), alcohol consumption and demographic data. A strongly positive correlation was found between aggregate problems and dependence scores (r = 0.63; p = 0.001) which existed independently of the quantity of alcohol consumed. Analysis of questionnaire subscales revealed that certain problem domains were more closely related to particular aspects of dependence than others. A higher level of problems was found in subjects of younger age and lower socio-economic class. No significant sex differences were found. The implications of these findings are discussed.

Adult↗
PubMedDate not supplied

N-tert-butyl-alpha-phenylnitrone administration fails to modify alcohol dependence and alcohol induced hypervascularization.

Chronic alcoholization by ethyl-alcohol inhalation was used to study the properties of a spin-trapping agent on different alcohol manifestations in rat. The spin-trapping agent, i.e. N-tert-butyl-alpha-phenylnitrone (PBN), was given at the dose of 32 mg/kg twice a day during the whole alcoholization procedure. The blood alcohol level, the hypermotility which accompanied the ethanol withdrawal, the behavioral dependence as estimated by a free-choice program and the hypervascularization which is developed after a chronic pulmonary alcoholization were quantified. The rats treated with PBN differ from the control rats only by their higher blood alcohol level at the end of the chronic alcoholization while the other quantified alcohol-induced manifestations remained unchanged.

Alcoholism↗
PubMed2005

Follow-up study of anxiety disorder and alcohol dependence in comorbid alcoholism treatment patients.

BACKGROUND: Anxiety disorders are present in a high percentage of alcoholism treatment patients. We tested the prediction that having a comorbid anxiety disorder increases the prospective risk for relapse to drinking after alcoholism treatment. We also explored the prospective associations of specific anxiety syndromes (and depression) with drinking and anxiety outcomes. METHODS: We assessed the diagnostic status and daily drinking patterns of 82 individuals approximately one week after they entered alcoholism treatment (baseline) and again approximately 120 days later (follow-up) (n=53). RESULTS: Consistent with study predictions, those with a baseline anxiety disorder (approximately 55%) were significantly more likely than others to meet various definitions of drinking relapse over the course of the follow-up. Regression models showed that baseline social phobia was the single best predictor of a return to any drinking after treatment, whereas panic disorder was the single best predictor of a relapse to alcohol dependence after treatment. Having multiple anxiety disorders (versus any specific anxiety disorder) at the baseline was the strongest predictor of having at least one active ("persistent") anxiety disorder at the follow-up. Cross-sectional analysis at the follow-up showed that anxiety disorder persisted in the absence of a relapse to alcohol dependence far more often than relapse to alcohol dependence occurred in the absence of a persistent anxiety disorder. CONCLUSIONS: Screening for comorbid anxiety disorder in alcoholism treatment patients is warranted and, where found, should be considered a marker of high relapse risk relative to that of noncomorbid patients. The capacity of specific anxiety treatment to mitigate relapse risk among comorbid patients remains an open question.

Adult↗
PubMed2006

Diagnosis of alcohol dependence in epidemiological surveys: an epidemic of youthful alcohol dependence or a case of measurement error?

AIMS: To review the literature on the prevalence of alcohol dependence according to age, presenting data suggesting that the increased prevalence of alcohol dependence among young adults may be inflated because of measurement error. DESIGN: Household surveys with random selection of respondents. SETTING: General population. PARTICIPANTS: Survey respondents 12 years of age and older. MEASUREMENTS: Alcohol dependence. FINDINGS: Data for male current drinkers show that 4.6% of adolescents (aged 12-17 years) meet criteria for past year dependence, and the rate increases to 8.5% in the 18-23 age group, decreasing thereafter. Symptom level prevalence estimates indicate that younger age groups report higher rates of tolerance and withdrawal symptoms than older age groups. CONCLUSION: Young adults may be reporting tolerance and withdrawal symptoms partly because the wording of structured interview schedules leads to confusion of binge drinking and its sequelae with physical symptoms of alcohol dependence. There is a need to examine whether young adults are confusing the sequelae of acute intoxication with alcohol withdrawal, and rapid initial tolerance with the classical tolerance reported by alcoholics. Epidemiologists and clinicians need to be cautious of the tendency of structured psychiatric interviews to classify young adults as being alcohol-dependent. It may be useful to characterize individuals who meet alcohol dependence criteria at a young age (e.g. prior to age 25 years) as manifesting a form of 'adolescent alcohol dependence', which may represent a less severe form of alcohol use disorder than that observed in adults.

Adolescent↗
PubMed2004

Increased P3 amplitudes induced by alcohol-related pictures in patients with alcohol dependence.

BACKGROUND: Alcohol craving, a key element in alcohol dependence, is recognized as being a kind of motivational or emotional state. It is meaningful in research and clinical practice involving alcohol dependence to explore ways of measuring alcohol craving. The aim of this study was to measure the P3 event-related potentials induced by alcohol-related pictures in patients with alcohol dependence; these potentials are considered to constitute a neuronal correlate of alcohol craving. METHODS: On the basis of our previous study, six alcohol-related pictures and six neutral pictures were chosen as the visual stimuli. Each set of stimuli consisted of alcohol-related or neutral pictures as the target stimuli and same-sized checkerboards as the nontarget stimuli. The stimuli were presented by using the oddball paradigm for 300 msec, with an interstimulus interval of 1000 msec, in 12 controls and 16 abstinent patients with alcohol dependence. Each electroencephalography session consisted of three blocks: a practice block, a neutral block, and an alcohol-craving block. RESULTS: The amplitudes of P3 elicited by the alcohol-related pictures were significantly larger than those elicited by the neutral pictures in the patients with alcohol dependence, whereas there was no significant difference according to the stimuli in the P3 amplitudes of controls. Repeated-measures ANOVA on the amplitudes of P3 revealed that there was a significant interaction effect of block by subject group. CONCLUSIONS: These results suggest that event-related potentials can be used as a neuronal correlate of alcohol craving in alcohol-dependent patients. Future investigations will be needed to assess the frequency of relapse in the patients included in this study, to elucidate the meaning of the observed results with regard to the therapeutic outcomes.

Adult↗
PubMed2006

Association between two mu-opioid receptor gene (OPRM1) haplotype blocks and drug or alcohol dependence.

We examined 13 single nucleotide polymorphisms (SNPs) spanning the coding region of the mu-opioid receptor gene (OPRM1), among 382 European Americans (EAs) affected with substance dependence [alcohol dependence (AD) and/or drug dependence (DD)] and 338 EA healthy controls. These SNPs delineated two haplotype blocks. Genotype distributions for all SNPs were in Hardy-Weinberg equilibrium (HWE) in controls, but in cases, four SNPs in Block I and three SNPs in Block II showed deviation from HWE. Significant differences were found between cases and controls in allele and/or genotype frequencies for six SNPs in Block I and two SNPs in Block II. Association of SNP4 in Block I with DD (allele: P=0.004), SNP5 in Block I with AD and DD (allele: P< or =0.005 for both) and two SNPs in Block II with AD (SNP11 genotype: P=0.002; SNP12 genotype: P=0.001) were significant after correction for multiple testing. Frequency distributions of haplotypes (constructed by five tag SNPs) differed significantly for cases and controls (P<0.001 for both AD and DD). Logistic regression analyses confirmed the association between OPRM1 variants and substance dependence, when sex and age of subjects and alleles, genotypes, haplotypes or diplotypes of five tag SNPs were considered. Population structure analyses excluded population stratification artifact. Additional supporting evidence for association between OPRM1 and AD was obtained in a smaller Russian sample (247 cases and 100 controls). These findings suggest that OPRM1 intronic variants play a role in susceptibility to AD and DD in populations of European ancestry.

Adult↗