Paternal alcoholism predicts the occurrence but not the remission of alcoholic drinking: a 40-year follow-up.

OBJECTIVE: To test the effects of father's alcoholism on the development and remission from alcoholic drinking by age 40. METHOD: Subjects were selected from a Danish birth cohort that included 223 sons of alcoholic fathers (high risk; HR) and 106 matched controls (low risk; LR). Clinical examinations were performed at age 40 (n = 202) by a psychiatrist using structured interviews and DSM-III-R diagnostic criteria. RESULTS: HR subjects were significantly more likely than LR subjects to develop alcohol dependence (31% vs. 16%), but not alcohol abuse (17% vs. 15%). More subjects with alcohol abuse were in remission at age 40 than subjects with alcohol dependence. Risk did not predict remission from either alcohol abuse or alcohol dependence. CONCLUSION: Familial influences may play a stronger role in the development of alcoholism than in the remission or recovery from alcoholism.

Prediction of mortality at age 40 in Danish males at high and low risk for alcoholism.

OBJECTIVE: This prospective high-risk study examined the influence of father's alcoholism and other archival-generated measures on premature death. METHOD: Sons of alcoholic fathers (n = 223) and sons of non-alcoholic fathers (n = 106) have been studied from birth to age 40. Archival predictors of premature death included father's alcoholism, childhood developmental data, and diagnostic information obtained from the Psychiatric Register and alcoholism clinics. RESULTS: By age 40, 21 of the 329 subjects had died (6.4%), a rate that is more than two times greater than expected. Sons of alcoholic fathers were not more likely to die by age 40. Premature death was associated with physical immaturity at 1-year of age and psychiatric/alcoholism treatment. No significant interactions were found between risk and archival measures. CONCLUSION: Genetic vulnerability did not independently predict death at age 40. Death was associated with developmental immaturities and treatment for a psychiatric and/or substance abuse problem.

Methadone therapy for opioid dependence.

The 1999 Federal regulations extend the treatment options of methadone-maintained opioid-dependent patients from specialized clinics to office-based opioid therapy (OBOT). OBOT allows primary care physicians to coordinate methadone therapy in this group with ongoing medical care. This patient group tends to be poorly understood and underserved. Methadone maintenance therapy is the most widely known and well-researched treatment for opioid dependency. Goals of therapy are to prevent abstinence syndrome, reduce narcotic cravings and block the euphoric effects of illicit opioid use. In the first phase of methadone treatment, appropriately selected patients are tapered to adequate steady-state dosing. Once they are stabilized on a satisfactory dosage, it is often possible to address their other chronic medical and psychiatric conditions. The maintenance phase can be used as a long-term therapy until the patient demonstrates the qualities required for successful detoxification. Patients who abuse narcotics have an increased risk for human immunodeficiency virus infection, hepatitis, tuberculosis and other conditions contributing to increased morbidity and mortality. Short- or long-term pain management problems and surgical needs are also common concerns in opioid-dependent patients and are generally treatable in conjunction with methadone maintenance.

Breast-feeding and alcoholism: the Trotter hypothesis.

OBJECTIVE: The authors' goal was to determine whether early termination of breast-feeding contributes to later alcohol dependence, as proposed more than 200 years ago by the British physician Thomas Trotter. METHOD: In 1959-1961, a multiple-specialty group of physicians studied 9, 182 consecutive deliveries in a Danish hospital, obtaining data about prepartum and postpartum variables. The present study concentrates on perinatal variables obtained from 200 of the original babies who participated in a 30-year high-risk follow-up study of the antecedents of alcoholism. RESULTS: Of the 27 men who were diagnosed as alcohol dependent at age 30, 13 (48%) came from the group weaned from the breast before the age of 3 weeks; only 33 (19%) of the 173 non-alcohol-dependent subjects came from the early weaning group. When challenged by other perinatal variables in a multiple regression analysis, early weaning significantly contributed to the prediction of the severity of alcoholism at age 30. CONCLUSIONS: The data support the hypothesis that early weaning may be associated with a greater risk of alcohol dependence later in life.

Efficacy of outpatient intensive treatment for drug abuse.

OBJECTIVE: Outpatient intensive treatment for drug and alcohol abuse has become an alternative approach to management of substance abuse. We evaluated the efficacy of an outpatient intensive treatment program for crack cocaine; and the impact of psychiatric diagnosis on outcome variables. METHOD: Subjects participating in an outpatient intensive treatment program underwent descriptive testing at entry and at six-month followup. Outcome variables included Addiction Severity Index composite scores and retention in treatment. RESULTS: Subjects demonstrated significant improvement in ASI scales, over time, with an interaction effect of time and scale. Minimal interaction of psychiatric diagnosis and outcome was found. CONCLUSION: Outpatient intensive treatment demonstrated efficacy in reduction of ASI composite scores. Comparison with standard outpatient treatment and inpatient treatment is needed.

Sertraline response in adults with mental retardation and autistic disorder.

BACKGROUND: Self-injury and aggression are common reasons for urgent psychiatric referral of persons with mental retardation and autistic spectrum disorders. Although the treatment prescribed for these problems has traditionally been neuroleptic medication, serotonin reuptake inhibitors such as sertraline may result in significant clinical improvement as well as fewer side effects. METHOD: The authors administered sertraline in an open trial to nine consecutively admitted adult mentally retarded outpatients presenting with target behaviors of self-injury and/or aggression. Most patients (N = 6) were mildly or moderately mentally retarded by DSM-III-R criteria; five had comorbid autistic disorder. Prescribed dosages ranged from 25 mg to 150 mg daily, based on observed clinical responses. Clinical Global Impressions (CGI) ratings were made at baseline and again after sertraline treatment for at least 28 days. RESULTS: Sertraline led to improvement in CGI ratings of overall clinical severity in eight of nine subjects; mean +/- SD improvement in CGI ratings was 2.44 points +/- 1.67. Discontinuation of the treatment was necessary in only one patient, after 18 weeks of sertraline treatment, because of agitation and worsening of self-picking. Side effects were otherwise minimal. CONCLUSION: These findings from a clinical sample suggest that sertraline is promising in the treatment of self-injury and aggression. Double-blind controlled studies of sertraline and other serotonin reuptake inhibitors in the treatment of self-injury and aggression in patients with mental retardation and with autistic disorder are warranted.

The electroencephalogram after alcohol administration in high-risk men and the development of alcohol use disorders 10 years later.

BACKGROUND: In 1979 through 1980, electroencephalographic (EEG) responses to an alcohol challenge in 19 year-old sons of alcoholics as well as in sons of nonalcoholic control subjects were examined. The familial risk status of the subjects and greater EEG sensitivity to alcohol were hypothesized to predict the development of alcoholism 10 years later. METHODS: In 1990 through 1992, diagnostic interviews were completed to ascertain alcohol and other substance use disorders in these subjects and to update their family history. RESULTS: Updated family history of alcoholism predicted the development of substance dependence. Density of alcoholic relatives (the number of alcoholic relatives divided by the number of known relatives) was positively related to the severity of alcohol use disorders in the probands. Contrary to expectation, a greater EEG response at age 19 years was not related to the later development of alcohol dependence. Instead, the opposite was observed: a smaller EEG alpha frequency response to alcohol at age 19 years was related to the development of alcohol dependence and high quantity and frequency of alcohol consumption 10 years later. CONCLUSIONS: Lower EEG response to a small dose of alcohol may be associated with the later development of alcohol dependence. This result is based on a small number of subjects and should be interpreted with caution. Although this result is opposite to our 1980 hypothesis, it is consistent with much of the recent literature.

Personality and EEG beta in older adults with alcoholic relatives.

Research indicates that biological relatives of alcoholics are more likely to develop alcoholism than individuals without alcoholic relatives. Most research on these groups had focused on individuals who were relatively young (i.e., under 30 years old). In the present study, we evaluated middle-aged and elderly nonalcoholic men and women who did and did not have alcoholic biological relatives to assess factors that might be involved in a later, rather than an earlier, onset of alcoholism. Psychological characteristics were assessed using the Tridimensional Personality Questionnaire. Biological characteristics were assessed using quantitative measures of the spontaneous electroencephalogram. The psychological measures did not distinguish the groups, but biological measures did. The results indicated that nonalcoholic individuals with alcoholic relatives showed elevated beta as compared with sex- and age-matched control subjects. Factors that might have mediated these findings are discussed, as are the implications of these outcomes.

Impact of desipramine or carbamazepine on patient retention in outpatient cocaine treatment: preliminary findings.

This is a preliminary report of a double-blind comparison of desipramine or carbamazepine to placebo among subjects participating in an outpatient cocaine treatment program. Sixty-five subjects were randomly assigned to one of the active drugs or placebo and followed until treatment completion or drop-out to determine if either drug enhanced retention in treatment and/or increased cocaine abstinence. There was no significant difference between carbamazepine or desipramine and placebo on either outcome measure in this preliminary analysis. While this is a preliminary report and does not take into account the heterogeneity of the patients in cocaine treatment, the results are consistent with those of other investigators and suggest that use of desipramine or carbamazepine may not offer any advantage in retaining cocaine-dependent patients in treatment.

A 30-year follow-up study of the sons of alcoholic men.

The nature-nurture question in the etiology of alcoholism is discussed. The research results from twin and adoption studies indicate a considerable genetic (= biological) component in the etiology of alcoholism. A longitudinal high-risk study of alcoholism is presented. The sons of alcoholic men and matched controls have been followed prospectively since before birth. The main results from previous phases of the study and a recent 30-year follow-up assessment are presented.

Anticipated and subjective sensitivities to alcohol.

The development and maintenance of alcohol use patterns may depend, in part, on differences between how an individual anticipates he will respond to alcohol and how he appears to others when he is drinking. Such differences may introduce bias in decisions regarding which activities are safe while under the influence of an intoxicating amount of alcohol. This study of 387 participants of the Colorado Alcohol Research on Twins and Adoptees project examined the interrelationships of anticipated, subjective and observer-judged sensitivity to a blood alcohol concentrations of about 0.1 g/dl (approximated by breath alcohol concentration). Differences among the sensitivity measures were dependent upon recent alcohol drinking history and individual differences in actual sensitivity (as observer-rated). The results were consistent with hypotheses that people with little drinking experience may overestimate how intoxicated they will be, that heavier drinkers may develop chronic tolerance to the intoxicating effects and that denial may play a role in both subjective and anticipated sensitivity.

Examination of Cloninger's type I and type II alcoholism with a sample of men alcoholics in treatment.

Cloninger's clinical method of classifying alcoholics into two groups (Types I and II) was examined with data obtained from 360 VA hospitalized male alcoholic patients. For operational criteria, the Cloninger clinical method of subtyping alcoholics employs age-of-onset of problem drinking and symptom-clusters supposedly associated with each subtype. Marked overlap was found between the symptom-clusters used to define the two subtypes. Ninety-one percent of the entire sample satisfied criteria for both symptom-clusters. Dividing the sample by early-onset (Type II, less than or equal to 25 years) and late-onset (Type I, greater than 26 years) alcoholism did not substantially reduce the overlap between symptom-clusters; i.e., 96% of the early-onset and 83% of the late-onset subgroups were positive for both symptom-clusters. Only 21 men (6%) could be classified when both age-of-onset and the type-appropriate symptom-cluster were used to separate patients. In hospital settings, at least, these findings suggest that the two-group clinical alcoholism typology proposed by Cloninger basically reflects the age-of-onset of problem drinking.

Pattern reversal visual evoked potentials after alcohol administration among men at risk for alcoholism.

The P100 component of the pattern reversal visual evoked potential was used to compare men at high risk for alcoholism and control subjects before and after a low (0.5 g/kg) dose of ethanol. The high risk and control subjects did not differ in age, self-reported ethanol consumption, or estimates of ethanol metabolism rates, but changes in the occipital P100 latency differentiated them following ethanol administration. The P100 latency changes that distinguished high risk from control subjects were lateralized and provide preliminary evidence that perceptual visual stimulus processing is differentially affected in the two groups following ethanol administration.

A family-genetic study of dementia of Alzheimer type.

A family study of 22 rigorously diagnosed subjects with dementia of Alzheimer type (DAT) and 24 nondemented controls revealed a morbid risk of DAT to first-degree relatives of probands of 41% by age 83 years compared with a risk of 23% by age 85 years in control relatives. Senescent forgetfulness, defined as consistent but not incapacitating memory deficit, may have represented early DAT in some instances. When such cases were included as secondary cases, the morbid risk to first-degree relatives of probands was 67% by age 86 years while risk to comparable control relatives remained 23%. No cases of Down's syndrome were observed. A significant excess of hematologic malignant neoplasms was found among first-degree relatives of probands, supporting an association with DAT. Overall, the findings add further evidence of the action of familial-genetic factors in the etiology of DAT. The magnitude of the effect is consistent with an autosomal dominant mode of inheritance, with penetrance nearly complete by age 85 years. The probands were not selected on the basis of factors posited by some to indicate a familial form of DAT, suggesting that such a genetic mechanism may be involved in the occurrence of DAT in general.

EEG identification of subgroups of men at risk for alcoholism?

Biological sons of male alcoholics constitute one group at high risk (HR) for the development of alcoholism, and were the subjects of this study. A low dose of alcohol (0.5 g/kg) was administered to HR and control subjects. On the basis of changes in the electroencephalographic (EEG) mean alpha frequency that occurred following alcohol administration, two HR subgroups were identified. Measures obtained after alcohol administration, comprising self-ratings and an observer's assessment, distinguished the HR subgroups and control subjects; measures of visuomotor performance did not. The findings are discussed in relation to two current etiological theories bearing on the development of alcoholism: a biopsychological perspective and an initial tolerance for alcohol effects.

Pattern reversal visual evoked potential among men at risk for alcoholism.

The biological sons of male alcoholics, deemed to be at high risk (HR) for the development of alcoholism, were compared to control males, aged 18 to 21, using measures of the visual evoked potential elicited by checkerboard pattern reversal. Overall, the HR and control groups were not distinguished on the basis of visual evoked potential measures acquired from the occipital scalp region; however, when comparisons were restricted to right-handed subjects, the HR subjects showed more symmetry in a positive component with approximate latency of 242 ms compared with control subjects. The results are discussed in relation to hemispheric differences and alcoholism.

Antihistamine blockade of alcohol-induced flushing in orientals.

The so-called Oriental flushing reaction associated with ingestion of small amounts of alcohol was antagonized by combined antihistamine administration. In stage one of the study, the flushing reaction to low doses of alcohol was produced in Orientals. Most subjects experienced a cutaneous flush, an increase in skin temperature, a decrease in blood pressure, an increase in pulse rate and subjective symptoms such as dizziness, sleepiness, anxiety, headache, generalized weakness and nausea. Before the administration of alcohol, one-half of the subjects were given 50 mg of diphenhydramine (H1 receptor antagonist) and 300 mg of cimetidine (H2 receptor antagonist). The second half received placebo tablets. The clearest difference between the antihistamine group and placebo group was in the skin flushing reaction. The antihistamine group showed a significant reduction in the skin flush. The antihistamine also neutralized the systolic hypotension induced by the administration of alcohol. The possible importance of histamine in the expression of sensitivity to alcohol is considered. The relevance to genetic susceptibility for development of alcoholism is discussed.

Histamine receptor antagonism of intolerance to alcohol in the Oriental population.

The Oriental flushing reaction is an adverse response to alcohol that appears to be genetically determined. In this study, the Oriental flushing reaction that was produced with ingestion of small amounts of alcohol was antagonized by antihistamine administration. A group of 17 subjects was tested. Each subject received placebo, diphenhydramine 50 mg (H-1 receptor antagonist), and cimetidine 300 mg (H-2 receptor antagonist) singularly and in combination. Alcohol was then administered orally. Most subjects given placebo experienced the typical flushing reaction that included a cutaneous flush, increase in skin temperature, decrease in blood pressure, increase in pulse rate and subjective symptoms such as dizziness, sleepiness, anxiety, headache, generalized weakness, and nausea. The flush, temperature and systolic hypotension were significantly blocked by the combined antihistamine administration. Cimetidine given alone blocked the flush, temperature increase, and systolic hypotension significantly more than diphenhydramine but less than the combined antihistamines. Diphenhydramine was similar to placebo in its effect on the flushing reaction. The role of histamine in the expression of tolerance to alcohol is not known. Antihistamine antagonism of the adverse flushing reaction suggests that histamine receptors may participate in the intolerance to ethanol in Orientals. Histamine may be an important protective factor in the low prevalence of alcoholism in Orientals.

Sex of parent and offspring in the transmission of alcoholism. A meta-analysis.

Familial studies of alcoholism were reviewed to evaluate the role of sex of parent and offspring in alcoholism transmission. Data from 32 familial alcoholism studies were evaluated by meta-analysis. The results indicated that both male and female alcoholic patients more frequently come from homes in which their father, rather than their mother, is alcoholic, even when sex differences in alcoholism prevalence rates are taken into account. Although female offspring of alcoholic mothers show alcoholism rates that are elevated relative to those expected in the general population, male offspring of alcoholic mothers do not.