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Objective: A large Danish birth cohort was used to test the independent and joint effects of perinatal measures associated with premature birth as predictors of the development of alcoholism in male and female subjects. Method: Subjects were born at the Copenhagen University Hospital between 1959 and 1961 (N = 9,125). A comprehensive series of measures was obtained for each of the 8,109 surviving and eligible infants before birth, during birth, shortly after birth, and at 1 year. The adult alcoholism outcome was defined as any ICD-10 F10 diagnosis (Mental and behavioral disorders due to alcohol use) or an equivalent ICD-8 diagnosis found in the Danish Psychiatric Central Research Register or the Municipal Alcohol Clinics of Copenhagen by 2007. Results: Multiple perinatal markers of premature birth independently predicted the development of an alcoholism diagnosis in male (n = 310) but not female (n = 138) subjects. Logistic regression modeling with a global prematurity score, adjusted for social status, maternal smoking, and gender, indicated a significant association of prematurity score for males (p < .02), but not females (p = .51), on the risk of developing an alcohol use disorder. Conclusions: The results suggest that neurodevelopmental sequelae of premature birth are associated with gender-specific effects on the development of alcoholism in the male baby: small, premature, or growth-delayed male babies appear to be selectively vulnerable to alcoholic drinking years later. The findings implicate neurodevelopmental influences in alcoholism pathophysiology in males and suggest the possibility of distinct, gender-specific pathways in the etiology of severe problem drinking. (J. Stud. Alcohol Drugs, 72, 390-398, 2011), PREMATURE BIRTH and very low birth weight are associated with increased rates of a variety of health problems later in life, including cardiovascular and respiratory disease in adulthood and possibly [...]

Objective: In a search for viable endophenotypes of alcoholism, this longitudinal study attempted to identify premorbid predictors of alcohol dependence that also predicted the course of alcoholism. Method: The 202 male subjects who completed a 40-year follow-up were originally selected from a Danish birth cohort (N = 9,182). Two thirds of the subjects were high-risk biological sons of treated alcoholics. A large number of measures (361) were obtained at different periods before any subject had developed an alcohol-use disorder. At age 40, a psychiatrist provided mutually exclusive lifetime diagnoses of alcohol abuse or alcohol dependence that were characterized as currently active or currently in remission according to Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, course specifiers. Results: The majority of subjects with a diagnosis of alcohol abuse were in remission at age 40 compared with those with a diagnosis of alcohol dependence (88% vs. 58%). Treatment did not predict remission. Fourteen of the 18 predictors of remission that also predicted dependence were submitted to an exploratory factor analysis (varimax). Two premorbid dimensions were identified: cognitive efficiency and early behavioral dyscontrol in childhood. Both factors predicted the failure to remit (low cognitive efficiency and high behavioral dyscontrol) even when lifetime alcoholism severity was controlled. Conclusions: This 4-decade study found a striking disconnect between measures that predicted alcohol dependence and measures that predicted remission from alcohol dependence. Reduced cognitive efficiency and increased behavioral dyscontrol may be basic to gaining a fuller understanding of the etiology of alcoholism., IN THE LAST 60 YEARS, prospective longitudinal studies have attempted to identify the premorbid antecedents of the alcohol-use disorders, especially alcohol dependence, by examining subjects before drinking problems began and [...]

Objective: The Danish Longitudinal Study on Alcoholism was designed to identify antecedent predictors of adult male alcoholism. The influence of premorbid behaviors consistent with childhood conduct disorder (CD) and attention-deficit/hyperactivity disorder (ADHD) on the development of alcohol misuse was examined. Method: Subjects were selected from a Danish birth cohort (9,125), which included 223 sons of alcoholic fathers (high risk) and 106 matched sons of nonalcoholic fathers (low risk). These subjects have been studied systematically over the past 40 years. They were evaluated in their teens (n = 238), later as adults at age 30 (n = 241), and more recently at age 40 (n = 202). At 19-year/20-year follow-ups, an ADHD scale was derived from teacher ratings and a CD scale was derived from a social worker interview. At 30-year and 40-year follow-ups, a psychiatrist used structured interviews and criteria from the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, to quantify lifetime alcoholism severity and to diagnose alcohol-use disorder. Of the original subjects, 110 had complete data for the two childhood measures and the adult alcoholism outcomes. Results: In this smaller subsample, paternal risk did not predict adult alcohol dependence. Subjects who were above a median split on both the ADHD and the CD scales were more than six times more likely to develop alcohol dependence than subjects who scored below the median on both. Although the two childhood measures were correlated, a multiple regression showed that each independently predicted a measure of lifetime alcoholism severity. Conclusions: ADHD comorbid with CD was the strongest predictor of later alcohol dependence., THE Danish Longitudinal Study on Alcoholism (Goodwin et al., 1994) has examined two groups of males for 40 years: (1) high-risk sons of fathers diagnosed and treated for alcoholism and [...]

ABSTRACT. Objective: Levels of oxidative defenses and blood-clotting factors are normally reduced in newborns, increasing the risk of injury to developing brain structures around the time of birth. This early [...]

Objective: The Danish Longitudinal Study of Alcoholism utilized a prospective, high-risk research paradigm to identify putative markers of adult male alcoholism from a comprehensive database that began with the birth of the subject and extended over three decades. This article focuses on measures antedating abusive drinking that predicted lifetime alcohol abuse/dependence at age 30 years. Method: The original 330 subjects of this study were drawn from a large Danish birth cohort (N = 9,125) born between 1959 and 1961. The sample included 223 sons of treated alcoholic fathers (high-risk group) and 107 matched sons whose biological fathers had no record of treatment for alcoholism (low-risk group). This sample has been thoroughly investigated with a variety of methods representing multiple domains that included per/natal records, pediatric records, school records, teacher ratings, school physician records and a series of structured interviews and psychometric tests at ages 19-20 and 30 years. The present analysis focuses on the degree to which premorbid differences between the high- and low-risk groups later predicted lifetime drinking problems at age 30 (n = 241). Results: As expected, lifetime alcohol abuse/dependence by age 30 was reported significantly more often in the high-risk group. Of the 394 premorbid variables tested, 68 were found to distinguish the high- from the low-risk group before any subjects had developed a drinking problem. Of these 68 variables, 28 (41%) were also associated with DSM-III-R alcohol abuse/ dependence at age 30. These 28 putative markers were reduced to 12 that were entered into a multiple regression analysis to search for the most powerful unique predictors of alcoholism. Four of the 28 putative markers were independently associated with problem drinking at age 30: low birth weight, number of life crises in childhood, ratings of childhood unhappiness and antisocial personality disorder. The regression model accounted for 46% of the drinking outcome variance. A father's alcoholism by itself no longer independently contributed to the prediction of his son's drinking and, with one exception, did not systematically interact with the putative markers to facilitate the prediction of alcohol dependence at age 30. Conclusions: Risk itself, which significantly predicted problem drinking at age 30, was not uniquely associated with the development of alcoholism in adulthood. These findings, rather, provide broad support for the biopsychosocial model of alcoholism, especially for those models that emphasize the cumulative influence over time of internal and external variables in biologically vulnerable individuals., KNOWLEDGE ABOUT the specific etiology or etiologies of alcoholism is still limited, despite extensive research focused on this condition. There appear to be three main reasons why the etiology of [...]

A study of 177 patients at an adult psychiatric clinic revealed the utility of employing the E, F and G trait versions of the Depressive Adjective Check Lists (DACL) in accurately diagnosing subjects of differing psychiatric levels. The DACL scales are also of utility in precisely detecting depression levels in subjects.

We studied 345 alcoholic inpatients utilizing a 43-item questionnaire designed to assess these patients' attitudes toward and experiences with disulfiram. A surprisingly high number of patients who had received disulfiram drank ethanol while taking or within 1 week of stopping disulfiram and experienced a disulfiram ethanol reaction. This finding and others derived from the questionnaire are reported, and the potential implications of the findings are discussed., Disulfiram (Antabuse) is a medication given to patients during the initial phase of recovery from alcoholism as a deterrent to drinking; if alcohol is ingested while taking it, an unpleasant physical reaction occurs. This reaction is known as the disulfiram ethanol reaction (DER). No comprehensive study has been done to investigate alcoholics' attitudes toward and experiences with disulfiram, and so a study was designed to obtain these data. Since alcoholics must choose to take the medication, their attitudes are important in assuring its effectiveness. Three hundred forty-five male patients in an inpatient alcoholism treatment facility participated by filling out an extensive questionnaire. Approximately half the subjects had taken disulfiram before. A large number of subjects (96) reported that they had consumed alcohol while on disulfiram or within one week of discontinuing the medication. Of these subjects, 74 experienced a DER. Symptoms included nausea and vomiting, stomach pain, diarrhea, palpitations, chest pain, dizziness, fainting and difficulty breathing. Over one-third of the subjects who had a reaction said it was severe. But the previous experience of having a DER did not dissuade patients from agreeing to take it again. The results suggest that many patients will drink within one week of discontinuing the medication and will have a DER, which may be serious. A method of counteracting DER that patients could use on their own is needed, particularly because few subjects sought medical help during the reaction. A major reason for stopping disulfiram was the desire to drink, and counseling programs should prepare patients for the possibility that they may feel this urge and that it may lead to a relapse of drinking. Another reason for stopping the medication was that the patient thought he did not need it. (Consumer Summary produced by Reliance Medical Information, Inc.), INTRODUCTION Disulfiram has been used extensively for the clinical management of alcoholism since its introduction for this purpose in 1948. The drug's pharmacology [1] and efficacy [2] have been studied [...]

Aims: To examine if (1) there is a positive association between drinking volume in young men and life‐time risk of alcohol dependence (AD) and (2) there are other associations between young adulthood factors and life‐time risk of AD. Design Prospective cohort study of sons of fathers with alcohol use disorder (AUD) and matched low‐risk controls without paternal AUD. Setting and participants A total of 204 men, who were assessed at baseline in 1979 at age 19–20 years, were followed through record linkage with Danish registers and consecutive psychiatric interviews at the ages of 33, 43 and 53 years. Measurements AD diagnoses were interview‐based according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, or made by treating clinicians according to the International Classification of Diseases (ICD) revision 8 (ICD‐8) until 1993 and revision 10 (ICD‐10) from 1994.We estimated odds ratios (ORs) with 95% confidence intervals (CI) for the development of AD after adjustment for confounders including smoking, social status and paternal AUD. Findings The following variables from the examination at age 19–20 independently predicted life‐time AD: alcohol consumption > 21 beverages/week versus 0–21 [odds ratio (OR) = 2.46, 95% confidence interval (CI) = 1.22–4.97], police contact (OR = 2.60, 95% CI = 1.28–5.28) and institutionalization related to the individual (OR = 2.90, 95% CI = 1.39–6.02). Compared with < 1 beverages/week, the risk for AD did not increase significantly for drinking volume categories: 1–7, 8–14 or 15–21 beverages/week. Conclusion: Independently of other risk factors in young adulthood, young Danish men's risk for life‐time alcohol dependence appears to be predicted by a drinking volume at age 19–20 years exceeding 21 beverages per week. [ABSTRACT FROM AUTHOR]

Objective: Alcoholics frequently die prematurely. The purpose of this study was to determine: (1) whether subjects in a sample of 360 male alcoholics, followed over a period of 10-14 years, died prematurely; (2) if so, from what causes; and (3) whether such deaths are predictable from characteristics present at initial assessment. Method: Subjects were male veterans (N = 360) with a diagnosis of alcoholism admitted to an inpatient substance abuse treatment program at the Kansas City Veterans Affairs (VA) Medical Center during 1980-1984 who consented to participate in intake evaluations and subsequent follow-ups at 1 year and 10-14 years later. Of the 357 (99.2%) men located at the 10-14 year follow-up, 96 (26.6%) were confirmed as deceased, 255 survivors agreed to be reassessed and 6 subjects refused reassessment. Information regarding cause of death was obtained from death certificates, VA records and other sources. Results: At intake, the subsequently deceased men were older, had less education, lower psychosocial functioning, more medical problems and greater psychiatric severity. Their overall death rate was 2.5 times greater than that of a reference group of men. Men in the 35-44 year age group were 5.5 times as likely to die. A statistical model utilizing measures of alcohol dependence to predict mortality from intake to 10-14 year follow-up indicated that alcoholics who limited drinking were half as likely to die whereas those who engaged in morning drinking were 2.5 times more likely to die. Conclusions: Alcoholic men, especially those in the group aged 35 to 44 years, have a significantly higher risk of premature death than a reference group of men. Men who engaged in morning drinking and could not limit drinking appeared to be at higher risk of mortality 10 years later. (J. Stud. Alcohol 61: 853-861, 2000), MORE THAN two dozen long-term follow-up studies over the past 50 years have clearly established that misuse of alcohol (encompassing alcohol abuse, alcoholism and persistent heavy drinking of more than [...]

Chronic alcohol use alters adaptive immunity and cytokine activity influencing immunological and hormone responses, inflammation, and wound healing. Brain cytokine disturbances may impact neurological function, mood, cognition and traits related to alcoholism including impulsiveness. We examined the relationship between plasma cytokine levels and self-rated psychiatric symptoms in 40 adult males (mean age 51 ± 6 years; range 33-58 years) with current alcohol dependence and 30 control males (mean age 48 ± 6 years; range 40-58 years) with no history of alcoholism using multiplex sandwich immunoassays with the Luminex magnetic-bead based platform. Log-transformed cytokine levels were analyzed for their relationship with the Symptom Checklist-90R (SCL-90R), Barratt Impulsivity Scales (BIS) and Alcoholism Severity Scale (ASS). Inflammatory cytokines (interferon γ-induced protein-10 (IP-10); monocyte chemoattractant protein-1 (MCP1); regulated on activation, normal T cell expressed and secreted (RANTES)) were significantly elevated in alcoholism compared to controls while bone marrow-derived hematopoietic cytokines and chemokines (granulocyte-colony stimulating factor (GCSF); soluble CD40 ligand (sCD40L); growth-related oncogene (GRO)) were significantly reduced. GRO and RANTES levels were positively correlated with BIS scales; and macrophage-derived chemokine (MDC) levels were positively correlated with SCL-90R scale scores (p < 0.05). Elevated inflammatory mediators in alcoholism may influence brain function leading to increased impulsiveness and/or phobia. The novel association between RANTES and GRO and impulsivity phenotype in alcoholism should be further investigated in alcoholism and psychiatric conditions with core impulsivity and anxiety phenotypes lending support for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Objective: This study directly compared the clinical validity of 11 empirically defined alcoholism typologies to determine whether some typologies are clinically more valid than others. Method: A sample of 360 hospitalized alcoholic men were extensively evaluated at entry into the study and again 1 year later. Twenty-three measures of clinical validity were employed; 15 were postdictive and 8 were predictive. Postdictive retrospective measures obtained at entry into the study included family history, age of onset and lifetime course characteristics associated with alcoholism severity, general psychopathology and psychosocial functioning. Predictive outcome measures drawn from information obtained during the 1-year follow-up included: abstinence, alcoholism severity and clinician ratings of outcome. The measures were subjected to various statistical analyses, including factor analysis. Results: We found that all of the alcoholism typologies met at least 7 of the 23 a priori measures of clinical validity. The correlations between these conceptually and methodologically disparate typologies were often striking. Exploratory factor analysis, which explained 35% of the variance, suggested three possible underlying dimensions to account for the overlap among typologies: (1) age and its correlates, including age-of-alcoholism onset; (2) 'pure' alcoholism versus psychiatrically heterogeneous alcoholism that encompassed antisocial personality disorder; and (3) current severity of psychiatric distress, impairment and dysfunction. Conclusions: No single method of subtyping alcoholics clearly emerged as superior. All demonstrated some degree of predictive and postdictive clinical validity. Most methods of subtyping correlated positively with each other at moderate, but typically significant, levels. (J. Stud. Alcohol 60:188-202, 1999), There is considerable agreement among clinicians and researches that the diagnosis of alcoholism reflects a clinically heterogeneous group of individuals whose onset, course, outcome and response to treatment vary enormously [...]