Metabolic effects of 1-week binge drinking and fast food intake during Roskilde Festival in young healthy male adults.

AIMS/HYPOTHESIS: Metabolic effects of intermittent unhealthy lifestyle in young adults are poorly studied. We investigated the gluco-metabolic and hepatic effects of participation in Roskilde Festival (1 week of binge drinking and junk food consumption) in young, healthy males. METHODS: Fourteen festival participants (FP) were studied before, during and after 1 week's participation in Roskilde Festival. Fourteen matched controls (CTRL) who did not participate in Roskilde Festival or change their lifestyle in other ways were investigated along a similar timeline. RESULTS: The FP group consumed more alcohol compared to their standard living conditions (2.0 ± 3.9 vs 16.3 ± 8.3 units/day, P < 0.001). CTRLs did not change their alcohol consumption. AUC for glucose during OGTT did not change in either group. C-peptide responses increased in the FP group (206 ± 24 vs 236 ± 17 min × nmol/L, P = 0.052) and the Matsuda index of insulin sensitivity decreased (6.2 ± 2.4 vs 4.7 ± 1.4, P = 0.054). AUC for glucagon during oral glucose tolerance test (OGTT) increased in the FP group (1037 ± 90 vs 1562 ± 195 min × pmol/L, P = 0.003) together with fasting fibroblast growth factor 21 (FGF21) (62 ± 30 vs 132 ± 72 pmol/L, P < 0.001), growth differentiation factor 15 (GDF5) (276 ± 78 vs 330 ± 83 pg/mL, P = 0.009) and aspartate aminotransferase (AST) levels (37.6 ± 6.8 vs 42.4 ± 11 U/L, P = 0.043). Four participants (29%) developed ultrasound-detectable steatosis and a mean strain elastography-assessed liver stiffness increased (P = 0.026) in the FP group. CONCLUSIONS/INTERPRETATION: Participation in Roskilde Festival did not affect oral glucose tolerance but was associated with a reduction in insulin sensitivity, increases in glucagon, FGF21, GDF15 and AST and lead to increased liver stiffness and, in 29% of the participants, ultrasound-detectable hepatic steatosis.

Young adult predictors of alcohol dependence to age 53: a 44-year prospective cohort study of Danish men.

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.

Intelligence in young adulthood and alcohol use disorders in a prospective cohort study of Danish men: the role of psychiatric disorders and parental psychiatric history.

OBJECTIVES: The aims were to estimate the association between intelligence measured in young adulthood and risk of alcohol use disorders (AUD) in men and to investigate the potential modification of this association by psychiatric disorders, parental AUD and parental psychiatric disorders. DESIGN: Prospective cohort study based on a linkage of intelligence test scores from draft board examinations and register data on AUD diagnoses during 36 years of follow-up. SETTING: Denmark. PARTICIPANTS: 3287 Danish men from the Copenhagen Perinatal Cohort (born 1959-1961) who appeared before the draft board at a mean age of 18.7 years. PRIMARY OUTCOME MEASURE: First registration with AUD during follow-up was the primary outcome. Information on AUD was based on diagnoses retrieved from national hospital and outpatient treatment registers, defined according to the International Classification of Diseases. RESULTS: 361 (11.0%) men were registered with AUD during follow-up. Low intelligence scores were associated with increased odds of AUD adjusting for parental AUD, parental psychiatric disorders, maternal smoking during pregnancy, birth weight, maternal age at birth, parity and childhood socioeconomic position (OR per SD decrease in intelligence=1.69, 95% CI 1.49 to 1.92). Separate analyses indicated significant interaction (p<0.001) between intelligence and psychiatric disorders. The adjusted OR per SD decrease in intelligence score was 2.04 (95% CI 1.67 to 2.49) in men without other psychiatric disorders whereas the OR was 1.21 (95% CI 1.01 to 1.46) in men with other psychiatric disorders. No interaction was found between intelligence and parental AUD or between intelligence and parental psychiatric disorders. CONCLUSIONS: The association between intelligence in young adulthood and AUD is modified by other psychiatric disorders as low intelligence is primarily a risk factor for men without other psychiatric disorders. Future studies should take other psychiatric disorders into account when investigating associations between intelligence and AUD.

Triage in psychiatric emergency services in Copenhagen: results from a descriptive 1-year evaluation study.

Inspired by the Australasian triage system, a regional psychiatric triage system was introduced in the psychiatric emergency units (PEUs) in Copenhagen in 2011. Our aim of the study is to determine the characteristics of the patient according to the defined triage criteria and check if this is in accordance with recommendations. A random 10% data sample was obtained throughout 2012 in three PEUs of Copenhagen. Triage category, demographic, social and clinically relevant variables were collected. A total of 929 contacts were registered. We found significant associations between triage category and several clinical parameters. Time of visit was correlated to diagnoses. The results indicate that use of the new triage system in emergency psychiatry has facilitated urgency categorization, reduced waiting time, and optimized clinical decisions. These goals are important clinical implications of the service in PEUs. The need for PEUs out-of-daytime (when all Community Mental Health Centers are closed) has also been demonstrated.

Psychiatric Disorders and Psychopharmacologic Treatment as Risk Factors in Elective Fast-track Total Hip and Knee Arthroplasty.

BACKGROUND: Psychiatric disorder (PsD) is rarely considered when evaluating perioperative risk factors. Studies on PsD are often limited by use of administrative coding, incomplete follow-up, and lack of preoperative data on psychopharmacological treatment. METHODS: A multicenter study with prospective registration on preoperative comorbidity, complete 90-day follow-up, and information on dispensed prescriptions on psychopharmacological treatment (excluding benzodiazepines). All departments used similar fast-track approaches and discharge to home. Evaluation of postoperative morbidity was based on discharge records. Odds ratios for length of stay (LOS) more than 4 days and surgery-related readmissions were calculated using multiple logistic regression adjusting for potential confounders. RESULTS: Of 8,757 procedures, 1,001 (11.4%) were in PsD patients. Of these, 43.4% used selective serotonin inhibitors (SSRIs), 31.6% used other antidepressants, 8.5% used a combination, and 16.5% used antipsychotics. PsD was associated with increased risk of LOS more than 4 days (16.5 vs. 7.3%; odds ratio, 1.90; 95% CI, 1.52 to 2.37), regardless of treatment with SSRIs (2.19; 1.62 to 2.97), other antidepressants (1.81; 1.25 to 2.61), or antipsychotics (1.90; 1.62 to 3.16). PsD was associated with increased 30- (9.9 vs. 5.1%; 1.93; 1.49 to 2.49) and 90-day surgery-related readmissions (12.8 vs. 7.4%; 1.68; 1.34 to 2.10), significant for SSRIs (1.97; 1.38 to 2.82 and 1.77; 1.29 to 2.43), other antidepressants (2.24; 1.51 to 3.32 and 1.82; 1.27 to 2.61), and antipsychotics (1.85; 1.03 to 3.31, 30 days only). In PsD patients, pain (1.4%), postoperative anemia (1.1%), and pulmonary complications (1.1%) were the most frequent causes of LOS more than 4 days. Hip displacements (2.8%) and falls (1.9%) were the most frequent readmissions, and 90-day surgery-related mortality was 0.7% with and 0.2% without PsD. CONCLUSIONS: Psychopharmacologically treated PsD is a risk factor for postoperative morbidity after fast-track arthroplasty, regardless of treatment type. This may be due to PsD per se and/or drug-related side effects.

Psychiatric emergency services in Copenhagen 2012: A 27-year psychiatric and demographic follow-up study.

BACKGROUND: Since the first publication of the psychiatric emergency units (PEUs) in Copenhagen 1985, outpatient facilities have undergone considerable changes. Our aim is to examine how these changes have influenced the activities in the PEUs in the same catchment area. METHODS: We conducted a follow-up study to describe this development in the past 27 years by comparing 1985 variables with same measures in 2012. A random sample of all visits every 10 days in 2012 to three PEUs in Copenhagen were registered and compared with data collected, using the same study design in 1985. MAIN RESULTS: The number of visits has decreased significantly from 367 visits/year/10,000 inhabitants in 1985 to 225 in 2012. Apart from a considerable number (15.6%) of visitors with non-Danish background, the demographic variables have not changed significantly since 1985. Compared with 1985, the diagnostic distribution among the 2012 visitors shows an increased frequency of affective disorders and neurotic and stress disorders, while schizophrenia spectrum and personality disorders show almost the same frequencies in 1985 and 2012. Rates of alcoholism and organic mental disorders show a minor reduction during the 27-year follow-up period. In 1985, 20.7% of the visits ended up without any referrals, compared with 4.8% in 2012. The rate of acute admissions into a psychiatric ward was 60.8% in 2012 compared with 35.65% in 1985. CONCLUSION: The extension of the psychiatric outpatients' facilities since 1985 has reduced the number of visits in the PEUs considerably. The results have shown a change of diagnostic distribution and more severe conditions requiring acute admissions for emergency treatment. Close collaboration with the patients' families, GPs, social authorities and specialized psychiatric outpatient clinics is emphasized.

The influence of early exposure to vitamin D for development of diseases later in life.

BACKGROUND: Vitamin D deficiency is common among otherwise healthy pregnant women and may have consequences for them as well as the early development and long-term health of their children. However, the importance of maternal vitamin D status on offspring health later in life has not been widely studied. The present study includes an in-depth examination of the influence of exposure to vitamin D early in life for development of fractures of the wrist, arm and clavicle; obesity, and type 1 diabetes (T1D) during child- and adulthood. METHODS/DESIGN: The study is based on the fact that in 1961 fortifying margarine with vitamin D became mandatory in Denmark and in 1972 low fat milk fortification was allowed. Apart from determining the influences of exposure prior to conception and during prenatal life, we will examine the importance of vitamin D exposure during specific seasons and trimesters, by comparing disease incidence among individuals born before and after fortification. The Danish National databases assure that there are a sufficient number of individuals to verify any vitamin D effects during different gestation phases. Additionally, a validated method will be used to determine neonatal vitamin D status using stored dried blood spots (DBS) from individuals who developed the aforementioned disease entities as adults and their time and gender-matched controls. DISCUSSION: The results of the study will contribute to our current understanding of the significance of supplementation with vitamin D. More specifically, they will enable new research in related fields, including interventional research designed to assess supplementation needs for different subgroups of pregnant women. Also, other health outcomes can subsequently be studied to generate multiple health research opportunities involving vitamin D. Finally, the results of the study will justify the debate of Danish health authorities whether to resume vitamin D supplementation policies.

Forty-five-year mortality rate as a function of the number and type of psychiatric diagnoses found in a large Danish birth cohort.

OBJECTIVE: Psychiatric comorbidities are common among psychiatric patients and typically associated with poorer clinical prognoses. Subjects of a large Danish birth cohort were used to study the relation between mortality and co-occurring psychiatric diagnoses. METHOD: We searched the Danish Central Psychiatric Research Registry for 8109 birth cohort members aged 45 years. Lifetime psychiatric diagnoses (International Classification of Diseases, Revision 10, group F codes, Mental and Behavioural Disorders, and one Z code) for identified subjects were organized into 14 mutually exclusive diagnostic categories. Mortality rates were examined as a function of number and type of co-occurring diagnoses. RESULTS: Psychiatric outcomes for 1247 subjects were associated with 157 deaths. Early mortality risk in psychiatric patients correlated with the number of diagnostic categories (Wald χ² = 25.0, df = 1, P < 0.001). This global relation was true for anxiety and personality disorders, but not for schizophrenia and substance abuse, which had intrinsically high mortality rates with no comorbidities. CONCLUSIONS: Risk of early mortality among psychiatric patients appears to be a function of both the number and the type of psychiatric diagnoses.

The contribution of parental alcohol use disorders and other psychiatric illness to the risk of alcohol use disorders in the offspring.

BACKGROUND: Few population-based studies have investigated associations between parental history of alcoholism and the risk of alcoholism in offspring. The aim was to investigate in a large cohort the risk of alcohol use disorders (AUD) in the offspring of parents with or without AUD and with or without hospitalization for other psychiatric disorder (OPD). METHODS: Longitudinal birth cohort study included 7,177 men and women born in Copenhagen between October 1959 and December 1961. Cases of AUD were identified in 3 Danish health registers and cases of OPD in the Danish Psychiatric Central Register. Offspring registration with AUD was analyzed in relation to parental registration with AUD and OPD. Covariates were offspring gender and parental social status. RESULTS: Both maternal and paternal registration with AUD significantly predicted offspring risk of AUD (odds ratios 1.96; 95% CI 1.42 to 2.71 and 1.99; 95% CI 1.54 to 2.68, respectively). The association between maternal, but not paternal, OPD and offspring AUD was also significant (odds ratios 1.46; 95% CI 1.15 to 1.86 and 1.26; 95% CI 0.95 to 1.66, respectively). Other predictors were male gender and parental social status. A significant interaction was observed between paternal AUD and offspring gender on offspring AUD, and stratified analyses showed particularly strong associations of both paternal and maternal AUD with offspring AUD in female cohort members. CONCLUSIONS: Parental AUD was associated with an increased risk of offspring AUD independent of other significant predictors, such as gender, parental social status, and parental psychiatric hospitalization with other diagnoses. Furthermore, this association appeared to be stronger among female than male offspring. The results suggest that inherited factors related to alcoholism are at least as important in determining the risk of alcoholism among daughters as among sons.

Effects of premature birth on the risk for alcoholism appear to be greater in males than females.

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.

Alcohol consumption and later risk of hospitalization with psychiatric disorders: prospective cohort study.

The potential effects of alcohol intake upon the risk of psychiatric disorders have not often been investigated. The purpose of this study was to investigate, in a population sample, the association between self-reported amount of alcohol intake and the later risk of being registered in a Danish hospital with a psychiatric disorder. The prospective cohort study, the Copenhagen City Heart Study (n=18,146), was used, containing three updated sets of alcohol intake and lifestyle covariates and up to 26 years follow-up. Alcohol intake was measured by self-report while psychiatric disorders were measured through registers. For women, the overall pattern showed that drinking above the sensible limits increased the risk of psychiatric disorders in general, especially for anxiety disorders where women drinking above the sensible drinking limits had a risk of 2.00 (confidence interval: 1.31-3.04) compared to women drinking below the sensible drinking limits. For men, the risk functions were slightly U-shaped; thus, a weekly low or moderate alcohol intake seemed to have a protective effect towards developing psychiatric disorders. The findings suggest sex differences in the association between alcohol consumption and risk of psychiatric disorders.

Do premorbid predictors of alcohol dependence also predict the failure to recover from alcoholism?

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.

Comorbidity and temporal ordering of alcohol use disorders and other psychiatric disorders: results from a Danish register-based study.

BACKGROUND: Understanding the comorbidity of alcohol use disorders (AUD) and other psychiatric disorders may have important implications for treatment and preventive interventions. However, information on the epidemiology of this comorbidity is lacking. The objective of this study was to present results on lifetime psychiatric comorbidity of AUD in a large Danish community population. METHODS: A prospective cohort study was used, comprising 3 updated measures of sets of lifestyle covariates and 26 years of follow-up data on 18,146 individuals from the Copenhagen City Heart Study, Denmark. The study population was linked to national Danish hospital registers and a greater Copenhagen alcohol unit treatment register to detect registrations with AUD and other psychiatric disorders. RESULTS: Of the individuals invited to the study, 7.6% were registered with AUD, and among these, 50.3% had a lifetime comorbid psychiatric disorder. Personality disorders were the most common comorbid disorders (24%) together with mood disorders (16.8%) and drug abuse (16.6%). The risk of developing a psychiatric disorder in individuals who were already registered with AUD was larger than the risk of developing AUD in individuals who were already registered with another psychiatric disorder; these differences in risk were especially noticeable for anxiety disorders, personality disorders, and drug abuse. CONCLUSIONS: AUD is frequently comorbid with other psychiatric disorders, and it is likely that AUD is both an etiologic factor in other mental disorders and a consequence of mental disease. However, in interpreting these complex and perhaps circular causal links, it is important to consider that AUD is registered before a comorbid psychiatric diagnosis more often than the reverse temporal order.

Alcohol use disorders increase the risk of completed suicide--irrespective of other psychiatric disorders. A longitudinal cohort study.

Knowledge of the epidemiology of suicide is a necessary prerequisite for developing prevention programs. The aim of this study was to analyze the risk of completed suicide among individuals with alcohol use disorders (AUD), and to assess the role of other psychiatric disorders in this association. A prospective cohort study was used, containing three updated sets of lifestyle covariates and 26 years follow-up of 18,146 individuals between 20 and 93 years of age from the Copenhagen City Heart Study in Denmark. The study population was linked to four different registers in order to detect: Completed suicide, AUD, Psychotic disorders, Anxiety disorders, Mood disorders, Personality disorders, Drug abuse, and Other psychiatric disorders. Individuals registered with AUD were at significantly increased risk of committing suicide, with a crude hazard ratio (HR) of 7.98 [Confidence interval (CI): 5.27-12.07] compared to individuals without AUD. Adjusting for all psychiatric disorders the risk fell to 3.23 (CI: 1.96-5.33). In the stratified sub-sample of individuals without psychiatric disorders, the risk of completed suicide was 9.69 (CI: 4.88-19.25) among individuals with AUD. The results indicate that individuals registered with AUD are at highly increased risk of completed suicide, and that registered co-morbid psychiatric disorders are neither sufficient nor necessary causes in this association.

Childhood ADHD and conduct disorder as independent predictors of male alcohol dependence at age 40.

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.

Beverage preference and risk of alcohol-use disorders: a Danish prospective cohort study.

OBJECTIVE: The purpose of this study was to examine whether preferred type of alcoholic beverage influences the later risk of alcohol-use disorders (AUD). METHOD: A prospective cohort study was used, comprising three updated measures of alcohol intake and covariates, and 26 years of follow-up data on 18,146 individuals from the Copenhagen City Heart Study, Denmark. The study population was linked to three different registers to detect AUD registrations. RESULTS: For both genders, wine drinking was associated with lower risk of AUD irrespective of the weekly amount of alcohol consumed. Women drinking 15-21 drinks per week of only beer and distilled spirits had a risk of 15.8 (95% confidence interval [CI]: 7.8-33.3) for AUD, whereas those whose total alcohol intake comprised more than 35% wine had a risk of 2.0 (CI: 0.7-5.2). Men drinking 15-21 drinks per week of only beer and distilled spirits had a risk of 3.1 (CI: 1.8-5.4), whereas those whose total alcohol intake comprised more than 35% wine had a risk of 0.8 (CI: 0.3-2.1). Consuming more than 35% beer increased the risk of AUD for women, whereas the percentage of distilled spirits intake did not influence the risk of AUD for either women or men. CONCLUSIONS: Individuals who include wine when they drink alcohol have lower risks of AUD, independent of the total amount of alcohol consumed. The most likely explanation of these results is that lifestyle factors and personal characteristics are associated with beverage preference.

Amount of alcohol consumption and risk of developing alcoholism in men and women.

AIMS: It is generally accepted, but not yet documented that the risk of future alcoholism increases with the amount of alcohol consumed. The objective of this study was to investigate this association using the Copenhagen City Heart Study. METHODS: Quantity and frequency of alcohol intake was measured in 19 698 men and women randomly drawn from the Copenhagen Population Register in 1976-78. The study population was linked to three different registers in order to detect alcoholism, and average follow-up time was 25 years. RESULTS: After adjustment for all putative confounders, the risk of alcoholism for women increased significantly at 1-7 drinks per week with a hazard ratio (HR) of 2.02 (95% confidence interval (CI): 1.16, 3.53) compared to never/almost never drinking; the HR for drinking monthly was 1.75 (95% CI: 1.08, 2.85). The risk for men did not increase significantly before 22-41 drinks per week (HR = 3.81, 95 % CI: 2.18, 6.68) or if they had a daily alcohol intake (HR = 3.55, 95 % CI: 2.11, 5.99). Smoking was independently associated with the risk of alcoholism for both men and women. CONCLUSION: The risk of developing alcoholism increased significantly by very low intakes of alcohol in women, while the risk is only increased significantly in men consuming more than 21 drinks per week.

Neonatal vitamin K might reduce vulnerability to alcohol dependence in Danish men.

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 neonatal vulnerability corresponds to a timeframe in which the development of reward-related limbic structures is particularly active. Taking advantage of a serendipitous event in the history of treating newborns, we tested the hypothesis that vitamin K supplementation, administered to facilitate the synthesis of blood-clotting proteins within this critical timeframe, might also reduce the development of alcohol dependence later in life. METHOD: Subjects were approximately full-term male infants, selected from a large Danish birth cohort. Two thirds of the original 330 subjects in this study were high-risk sons of alcoholic fathers; 241 of the total completed the 30-year follow-up. Of subjects reported on for this article (N = 238), 44 received vitamin K supplementation at birth; 161 were considered high risk, and 66 were categorized as having lower birth weight (<6 lbs). A comprehensive series of measures was obtained on each subject before, during and shortly after birth as well as at 1 year of age. The Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, diagnosis of alcohol dependence and a measure of lifetime problem drinking served as the 30-year outcome variables. RESULTS: Vitamin K treatment, inherited risk and low birth weight each independently predicted alcohol dependence and problem drinking at age 30. Vitamin K treatment was associated with significantly lower rates of alcohol dependence and fewer symptoms of problem drinking. CONCLUSIONS: Vitamin K treatment at birth might protect against the development of alcoholism in adults by reducing early postnatal hemorrhage and oxidative brain damage.

Developmental differences in childhood motor coordination predict adult alcohol dependence: proposed role for the cerebellum in alcoholism.

BACKGROUND: The Danish Longitudinal Study of Alcoholism has identified a number of early biological indicators that predicted alcohol dependence 30 years later. In light of recent evidence linking deficits of the cerebellum to certain neuropsychiatric disorders often comorbid with alcoholism, we hypothesized that developmental deficits in the cerebellar vermis may also play a role in the initiation of adult alcohol dependence. The present study evaluated whether measures of motor development in the first year of life predict alcohol dependence three decades later. METHODS: A total of 241 subjects of the original 330 infants who were entered into this study completed the 30-year follow-up (12 had died). The subjects were men who were drawn from a large birth cohort born in Copenhagen, Denmark, from 1959 to 1961. A comprehensive series of measures were obtained on each subject before, during, and shortly after birth as well as at 1 year of age. Muscle tone at birth and day 5 as well as 1-year measures of motor coordination--age to sitting, standing, and walking--were examined. A DSM-III-R diagnosis of alcohol dependence and a measure of lifetime problem drinking served as the 30-year outcome variables. RESULTS: Several measures of childhood motor development significantly predicted alcohol dependence at 30 years of age. These included deficits in muscle tone 5 days after birth, delays in the age to sitting, and delays in the age to walking. CONCLUSIONS: Relationships found between adult alcoholism and early delays in motor development offer support for the theory that cerebellar deficits may play a causal role in the addiction process.