Multiplex Immunoassay of Plasma Cytokine Levels in Men with Alcoholism and the Relationship to Psychiatric Assessments.

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.

X chromosome inactivation in women with alcoholism.

BACKGROUND: All female mammals with 2 X chromosomes balance gene expression with males having only 1 X by inactivating one of their X chromosomes (X chromosome inactivation [XCI]). Analysis of XCI in females offers the opportunity to investigate both X-linked genetic factors and early embryonic development that may contribute to alcoholism. Increases in the prevalence of skewing of XCI in women with alcoholism could implicate biological risk factors. METHODS: The pattern of XCI was examined in DNA isolated in blood from 44 adult women meeting DSM-IV criteria for an alcohol use disorder and 45 control women with no known history of alcohol abuse or dependence. XCI status was determined by analyzing digested and undigested polymerase chain reaction (PCR) products of the polymorphic androgen receptor (AR) gene located on the X chromosome. Subjects were categorized into 3 groups based upon the degree of XCI skewness: random (50:50 to 64:36%), moderately skewed (65:35 to 80:20%), and highly skewed (>80:20%). RESULTS: XCI status from informative women with alcoholism was found to be random in 59% (n = 26), moderately skewed in 27% (n = 12), or highly skewed in 14% (n = 6). Control subjects showed 60, 29, and 11%, respectively. The distribution of skewed XCI observed among women with alcoholism did not differ statistically from that of control subjects (χ(2) test = 0.14, 2 df, p = 0.93). CONCLUSIONS: Our data did not support an increase in XCI skewness among women with alcoholism or implicate early developmental events associated with embryonic cell loss or unequal (nonrandom) expression of X-linked gene(s) or defects in alcoholism among women.

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.

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.

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.

Change in psychiatric symptomatology after benfotiamine treatment in males is related to lifetime alcoholism severity.

BACKGROUND: Severe alcoholism can be associated with significant nutritional and vitamin deficiency, especially vitamin B1 (thiamine) which is associated with neurological deficits impacting mood and cognition. Alcohol consumption was reduced among female but not male alcoholics after supplementation with the high potency thiamine analog benfotiamine (BF). We examined the relationship between lifetime alcoholism severity, psychiatric symptoms and response to BF among the alcohol dependent men from this cohort. METHODS: Eighty-five adult men (mean age=48±8 years) meeting DSM-IV-TR criteria for a current alcohol use disorder who were abstinent <30days participated in a randomized, double-blind, placebo-controlled trial of 600mg BF vs placebo (PL) for 6 months. Psychometric testing included a derived Lifetime Alcoholism Severity Score (AS), Symptom Checklist 90R (SCL-90R), and the Barratt Impulsivity Scale (BIS) at baseline and at 6 months. RESULTS: Baseline SCL-90-R scale scores for men with high alcoholism severity (AS≥24; N=46 HAS) were significantly greater than for men with low alcoholism severity (AS<24; N=39 LAS), but BIS scores did not differ. MANOVA modeling at follow-up (N=50 completed subjects) identified a significant treatment effect (F=2.5, df=10, p<0.03) and treatment×alcoholism severity level interaction (F=2.5, dfnum=10, dfden=30, p<0.03) indicating reduced SCL-90-R scores among BF treated, HAS males. Above normal plasma thiamine levels at follow-up predicted reduced depression scores in a BF-treated subset (F=3.2, p<0.09, N=26). CONCLUSION: BF appears to reduce psychiatric distress and may facilitate recovery in severely affected males with a lifetime alcohol use disorder and should be considered for adjuvant therapy in alcohol rehabilitation. TRIAL REGISTRATION: #NCT00680121 High Dose Vitamin B1 to Reduce Abusive Alcohol Use.

Risk factors that predicted problem drinking in Danish men at age thirty.

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 perinatal 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.

A preliminary case study of androgen receptor gene polymorphism association with impulsivity in women with alcoholism.

OBJECTIVE: The androgen receptor (AR) gene, located on the X chromosome, contains a common polymorphism involving cytosine-adenine-guanine (CAG) repeats, which impacts disease and could contribute to the unequal sex ratio in alcoholism. CAG repeats in the AR gene are known to correlate with impulsivity in males. We report the first preliminary study examining the association between the number of CAG repeats and measures of impulsivity in females with chronic alcoholism. METHODS: A total of 35 women and 85 men with chronic alcoholism were previously recruited for a nutritional clinical trial, and 26 well-characterized females (19 African-American and seven Caucasian) with alcoholism agreed to participate for genetic testing. Genomic deoxyribonucleic acid (DNA) was isolated from peripheral blood and CAG repeats determined by analyzing polymerase chain reaction (PCR)-amplified products, using the polymorphic AR gene assay. CAG repeat length was correlated with raw scores from the Barratt Impulsivity Scale, version 11 and the Alcoholism Severity Scale. RESULTS: CAG repeat lengths were significantly longer in Caucasian alcoholic women compared with African-Americans, and the average number of CAG repeats were significantly, positively correlated (P<0.05) with impulsivity scores. Women with average CAG repeat length (CAGave) ≥18, representing the upper quartile of the repeat range, showed significantly greater mean raw impulsivity scores. CAG repeat length appeared to have less effect in African-American compared with Caucasian women, possibly due to a shorter average repeat length. CONCLUSION: We found an association between the number of CAG repeats and impulsivity in females with chronic alcoholism, specifically in women with CAGave ≥18, seen more commonly in Caucasian compared with African-American women.

Double-blind, randomized placebo-controlled clinical trial of benfotiamine for severe alcohol dependence.

Alcohol dependence is associated with severe nutritional and vitamin deficiency. Vitamin B1 (thiamine) deficiency erodes neurological pathways that may influence the ability to drink in moderation. The present study examines tolerability of supplementation using the high-potency thiamine analog, benfotiamine (BF), and BF's effects on alcohol consumption in severely affected, self-identified, alcohol dependent subjects. A randomized, double-blind, placebo-controlled trial was conducted on 120 non-treatment seeking, actively drinking, alcohol dependent men and women volunteers (mean age=47 years) from the Kansas City area who met DSM-IV-TR criteria for current alcohol dependence. Subjects were randomized to receive 600 mg benfotiamine or placebo (PL) once daily by mouth for 24 weeks with 6 follow-up assessments scheduled at 4 week intervals. Side effects and daily alcohol consumption were recorded. Seventy (58%) subjects completed 24 weeks of study (N=21 women; N=49 men) with overall completion rates of 55% (N=33) for PL and 63% (N=37) for BF groups. No significant adverse events were noted and alcohol consumption decreased significantly for both treatment groups. Alcohol consumption decreased from baseline levels for 9 of 10 BF treated women after 1 month of treatment compared with 2 of 11 on PL. Reductions in total alcohol consumption over 6 months were significantly greater for BF treated women (BF: N=10, -611 ± 380 standard drinks; PL: N=11, -159 ± 562 standard drinks, p-value=0.02). BF supplementation of actively drinking alcohol dependent men and women was well-tolerated and may discourage alcohol consumption among women. The results do support expanded studies of BF treatment in alcoholism.

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.

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.

Minor versus major depression: a comparative clinical study.

OBJECTIVE: To examine whether minor depression differs from major depression in clinically relevant ways. METHOD: Structured interviews, Symptom Checklist-90-Revised (SCL-90-R) scores, and physicians' treatment recommendations were obtained systematically from 1,458 admissions to an outpatient teaching clinic during a 5-year period from 1981 to 1986. Of these, 1,002 (69%) satisfied inclusive DSM-III lifetime criteria for a major depressive episode. Of the 456 outpatients who did not formally satisfy criteria for a major depressive episode, 79 (17%) acknowledged significant depressive symptoms that caused major interference in their lives. These 79 outpatients were classified as suffering from minor depression. RESULTS: No gender or other sociodemographic differences were found between the 2 outpatient groups except that the minor depression group had achieved a higher level of education. No differences were found for a family history of psychiatric illness among first-degree relatives, including a family history of depression. Ratings of childhood unhappiness/problems did not distinguish the 2 groups. The major depression group endorsed more lifetime depressive symptoms and met criteria for more co-occurring disorders, principally mania and the anxiety disorders. The group with major depression reported poorer psychosocial functioning when first seen and more past psychiatric treatment. The Symptom Checklist-90-Revised (SCL-90-R) profile was significantly elevated in both groups. The type of initial treatment recommended did not distinguish the major from minor depression groups. CONCLUSIONS: Minor depression seems to represent the same illness as major depression but in a less severe form that, nevertheless, requires the attention of professional health care providers in both primary and specialized care settings.

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.

Indicators of mania in depressed outpatients: a retrospective analysis of data from the Kansas 1500 study.

OBJECTIVE: Previous prospective studies have shown that unipolar depressed patients often switch to a manic episode. Some of these studies have reported that the conversion to bipolar disorder is predicted by an early onset of depression, a positive family history for mania, and psychotic symptoms. The present study examines the strength of the relationship between these 3 indicators, both alone and in combination, and the presence of mania in a large retrospective analysis. METHOD: 1458 consecutive admissions to a large, Midwestern university outpatient clinic between 1981 and 1986 were interviewed, and 1002 patients met DSM-III inclusive criteria for major depressive disorder. Of these, information about age at onset of depression, family history of mania, and psychotic symptoms was available on 744 outpatients. Two structured interviews were used to assess the 3 indicators. RESULTS: In this large depressed outpatient sample, the incidence of lifetime mania was 27%. Each of the 3 indicators was significantly associated with the report of mania (p < .0001 for all 3 indicators). The rates of mania increased as the number of indicators increased. Psychotic symptoms were the strongest indicator, followed by a family history of mania and an early age at onset of depression. CONCLUSION: Depressed patients with 1 or more of these 3 indicators should be monitored for the presence of bipolar disorder. Patients with 2 or more of these indicators are especially at risk to develop mania.

A theoretical argument for inherited thiamine insensitivity as one possible biological cause of familial alcoholism.

Thiamine deficiency has been specifically linked to the development of Wernicke-Korsakoff syndrome (WK)--a degenerative brain disorder that is typically associated with alcoholic drinking. Alcoholism-related thiamine deficiency is a major cause of WK. However, an inherited abnormality in thiamine utilization has been identified in some WK patients that may predispose heavy drinkers to this severe neurological syndrome. Individuals who possess this variant require more thiamine throughout their lives to prevent them from experiencing thiamine deficiency. Recent prospective studies have implicated early childhood nutritional and environmental influences in the etiology of alcoholism in adults. These studies have suggested that developmental abnormalities involving brain white matter growth might precipitate the later development of alcoholism possibly by altering the emerging reward-related brain systems. Brain white matter growth is highly sensitive to nutritional deficiency (including thiamine deficiency) and oxidative injury, especially during the perinatal period. The proposed model of familial alcoholism hypothesizes that an inherited insensitivity to thiamine can precipitate brain abnormalities very early in life that will greatly increase the risk of developing alcoholism in adulthood. This paper offers a heuristic model of a possible mechanism by which both inherited and environmental factors related to thiamine utilization might coaggregate to cause alcoholism.

Development of scales to screen for eight common psychiatric disorders.

The present study was designed to create a group of scales from the items on the Symptom Checklist 90 (SCL-90) to identify common psychiatric diagnoses. Subjects were 1457 adult psychiatric outpatients who completed the Symptom Checklist-90 and a structured diagnostic interview at the time of their initial evaluation. A combination of rational and empirical test construction methods was used to create the SCL-90 Diagnostic Scales, item sets that identify eight common psychiatric conditions: major depression, bipolar disorder, schizophrenia, antisocial personality disorder, somatization disorder, obsessive-compulsive disorder, panic disorder, and agoraphobia. These specially constructed scales were found to possess good internal reliability. These scales were also shown to differentiate patients positive for each of the eight psychiatric disorders from other psychiatric patients who did not have that disorder. Sensitivities and specificities are reported for each item set. In addition to their utility at the time of initial assessment as an aid in identifying diagnosis, the SCL-90 Diagnostic Scales may have other potential uses, such as in monitoring the symptom course of the patient's disorder or disorders over time.

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.

Comparison of desipramine or carbamazepine to placebo for crack cocaine-dependent patients.

The authors compared the effects of desipramine or carbamazepine to placebo in an intensive outpatient program for cocaine abuse. Subjects recruited from an urban drug treatment program were randomly assigned to a double-blind, placebo-controlled, eight-week trial of desipramine, carbamazepine, or placebo. Patient ratings, urine drug screens, and blood samples were obtained weekly. Using survival analysis, the three groups did not differ in time to drop out of treatment. While subjects improved over time on all self-ratings related to cocaine use, mood, and craving, only two items related to mood were significantly different over time as a function of treatment group. Subjects in the two treated groups reported significantly more improvement on self-ratings of depression and irritability. No treatment differences were noted for sustained abstinence or for proportion of positive urine drug screens. Desipramine subjects who attained a minimum blood level were retained in treatment significantly longer than placebo or other non-compliant treatment groups. This finding supports previous reports of a possible role for desipramine in cocaine abuse treatment.