Objective diagnosis of alcohol abuse: compared values of carbohydrate-deficient transferrin (CDT), gamma-glutamyl transferase (GGT), and mean corpuscular volume (MCV)

BACKGROUND: Alcohol abuse is roughly twice as common as alcohol dependence. Subjects with alcohol problems are usually diagnosed only when medical complications are present. Therefore, both doctors and patients need a method for early diagnosis of alcohol abuse. METHODS: The mean corpuscular volume, gamma-glutamyl transferase, and carbohydrate-deficient transferrin in alcohol abusers, alcohol-dependent patients, and "nonalcohol hospital" individuals were compared. RESULTS: For objective diagnosis of alcohol abuse, we found a sensitivity of 24%, a specificity of 96%, and a global predictive value of 63% for mean corpuscular volume; a sensitivity of 42%, a specificity of 76%, and a global predictive value of 61% for gamma-glutamyl transferase; and a sensitivity of 67%, a specificity of 97%, and a global predictive value of 84% for carbohydrate-deficient transferrin. CONCLUSIONS: Carbohydrate-deficient transferrin proves to be the best marker of alcohol abuse. It allows objective detection so that therapeutic action can be started early, which is easier and more effective than in alcohol dependence.     

Dosing Issues in the Pharmacotherapy of Alcoholism

Pharmacological treatments for alcohol dependence have focused increasingly on agents that reduce alcohol craving and consumption or that treat psychiatric disorders associated with drinking relapse. Clinicians who treat alcohol-dependent patients must find the optimal dose of these agents to maximize response. Determining the best dosing strategy has been the goal of recent treatment studies with alcohol-dependent patients. One study, for example, showed that an opiate antagonist medication had a dose-dependent relationship with patient outcome and retention in treatment. Another dosing consideration involves the effect of long-term alcohol abuse on drug metabolism (e.g., when treating alcohol-dependent patients for comorbid psychiatric disorders). This was demonstrated in a study of recently abstinent patients who were taking the antidepressant desipramine for major depression. Alcohol-dependent patients had higher hepatic enzyme activities and lower plasma levels of desipramine relative to oral dose than did a comparison group of depressed patients without an alcohol use disorder.     

Screening for drug and alcohol abuse among older adults using a modified version of the CAGE.

This study examined the sensitivity, specificity, and receiver operating characteristics (ROC) curves of a modified version of the CAGE, a screening measure used in the detection of older alcohol- and drug-abusing individuals. In a retrospective review of clinical records of 976 patients screened by a geriatric substance abuse program, the authors examined patients' responses on a modified version of the CAGE that included queries regarding drug use. The CAGE was administered to individuals age 50 or over draw from three diagnostic groups: alcohol abuse/dependence, drug abuse/dependence, and normal controls. Analysis of variance and discriminant function analyses revealed that the modified CAGE was able to discriminate both alcohol and drug abusers from controls. Analyses examining test sensitivity, specificity, and ROC curves revealed the CAGE to demonstrate excellent sensitivity but poor specificity. Omitting the "cut down' item from the CAGE significantly improved specificity with only a modest drop in sensitivity. Given the ease of administration and sensitivity to both alcohol and drug abuse, these data suggest that the modified CAGE is well suited as a screening instrument for geriatric drug and alcohol abuse.     

Anxiety disorders: treatable regardless of the severity of comorbid alcohol dependence

AIMS: Clinical and epidemiological research has shown that comorbidity is the rule rather than exception in the case of psychiatric disorders. Cognitive behavioral therapy (CBT) has been clearly demonstrated to be effective in treating anxiety and avoidance symptoms in patient samples of social phobia and agoraphobia without comorbid alcohol use disorders. It has recently been shown that treatment of comorbid anxiety disorders in alcohol-dependent patients can also be very successful. The purpose of the present study was to find predictors of treatment success for comorbid anxiety disorders in alcohol-dependent patients. METHODS: The study was conducted in a sample of 34 completers with a double diagnosis of alcohol dependence and agoraphobia or social phobia who received CBT for their comorbid anxiety disorder in a 32-week randomized controlled trial comparing alcohol and CBT anxiety disorder treatment with alcohol treatment alone. In the current report, treatment success was defined as a clinically significant change (recovery) on the anxiety discomfort scale. RESULTS: The severity of comorbid alcohol dependence did not influence the beneficial effect of CBT on the anxiety disorder. Psychological distress (SCL-90), neuroticism (NEO N), conscientiousness (NEO C), gender, employment and age of onset of alcohol dependence showed some predictive value. CONCLUSIONS: Alcohol-dependent males with a comorbid anxiety disorder seem to benefit most from CBT if their alcohol dependence started after age 25, if they are employed and if their general psychopathology is less severe. The most important conclusion, however, is that even severely alcohol-dependent patients with an anxiety disorder can benefit from psychotherapy for their anxiety disorder.     

Alcoholism and phobic anxiety—a clinical-demographic comparison

The prevalence of anxious and phobic symptoms in 97 alcohol-dependent and alcohol abuse patients, and that of alcohol abuse and dependence in 90 patients with panic/agoraphobia (PAG), were respectively determined in out-patients attending alcoholism and anxiety clinics in a university psychiatric hospital. The clinical and socio-demographic data of both the phobics and non-phobics of the alcoholic sample, and the alcohol dependents and non-dependents of the PAG sample, were compared. Panic attacks and phobias were associated with increased severity and worse prognosis for alcoholism. The infrequent instances of alcohol use to cope with anxiety in the PAG sample were associted with symptoms of social phobia. Alcohol abuse and dependence were more frequent in PAG men who used alcohol to cope with anxiety. Finally, the frequency and intensity of the panic and phobic symptoms of the alcoholic and PAG samples were contrasted. The alcoholism clinic patients with anxiety had less frequent and milder panic attacks. The predominant diagnosis of this group was agoraphobia, which was infrequent in the anxiety disorders clinic.     

Multicenter validation study of the %CDT TIA kit in alcohol abuse and alcohol dependence

Background: Carbohydrate-deficient transferrin (CDT) and γ-glutamyl transferase (GGT) are used as biomarkers of alcohol misuse. The aim of this study was to evaluate, in terms of sensitivity and specificity, the performance of the new Bio-Rad %CDT TIA kit and GGT assay for identifying alcohol abuse and alcohol dependence (according to the DSM-IV criteria).
Methods: An open multicenter study (30 centers) over 3 months, including patient groups of "abusers,""dependents," and controls, was conducted in France.
Results: In alcohol abuse, the sensitivity of GGT was 0.56, and that of CDT was 0.80; in alcohol dependence, the sensitivity of GGT was 0.86, and that of CDT was 0.91. The specificity of GGT was 0.77, and that of CDT was 0.83. The association of GGT with CDT increased sensitivity for alcohol abuse to 0.90 and for alcohol dependence to 0.99, but it appreciably decreased specificity (0.63).
Conclusions: %CDT is the better screening marker for alcohol abuse and dependence, but GGT is still a useful marker for the detection of alcohol dependence. As an assay method, the second-generation Bio-Rad %CDT immunoassay can be recommended for routine CDT measurement.     

Biological markers of alcohol consumption in nondrinkers,drinkers, and alcohol-dependent Brazilian patients

BACKGROUND: The purpose of this study was to compare the sensitivity and specificity of some new and traditional biological markers and indicators of health among Brazilian nondrinkers, drinkers, and alcohol-dependent patients. MATERIAL AND METHODS: We evaluated 130 nondrinkers, 167 drinkers, and 183 alcohol-dependent drinkers from Brazil who participated in the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence. A standardized WHO/ISBRA Interview Schedule provided background information on the subjects' characteristics including reported health problems and alcohol consumption. Blood samples were analyzed for aspartate aminotransferase (AST), carbohydrate deficient transferrin (CDT), gamma-glutamyltransferase (GGT), blood alcohol levels (BAL), and platelet adenylate cyclase activity (basal levels [AC] and levels after stimulation with Gpp(NH)p, cesium fluoride, and forskolin). RESULTS: The alcohol-dependent drinkers presented higher levels of AST, GGT, AC, CDT, and BAL than the nondrinkers and drinkers, whose levels were similar. Sex differences in the sensitivity of CDT and AC were found. The alcohol-dependent women presented a lower prevalence of abnormal values of CDT and Gpp(NH)p-stimulated AC than the alcohol-dependent men, despite the fact that they presented similar alcohol consumption levels. The alcohol-dependent drinkers presented a higher prevalence of clinical disorders than the nondrinkers and drinkers. The drinkers and alcohol-dependent patients presented significantly higher rates of gastritis than the nondrinkers. CONCLUSIONS: Sex differences in the sensitivity of CDT and AC suggest that these markers are not as sensitive at detecting excessive alcohol use in women as they are in men. If data from this Brazilian sample are compared with those reported for international samples, relevant differences are detected, which suggests that genetic and cultural differences should be considered in the selection of biological markers of heavy alcohol consumption.     

Comparison of 3190 alcohol-dependent individuals with and without suicide attempts

INTRODUCTION: Suicidal behaviors are often seen in alcohol-dependent individuals. The aim of this study is to identify and confirm risk factors for suicide attempts in a large, family-based sample of alcoholics. METHODS: Semistructured, detailed interviews were administered to 3190 alcohol-dependent individuals as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Information about suicidal behavior, socioeconomic characteristics, psychiatric comorbidity, substance use disorders, and characteristics of alcohol dependence were obtained from alcohol-dependent probands, controls, and their relatives. RESULTS: As determined by both univariate comparison and multivariate logistic regression analysis, alcohol-dependent individuals with a history of suicide attempts were found to have a significantly more severe course of alcohol dependence and a higher prevalence of both independent and substance-induced psychiatric disorders and other substance dependence. First-degree relatives of subjects with suicide attempts showed a significantly higher rate of suicide attempts, even after controlling for additional relevant diagnoses. CONCLUSION: These results support the hypothesis that alcohol-dependent individuals with a history of suicide attempts are more severely impaired. Screening and subsequent treatment of alcohol use disorder, psychiatric comorbidity, and substance use disorders among alcoholics may be crucial in preventing suicide attempts and completions.     

Comparison of Diagnostic Interview Schedule to psychiatrist diagnoses of alcohol use disorder in psychiatric inpatients

This study provides data about the extent of alcohol use disorders among general adult psychiatric inpatients. The accuracy of alcohol use disorder diagnoses given by the lay-administered Diagnostic Interview Schedule (DIS) and by staff psychiatrists, as compared to each other, was investigated. From consecutive admissions to a private psychiatric hospital, 55 patients with alcohol use disorders were identified by trained research assistants using the DIS (n = 162). A comparison of DIS diagnoses to clinicians' diagnoses revealed that 66 patients (40.7% of all admissions) were given an alcohol diagnosis by the DIS or clinician, 35 patients (21.6%) by DIS and clinician, 20 (12.3%) by DIS only, and 11 (6.8%) by clinician only. The two diagnostic approaches were also compared using several accuracy measures (sensitivity and specificity ratios, percentage of agreement, and kappa). With psychiatrists' diagnoses as reference, the DIS sensitivity ratio was 76 and specificity ratio 83. There were 12.3% false positive and 6.8% false negative diagnoses assigned by the DIS. Kappa was .56 and percentage of agreement 80.9%. Recomputing accuracy measures for the psychiatrist, using the DIS as the reference, clinician assessment sensitivity was 64 and specificity 90. Compared to each other, the DIS "overdiagnosed" and the staff psychiatrists "underdiagnosed" by about 1 in 20 cases. Among those alcohol use diagnoses upon which both clinician and DIS agreed, alcohol abuse was the predominant diagnosis. Among all patients with an alcohol diagnosis, the main nonsubstance abuse diagnoses (as assigned by the clinician) were: major depressive, dysthymic, bipolar, schizophrenic, and personality disorders.     

Screening for alcohol problems in the U.S. general population: comparison of the CAGE,RAPS4, and RAPS4-QF by gender,ethnicity, and service utilization. Rapid Alcohol Problems Screen

BACKGROUND: The purpose of this study was to compare the performance (sensitivity and specificity) of two brief screening instruments, CAGE and the Rapid Alcohol Problems Screen 4 (RAPS4), against ICD-10 and DSM-IV criteria for alcohol dependence and abuse in a representative sample of the U.S. adult household population by gender, ethnicity, and service utilization (emergency room and primary care) in the last year. METHODS: Data are from the Alcohol Research Group's 2000 National Alcohol Survey (n = 7612), which is a computer-assisted telephone interview survey of the U.S. general population 18 and over in all 50 U.S. states and the District of Columbia. RESULTS: Sensitivity of the RAPS4 (0.86) was better than the CAGE (0.67) given similar specificity (0.95 vs. 0.98) and outperformed the CAGE for alcohol dependence across all gender, ethnic, and service utilization groups, except among blacks and Hispanics. The RAPS4 also performed equally well for females and males (0.88 vs. 0.85), whereas sensitivity of the CAGE was lower for females. Although sensitivity of the RAPS4 was better than the CAGE for alcohol abuse, sensitivity was low for both (0.56 and 0.36, respectively). When quantity-frequency (QF) questions (drinking five or more drinks on at least one occasion during the last year and drinking as often as once a month during the last year) were added to the RAPS4, the RAPS4-QF performed significantly better for alcohol abuse and outperformed the CAGE at a cut point of one across all gender, ethnic, and service utilization groups. The RAPS4-QF appeared to be most sensitive for alcohol abuse among both males and females reporting emergency room use (0.90). CONCLUSIONS: The data suggest that the RAPS4 outperforms the CAGE in this general population sample. The addition of a QF question to the RAPS4 improves performance in relation to sensitivity for alcohol abuse, and the RAPS4 and RAPS4-QF may be the instruments of choice in brief screening for alcohol use disorders. Additional research is needed to further explore these issues.     

Validity of carbohydrate-deficient transferrin (%CDT), gamma-glutamyltransferase (gamma-GT) and mean corpuscular erythrocyte volume (MCV) as biomarkers for chronic alcohol abuse: a study in patients with alcohol dependence and liver disorders of non-alcoholic and alcoholic origin

AIM: To test the clinical performance of carbohydrate-deficient transferrin (%CDT), gamma-glutamyltransferase (gamma-GT) and mean corpuscular erythrocyte volume (MCV) as biomarkers for alcoholism with a special focus on patients suffering from liver diseases. DESIGN: Well-characterized collectives of alcohol-dependent patients with current consumption (ALC patients, n = 101), and relevant control groups (115 social drinkers, 46 patients with unspecifically increased gamma-GT, 51 hepatitis patients and 20/31 patients with non-alcohol/alcohol-dependent liver cirrhosis) were included into the study. The Positive Alcohol Use Disorders Test (AUDIT) score, International Classification of Diseases version 10 (ICD-10)/Diagnostic and Statistical Manual version IV (DSM-IV) criteria and blood drawn within 4 days of last drinking were inclusion criteria for subjects with regular heavy drinking. %CDT was determined using an automated assay which recently had been completely modified. FINDINGS: Median AUDIT scores of patients without/with regular heavy drinking were 1-3/27. The following medians/95th percentiles were obtained for %CDT: social drinkers 2.2/3.0, patients with unspecifically increased gamma-GT 2.1/3.0, hepatitis 2.0/4.4, non-alcohol-dependent liver cirrhosis 2.4/4.8, alcohol-dependent liver cirrhosis 3.0/5.9, ALC patients 3.9/14.9. Differences between patients without and with alcohol abuse were highly significant (P < 0.001). No differences in CDT values were found between males and females. There was no correlation between %CDT values, gamma-GT, MCV and the amount of alcohol consumed in ALC patients; 3.0%CDT (95th percentile social drinkers) is proposed as cut-off for the test used (Tina-quant %CDT 2nd-generation). At this cut-off, the sensitivity for ALC patients was 73.3%, whereas gamma-GT/MCV had a sensitivity of 71.3%/64.4%. Multivariate analysis performed at 95% specificity resulted in an improvement of the sensitivity by combining %CDT with gamma-GT (83.2%). A further enhancement of the sensitivity to 88.1% was obtained by combination of %CDT, gamma-GT and MCV. The diagnostic specificity of %CDT calculated at the cut-off of 3% was 93.5% in patients with unspecifically increased gamma-GT, 88.2% in hepatitis patients and 70.0% in patients with non-alcohol-dependent liver cirrhosis. %CDT was more specific in these patient collectives than MCV, and especially more than gamma-GT (specificity in hepatitis 52.9%, and 35.0% in non-alcohol-dependent liver cirrhosis). CONCLUSION: %CDT is of high diagnostic value to support diagnosis of alcohol-use disorders. The specificity of this marker in patient groups with liver disorders is superior to the biomarkers gamma-GT and MCV.     

Implications of co-occurring alcohol abuse for role impairment, health problems, treatment seeking, and early course of alcohol dependence

This article explores the nosological and clinical implications of co-occurring alcohol abuse and alcohol dependence and examines the hierarchical relationship between these diagnostic categories in the DSM-IV. Among 2,307 alcohol-dependent participants in the 2003 US National Survey on Drug Use and Health, 1,646 (68.1%) additionally met the criteria for alcohol abuse. In multivariate analyses, alcohol-dependent participants with alcohol abuse reported an earlier age of first alcoholic drink compared to those without alcohol abuse. They also reported a higher prevalence of health problems, non-alcohol drug use, impairment, treatment seeking, and early remission. The two groups had different symptom profiles. Revisions to future DSM editions are proposed to better capture these differences.     

Screening for alcohol abuse using CAGE scores and likelihood ratios

OBJECTIVE: To assess the performance of the CAGE (acronym referring to four questions, see below) questionnaire in discriminating between medicine outpatients with and without an alcohol abuse or dependence disorder. DESIGN: A cross-sectional design of a sample of consecutive patients who received both the alcohol module of the diagnostic interview schedule and the CAGE (Cut down, Annoyed, Guilty, Eye-opener) screening questionnaire. SETTING: The outpatient medical practice of an urban university teaching hospital. PATIENTS: All patients 18 years or older who signed a consent form approved by the university's institutional review board. MEASUREMENT: Calculation of the sensitivity, specificity, receiver operating characteristic (ROC) curve, and likelihood ratio for CAGE scores of 0 to 4. RESULTS: Thirty-six percent of the sample group met criteria for a history of alcohol abuse or dependence. A CAGE score of 2 or more was associated with a sensitivity and specificity of 74% and 91%. The calculated area under the ROC curve was 0.89, whereas the likelihood ratios for CAGE scores of 0 to 4 were 0.14, 1.5, 4.5, 13, and 100, respectively. These ratios were associated with posterior probabilities for an abuse or dependence disorder of 7%, 46%, 72%, 88%, and 98%, respectively. CONCLUSION: Clinicians can improve their ability to estimate a patient's risk for an alcohol abuse or dependence disorder using likelihood ratios for CAGE scores.     

Resting Hand Tremor in Abstinent Cocaine-Dependent, Alcohol-Dependent, and Polydrug-Dependent Patients

Laboratory studies of cocaine-exposed rodents, and positron emission tomographic studies of human cocaine abusers have suggested that chronic cocaine abuse downregulates dopaminergic function in the basal ganglia. The present study sought to provide behavioral evidence for this phenomenon by demonstrating enhanced levels of resting hand tremor among patients with previous histories of cocaine dependence. To determine the specificity of the phenomenon, patients with previous histories of alcohol dependence, cocaine/alcohol codependence, and cocaine/opiate codependence were also evaluated. Patients were assigned to one of four groups according to DSM-IIIR diagnostic criteria: (1) cocaine dependent (n = 19); (2) cocaine and alcohol dependent (n = 12); (3) cocaine and opiate dependent (n = 7); (4) alcohol dependent (n = 9). All were abstinent from their primary drug of abuse for a period of 1 to 5 months. The three patient groups with histories of cocaine dependence exhibited significantly more resting hand tremor than the alcohol-dependent and normal control groups. Furthermore, hand tremor in the former three groups was positively related to the number of self-reported uses of cocaine and negatively related to the number of months of cocaine abstinence.     

Alcoholism screening questionnaires

Objective: To assess the validity of the CAGE (cut down, annoyed, guilty feelings, eye-opener) questionnaire and the Michigan Alcoholism Screening Test (MAST) in distinguishing between elderly patients with and without alcohol abuse or dependence disorders. Design: A cross-sectional study, in which patients were interviewed with a “gold standard,” the alcohol module of the Revised Diagnostic Interview Schedule (DIS-III-R), and two screening questionnaires: the CAGE and the MAST. Setting: The study was conducted in the outpatient medical practice of a university teaching hospital. Patients: All English-speaking continuity patients 65 years of age or older able to participate were eligible; complete data were available for 154 (91%) of the 170 people who agreed to participate. Results: Sixty-seven patients (44%) were active drinkers, whereas 87 (56%) reported abstinence. Twenty-five patients (16%) metDiagnostic and Statistical Manual ofMental Disorders-III-Revised (DSM-III-R) criteria for alcohol abuse or dependence. A CAGE score of 2, the conventional cutoff point, had a sensitivity and a specificity of 48% and 99%, respectively. A MAST score of 5, the originally recommended cutoff point, had a sensitivity and a specificity of 52% and 91%, respectively. The areas under the receiver operating characteristic (ROC) curves were 0.91 for the CAGE and 0.61 for the MAST. Conclusion: The CAGE and the MAST were both characterized by low sensitivities at conventional cufoff points, but the CAGE was significantly more effective than the MAST in discriminating between elderly medical outpatients with and without alcohol abuse or dependence.     

Alcohol use disorders among emergency department-treated older adolescents: a new brief screen (RUFT-Cut) using the AUDIT, CAGE, CRAFFT, and RAPS-QF

BACKGROUND: Early identification of alcohol use disorders (AUD) among emergency department (ED)-treated patients is important for facilitating intervention and further evaluation outside EDs. A number of brief screening instruments have been developed for identifying patients with AUD, but it is not clear whether they are practical and perform well with older adolescents in an ED setting. This study contrasted four brief screening instruments for detecting DSM-IV-defined AUD and tested a newly developed brief screen for use among ED-treated older adolescents. METHODS: The Alcohol Use Disorders Identification Test (AUDIT), the CAGE, the CRAFFT, and a modified RAPS-QF were given to 93 alcohol-using older adolescents (55% men; aged 18-20 years) in an ED. Receiver operator characteristic analyses were used to evaluate the performance of brief screens against the criterion of a lifetime DSM-IV alcohol abuse or dependence diagnosis. RESULTS: Of existing instruments, the AUDIT had the best overall performance in identifying AUD (sensitivity, 82%; specificity, 78%). A new, shorter screening instrument composed of two AUDIT items, two CRAFFT items, and one CAGE item (RUFT-Cut) performed as well as the AUDIT (sensitivity, 82%; specificity, 78%). CONCLUSIONS: Among existing alcohol screening instruments, the AUDIT performed best for identifying ED-treated older adolescents with alcohol use disorders. The RUFT-Cut is a brief screening instrument for AUD that shows promise for identifying ED-treated older adolescents who are in need of intervention or further evaluation. Future research should focus on use of the RUFT-Cut in other settings with larger, more diverse samples of adolescents.     

Platelet adenylyl cyclase activity as a trait marker of alcohol dependence. WHO/ISBRA Collaborative Study Investigators. International Society for Biomedical Research on Alcoholism

BACKGROUND: There is compelling evidence that genetic factors play a major role in the development of alcohol dependence. Platelet adenylyl cyclase (AC) activity has been proposed as a biochemical marker for differentiating alcohol-dependent and nondependent subjects, but the sensitivity and specificity of this marker have not been ascertained. The objective of this study was to determine the sensitivity and specificity of platelet AC activity in identifying alcohol-dependent subjects and to ascertain the effect of medical/ psychiatric variables, drinking and smoking history, and age and body weight on AC activity. METHODS: The cross-sectional study was conducted from 1995 to 1998. Participants were 210 Australian White men who were community volunteers and alcohol treatment inpatients in Sydney, Australia. There were 41 nondrinkers, 140 drinkers, and 29 men who were entering alcohol treatment. The main outcome measure was platelet AC activity. Classification variables were plasma ethanol, gamma-glutamyltransferase, aspartate aminotransferase, serum carbohydrate-deficient transferrin (CDT), and urinary 5-hydroxytryptophol/5-hydroxyindoleacetic acid (5-HTOL/5-HIAA) levels, and World Health Organization/International Society for Biomedical Research on Alcoholism Interview Schedule variables, which included alcohol use and dependence criteria. RESULTS: Among subjects who reported abstinence for at least 4 days, both cesium fluoride (CsF)- and forskolin-stimulated platelet AC activities were significantly lower in those with a lifetime history of alcohol dependence compared with those with no such history (p < 0.005 and p < 0.05, respectively). The sensitivity and specificity of CsF-stimulated AC activity to discriminate individuals with a lifetime history of alcohol dependence were 75% and 79%, respectively. Similar values for sensitivity and specificity for CsF-stimulated AC activity were calculated when discriminating current alcohol dependence in the subjects in our sample. Irrespective of the history of alcohol dependence, persons who had consumed alcohol recently (within the last 3-4 days) showed significantly higher mean basal, CsF-stimulated, and forskolin-stimulated AC activity (p < 0.001), as did those who had elevated 5-HTOL/5-HIAA ratios or CDT levels, indicative of recent (heavy) drinking. The "normalization" of platelet AC activity to baseline levels after an individual stops drinking may be related to the generation of new platelets during the abstinence period. Conduct disorder and antisocial personality disorder were not associated with low AC activity, but low forskolin-stimulated AC activity was associated with major depression. CONCLUSIONS: We found that CsF- and forskolin-stimulated platelet AC activity discriminates between subjects with and without alcohol dependence in a population of subjects who had not consumed significant quantities of ethanol recently. Recent alcohol consumption is a confounding variable that can alter the measured levels of AC activity. Forskolin-stimulated platelet AC activity also may be influenced by a history of major depression.     

The Detection of Alcoholism in Hospitalized Schizophrenics: A Comparison of the MAST and the MAC

The Michigan Alcoholism Screening Test (MAST) and the MacAndrew Alcoholism Scale (MAC) were administered to forty-one schizophrenic inpatients also meeting DSM-III criteria for either alcohol abuse or alcohol dependence and 29 schizophrenic inpatients who did not qualify for an additional substance abuse diagnosis other than marijuana abuse/dependence. The MAC failed to differentiate between the alcoholic and nonalcoholic groups and both groups scored above the recommended cutting score. The MAST significantly differentiated the alcoholic and nonalcoholic schizophrenic patients and was as sensitive to a history of alcohol abuse as to alcohol dependence. Neither the MAST nor MAC was sensitive to recent versus more remote drinking. The overall classificatory accuracy of the MAST was found to be 80% and that of the MAC was 56%. A logistic regression analysis revealed that the use of just four MAST items can yield a group classificatory rate of 83%. It was concluded that the MAST exhibited sufficient sensitivity and specificity to be used as an initial screening instrument for alcoholism in schizophrenic patients.     

Alcohol dependence with comorbid drug dependence: genetic and phenotypic associations suggest a more severe form of the disorder with stronger genetic contribution to risk

BACKGROUND: Twin data suggest that alcohol dependence comorbid with illicit drug dependence represents a more heritable form of the disorder. In the Collaborative Study on the Genetics of Alcoholism sample, approximately half the alcohol-dependent individuals also meet diagnostic criteria for illicit drug dependence. In this study, we tested for heterogeneity in the association between the muscarinic acetylcholine M2 receptor gene (CHRM2) and alcohol dependence, reported previously in the full sample, among the subgroups of alcohol-dependent individuals with and without comorbid drug dependence. METHODS: Family-based association tests were conducted separately (a) in individuals with alcohol dependence with comorbid drug dependence (n = 477) and (b) in individuals with alcohol dependence without comorbid drug dependence (n = 433). These subgroups were subsequently compared on other phenotypic characteristics. RESULTS: The evidence for association between CHRM2 and alcohol dependence came entirely from the subgroup of individuals with comorbid drug dependence. There was no evidence of association with CHRM2 among the alcohol-dependent individuals without drug dependence. Subsequent phenotypic analyses suggest that the subgroup of alcohol-dependent individuals with comorbid drug dependence differ on a number of other phenotypic characteristics, including several measures of the severity of their alcohol problems, personality traits and comorbid psychiatric disorders. CONCLUSIONS: These analyses provide specific genetic evidence suggesting that alcohol dependence with comorbid drug dependence represents a particularly severe form of the disorder, with higher genetic contribution to vulnerability.