DSM-IV Alcohol Dependence Diagnosis Research Articles

Genome-wide admixture mapping of DSM-IV alcohol dependence, criterion count, and the self-rating of the effects of ethanol in African American populations.

African Americans (AA) have lower prevalence of alcohol dependence and higher subjective response to alcohol than European Americans. Genome-wide association studies (GWAS) have identified genes/variants associated with alcohol dependence specifically in AA; however, the sample sizes are still not large enough to detect variants with small effects. Admixture mapping is an alternative way to identify alcohol dependence genes/variants that may be unique to AA. In this study, we performed the first admixture mapping of DSM-IV alcohol dependence diagnosis, DSM-IV alcohol dependence criterion count, and two scores from the self-rating of effects of ethanol (SRE) as measures of response to alcohol: the first five times of using alcohol (SRE-5) and average of SRE across three times (SRE-T). Findings revealed a region on chromosome 4 that was genome-wide significant for SRE-5 (p value=4.18E-05). Fine mapping did not identify a single causal variant to be associated with SRE-5; instead, conditional analysis concluded that multiple variants collectively explained the admixture mapping signal. PPARGC1A, a gene that has been linked to alcohol consumption in previous studies, is located in this region. Our finding suggests that admixture mapping is a useful tool to identify genes/variants that may have been missed by current GWAS approaches in admixed populations.

Effects of alcohol intoxication on self-reported drinking patterns, expectancies, motives and personality: a randomized controlled experimental study.

Alcohol intoxication may affect self-reports of alcohol use and related constructs, such as impulsivity and dependence symptoms. Improved knowledge about potential systematic reporting biases induced by alcohol, e.g. through disinhibition, may be relevant for the assessment of intoxicated individuals both in clinical routine and research. We therefore randomly assigned 54 socially drinking males aged 18 to 19 without lifetime diagnosis of DSM-IV alcohol dependence to one of two experimental arms: either placebo infusion at day 1 and alcohol infusion at day 2, or vice versa. The lab-based intravenous alcohol infusion produced a constant blood alcohol level of 0.08 percent. On each day, participants completed the Alcohol Use Disorders Identification Test, as well as other questionnaires on alcohol expectancies, drinking motives and substance use-related temperament traits. We found that alcohol significantly increased self-reported expectancies (tension reduction) and motives (conformity; η2 =.16-.23), but we observed no effect of sequence, i.e. alcohol first versus placebo first (Pcorr ≥.118). High baseline alcohol expectancies did not moderate alcohol effects (Pcorr ≥.462). We conclude that moderate alcohol intoxication might not generally affect the reliability of self-reported alcohol use, alcohol use problems and psychological concepts related to drinking behavior in young males without alcohol dependence. Future studies could examine larger, less selective and clinical samples for possible alcohol effects on self-report measures related to alcohol consumption.

Genome-wide association study of body mass index in subjects with alcohol dependence.

Outcomes related to disordered metabolism are common in alcohol dependence (AD). To investigate alterations in the regulation of body mass that occur in the context of AD, we performed a genome-wide association study (GWAS) of body mass index (BMI) in African Americans (AAs) and European Americans (EAs) with AD. Subjects were recruited for genetic studies of AD or drug dependence and evaluated using the Semi-structured Assessment for Drug Dependence and Alcoholism. We investigated a total of 2587 AAs and 2959 EAs with DSM-IV AD diagnosis. In the stage 1 sample (N = 4137), we observed three genome-wide significant (GWS) single-nucleotide polymorphism associations, rs200889048 (P = 8.98 * 10-12 ) and rs12490016 (P = 1.44 * 10-8 ) in EAs and rs1630623 (P = 5.14 * 10-9 ) in AAs and EAs meta-analyzed. In the stage 2 sample (N = 1409), we replicated 278, 253 and 168 of the stage 1 suggestive loci (P < 5*10-4 ) in AAs, EAs, and AAs and EAs meta-analyzed, respectively. A meta-analysis of stage 1 and stage 2 samples (N = 5546) identified two additional GWS signals: rs28562191 in EAs (P = 4.46 * 10-8 ) and rs56950471 in AAs (P = 1.57 * 10-9 ). Three of the GWS loci identified (rs200889048, rs12490016 and rs1630623) were not previously reported by GWAS of BMI in the general population, and two of them raise interesting hypotheses: rs12490016-a regulatory variant located within LINC00880, where there are other GWAS-identified variants associated with birth size, adiposity in newborns and bulimia symptoms, which also interact with social stress in relation to birth size; rs1630623-a regulatory variant related to ALDH1A1, a gene involved in alcohol metabolism and adipocyte plasticity. These loci offer molecular insights regarding the regulatory mechanisms of body mass in the context of AD.

Prospective developmental subtypes of alcohol dependence from age 18 to 32 years: Implications for nosology, etiology, and intervention

The purpose of the present study is to identify child and adult correlates that differentiate (a) individuals with persistent alcohol dependence from individuals with developmentally limited alcohol dependence and (b) individuals with adult-onset alcohol dependence from individuals who never diagnose. There are 1,037 members of the Dunedin Longitudinal Study, which is a birth cohort followed prospectively from birth until age 32. Past-year DSM-IV alcohol dependence diagnoses are ascertained with structured diagnostic interviews at ages 18, 21, 26, and 32. Individuals are classified as developmentally limited, persistent, or adult-onset subtypes based on their time-ordered pattern of diagnoses. The persistent subtype generally exhibits the worst scores on all correlates, including family psychiatric history, adolescent and adult externalizing and internalizing problems, adolescent and adult substance use, adult quality of life, and coping strategies. The prospective predictors that distinguished them from the developmentally limited subtype involved family liability, adolescent negative affectivity, daily alcohol use, and frequent marijuana use. Furthermore, young people who develop the persistent subtype of alcohol dependence are distinguished from the developmentally limited subtype by an inability to reduce drinking and by continued use despite problems by age 18. The adult-onset group members are virtually indistinguishable from ordinary cohort members as children or adolescents; however, in adulthood, adult-onset cases are distinguished by problems with depression, substance use, stress, and strategies for coping with stress. Information about age of onset and developmental course is fundamental for identifying subtypes of alcohol dependence. Subtype-specific etiologies point to targeted prevention and intervention efforts based on the characteristics of each subtype.

Ethnicity and Gender Comparisons of Health Consequences in Adults with Alcohol Dependence

The moderating effects of ethnicity and gender on factors associated with physical health consequences in adults manifesting alcohol dependence were examined using data from the 2001–2002 US National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Black and white respondents with a lifetime diagnosis of DSM-IV alcohol dependence were selected for the study (n = 3,852). A multiple-group structural equation model tested ethnicity, gender, and intervening variables as predictors of physical health status in alcohol-dependent men and women. Study findings offer implications for clinical practice with alcohol-dependent individuals by identifying likely target groups and problems for intervention.

Age of Onset and Neuropsychological Functioning in Alcohol Dependent Inpatients

Differences in clinical characteristics between early and late onset alcohol dependent patients have been examined intensively, but little is known about the differences in neuropsychological functioning between these patient groups. Clinical characteristics and neuropsychological functions of inpatients with early onset and late onset alcohol dependence are therefore investigated in this study. Ninety-three abstinent alcohol dependent inpatients meeting a current diagnosis of DSM-IV alcohol dependence were divided into early onset alcohol dependent patients (EOA; ≤25 years; n = 36) and late onset alcohol dependent patients (LOA; >25 years; n = 57). Patients using psychoactive medication and patients dependent on other substances than alcohol (and nicotine) were excluded. A comprehensive neuropsychological test battery was administered. EOA reported higher trait impulsivity, antisocial traits, and attention deficit hyperactivity disorder-related traits and exhibited an impulsive reflection style, especially in a high-risk context, compared with LOA. Against expectations, EOA performed significantly better on measures of planning, cognitive control, visual memory, and delayed recognition memory than LOA, whereas no significant group differences occurred on measures of delay discounting, digit span, and attention. Better Stroop interference, better visual memory, and a more impulsive reflection style was predictive of an early age of onset, and explained a significant and additional amount of variance (18.8%) on top of the clinical characteristics, together explaining 53.4% of the variance. Both clinical characteristics and neuropsychological variables contributed independently to the age of onset of problematic alcohol use. Results indicate that especially an impulsive reflection style, besides higher trait impulsivity, may be the core feature of early onset alcohol dependence. However, the contribution of the neuropsychological variables is complex and more research is needed to clarify the role of psychiatric comorbidity and poly-substance abuse in an unselected sample of alcohol dependent patients.

Linkage scan of alcohol dependence in the UCSF Family Alcoholism Study

Ample data suggest that alcohol dependence represents a heritable condition, and several research groups have performed linkage analysis to identify genomic regions influencing this disorder. In the present study, a genome-wide linkage scan for alcohol dependence was conducted in a community sample of 565 probands and 1080 first-degree relatives recruited through the UCSF Family Alcoholism Study. The Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was used to derive DSM-IV alcohol dependence diagnoses. Although no loci achieved genome-wide significance (i.e., LOD score > 3.0), several linkage peaks of interest (i.e., LOD score > 1.0) were identified. When the strict DSM-IV alcohol dependence diagnosis requiring the temporal clustering of symptoms served as the phenotype, linkage peaks were identified on chromosomes 1p36.31–p36.22, 2q37.3, 8q24.3, and 18p11.21–p11.2. When the temporal clustering of symptoms was not required, linkage peaks were again identified on chromosomes 1p36.31–p36.22 and 8q24.3 as well as novel loci on chromosomes 1p22.3, 2p24.3–p24.1, 9p24.1–p23, and 22q12.3–q13.1. Follow-up analyses were conducted by performing linkage analysis for the 12 alcohol dependence symptoms assessed by the SSAGA across the support intervals for the observed linkage peaks. These analyses demonstrated that different collections of symptoms often assessing distinct aspects of alcohol dependence (e.g., uncontrollable drinking and withdrawal vs. tolerance and drinking despite health problems) contributed to each linkage peak and often yielded LOD scores exceeding that reported for the alcohol dependence diagnosis. Such findings provide insight into how specific genomic regions may influence distinct aspects of alcohol dependence.

The dimensionality of alcohol use disorders and alcohol consumption in a cross‐national perspective

To replicate the finding that there is a single dimension trait in alcohol use disorders and to test whether the usual 5+ drinks for men and 4+ drinks for women and other measures of alcohol consumption help to improve alcohol use disorder criteria in a series of diverse patients from emergency departments (EDs) in four countries. Cross-sectional surveys of patients aged 18 years and older that reflected consecutive arrival at the ED. The Composite International Diagnostic Interview Core was used to obtain a diagnosis of DSM-IV alcohol dependence and alcohol abuse; quantity and frequency of drinking and drunkenness as well as usual number of drinks consumed during the last year. Participants were 5195 injured and non-injured patients attending seven EDs in four countries: Argentina, Mexico, Poland and the United States (between 1995-2001). Using exploratory factor analyses alcohol use disorders can be described as a single, unidimensional continuum without any clear-cut distinction between the criteria for dependence and abuse in all sites. from item response theory analyses showed that the current DSM-IV criteria tap people in the middle-upper end of the alcohol use disorder continuum. Alcohol consumption (amount and frequency of use) can be used in all EDs with the current DSM-IV diagnostic criteria to help tap the middle-lower part of this continuum. Even though some specific diagnostic criteria and some alcohol consumption variables showed differential item function across sites, test response curves were invariant for ED sites and their inclusion would not impact the final (total) performance of the diagnostic system. DSM-IV abuse and dependence form a unidimensional continuum in ED patients regardless of country of survey. Alcohol consumption variables, if added, would help to tap patients with more moderate severity. The DSM diagnostic system for alcohol use disorders showed invariance and performed extremely well in these samples.

GENETIC STUDY: H2 haplotype at chromosome 17q21.31 protects against childhood sexual abuse‐associated risk for alcohol consumption and dependence

Animal research supports a central role for corticotropin-releasing factor (CRF) in actions of ethanol on brain function. An examination of alcohol consumption in adolescents reported a significant genotype x environment (G x E) interaction involving rs1876831, a corticotropin-releasing hormone receptor 1 (CRHR1) polymorphism, and negative events. CRHR1 and at least four other genes are located at 17q21.31 in an extremely large block of high linkage disequilibrium resulting from a local chromosomal inversion; the minor allele of rs1876831 is contained within the H2 haplotype. Here, we examine whether G x E interactions involving this haplotype and childhood sexual abuse (CSA) are associated with risk for alcohol consumption and dependence in Australian participants (n = 1128 respondents from 476 families) of the Nicotine Addiction Genetics project. Telephone interviews provided data on DSM-IV alcohol dependence diagnosis and CSA and enabled calculation of lifetime alcohol consumption factor score (ACFS) from four indices of alcohol consumption. Individuals reporting a history of CSA had significantly higher ACFS and increased risk for alcohol dependence. A significant G x E interaction was found for ACFS involving the H2 haplotype and CSA (P < 0.017). A similar G x E interaction was associated with protective effects against alcohol dependence risk (odds ratio 0.42; 95% confidence interval 0.20-0.89). For each outcome, no significant CSA-associated risk was observed in H2 haplotype carriers. These findings support conducting further investigation of the H2 haplotype to determine the gene(s) responsible. Our results also suggest that severe early trauma may prove to be an important clinical covariate in the treatment of alcohol dependence.

DSM-IV alcohol dependence and sustained reduction in drinking: investigation in a community sample.

A common clinical conception of alcohol dependence is that it is chronic, and the idea of impaired control figures prominently in an influential definition of alcohol dependence. We investigated the meaning of a diagnosis of DSM-IV alcohol dependence in untreated individuals. Household residents screened for elevated drinking were assessed for DSM-IV alcohol dependence and re-interviewed 1 year later. We report on 115 subjects with and 460 subjects without current DSM-IV alcohol dependence at baseline. Follow-up drinking indicators included a measure of sustained reduction in drinking. No support was found for a lower probability of sustained reduction in drinking at follow-up among the group with baseline DSM-IV alcohol dependence. Significant group differences indicated that the dependent group was more likely to reduce drinking. A diagnosis of DSM-IV alcohol dependence among untreated individuals implies a prognosis that is different from that for the same diagnosis among those seen in treatment settings. This does not necessarily indicate that the diagnosis is invalid, but rather suggests that risk factors for chronic course are more applicable to cases of DSM-IV alcohol dependence seen in treatment settings.

Reliability and discriminant validity of the Type I/II and Type A/B alcoholic subtype classifications in untreated problem drinkers: a test of the Apollonian–Dionysian hypothesis

The present study tested the hypothesis that there are two broad groups of problem drinkers: the Apollonian–Dionysian distinction. Apollonian drinkers are defined by a later onset of alcohol problems, a slower developmental course, and less problem severity. Dionysian drinkers are defined by more severe alcohol problems, an earlier onset, and worse prognosis. The discriminant validity and classification agreement of five operations of the Apollonian–Dionysian model were tested in a general population ( n=8643) and community sample ( n=664). A κ-means cluster analysis supported the Apollonian–Dionysian distinction. Dionysian problem drinkers were more likely to be males, report greater alcohol consumption, more alcohol related antisocial behavior, have a current DSM-IV alcohol dependence diagnosis, and comorbid depression. Apollonian problem drinkers were more prevalent in the general population and reported less severe drinking problems. Classification agreement was stronger for subtype models that incorporate dimensions of alcohol use and/or the frequency of negative consequences. Babor's Type A–Type B model demonstrated the strongest reliability and consistency over time.

Using cluster analysis of alcohol use disorders to investigate ‘diagnostic orphans’: subjects with alcohol dependence symptoms but no diagnosis

The purpose of this paper is to examine the characteristics of community subjects with one or two alcohol dependence symptoms who did not satisfy the criteria for Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) alcohol dependence or abuse (sub-diagnostic group or diagnostic orphans). Variables not included in the DSM-IV alcohol abuse and dependence criteria are used to compare the different alcohol statuses. The results indicate that the sub-diagnostic group ‘diagnostic orphans’ formed a cluster distinct from that of the non-problem drinkers group, and appeared to be closer to those with alcohol abuse than to those with alcohol dependence. The diagnosis of DSM-IV alcohol dependence (with three, four, or five or more symptoms) appeared to be its own entity. The findings lend credence to the requirement of three symptoms (in any 12 months) for the diagnosis of alcohol dependence in DSM-IV. However, those with one or two symptoms of alcohol dependence should be considered along with alcohol abuse as an entity in future DSM classifications.

Drinking to cope with negative affect and DSM-IV alcohol use disorders: a test of three alternative explanations.

Previous studies of drinking motives have demonstrated greater levels of drinking to cope with negative affect among problem drinkers relative to nonproblem drinkers. These findings suggest that the use of alcohol to cope with negative affect may place individuals at greater risk for the development of alcohol problems. However, several alternative explanations exist, each with different intervention implications. This study evaluated three alternative explanations or models: risk-factor, generalizing, and epiphenomena. A cross-sectional design was used to compare levels of self-reported drinking to cope with negative affect between individuals who had current DSM-IV alcohol use disorders and those who did not. Participants consisted of a sample of community residents (N = 777, 55% men). All participants completed an in-person structured psychiatric interview and a self-report questionnaire assessing alcohol use, drinking motives, depressive affect, and negative alcohol consequences. Linear regression models yielded significant differences in mean drinking to cope with negative affect scores between participants with a DSM-IV alcohol dependence diagnosis and participants with no diagnosis. These differences remained after controlling for depressive affect and frequency of negative alcohol consequences in three of the four adjusted comparisons. No significant differences in adjusted mean drinking to cope with negative affect scores were demonstrated between subjects with a DSM-IV alcohol abuse diagnosis and those with no diagnosis. The DSM-IV alcohol dependence and no-diagnosis comparisons were most consistent with the predictions of a risk-factor model. These results provide further evidence that drinking to cope with negative affect may have an etiological role in development of alcohol dependence.

DSM-IV alcohol abuse: investigation in a sample of at-risk drinkers in the community.

Although a category for alcohol abuse has been included in the major nomenclatures since DSM-III, many questions have been raised about the definitions and validity of this category. We investigated DSM-IV alcohol abuse in 628 at-risk drinkers residing in households who never met criteria for DSM-IV alcohol dependence at the time of a baseline interview. Cross-sectional and prospective longitudinal information were used. Subjects most often met criteria for abuse with the single criterion, recurrent hazardous use (usually driving after drinking too much, on average 4.5 times per year). Younger and white subjects were more likely to receive the abuse diagnosis at baseline, as were drug users and those who drank five or more drinks per occasion frequently. Very few subjects received a diagnosis of DSM-IV alcohol dependence at follow-up, and those who did were equally likely to come from the abuse and non-abuse baseline groups. A current abuse diagnosis at baseline strongly and significantly predicted an abuse diagnosis at follow-up, although a past-only (remitted) abuse diagnosis at baseline was not clearly predictive of abuse at follow-up. The DSM-IV alcohol abuse category has some predictive validity. However, given the manner in which respondents met criteria for the disorder, its merits as a diagnostic category remain in question. Researchers should be cautious about combining alcohol dependence and abuse into the same category.

Dependence symptoms but no diagnosis: diagnostic ‘orphans’ in a 1992 national sample

The alcohol dependence syndrome was initially presented as a condition with graded severity. However, to receive a diagnosis that is categorical, a diagnostic threshold must be determined. Much previous research on this issue has focused on setting a threshold that will produce the highest possible consistency in rates between one set of diagnostic criteria and the next. It is possible that a different threshold may be more valid. Results from a community sample supported a minimum diagnostic threshold of three or more dependence symptoms but the sample was not nationally representative. Therefore, we investigated the meaning of the ‘orphan’ status (one or two dependence symptoms but no DSM-IV alcohol dependence diagnosis) in a large national sample. Two sets of analyses were performed, the first using a current timeframe and the second using a lifetime timeframe. Abstainers were excluded from all analyses. In each set of analyses, three groups were compared: subjects with no symptoms of any alcohol use disorder; diagnostic ‘orphans’ with one or two symptoms of dependence; and subjects who met full criteria for DSM-IV alcohol dependence. Several variables significantly differentiated the three groups, including heavy drinking and family history of alcoholism. Group differences were reduced among ‘orphans’ and subjects with no symptoms who had at least one occasion of drinking five or more drinks in the year prior to the interview. The results provide support for the decision to require a minimum of three symptoms to make a diagnosis of alcohol dependence, for scientific as well as pragmatic reasons.

Dependence symptoms but no diagnosis: diagnostic `orphans' in a community sample

To receive a DSM-IV diagnosis of alcohol dependence, an individual must manifest at least three out of seven possible dependence criteria. Thus, individuals may manifest one or two dependence criteria yet not receive the dependence diagnosis. In a sense, these latter individuals may be seen as diagnostic `orphans', since they have individual symptoms of dependence but no diagnoses. A study of these individuals sheds light on the validity of the three-symptom severity threshold for a diagnosis of DSM-IV alcohol dependence. Thus, we investigated the meaning of the `orphan' status through cross-sectional and longitudinal research in a general population sample. Three groups were compared at baseline, subjects with no symptoms of any alcohol use disorder (148), diagnostic `orphans' with one or two symptoms of dependence (136) and subjects who met full criteria for DSM-IV alcohol dependence (140). Several variables significantly differentiated the three groups, including binge drinking and family history of alcoholism. At a 1-year follow-up point, very few of the `orphans' met criteria for DSM-IV alcohol dependence. The proportion of new onsets from the `orphan' group and the group with no symptoms did not differ significantly. Binge drinking predicted chronicity of `orphan' status, but family history of alcoholism did not. The results support the decision to require a minimum of three symptoms to make a diagnosis of alcohol dependence.

A prospective evaluation of the relationship between reasons for drinking and dsm-iv alcohol-use disorders

Previous research has demonstrated an association between self-reported reasons for drinking and alcohol consumption. The most consistent relationships have been demonstrated between alcohol consumption and drinking for positive affect enhancement and coping with negative affect. However, most of the results have been from cross-sectional research designs that have not controlled for diagnostic status. The present study was a prospective investigation of the relationship between reasons for drinking and the Diagnostic and Statistical Manual of Mental Disorders (4th ed.), diagnoses of alcohol abuse and dependence. Subjects consisted of 508 community residents (264 male and 244 female) who did not meet DSM-IV criteria for an alcohol-use disorder at a baseline interview, who completed a completely structured interview (AUDADIS) and a self-report assessment battery, and who were re-interviewed approximately 1 year later. Results indicated a significant relationship between baseline reasons for drinking and follow-up diagnostic classification. Drinking to reduce negative affect predicted having a DSM-IV alcohol dependence diagnosis at follow-up, but not a diagnosis of alcohol abuse. No significant association was demonstrated between the baseline motive of drinking for positive affect enhancement and a follow-up DSM-IV alcohol-use disorder.

AA and other helpseeking for alcohol problems: former drinkers in the U.S. general population.

Former drinkers comprise 18.5% of the adult U.S. population. However, no epidemiologic data has been published on the histories of seeking help for alcohol problems from Alcoholics Anonymous (AA) or professional or informal sources of help. Using a sample of 8,057 former drinkers surveyed in the 1988 National Health Interview Survey, prevalence and characteristics associated with histories of such helpseeking were investigated. About 7% of the former drinkers had gone to AA or sought other types of help. Characteristics associated with such helpseeking were a diagnosis of DSM-IV alcohol dependence or abuse, a sense of compulsion to drink, social pressure to cut down, and highest ever alcohol consumption. The effects of alcohol consumption were stronger among younger respondents than older ones for professional or informal helpseeking.