A Prospective Comparison of Bipolar I and II Subjects with and without Comorbid Cannabis Use Disorders from the COGA Dataset.

OBJECTIVE: The comorbidity of alcohol and substance use disorders among persons with bipolar disorder is elevated, as indicated by epidemiological and clinical studies. Following alcohol use, cannabis is the most frequently used and abused illicit substance among bipolar individuals, and such use may lead to comorbid cannabis use disorders (CUD). Previous research indicated that CUDs were related to a more severe course of bipolar disorder and higher rates of other comorbid alcohol and substance use disorders. Few studies, however, have conducted longitudinal research on this comorbidity. The aim of this study is to investigate the influence of CUD on the course of bipolar I and II individuals during a 5-year follow-up. METHODS: The characteristics of bipolar disorder, cannabis use disorders, and other alcohol and substance use disorders, as well as comorbid mental disorders, were assessed using a standardized semi-structured interview (SSAGA) at both baseline and the 5-year follow-up. N = 180 bipolar I and II patients were subdivided into groups of with and without comorbid cannabis use disorders (CUD). RESULTS: Of the 77 bipolar I and 103 bipolar II patients, n = 65 (36.1%) had a comorbid diagnosis of any CUD (DSM-IV cannabis abuse or dependence). Comorbid bipolar patients with CUD had higher rates of other substance use disorders and posttraumatic stress disorders, more affective symptoms, and less psychosocial functioning at baseline and at 5-year follow-up. In contrast to previously reported findings, higher rates of anxiety disorders and bipolar disorder complications (e.g., mixed episodes, rapid cycling, and manic or hypomanic episodes) were not found. The effect of CUD on other substance use disorders was confirmed using moderation analyses. CONCLUSIONS: A 5-year prospective evaluation of bipolar patients with and without CUD confirmed previous investigations, suggesting that the risk of other substance use disorders is significantly increased in comorbid individuals. CUD has a moderation effect, while no effect was found for other mental disorders. Findings from this study and previous research may be due to the examination of different phenotypes (Cannabis use vs. CUD) and sample variation (family study vs. clinical and epidemiological populations).

Do personality characteristics predict future alcohol problems after considering current demography, substance use, and alcohol response?

BACKGROUND: Several personality traits predict future alcohol problems but also relate to demographic and substance-related variables that themselves correlate with later adverse alcohol outcomes. Few prospective studies have evaluated whether personality measures predict alcohol problems after considering current demographic and substance-related variables. METHODS: Data from 414 drinkers without alcohol use disorder (AUD) from the Collaborative Study on the Genetics of Alcoholism (average age 20, 44% male) were followed over an average of 9 years. Time 1 (baseline) demography, AUD family history (FH), substance use and problems, and psychiatric histories were gathered using a standardized interview; the Level of Response (LR) to alcohol was measured by the Self-Report of the Effects of alcohol (SRE) questionnaire; and seven personality dimensions were extracted from the NEO Five-Factor Personality, Barratt, and Zuckerman scales. Analyses involved product-moment correlations of each baseline measure with the highest number of DSM-IV AUD criteria endorsed in any follow-up period, and hierarchical regression analyses evaluated whether the personality domains added significantly to the prediction of the outcome after adjusting for other baseline variables. RESULTS: Significant correlations with the outcome were observed for baseline age, sex, length of follow-up, AUD family history, past cannabis use, and all alcohol-related baseline variables, including SRE-based LR, but not prior mood or anxiety disorders. All personality characteristics except extraversion also correlated with outcomes. A hierarchical regression analysis that included all relevant personality scores together demonstrated significant contributions to the prediction of future alcohol problems for demographics in Step 1; demographics and most baseline alcohol items, including response level, in Step 2; and cannabis use in Step 3; after which demographics, LR, baseline alcohol problems, cannabis use, and higher sensation seeking added significantly in Step 4. Regression for each personality domain separately revealed significant contributions to Step 4 for all personality domains except openness. Lower levels of response to alcohol added significantly to all regression analyses. CONCLUSIONS: Most tested personality scores and lower levels of response to alcohol contributed to predictions of later alcohol problems even after considering baseline demographic and substance use measures.

Changes over time in endorsement of 11 DSM-IV alcohol use disorder (AUD) criteria in young adults with persistent or recurrent AUD in The Collaborative Study on the Genetics of Alcoholism.

BACKGROUND: Endorsement of specific Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) alcohol use disorder (AUD) criteria have been shown to change significantly over time in men in their thirties who have persistent or recurrent AUD. However, few studies have documented whether the endorsement of AUD items changes over time in younger individuals or in women. We evaluated changes in the endorsement of AUD criteria in 377 men and women with persistent or recurrent AUD during their twenties. METHODS: Information on AUD-item endorsement over time was available for 223 men and 154 women aged 20-25 with persistent or recurrent AUD in at least three interviews in the Collaborative Study on the Genetics of Alcoholism. The statistical significance of endorsement changes over time was evaluated using the related-sample Cochran's Q test for the full sample and for men and women separately. Additional analyses evaluated sex differences in the patterns of change. RESULTS: In the full sample, the predominant pattern was for a significant increase in the rates of endorsement for six of the seven alcohol dependence criteria but not in the four abuse criteria. A similar pattern was seen within men, but women had significant changes in only three of the seven dependence criteria. CONCLUSIONS: Endorsement of the seven alcohol dependence criteria among individuals with persistent or recurrent AUD in their twenties generally increased, but few changes were observed in the rates of endorsement of the four abuse criteria. These results are discussed in terms of how they reflect on the nature of AUD and the DSM criteria.

A latent class analysis of alcohol and posttraumatic stress symptoms among offspring of parents with and without alcohol use disorder.

The co-occurrence of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) is widely known, yet few studies have examined whether and how AUD symptoms co-occur with PTSD symptom clusters of hypervigilance, avoidance/numbing, and re-experiencing. The purpose of this study was to examine potential overlap between AUD and posttraumatic stress symptomatology, and to characterize the resultant latent classes in terms of demographics, drinking behaviors, parental AUD, and specific traumas experienced (physical violence, sexual violence, and non-assaultive trauma). We hypothesized that classes would be differentiated by type and severity of AUD and PTS symptoms. Drawing from a sample of white and Black participants from the Collaborative Study on the Genetics of Alcoholism (COGA), we examined young adults between the ages of 18-35 who had experienced trauma (N = 2478). A series of LCA models based on the type of trauma experienced, posttraumatic stress symptoms and problematic alcohol use were then fitted to the data. A four-class solution provided the best fit, consisting of a low symptom class (N = 1134), moderate alcohol/low PTS severity (N = 623), mild alcohol/high PTS severity (N = 544), and high symptom severity (N = 177). Higher prevalence of sexual assault was associated with membership in high PTS severity classes, and parent AUD was associated with membership in each class, particularly when the mother or both parents had the disorder. Using person-centered methods such as LCA is a commonsense approach to understanding the heterogeneity of symptoms, trauma types, and individual-level characteristics associated with trauma-exposed individuals and comorbid AUD-PTSD, and our study is one of relatively few to empirically ascertain the co-occurrence of alcohol and PTS symptoms in a high-risk family sample.

Subtypes of Alcohol Dependence and 36-Year Mortality.

BACKGROUND: Chronic, heavy alcohol use is associated with multiple health problems, including premature death. Further, the clinical presentation of alcohol dependence may differentially affect and predict the long-term health consequences of affected individuals. Subtypes of alcohol dependence based upon treatment intake information can help identify homogenous groups of patients for treatment purposes, but have not been used to predict long-term outcomes. The current study examined mortality in a 36-year posttreatment interval among 4 subtypes of alcohol-dependent patients based upon their initial intake data. METHODS: Extensive baseline data were collected from n = 316 male and female patients receiving inpatient treatment for alcohol dependence between 1980 and 1982. Four alcohol dependent subtypes (Del Boca & Hesselbrock, Alcohol Health Res World, 20:56, 1996) derived from the baseline data were used to examine the 1-year posttreatment drinking status and the risk of death 36 years postdischarge. Public records were used to determine patient deaths in the 36 years since discharge. RESULTS: At the 36-year follow-up interval since discharge, 68.4% of the sample had died. The 4 subtypes were found to be associated with different rates of resumption of regular drinking in the first year posttreatment and a differential risk of mortality. An increased risk for returning to regular drinking (once a week or more) and early death were associated with subtypes defined, in part, by conduct problems and externalizing disorders. Regardless of subtype membership, women had the highest risk of death following treatment. CONCLUSIONS: This study demonstrates the clinical usefulness of subtypes of alcohol dependence for examining different alcohol use outcomes, including predicting mortality. The increased risks for returning to regular drinking once a week or more and early death posttreatment among subtypes associated with conduct problems and externalizing disorders suggest the need for continued monitoring and possible additional intervention postdischarge.

Trauma Exposure and Post-Traumatic Stress Disorder Among Youth in a High-Risk Family Study: Associations with Maternal and Paternal Alcohol Use Disorder.

This study presents findings regarding the prevalence of trauma exposure and Posttraumatic Stress Disorder (PTSD) based on discrete types of trauma (physical, sexual, witnessed violence, and non-assaultive trauma) among 3404 youth in a family study of Alcohol Use Disorder (AUD). Data from the Collaborative Study on the Genetics of Alcoholism (COGA) were used to examine associations of parent AUD with offspring's childhood trauma exposure, and with lifetime diagnosis of DSM-IV PTSD among White and Black participants aged 12-35. Of 3404 youth, 59.7% had parents affected by AUD and 78% experienced ≤1 traumatic events before age 18. AUD in one or both parents was associated with physical, sexual, and witnessed violence among Whites. Among African Americans, maternal AUD was associated with sexual assault. The lifetime PTSD rate among youth exposed to childhood trauma was 8.6%, and mother-only AUD was significantly associated with lifetime PTSD among participants in both groups. PTSD among youth in this study were somewhat higher (7.9% to 8.83%) than those found in general population studies of the same demographic (5% to 6.8%). Maternal AUD appears to be a salient risk factor for sexual assault before age 18 among Black and development of lifetime PTSD among White youth.

A Pilot Follow-Up Study of Older Alcohol-Dependent COGA Adults.

BACKGROUND: Alcohol consumption and problems are increasing among older adults, who are at elevated risk for alcohol-related accidents and medical problems. This paper describes a pilot follow-up of older adults with a history of alcohol dependence that was designed to determine the feasibility of conducting a more extensive investigation. METHODS: The sample consisted of previously assessed subjects in the Collaborative Studies on the Genetics of Alcoholism who: (i) were age 50+; (ii) had lifetime DSM-IV AD; and (iii) had DNA available. Individuals were located through family contacts, Internet searches, and death registries. A brief telephone interview assessed demographics, health, and alcohol involvement. RESULTS: Of the total sample (N = 2,174), 36% were contacted, 24% were deceased, and 40% were not yet located. Most (89%) contacted subjects were interviewed, and 99% of them agreed to future evaluation. Thirty percent of interviewed subjects reported abstinence for 10+ years, 56% reported drinking within the past year, and 14% last drank between >1 and 10 years ago. There were no age-related past-year differences in weekly consumption (overall sample mean: 16 drinks), number of drinking weeks (30.8), maximum number of drinks in 24 hours (8.1), or prevalence of weekly risky drinking (19%). Among those who drank within the past 5 years, the 3 most common alcohol-related problems were spending excessive time drinking or recovering (49%), drinking more/longer than intended (35%), and driving while intoxicated (35%); and about a third (32%) received some form of treatment. CONCLUSIONS: Over a 1-year period, we located 60% of individuals last seen an average of 23 years ago. The majority of contacted individuals were interviewed and willing to be evaluated again. Although the proportion of individuals currently drinking diminished with age, subjects exhibited troublesome levels of alcohol consumption and problems. Our findings suggest the importance and feasibility of a more comprehensive follow-up.

Reliability and validity of an internalizing symptom scale based on the adolescent and adult Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA).

BACKGROUND: The Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) is an interview that assesses psychiatric symptoms and diagnoses, including substance use disorders and anxiety and mood (i.e., internalizing) disorders. Although the SSAGA is widely used, there exists no overall internalizing characteristics scale based on items drawn from SSAGA's mood and anxiety disorder sections. OBJECTIVES: To design and assess a SSAGA-based measurement instrument capturing the overall internalizing dimension that underlies more specific internalizing conditions. METHODS: We developed, assessed, and characterized a new scale for measuring internalizing problematic characteristics derived from the SSAGA interview. All samples were drawn from the Collaborative Studies on the Genetics of Alcoholism, a prospective multi-site genetic study of families at high risk for alcohol use disorders. All participants taking part in the study between September 2005 and September 2017 were eligible (n = 904, 52.2% female). RESULTS: The scale had adequate internal consistency (ordinal α = 0.85, 95% CI = [0.81, 0.89]). Construct validity was supported by its association with other measures of internalizing characteristics (Internalizing Scale from Achenbach Self Reports; Neuroticism Scale from the Neuroticism-Extraversion-Openness Five-Factor Personality Inventory). Several indices of alcohol, marijuana, and nicotine misuse were also positively associated with Internalizing Scale scores. CONCLUSIONS: The Internalizing Scale has very good psychometric properties and can be used in studies that incorporate the SSAGA interview to study the association between internalizing characteristics and problematic alcohol and other substance use. These associations can potentially be utilized to identify individuals at risk for substance problems and to design treatments targeting such individuals.

A 22-Year Follow-Up (Range 16 to 23) of Original Subjects with Baseline Alcohol Use Disorders from the Collaborative Study on Genetics of Alcoholism.

BACKGROUND: Recent reports indicate higher-than-expected problematic drinking in older populations. However, few data describe how to predict which older individuals are most likely to demonstrate alcohol-related problems, including those with earlier alcohol use disorders (AUDs). These analyses evaluate predictors of alcohol outcomes in individuals with earlier AUDs in the Collaborative Study on Genetics of Alcoholism (COGA). METHODS: Original COGA participants with baseline AUDs at about age 40 were interviewed 13 to 26 years later and placed into clinically derived outcome categories. Chi-square and analysis of variance evaluated baseline differences across 4 outcome groups, with significant items entered into binary logistic regression backwards elimination analyses predicting outcomes. RESULTS: Low-Risk Drinkers (N = 100) at follow-up were predicted by baseline higher levels of response to alcohol (high LRs), lower histories of alcohol treatment, experience with fewer types of illicit drugs, and were more likely to have been widowed. At follow-up, Problem Drinkers (N = 192) differed from High-Risk Drinkers (N = 93) who denied multiple alcohol problems by exhibiting baseline lower LRs, higher Sensation Seeking, and a higher proportion who were widowed. Abstinent (N = 278) outcomes were predicted by a history of higher baseline AUD treatments, higher alcohol problems, lower usual drinks, as well as older age and European American heritage. Thirty-four subjects (4.9%) could not be classified and were not included in these analyses. CONCLUSIONS: These results generated from AUD individuals from both treatment and nontreatment settings reinforce low probabilities of recent Low-Risk Drinking in individuals with AUDs, but also suggest many individuals with AUDs demonstrate good outcomes 2 decades later.

A GABRA2 polymorphism improves a model for prediction of drinking initiation.

BACKGROUND: Survival analysis was used to explore the addition of a single nucleotide polymorphism (SNP) and covariates (sex, interview age, and ancestry) on a previously published model's ability to predict onset of drinking. A SNP variant of rs279871, in the chromosome 4 gene encoding gamma-aminobutyric acid receptor (GABRA2), was selected due to its associations with alcoholism in young adults and with behaviors that increased risk for early drinking. METHODS: A subsample of 674 adolescents (ages 14-17) participating in the Collaborative Study on the Genetics of Alcoholism (COGA) was examined using a previously derived Cox proportional hazards model containing: 1) number of non-drinking related conduct disorder (CD) symptoms, 2) membership in a high-risk alcohol-dependent (AD) family, 3) most best friends drank (MBFD), 4) Achenbach Youth Self Report (YSR) externalizing score, and 5) YSR social problems score. The above covariates along with the SNP variant of GABRA2, rs279871, were added to this model. Five new prototype models were examined. The most parsimonious model was chosen based on likelihood ratio tests and model fit statistics. RESULTS: The final model contained four of the five original predictors (YSR social problems score was no longer significant and hence dropped from subsequent models), the three covariates, and a recessive GABRA2 rs279871 TT genotype (two copies of the high-risk allele containing thymine). The model indicated that adolescents with the high-risk TT genotype were more likely to begin drinking than those without this genotype. CONCLUSIONS: The joint effect of the gene (rs279871 TT genotype) and environment (MBFD) on adolescent alcohol initiation is additive, but not interactive, after controlling for behavior problems (CD and YSR externalizing score). This suggests that the impact of the high-risk TT genotype on the onset of drinking is affected by controlling for peer drinking and does not include genotype-by-environment interactions.

Conclusion: Special issue on genetic and alcohol use disorder research with diverse racial/ethnic groups: Key findings and potential next steps.

BACKGROUND AND OBJECTIVES: This special issue brings together papers focusing on a wide range of topics relevant to the research and understanding of the role of race/ethnicity and genetic variation for the susceptibility of developing an alcohol use disorder (AUD). METHODS: The key findings from the issue's 10 articles are reviewed and organized here around three topics: I: addictive behaviors and potential environmental influences; II: a focus on four racial/ethnic groups; and III: special methodologies. RESULTS: Several potential next steps in improving effective research strategies are highlighted: (1) implementing best practices for outreach and community engagement may reduce reluctance to participate; (2) recruiting adequately sized and racially/ethnically diverse samples will require new collaborations with investigators who successfully work in diverse communities; (3) identifying and assessing environmental influences that are both unique to, and common among, racial/ethnic groups may inform preventions for AUD; (4) use of standardized measures will facilitate the generation of larger samples and meta-analysis of research findings; and (5) use of better analytic approaches and experimental methods will improve replication in gene finding research and help advance new areas of research. CONCLUSIONS: Genetic research of AUD in diverse racial/ethnic populations is advancing. The articles in this issue examined the general theme of including diverse population groups in genetic studies and offered potential strategies for addressing some common problems. SCIENTIFIC SIGNIFICANCE: Greater inclusion of diverse racial/ethnic populations in this research is important to ensure that the benefits of new knowledge and technology are equally shared. (Am J Addict 2017;26:532-537).

Introduction: Special issue on genetic research of alcohol use disorder in diverse racial/ethnic populations.

This special issue of The American Journal on Addictions is an extension of a workshop held at the Research Society on Alcoholism (2015) highlighting several important issues related to studies of the genetic bases of alcohol use disorder among racially/ethnically diverse populations. While not exhaustive in their coverage, the papers in this special issue focus on three important topics: (1) the importance of considering the social and environmental context in genetic analyses; (2) social and cultural considerations for engaging diverse communities in genetic research; and (3) methodologies related to phenotype development for use with racially/ethnically diverse populations. A brief overview of each paper included in these three sections is presented. The issue concludes with additional considerations for genetic research with racially/ethnically diverse population groups along with a commentary. (Am J Addict 2017;26:422-423).

Familial association of abstinent remission from alcohol use disorder in first-degree relatives of alcohol-dependent treatment-seeking probands.

BACKGROUND AND AIMS: Studies that have included family history of alcohol use disorder (AUD) as a predictor of remission from AUD have yielded few significant results. The goals of this study were to estimate the association of persistent AUD, non-abstinent remission and abstinent remission ('AUD/remission status') in a proband with AUD/remission status in a relative and to test whether this association differed in related and unrelated proband-relative pairs. DESIGN: High-risk family study of alcohol dependence. Probands were recruited from treatment settings and relatives were invited to participate. Baseline assessments occurred between 1991 and 1998 with follow-up between 1996 and 2005. Half of probands were matched with a biological 1st-degree relative with life-time AUD (related group) and half of probands were paired with an unrelated individual with life-time AUD (unrelated group). SETTING: Brooklyn, New York; Indianapolis, Indiana; Iowa City, Iowa; San Diego, California; Farmington, Connecticut; and St Louis, Missouri, USA. PARTICIPANTS: A total of 606 probands (25.7% female, mean age 37.7) with baseline and follow-up data and 606 of their 1st-degree relatives who had life-ime AUDs (45.8% female, mean age 36.2 years). MEASUREMENTS: Persistent AUD, non-abstinent remission and abstinent remission were based on self-report interview data on most recent AUD symptoms and alcohol consumption. Dependent variable was relatives' AUD/remission status. Independent variable was probands' AUD/remission status. FINDINGS: A total of 34.6% of probands and 20.6% of relatives were abstinent and 11.1% of probands and 22.8% of relatives were in non-abstinent remission. AUD/remission status was correlated significantly in related (r = 0.23, P = 0.0037) but not in unrelated pairs. A significant interaction of probands' abstinent remission with a variable representing related (versus unrelated, P = 0.003) pairs suggested a familial association for abstinent remission. In related pairs, individuals with an abstinent proband were more likely to be abstinent themselves than were individuals whose proband had persistent AUD [relative risk ratio = 3.27, 95% confidence interval (CI) = 1.56-6.85, P = 0.002]; this association was not significant in unrelated pairs. CONCLUSIONS: The likelihood of abstinent remission among people with alcohol use disorder appears to be more than three times greater for individuals who are related to an abstinent proband versus those related to a proband with persistent alcohol use disorder.

A Prospective Comparison of How the Level of Response to Alcohol and Impulsivity Relate to Future DSM-IV Alcohol Problems in the COGA Youth Panel.

BACKGROUND: Alcohol problems reflect both environmental and genetic characteristics that often operate through endophenotypes like low levels of response (low LRs) to alcohol and higher impulsivity. Relationships of these preexisting characteristics to alcohol problems have been studied, but few analyses have included both low LR and impulsivity in the same model. METHODS: We extracted prospective data from 1,028 participants in the Prospective Youth Sample of the Collaborative Study on the Genetics of Alcoholism (COGA). At Time 1 (age 18), these drinking but non-alcohol-dependent males and females completed the Barratt Impulsivity Scale and the Self-Report of the Effects of Alcohol questionnaire regarding drinks required for effects the first 5 times of drinking (SRE5-LR). Two years later, they reported perceived drinking patterns of peers (PEER), their own alcohol expectancies (EXPECT), and their drinking to cope with stress (COPE). Subsequently, at Time 3, participants reported numbers of up to 11 DSM-IV alcohol criterion items experienced in the 2 years since Time 2 (ALC PROBS). Data were analyzed using structural equation modeling (SEM). RESULTS: In the SEM, Baseline SRE5-LR and impulsivity were weakly related and did not interact in predicting later ALC PROBS. LR was directly linked to Time 3 ALC PROBS and to PEER, but had no direct path to EXPECT, with partial mediation to ALC PROBS through PEER to EXPECT and via COPE. Impulsivity did not relate directly to ALC PROBS or PEER, but was directly related to EXPECT and COPE, with effects on ALC PROBS also operating through EXPECT and COPE. CONCLUSIONS: Low LRs and impulsivity related to Time 3 ALC PROBS through somewhat different paths. Education- and counseling-based approaches to mitigate future alcohol problems may benefit from emphasizing different potential mediators of adverse alcohol outcomes for youth with low LRs versus those with high impulsivity or both characteristics.

Comparison of Parent, Peer, Psychiatric, and Cannabis Use Influences Across Stages of Offspring Alcohol Involvement: Evidence from the COGA Prospective Study.

BACKGROUND: All stages of development of alcohol use disorder (AUD) have not been equally studied. While initiation of drinking has been given considerable attention, other stages have not been as thoroughly investigated. It is not clear whether the same factors are associated consistently across early and late transitions in AUD involvement. High-risk family samples that are enriched for AUD vulnerability and transitions in AUD development offer an opportunity to examine influences across multiple stages of AUD development. METHODS: Data from adolescents and young adults from high-risk families were used to study 4 transitions in AUD development-time to first drink, first drink to first problem, first drink to first diagnosis, and first problem to first diagnosis. Cox modeling was used to compare associations of parental AUD, parental separation, peer substance use, offspring ever-use of cannabis, trauma exposures, and internalizing and externalizing psychopathology across transitions. RESULTS: Hazards of most transitions were elevated for those who had ever used cannabis, those who attributed substance use to their peers, those with externalizing disorders, and those with parents with AUD. Many risk factors were linked to early initiation of alcohol, particularly cannabis use. Internalizing disorders were associated with later stages. Nonassaultive trauma was associated only with early initiation; assaultive trauma was not associated with any transition. CONCLUSIONS: In this large, ethnically diverse sample of high-risk youth, significant influences across transitions were fairly consistent, with externalizing disorders and cannabis ever-use elevating the likelihood of each stage, and peer and parental (and especially maternal AUD) influences linked to initiation and some later stages. Finally, in light of the increasingly permissive legal and social stances toward cannabis in the United States, the marked elevations of all alcohol outcomes observed for cannabis use underscore the importance of studying the underpinnings of this relationship.

Predictors of Patterns of Alcohol-Related Blackouts Over Time in Youth From the Collaborative Study of the Genetics of Alcoholism: The Roles of Genetics and Cannabis.

OBJECTIVE: Alcohol-related blackouts (ARBs) are anterograde amnesias related to heavy alcohol intake seen in about 50% of drinkers. Although a major determinant of ARBs relates to blood alcohol concentrations, additional contributions come from genetic vulnerabilities and possible impacts of cannabis use disorders (CUDs). We evaluated relationships of genetics and cannabis use to latent class trajectories of ARBs in 829 subjects from the Collaborative Study of the Genetics of Alcoholism (COGA). METHOD: The number of ARBs experienced every 2 years from subjects with average ages of 18 to 25 were entered into a latent class growth analysis in Mplus, and resulting class membership was evaluated in light of baseline characteristics, including CUDs. Correlations of number of ARBs across assessments were also compared for sibling pairs versus unrelated subjects. RESULTS: Latent class growth analysis identified ARB-based Classes 1 (consistent low = 42.5%), 2 (moderate low = 28.3%), 3 (moderate high = 22.9%), and 4 (consistent high = 6.3%). A multinomial logistic regression analysis within latent class growth analysis revealed that baseline CUDs related most closely to Classes 3 and 4. The number of ARBs across time correlated .23 for sibling pairs and -.10 for unrelated subjects. CONCLUSIONS: Baseline CUDs related to the most severe latent ARB course over time, even when considered along with other trajectory predictors, including baseline alcohol use disorders and maximum number of drinks. Data indicated significant roles for genetic factors for alcohol use disorder patterns over time. Future research is needed to improve understanding of how cannabis adds to the ARB risk and to find genes that contribute to risks for ARBs among drinkers.

Polygenic risk for externalizing disorders: Gene-by-development and gene-by-environment effects in adolescents and young adults.

In this project, we aimed to bring large-scale gene identification findings into a developmental psychopathology framework. Using a family-based sample, we tested whether polygenic scores for externalizing disorders-based on single nucleotide polymorphism weights derived from genome-wide association study results in adults (n = 1,249)-predicted externalizing disorders, subclinical externalizing behavior, and impulsivity-related traits adolescents (n = 248) and young adults (n = 207), and whether parenting and peer factors in adolescence moderated polygenic risk to predict externalizing disorders. Polygenic scores predicted externalizing disorders in adolescents and young adults, even after controlling for parental externalizing disorder history. Polygenic scores also predicted subclinical externalizing behavior and impulsivity traits in the adolescents and young adults. Adolescent parental monitoring and peer substance use moderated polygenic scores to predict externalizing disorders. This illustrates how state of the science genetics can be integrated with psychological science to identify how genetic risk contributes to the development of psychopathology.

Association of substance dependence phenotypes in the COGA sample.

Alcohol and drug use disorders are individually heritable (50%). Twin studies indicate that alcohol and substance use disorders share common genetic influences, and therefore may represent a more heritable form of addiction and thus be more powerful for genetic studies. This study utilized data from 2322 subjects from 118 European-American families in the Collaborative Study on the Genetics of Alcoholism sample to conduct genome-wide association analysis of a binary and a continuous index of general substance dependence liability. The binary phenotype (ANYDEP) was based on meeting lifetime criteria for any DSM-IV dependence on alcohol, cannabis, cocaine or opioids. The quantitative trait (QUANTDEP) was constructed from factor analysis based on endorsement across the seven DSM-IV criteria for each of the four substances. Heritability was estimated to be 54% for ANYDEP and 86% for QUANTDEP. One single-nucleotide polymorphism (SNP), rs2952621 in the uncharacterized gene LOC151121 on chromosome 2, was associated with ANYDEP (P = 1.8 × 10(-8) ), with support from surrounding imputed SNPs and replication in an independent sample [Study of Addiction: Genetics and Environment (SAGE); P = 0.02]. One SNP, rs2567261 in ARHGAP28 (Rho GTPase-activating protein 28), was associated with QUANTDEP (P = 3.8 × 10(-8) ), and supported by imputed SNPs in the region, but did not replicate in an independent sample (SAGE; P = 0.29). The results of this study provide evidence that there are common variants that contribute to the risk for a general liability to substance dependence.

Predictors of subgroups based on maximum drinks per occasion over six years for 833 adolescents and young adults in COGA.

OBJECTIVE: A person's pattern of heavier drinking often changes over time, especially during the early drinking years, and reflects complex relationships among a wide range of characteristics. Optimal understanding of the predictors of drinking during times of change might come from studies of trajectories of alcohol intake rather than cross-sectional evaluations. METHOD: The patterns of maximum drinks per occasion were evaluated every 2 years between the average ages of 18 and 24 years for 833 subjects from the Collaborative Study on the Genetics of Alcoholism. Latent class growth analysis identified latent classes for the trajectories of maximum drinks, and then logistic regression analyses highlighted variables that best predicted class membership. RESULTS: Four latent classes were found, including Class 1 (69%), with about 5 maximum drinks per occasion across time; Class 2 (15%), with about 9 drinks at baseline that increased to 18 across time; Class 3 (10%), who began with a maximum of 18 drinks per occasion but decreased to 9 over time; and Class 4 (6%), with a maximum of about 22 drinks across time. The most consistent predictors of higher drinking classes were female sex, a low baseline level of response to alcohol, externalizing characteristics, prior alcohol and tobacco use, and heavier drinking peers. CONCLUSIONS: Four trajectory classes were observed and were best predicted by a combination of items that reflected demography, substance use, level of response and externalizing phenotypes, and baseline environment and attitudes.

Consensus paper of the WFSBP task force on biological markers: biological markers for alcoholism.

OBJECTIVES: This article presents an overview of the current literature on biological markers for alcoholism, including markers associated with the pharmacological effects of alcohol and markers related to the clinical course and treatment of alcohol-related problems. Many of these studies are well known, while other studies cited are new and still being evaluated. METHODS: In this paper we first describe known biomarkers of alcohol-related disorders, review their features and the problems involved in their use. We then consider future developments on biomarkers and their possible impact on the field. RESULTS: More recent findings cited include the work on type 7 adenylcyclase (AC) polymorphism and its lower expression levels in female alcoholics. Neuroimaging studies involving biomarkers have also reported brain volume reductions of gray and white matter, including amygdala and subcortical regions in alcoholic patients, while a high association between the copy number variations (CNVs) in 6q14.1/5q13.2 and alcohol dependence has more recently been identified in genetic studies. CONCLUSIONS: In addition to their possible importance for diagnosis, biomarkers may have utility for predicting prognosis, progression of the disorder, the development of new treatments, and monitoring treatment effects. Although such findings should be verified in independent studies, the search for new biomarkers is continuing. Several potential candidate biomarkers have been found recently in blood, imaging, and genetic studies with encouraging results.