Low versus high level of response to alcohol affects amygdala functional connectivity during processing of emotional stimuli.

BACKGROUND: Low levels of response (low LR) to alcohol predict heavy drinking and alcohol problems. Functional magnetic resonance imaging (fMRI) studies of emotion processing have shown that low LR individuals exhibit lower activation in task-related brain regions following both placebo and alcohol administration, but these studies did not examine functional brain networks that might contribute to the phenomena. The current study expands upon the earlier results by evaluating whether functional connectivity differences between the amygdala and other brain regions modulated by emotional face processing are associated with LR. Based on prior findings, we hypothesized that low LR is related to lower functional connectivity in fronto-amygdalar functional circuits, which underlie the processing of emotional stimuli. METHODS: Secondary analyses were conducted on data from a double-blind, placebo-controlled, within-subjects, cross-over study in 108 18-to-25-year-old low and high LR sex-matched pairs without alcohol use disorder at baseline. Participants performed modified emotional faces processing tasks after receiving placebo or approximately 0.7 ml/kg of ethanol. Psychophysiological interaction analyses examined functional connectivity between left and right amygdalae and related brain circuits using LR-by-alcohol general linear models. The data included 54 sex-matched pairs with 216 fMRI scans comprising alcohol and placebo conditions. RESULTS: Compared with individuals with high LR, low LR subjects demonstrated lower functional connectivity between the amygdala and the frontal lobes, insula, and parietal regions, while processing angry and happy faces. Interactions showed lower connectivity following alcohol in low LR and higher connectivity in high LR groups. CONCLUSIONS: Low LR individuals demonstrated lower functional connectivity in response both to placebo and a modest dose of ethanol. Attenuated connectivity among low LR individuals when processing emotional faces may contribute to an impaired ability to recognize alcohol intoxication in social situations and to appraise angry and happy emotions irrespective of whether alcohol is consumed.

Endorsement of specific alcohol use disorder criterion items changes with age in individuals with persistent alcohol use disorders in 2 generations of the San Diego Prospective Study.

BACKGROUND: Diagnostic and Statistical Manual (DSM) alcohol use disorder (AUD) criteria are written in broad enough terms to apply to diverse populations. The current analyses evaluate whether the endorsement of criteria changes with increasing age in individuals with persistent AUDs. METHODS: Data regarding AUDs persisting across 3 timepoints between average ages of 31 and 43 were gathered about every 5 years from 318 interviews for 106 San Diego Prospective Study (SDPS) AUD male probands. Similar data regarding persistent AUDs across 2 timepoints were obtained from 136 interviews with 68 SDPS AUD offspring between average ages of 21 and 27. Changes in the endorsement of each AUD criterion were evaluated using Cochran's Q test. RESULTS: For AUD probands across time, significant decreases were observed in the proportions endorsing 4 criteria (tolerance, withdrawal, failure to fulfill obligations, and using alcohol in hazardous situations). Increased rates of endorsement were documented for 3 criteria (drinking alcohol in higher amounts or for longer periods of time, spending a great deal of time regarding alcohol, and continued use despite social or interpersonal problems). Significant increases in rates of endorsements for offspring were seen for spending a great deal of time regarding alcohol and giving up or reducing important activities in order to drink. CONCLUSIONS: These data indicate that the salience of many DSM AUD criterion items changed significantly with age in both SDPS generations among individuals with persistent AUDs. The current results support the need for additional systematic research to determine whether specific criterion items might need to be weighted differently in evaluating older and younger individuals with persistent AUDs.

Relationship between level of response to alcohol and acute tolerance.

BACKGROUND: A low level of response (low LR) to alcohol correlates with the later development of alcohol-related problems. Although some of the underpinnings of LR are understood, little is known about the potential relationship between LR and acute tolerance. The current analyses tested the hypothesis that a low LR will be explained in part by more intense acute tolerance to alcohol during a drinking session. METHODS: Data were generated through a reanalysis of data from 120 individuals who were 18- to 25-year-old, sex-matched pairs of low and high LR drinkers who at baseline did not meet criteria for an alcohol use disorder. Each subject participated in an oral alcohol challenge in which they consumed about 0.7 ml ethanol per kg and acute tolerance was measured as the differences in alcohol's effects at similar breath alcohol levels (BrACs) during the rising and falling breath alcohol concentration (BrAC) curve. Measures included aspects of the Subjective High Assessment Scale (SHAS) and body sway. RESULTS: Contrary to our hypothesis, but similar to results with other alcohol measures, acute tolerance was significantly attenuated in low LR compared with high LR individuals on most SHAS scores. Neither LR group demonstrated acute tolerance to alcohol for sleepiness or body sway. Men and women did not differ on any of these measures. CONCLUSION: These data do not support a role of acute tolerance in the low LR to alcohol as measured by subjective feelings of intoxication or body sway in these subjects, findings that were similar across males and females. In addition, consistent with the literature, the analyses demonstrated differences across measures such that acute tolerance was observed for most measures of subjective effects but not for body sway. Among the subjective effects, acute tolerance was observed for alcohol's intoxicating effect but not for feeling sleepy.

Cross-sectional and prospective associations of drinking characteristics with scores from the Self-Report of the Effects of Alcohol questionnaire and findings from alcohol challenges.

BACKGROUND: Data from 2 generations of participants in the San Diego Prospective Study (SDPS) were used to compare cross-sectional and prospective relationships of 5 measures of the low level of response (low LR) to alcohol to 2 key alcohol-related outcomes. METHODS: The analyses used data from 373 SDPS male probands and 158 male and female offspring of these individuals to evaluate relationships of 5 LR measures to the prior 5-year maximum drinks per occasion and the number of 11 DSM-IV alcohol use disorder (AUD) criteria experienced. Probands' LR measures included responses to alcohol challenges administered 15 years previously, and ratings for both generations included measures of the number of standard drinks during four periods: the first five times of drinking (SRE-5), the prior three drinking months (SRE-3), the period of heaviest drinking (SRE-H), and a total average across all time frames (SRE-T). Analyses included zero-order correlations, correlations using covariates, and hierarchical multiple regression analyses. RESULTS: All 5 LR measures were correlated with aspects of maximum drinks and the number of AUD criteria, but the most robust results were seen for SRE-3 and maximum drinks. Correlations were less consistent for SRE-5, a measure more closely related to outcomes in the offspring. Hierarchical regression analyses supported most of these conclusions and showed that alcohol challenge-based LRs added significant information regarding maximum drinks even when evaluated with SRE values. The close correlation between SRE-H and SRE-T argues against the need for studies to include both measures. The patterns of results were similar irrespective of whether covariates were included. CONCLUSIONS: There were significant correlations of maximum drinks and the number of AUD criteria with findings from prior alcohol challenges and all SRE scores. Challenges and SRE reports are related but not identical LR measures. All SRE scores, including SRE-5, offered useful information regarding subsequent drinking behavior.

The Search for Contributors to Low Rates of Recognition of Paternal Alcohol Use Disorders in Offspring From the San Diego Prospective Study.

BACKGROUND: The most efficient approach for establishing family histories (FHs) asks informants about disorders in their relatives (a Family History Method [FHM]). However, FHMs underestimate family diagnoses. We evaluated if accuracies of young adult offspring report of their father's alcohol use disorders (AUDs) related to the age, sex, education, and/or substance-related patterns/problems of either the young adult informants or their AUD fathers. METHODS: Data from the San Diego Prospective Study (SDPS), a multigenerational 35-year investigation, compared father/offspring pairs where the proband father's alcohol problems were correctly (Group 1) or incorrectly (Group 2) noted by offspring. In the key analysis, Group 1 versus 2 results were entered into bootstrapped backward logistic regression analyses predicting Group 1 membership. RESULTS: Five proband and one offspring characteristic were associated with correct identification of their father's alcohol problems. None of these related to age, education, or sex. Characteristics associated with correct FHM diagnoses included the father's FH of AUDs, self-report of drinking despite social/interpersonal or physical/psychological alcohol-related problems, spending much time related to alcohol, and his having a religious preference. The single offspring item predicting correct identification of the father's problems was the number of DSM alcohol problems of the offspring. CONCLUSIONS: In the SDPS, FHM sensitivity was most closely related to the father's drinking characteristics, not the offspring characteristics. While unique aspects of SDPS families potentially limit generalizability of results, the data demonstrate how the FHM can offer important initial steps in the search for genetically related AUD risks in a subset of families.

Predictors of Increases in Alcohol Problems and Alcohol Use Disorders in Offspring in the San Diego Prospective Study.

BACKGROUND: The 35-year-long San Diego Prospective Study documented 2-fold increases in alcohol problems and alcohol use disorders (AUDs) in young-adult drinking offspring compared to rates in their fathers, the original probands. The current analyses use the same interviews and questionnaires at about the same age in members of the 2 generations to explore multiple potential contributors to the generational differences in adverse alcohol outcomes. METHODS: Using data from recent offspring interviews, multiple cross-generation differences in characteristics potentially related to alcohol problems were evaluated in 3 steps: first through direct comparisons across probands and offspring at about age 30; second by backward linear regression analyses of predictors of alcohol problems within each generation; and finally third through R-based bootstrapped linear regressions of differences in alcohol problems in randomly matched probands and offspring. RESULTS: The analyses across the analytical approaches revealed 3 consistent predictors of higher alcohol problems in the second generation. These included the following: (i) a more robust relationship to alcohol problems for offspring with a low level of response to alcohol; (ii) higher offspring values for alcohol expectancies; and (iii) higher offspring impulsivity. CONCLUSIONS: The availability of data across generations offered a unique perspective for studying characteristics that may have contributed to a general finding in the literature of substantial increases in alcohol problems and AUDs in recent generations. If replicated, these results could suggest approaches to be used by parents, healthcare workers, insurance companies, and industry in their efforts to mitigate the increasing rates of alcohol problems in younger generations.

Performance of the Self-Report of the Effects of Alcohol Questionnaire Across Sexes and Generations.

BACKGROUND: Low level of responses (low LRs) to alcohol established using the Self-Report of the Effects of Alcohol (SRE) questionnaire are genetically influenced phenotypes related to heavy drinking and alcohol problems. To date, most studies using SREs focused on scores for the number of drinks needed for effects across the first 5 times of drinking (SRE-5), and few evaluated scores that also included the prior 3 months and heaviest drinking periods (SRE-T). This paper evaluates characteristics of SRE-5 and SRE-T within and across generations. METHODS: Data were extracted from 407 participants across 2 generations of 107 families in the San Diego Prospective Study (SDPS). Pearson's product-moment correlations for SRE-5 and SRE-T were determined across first-degree relatives both within and across generations and sexes, as well as correlations of each measure to maximum drinking quantities and alcohol problems. RESULTS: Responding to 4 hypotheses, first the analyses demonstrated significant within-generation positive correlations for both SRE measures across brother-brother and sister-sister pairs as well as cross-generation correlations for fathers and sons, although correlations for mothers and daughters were not robust. Second, both SRE-5 and SRE-T correlated with maximum drinks and alcohol problems for both sexes and both generations. Third, within parental and offspring generations SRE-T correlated more robustly than SRE-5 to maximum drinks and alcohol problems. Fourth, across generations SRE values for sons were more closely related to drinking quantities and problems than for their fathers, but the mother-daughter SRE relationships to adverse alcohol characteristics were not different. CONCLUSIONS: Both the SRE-5 and SRE-T offered useful information about propensities toward heavier drinking and alcohol problems in SDPS families. Correlations with adverse alcohol outcomes were greater for the more broad-based SRE-T, but both scores appeared to be genetically influenced and continue to operate in a robust manner in both generations of these families.

The Relationship Between Regional Cerebral Blood Flow Estimates and Alcohol Problems at 5-Year Follow-Up: The Role of Level of Response.

BACKGROUND: Acute alcohol consumption is associated with temporarily increased regional cerebral blood flow (CBF). The extent of this increase appears to be moderated by individual differences in the level of response (LR) to alcohol's subjective effects. The low LR phenotype is a known risk factor for the development of alcohol problems. This study investigates how the low LR phenotype relates to the relationship between alcohol-related changes in CBF and alcohol problems 5 years later. METHODS: Young adults (ages 18 to 25) were selected based on their LR to alcohol and underwent a neuroimaging protocol including arterial spin labeling and functional scans. These participants were recontacted ~5 years later and assessed on alcohol outcomes. A final sample of 107 subjects (54 low and 53 high LR subjects) was included in the analyses. Whole-brain analysis revealed 5 clusters of significant alcohol-induced, versus placebo-induced, CBF changes that were consistent with a previous report. Peak alcohol-placebo CBF response was extracted from these regions and, along with the LR group, submitted to a hierarchical linear regression predicting alcohol problems. Analyses controlled for age, sex, and baseline alcohol problems. RESULTS: In the regression analysis, greater alcohol-placebo CBF difference in the right middle/superior/inferior frontal gyri and bilateral anterior cingulate gyri clusters predicted greater future alcohol problems for the low LR group, whereas this relationship was not found to be significant in the high LR group. CONCLUSIONS: This study demonstrates a clinically important relationship between CBF and future alcohol problems, particularly in individuals with a low LR phenotype. These initial results help to elucidate the neurobiological pathways involved in the development of alcohol use disorders for individuals with low LR.

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 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.

Drinking Patterns Across Spring, Summer, and Fall in 462 University Students.

BACKGROUND: Student heavy drinking and associated problems are common at most universities and fluctuate throughout the calendar year, with marked increases during celebrations. Most studies of student drinking are limited to the academic year itself, and relatively few focus specifically on special heavy drinking events. Even fewer studies include drinking during summer break and subsequent school return. METHODS: In the context of an experimental protocol, beginning in January 2014, alcohol-related characteristics were evaluated 8 times over 55 weeks for 462 college freshmen, including periods that incorporated a campus festival, summer, and school return. Baseline predictors of drinking quantities over time included demography, substance use patterns, as well as environmental and attitudinal characteristics. Product-moment correlations evaluated relationships between baseline characteristics and subsequent quantities, and simultaneous entry regression analyses evaluated which characteristics most robustly predicted usual and maximum drinks over time. RESULTS: Maximum drinks per occasion increased 18% from the early spring (4/8/14 to 5/6/14) to the campus festival period (5/7/14 to 6/3/14), decreased 29% in the summer (7/8/14 to 8/5/14), and increased 31% on school return (10/7/14 to 11/4/14). The most robust predictors of higher quantities in regression analyses included items from each of the 3 major domains with the most consistent results seen for most baseline alcohol-related items and descriptive drinking norms (R(2) = 0.20 to 0.31). CONCLUSIONS: These data demonstrate important changes in students' drinking during the calendar year, including expected large increases during the month of a 1-day festival, large decreases over the summer, and resumption of relatively high quantities upon return to school.

The Ability of Functional Magnetic Resonance Imaging to Predict Heavy Drinking and Alcohol Problems 5 Years Later.

BACKGROUND: Low levels of alcohol responses (low LRs) are genetically influenced phenotypes that are identified before alcohol dependence and predict future heavy drinking and alcohol problems. A recent paper described 13 LR-related blood oxygen level-dependent (BOLD) response contrast patterns observed during an emotional face recognition task that might reflect cognitive processes contributing to LR and that might themselves predict adverse alcohol outcomes (Paulus et al., Biol Psychiatry 2012; 72: 848). This paper evaluates the predictive implications of those functional magnetic resonance imaging (fMRI) patterns. METHODS: Of 120 subjects from Paulus and colleagues (2012), 114 (57 low and high LRs; ~50% females) were interviewed 5 years later at age 25. Correlations between baseline fMRI patterns and alcohol-related outcomes were evaluated, and regression analyses were used to determine if BOLD response contrasts incremented over LR in predicting outcomes. RESULTS: Baseline fMRI patterns in 5 of 13 baseline regions of interest correlated with adverse outcomes. Such patterns in insular regions, particularly the left anterior insula, and the right frontal gyrus, added to LR in predicting alcohol problems. The relationships remained robust when exact binomial procedures were used, but, reflecting the small sample size, it was not possible to adequately consider Bonferroni corrections. CONCLUSIONS: The data suggest that fMRI BOLD response contrasts predicted heavier drinking and alcohol problems 5 years later, even after considering baseline low LRs. Future work will focus on whether fMRI results can predict outcomes in larger samples and among young nondrinkers, as well as how the imaging results increase understanding of the processes through which LR operates.

Level of response to alcohol as a factor for targeted prevention in college students.

BACKGROUND: Heavy alcohol consumption and alcohol problems among college students are widespread and associated with negative outcomes for individuals and communities. Although current methods for prevention and intervention programming have some demonstrated efficacy, heavy drinking remains a problem. A previous pilot study and a recent large-scale evaluation (Schuckit et al., , ) found that a tailored prevention program based on a risk factor for heavy drinking, low level of response (low LR) to alcohol, was more effective at reducing heavy drinking than a state-of-the-art (SOTA) standard prevention program for individuals with the low LR risk factor. METHODS: This study enrolled 231 first-semester college freshmen with either high or low LR into the same level of response-based (LRB) or SOTA online prevention programs as in the previous reports (consisting of 4 weeks of video modules), as well as a group of matched controls not receiving alcohol prevention, and compared changes in alcohol use between these groups across a 6-month period. RESULTS: Individuals in alcohol prevention programs had a greater reduction in maximum drinks per occasion and alcohol use disorder symptoms than controls. There was limited evidence for interactions between LR and prevention group in predicting change in alcohol use behaviors; only among participants with strict adherence to the program was there an interaction between LR and program in predicting maximum drinks per occasion. However, overall, low LR individuals showed greater decreases in drinking behaviors, especially risky behaviors (e.g., maximum drinks, frequency of heavy drinking) than high LR individuals. CONCLUSIONS: These results indicate that prevention programs, including brief and relatively inexpensive web-based programs, may be effective for persons at highest risk for heavier drinking, such as those with a low LR. Tailored programs may provide incremental benefits under some conditions. Long-term follow-ups and further investigations of tailored prevention programs based on other risk factors are needed.

Latent trajectory classes for alcohol-related blackouts from age 15 to 19 in ALSPAC.

BACKGROUND: Alcohol-related blackouts (ARBs) are reported by ~50% of drinkers. While much is known about the prevalence of ARBs in young adults and their cross-sectional correlates, there are few prospective studies regarding their trajectories over time during mid-adolescence. This paper reports latent trajectory classes of ARBs between age 15 and 19, along with predictors of those patterns. METHODS: Latent class growth analysis (LCGA) was used to evaluate the pattern of occurrence of ARBs across 4 time points for 1,402 drinking adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC). Multinomial regression analyses evaluated age-15 demography, substance-related items, externalizing characteristics, and estimated peer substance use as predictors of latent class membership. RESULTS: ARBs were reported at age 15 in 30% and at age 19 in 74% of these subjects. Four latent trajectory classes were identified: Class 1 (5.1%) reported no blackouts; for Class 2 (29.5%), ARBs rapidly increased with age; for Class 3 (44.9%), blackouts slowly increased; and for Class 4 (20.5%), ARBs were consistently reported. Using Class 2 (rapid increasers) as the reference, predictors of class membership included female sex, higher drinking quantities, smoking, externalizing characteristics, and estimated peer substance involvement (pseudo R(2)  = 0.22). CONCLUSIONS: ARBs were common and repetitive in these young subjects, and predictors of their trajectories over time involved multiple domains representing diverse characteristics.

The impact of focusing a program to prevent heavier drinking on a pre-existing phenotype, the low level of response to alcohol.

BACKGROUND: Heavy drinking is common during transitions from high school to college. Optimal programs for diminishing risks for high alcohol consumption often tailor the approach to the specific needs of students. This study describes the results of an Internet-based prevention protocol that tailors the information to the risk associated with a pre-existing phenotype, the Low level of Response (Low LR) to alcohol. METHODS: Using stratified random assignment, 454 freshmen with Low and High LR values were assigned to 2 education groups (LR-based where all examples were given the context of the Low LR model of heavy drinking or a State Of The Art (SOTA) Group where the same lessons were taught but without an emphasis on LR) or a no-intervention Control Group. Individuals in the 2 education groups viewed 50-minute online videos once per week for 4 weeks. Changes in drinking patterns were assessed at Baseline, 4 weeks, and 8 weeks using a 2 (LR status) by 3 (education group) by 3 (time points) analysis of variance, with additional tests for ethnicity and sex. RESULTS: Low LR participants tended to decrease their usual (p < 0.06) and maximum (p < 0.05) drinks per occasion most prominently when assigned to the LR-based protocol, while those with High LRs improved more in the SOTA Group. The most robust differences were seen when controlling for ethnicity. The effect sizes were small to medium. CONCLUSIONS: These results support the advantages of carrying out prevention via the Internet and in tailoring the approach to a pre-existing phenotype.

The patterns of drug and alcohol use and associated problems over 30 years in 397 men.

BACKGROUND: Alcohol and drug use disorders (AUDs and SUDs) and their combination are relatively common and often occur together. However, the relationships of potential early life correlates of alcohol and drug disorders to the combined diagnoses have rarely been evaluated in long-term prospective studies or in populations at high risk of one of these diagnoses but not the other. METHODS: Data were analyzed from 397 males (half with an alcohol-dependent father) who had no AUDs or SUDs at age 20 and who were followed approximately every 5 years for 3 decades. Early life correlates and the course of AUDs, SUDs, and combined disorders were evaluated for 4 groups of subjects based on subsequent alcohol and/or drug diagnoses. RESULTS: While the overall rates of the development of AUDs and SUDs were 41 and 21%, respectively, the rates of the second substance-related diagnosis were almost 2-fold higher for individuals who had the first condition. Among potential risk factors, scores for externalizing traits were elevated for men with AUDs, SUDs, and their combination, but a low level of response (low LR) to alcohol was associated only with the risk of AUDs, even when observed in the context of SUDs. The same earlier life characteristics that related to AUDs and to SUDs also related to the combination of these diagnoses in the same person. Finally, in this prospective study, subjects with both AUDs and SUDs had a more severe course than subjects with either condition alone. CONCLUSIONS: This prospective evaluation of a group at high risk of AUDs confirmed the selective impact of the low LR on the risk of AUDs, the relationship of externalizing characteristics to both AUDs and SUDs and confirmed the more severe clinical course for both conditions when seen together.

Latent trajectories of persistence of cannabis use across 4 decades in 329 men from the San Diego Prospective Study.

OBJECTIVE: These analyses use data from a 40-year prospective study to extend information into the sixth and seventh decades of life regarding latent trajectory classes of cannabis use and predictors of those classes. METHOD: Data from the San Diego Prospective Study were analyzed for 329 men of European and Hispanic ethnicity who had used cannabis at about age 23 at study entry (Time 1) and who were interviewed about every 5-years through about age 60 to 70. Latent classes of cannabis use trajectories were evaluated using latent class growth analyses, baseline predictors of class membership were determined, and significant predictors of each class were established using logistic regression analyses. RESULTS: Four latent classes were identified ranging from 12.5% with cannabis use at every follow-up to 25.8% with no use after Time 1. Eight of 14 Time 1 predictors differed significantly across the trajectory classes, including five (age, marital status, religious identity, intensity of cannabis use, and sensation seeking) that significantly contributed to regression analyses when all significant predictors were considered together. DISCUSSION: Forty-two per percent of participants continued using cannabis long-term, including one-in-eight who used at every follow-up. Predictors of continued use and identification of those most likely to stop required gathering information on a range of demographic, prior substance use, and personality characteristics. CONCLUSION: Considering potential enhanced dangers of cannabis use in later life, the high rate of continued use over four decades implies that clinicians should ask all older patients about recent cannabis use, especially if they had used in their twenties.

Predictors of initial and sustained remission from alcohol use disorders: findings from the 30-year follow-up of the San Diego Prospective Study.

BACKGROUND: Individuals who report problematic drinking early in life often recover from alcohol-related disorders, with or without formal treatment. While risk factors associated with developing alcohol use disorders (AUDs), such as a family history of alcoholism and the genetically influenced low level of response (LR) to alcohol, have been identified, less is known about characteristics that relate to remission from AUDs. METHODS: The male subjects (98% Caucasian) for this study were 129 probands from the San Diego Prospective Study who were first evaluated at age 20 as drinking but not alcohol-dependent young men, most of whom were college graduates by follow-up. The individuals evaluated here met criteria for an AUD at their first follow-up at ages 28 to 33 and were followed every 5 years for the next 2 decades. Discrete-time survival analysis was used to examine rates of initial and sustained AUD remission and to evaluate the relationships of premorbid characteristics and other risk factors to these outcomes. RESULTS: Sixty percent of the sample met criteria for an initial AUD remission of 5 or more years, including 45% with sustained remission (i.e., no subsequent AUD diagnosis). Higher education, lower drinking frequency, and having a diagnosis of alcohol abuse (rather than dependence) were associated with higher rates of initial AUD remission. A lower LR to alcohol at age 20, as well as lower drinking frequency, having received formal alcohol treatment, and older age at the first follow-up all predicted a greater likelihood of sustained AUD remission. CONCLUSIONS: This study identified key factors associated with initial and sustained AUD remission in subjects diagnosed with AUD in young adulthood. Characteristics associated with better outcomes early in the life span, such as lower drinking frequency and early treatment, appear to have a lasting impact on remission from AUD across adulthood.

Effect of patient activation on self-management in patients with heart failure.

BACKGROUND/OBJECTIVE: Few studies have examined whether chronic heart failure (HF) outcomes can be improved by increasing patient engagement (known as activation) in care and capabilities for self-care management. The objective was to determine the efficacy of a patient activation intervention compared with usual care on activation, self-care management, hospitalizations, and emergency department visits in patients with HF. METHODS: This study used a randomized, 2-group, repeated-measures design. After consent was given, 84 participants were stratified by activation level and randomly assigned to usual care (n = 41) or usual care plus the intervention (n = 43). The primary outcomes and measures were patient activation using the Patient Activation Measure (PAM), self-management using the Self-Care of Heart Failure Index (SCHFI) and the Medical Outcomes Study (MOS) Specific Adherence Scale, and hospitalizations and emergency department visits. The intervention was a 6-month program to increase activation and improve HF self-management behaviors, such as adhering to medications and implementing health behavior goals. RESULTS: Participants were primarily male (99%), were white (77%), and had New York Heart Association III stage (52%). The mean (SD) age was 66 (11) years, and 71% reported 3 or more comorbidities. The intervention group compared with the usual care group showed a significant increase in activation/PAM scores from baseline to 6 months. No significant group-by-time interactions were found for the SCHFI scales. Although the baseline MOS Specific Adherence Scale mean was lower in the intervention group, results showed a significant group-by-time effect with the intervention group improving more over time. Participants in the intervention group had fewer hospitalizations compared with the usual care group when the baseline activation/PAM level was low or high. CONCLUSION: This study supports the importance of targeted interventions to improve patient activation or engagement in HF care. Further work is needed related to HF self-management measurement and outcomes.

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.