Tom L Smith

University of California, San Diego, San Diego, California, United States

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Publications (118)436.91 Total impact

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    ABSTRACT: 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. 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. 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. These results support the advantages of carrying out prevention via the Internet and in tailoring the approach to a pre-existing phenotype. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 02/2015; 39(2). DOI:10.1111/acer.12620 · 3.21 Impact Factor
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    ABSTRACT: 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.ResultsARBs 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 R2 = 0.22).ConclusionsARBs were common and repetitive in these young subjects, and predictors of their trajectories over time involved multiple domains representing diverse characteristics.
    Alcoholism Clinical and Experimental Research 12/2014; 39(1). DOI:10.1111/acer.12601 · 3.21 Impact Factor
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    ABSTRACT: 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.
    Journal of studies on alcohol and drugs 01/2014; 75(1):24-34. DOI:10.15288/jsad.2014.75.24 · 2.76 Impact Factor
  • Marc A Schuckit · Tom L Smith · Jelger A Kalmijn ·
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    ABSTRACT: 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. 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. 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. 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.
    Alcoholism Clinical and Experimental Research 07/2013; 38(1). DOI:10.1111/acer.12220 · 3.21 Impact Factor
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    ABSTRACT: Purposes/Aims: The primary purpose of this study was to evaluate the efficacy of an internet-delivered, stress management course called the Mantram Repetition Program (MRP) on burnout in a self-selected group of healthcare workers (HCWs). Rationale/Background: The negative effects of workplace stress and burnout can lower patient satisfaction, compromise patient safety, and be costly to healthcare organizations. With a severe staffing shortage and predictions of increased patient acuity, finding ways to minimize burnout in HCWs is needed to maintain safe patient care delivery. Research on the MRP has provided empirical evidence of its value in reducing the stress response and improving spiritual wellbeing in face-to-face group delivery. Methods: The MRP was delivered in 6 sessions over 3 months and was evaluated for efficacy in reducing burnout and improving wellbeing using a quasi-experimental, within subjects, repeated measures design. Fifty-four HCW’s participated in completing online assessments at baseline, post-course and 3-month follow-up using the Maslach Burnout Inventory-General Survey (MBI-GS). Outcomes were analyzed using repeated measures analysis of variance (ANOVA) with time as the repeated measure. Additional analyses included mixed design ANOVAs using demographic variables testing for group (e.g. gender, age, and prior meditation practice) by time interaction effects. Results: Participants completing all surveys were 39 HCWs (87% females; 80% white) with mean age of 51 (SD = 8.6) ranging from 27 to 67 years. There were statistically significant effects of the MRP showing a decrease in the MBI-GS exhaustion subscale across the three time points [F(2,76)=3.93, p<.04] and a quadratic effect for professional efficacy subscale showing an initial increase followed by a decrease [F(1,38) = 6.54, p<.02]. No significant change was found in the cynicism subscale. Implications: The MRP was effective in reducing exhaustion and improving professional efficacy, elements of burnout, in a group of HCWs. The findings will be of interest to those seeking innovative, portable methods to reduce burnout among healthcare workers. The MRP has the potential to improve symptom management and increase quality of life in HCWs. Additional controlled, longitudinal research is warranted.
    2014 Western Institute of Nursing Annual Communicating Nursing Research Conference; 04/2013
  • Ryan S Trim · Marc A Schuckit · Tom L Smith ·
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    ABSTRACT: 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. 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. 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. 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.
    Alcoholism Clinical and Experimental Research 03/2013; 37(8). DOI:10.1111/acer.12107 · 3.21 Impact Factor
  • Marc A Schuckit · Tom L Smith · Jelger Kalmijn ·
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    ABSTRACT: Objective: Although heavy drinking is related to sadness on multiple levels, the link between alcohol use disorders (AUDs) and major depressive episodes (MDEs) is more controversial. One complicating factor is that some MDEs are temporary and only occur in the context of heavy drinking, whereas other MDEs are longer lasting and occur independently of intense alcohol intake (i.e., independent depressive episodes [IDEs]). We hypothesized that a longitudinal study that uses validated interviews with subjects and relatives and distinguishes between IDEs and alcohol-induced depressive episodes would reveal little evidence of a link between IDEs and AUDs. Method: Histories of AUDs, IDEs, and substance-induced depressions were prospectively evaluated over 30 years in 397 male probands from the San Diego Prospective Study and in their 449 offspring using questions extracted from the Semi-Structured Assessment for the Genetics of Alcoholism interview. Results: The rate of IDEs over 30 years in the 397 probands was 15.3% overall. Among probands who developed AUDs, 31% of their depressive episodes were substance induced, not IDEs. For these men followed over 3 decades, those with IDEs had no increased rate of AUDs and evidenced no higher rate of use or abuse/dependence on illicit substances. Similar conclusions applied to their 449 offspring ages 12 years and older. Conclusions: These data support the importance of distinguishing between IDE and substance-induced depressions when evaluating the relationship between AUDs and depression syndromes.
    Journal of studies on alcohol and drugs 03/2013; 74(2):271-9. DOI:10.15288/jsad.2013.74.271 · 2.76 Impact Factor
  • Marc A Schuckit · Tom L Smith ·
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    ABSTRACT: Background: The low level of response (LR) to alcohol is an endophenotype that predicts future heavy drinking and alcohol use disorders (AUDs). LR can be measured by laboratory-based alcohol challenges or by the retrospective Self-Report of the Effects of Alcohol (SRE) questionnaire. This paper reports the relationships among these two measures and how each related to both recent and future drinking quantities and problems across 15 years in 235 men. Methods: Probands from the San Diego Prospective Study (SDPS) participated in alcohol challenges to determine their LR at age 20, and subsequently at ages 35, 40, 45 and 50 filled out an SRE regarding the number of standard drinks needed for up to four effects early in life (SRE5) and across early, recent, and heaviest drinking life epochs (SRET). Changes in SRE scores across time were evaluated with ANOVAs and Pearson correlations were used to evaluate how SRE5, SRET and earlier alcohol challenge-based LRs related to prior five-year drinking histories and future alcohol involvement. Results: While SRE scores decreased 9% over the 15 years, the relationships between SRE values with prior five-year drinking parameters and with future alcohol intake and problems remained robust, and even improved with advancing age. A similar pattern was seen for correlations between SRE and alcohol challenge-based LRs 15-30 years previously. Conclusions: Alcohol challenge and SRE-based LRs related to each other, to alcohol use patterns, and to future alcohol problems across age 35-50 in the men studied here.
    Drug and alcohol dependence 09/2012; 128(3). DOI:10.1016/j.drugalcdep.2012.08.022 · 3.42 Impact Factor
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    ABSTRACT: Introduction and Aims. A low level of response (LR), or low sensitivity, to alcohol is a genetically influenced characteristic that predicts future heavy drinking and alcohol problems. While previous analyses of how LR relates to heavier drinking reported the process is similar in males and females, some potential sex differences have been identified. This difference is further explored in these analyses. Design and Methods. Prospective structural equation models (SEMs) were evaluated for 183 young adult females and 162 males, none of Asian background, from the Collaborative Study on the Genetics of Alcoholism. Invariance analyses and SEM evaluations by sex were used to compare across females and males for these primarily Caucasian (75%), non-Asian young (mean age 19) subjects. Results. The prospective SEM for the full set of 345 subjects had good fit characteristics and explained 37% of the variance. While the initial invariance analyses identified few sex differences, comparisons of correlations and direct evaluations of path coefficients across males and females indicated that only females showed a link between a low LR and future alcohol problems that was partially mediated by more positive alcohol expectancies and drinking to cope. These sex differences were reflected in the different structures of the SEM results for female versus male subjects. Discussion and Conclusions. These prospective results indicate that there might be some important sex differences regarding how a lower LR relates to alcohol outcomes that should be considered in protocols focusing on preventing the impact of LR on future drinking problems.[Schuckit MA, Smith TL, Trim RS, Kuperman S, Kramer J, Hesselbrock V, Bucholz KK, Nurnberger Jr JI, Hesselbrock M, Saunders G. Sex differences in how a low sensitivity to alcohol relates to later heavy drinking. Drug Alcohol Rev 2012;31:871–880]
    Drug and Alcohol Review 06/2012; 31(7). DOI:10.1111/j.1465-3362.2012.00469.x · 1.55 Impact Factor
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    ABSTRACT: The low level of response (LR) or sensitivity to alcohol is genetically influenced and predicts heavy drinking and alcohol problems. Functional magnetic resonance imaging (fMRI) studies using cognitive tasks suggest that subjects with a low-LR process cognitive information differently after placebo and alcohol than those with a high LR, but no studies have evaluated whether similar LR group differences are seen during an emotional processing task. The fMRI data were gathered from 116 nonalcoholic subjects (60 women) after oral placebo or approximately .7 mL/kg of ethanol while performing a modified emotional faces processing task. These included 58 low- and high-LR pairs matched on demography and aspects of substance use. Blood alcohol levels and task performance were similar across LR groups, but low-LR subjects consumed approximately .8 drinks more/occasion. Thirteen brain regions (mostly the middle and inferior frontal gyri, cingulate, and insula) showed significant LR group or LR × placebo/alcohol condition interactions for emotional (mostly happy) faces relative to non-face trials. Low-LR subjects generally showed decreasing blood-oxygen level-dependent response contrasts across placebo to alcohol, whereas high LR showed increasing contrasts from placebo to alcohol, even after controlling for drinking quantities and alcohol-related changes in cerebral blood flow. Thus, LR group fMRI differences are as prominent during an emotional face task as during cognitive paradigms. Low-LR individuals processed both types of information in a manner that might contribute to an impaired ability to recognize modest levels of alcohol intoxication in a range of life situations.
    Biological psychiatry 05/2012; 72(10):848-55. DOI:10.1016/j.biopsych.2012.04.016 · 10.26 Impact Factor
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    ABSTRACT: This article presents the first direct comparison of level of response (LR)-based prospective models in two generations of the same families. To accomplish this, we describe results from the first prospective evaluation of potential mediators of how an earlier low LR to alcohol relates to adverse alcohol outcomes in offspring from the San Diego Prospective Study (SDPS). To compare with data from probands in the SDPS, new data were gathered from 86 drinking offspring (age ~20 years) during the 25-year follow-up of these families. Consistent with the usual effect of a low LR, outcomes 5 years later for both generations focused on drinking quantities as well as alcohol problems during the follow-up. A structural equation model (SEM) was used to analyze the relationships among variables, and the models in proband and offspring generations were compared using direct observations of the model results and through invariance procedures. In these drinking offspring, LR correlated with 5-year outcomes (r = .48, p < .001) and the SEM R² was .48, with good fit statistics. As predicted, the LR relationship to alcohol-related outcomes was both direct and partially mediated by heavier peer drinking, positive alcohol expectancies, and using alcohol to cope with stress. These results were similar to a previously published prospective model in SDPS probands, although path coefficients were generally higher in the younger group. The LR-based model of heavier drinking operated similarly across generations, with some modest differences. These results indicate that the model may be meaningful in both younger and middle-age groups.
    Journal of studies on alcohol and drugs 03/2012; 73(2):195-204. DOI:10.15288/jsad.2012.73.195 · 2.76 Impact Factor
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    ABSTRACT: 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.
    The Journal of cardiovascular nursing 02/2012; 28(1). DOI:10.1097/JCN.0b013e318239f9f9 · 2.05 Impact Factor
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    ABSTRACT: New approaches are needed to bolster the modest effects of campus drinking prevention programs. However, more definitive research on new paradigms is very expensive, and in the current economic climate, progress can be made by evaluating smaller pilot studies. This study describes one such approach. A sample of 18-year-old or older, healthy, drinking freshmen at our university was assigned to 2 groups stratified to be similar on demography, drinking histories, and their level of response (LR) to alcohol. In the spring quarter of the school year, the 32 subjects in each of 2 groups viewed four 45-minute Internet-based videotapes as part of 4 prevention sessions. All 8 modules were based on the same techniques and general content, but the 4 videos for the first group were structured around the validated model of how a low LR affects heavy drinking (the low level of response-based [LRB] Group), with partial mediation by heavier drinking peers, positive alcohol expectancies, and drinking to cope with stress. Videos for the state-of-the-art (SOTA) comparison group did not place the similar prevention messages into the low LR framework. Changes in drinking were evaluated at 3 times: before Module 1, before Module 4, and 1 month after Module 4. Usual and maximum drinks per occasion decreased over time for both high and low LR subjects in both LRB and SOTA groups. As predicted, the low LR students showed greater decreases in the LRB Group, while high LR students showed greater decreases in the more generic SOTA Group. The results support the hypothesis that tailoring prevention efforts to address specific predisposing factors, such as a low LR, may be associated with beneficial effects on drinking quantity. We hope that these data will encourage additional efforts to validate the low LR-based prevention paradigm and test other interventions that are targeted toward predisposing phenotypes such as impulsivity and negative affect.
    Alcoholism Clinical and Experimental Research 02/2012; 36(7):1244-52. DOI:10.1111/j.1530-0277.2011.01723.x · 3.21 Impact Factor
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    ABSTRACT: A low level of response (i.e., a low LR) to alcohol is a genetically influenced phenotype that predicts later alcoholism. While the low LR reflects, at least in part, a low brain response to alcohol, the physiological underpinnings of the low LR have only recently been addressed. Forty-nine drinking but not yet alcoholic matched pairs of 18- to 25-year-old subjects (N = 98; 53% women) with low and high LRs as established in separate alcohol challenges were evaluated in 2 event-related functional magnetic resonance imaging (fMRI) sessions (placebo and approximately 0.7 ml/kg of alcohol) while performing a validated stop signal task. The high and low LR groups had identical blood alcohol levels during the alcohol session. Significant high versus low LR group and LR group × condition effects were observed in blood oxygen level-dependent (BOLD) signal during error and inhibitory processing, despite similar LR group performance on the task. In most clusters with significant (corrected p < 0.05, clusters > 1,344 μl) LR group × alcohol/placebo condition interactions, the low LR group demonstrated relatively less, whereas the high LR group demonstrated more, error and inhibition-related activation after alcohol compared with placebo. This is one of the first fMRI studies to demonstrate significant differences between healthy groups with different risks of a future life-threatening disorder. The results may suggest a brain mechanism that contributes to how a low LR might enhance the risk of future heavy drinking and alcohol dependence.
    Alcoholism Clinical and Experimental Research 01/2012; 36(1):130-40. DOI:10.1111/j.1530-0277.2011.01590.x · 3.21 Impact Factor
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    ABSTRACT: Evaluations of how a genetically influenced characteristic, such as the low level of response (a low LR) to alcohol, relates to later heavy drinking and alcohol problems usually include environmental contributors. The best way to understand how LR works in the context of these additional characteristics is to study the process prospectively, but such analyses tend to be complex and the papers are sometimes cluttered with jargon. This report attempts to offer a more straightforward description of the results from such a prospective model of how a lower LR at age 20 relates to alcohol outcomes at age 40. A structural equation model of LR at age ∼20, outcomes of heavy drinking and problems at age ∼40, and additional characteristics at age ∼35 were tested in 378 men from the San Diego Prospective Study. The results support both direct effects of age-20 LR on age-40 heavy drinking and alcohol problems, as well as indirect effects of LR through characteristics of these men at age 35. The latter include using alcohol to cope with stress and heavier drinking among peers. A low LR to alcohol is an example of how both genes and environment can contribute to the risk for adverse alcohol outcomes. The identification of mechanisms through which LR impacts on later heavy drinking and problems can be approached in cross-sectional studies, but those may not be as sensitive as longitudinal models for identifying additional potential mediators of the LR-to-outcome relationship.
    The American Journal of Drug and Alcohol Abuse 07/2011; 37(6):479-86. DOI:10.3109/00952990.2011.598590 · 1.78 Impact Factor
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    ABSTRACT: The low level of response (LR) to alcohol is one of several genetically influenced characteristics that increase the risk for heavy drinking and alcohol problems. Efforts to understand how LR operates through additional life influences have been carried out primarily in modest-sized U.S.-based samples with limited statistical power, raising questions about generalizability and about the importance of components with smaller effects. This study evaluates a full LR-based model of risk in a large sample of adolescents from the United Kingdom. Cross-sectional structural equation models were used for the approximate first half of the age 17 subjects assessed by the Avon Longitudinal Study of Parents and Children, generating data on 1,905 adolescents (mean age 17.8 years, 44.2% boys). LR was measured with the Self-Rating of the Effects of Alcohol Questionnaire, outcomes were based on drinking quantities and problems, and standardized questionnaires were used to evaluate peer substance use, alcohol expectancies, and using alcohol to cope with stress. In this young and large U.K. sample, a low LR related to more adverse alcohol outcomes both directly and through partial mediation by all 3 additional key variables (peer substance use, expectancies, and coping). The models were similar in boys and girls. These results confirm key elements of the hypothesized LR-based model in a large U.K. sample, supporting some generalizability beyond U.S. groups. They also indicate that with enough statistical power, multiple elements contribute to how LR relates to alcohol outcomes and reinforce the applicability of the model to both genders.
    Alcoholism Clinical and Experimental Research 07/2011; 35(10):1897-904. DOI:10.1111/j.1530-0277.2011.01536.x · 3.21 Impact Factor
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    ABSTRACT: Although there are multiple indications that alcohol can alter many physiological brain functions, including cerebral blood flow (CBF), studies of the latter have generally used small- or modest-sized samples. Few investigations have yet evaluated how CBF changes after alcohol relate to subsets of subjects with elevated alcoholism risks, such as those with lower levels of response (LR) to alcohol. This study used arterial spin labeling (ASL) after alcohol administration to evaluate a large sample of healthy young men and women with low and high alcohol responses, and, thus, varying risks for alcohol use disorders (AUD). Healthy young adult social drinkers with low and high LR (N=88, 50% women) matched on demography and drinking histories were imaged with whole-brain resting ASL ~1 hour after ingesting ~3 drinks of ethanol and after a placebo beverage (i.e., 178 ASL sessions). The relationships of CBF changes from placebo to alcohol for subjects with low and high LR were evaluated. CBF increased after alcohol when compared to placebo in 5 frontal brain regions. Despite identical blood alcohol concentrations, these increases with alcohol were less prominent in individuals who required more drinks to experience alcohol-related effects (i.e., had a lower LR to alcohol). The LR group differences remained significant after covarying for recent drinking quantities. The results confirm that alcohol intake is associated with acute increases in CBF, particularly in frontal regions. Less intense CBF changes were seen in subjects with a genetically influenced characteristic, a low LR to alcohol, that relates to the future risk of heavy drinking and alcohol problems.
    Alcoholism Clinical and Experimental Research 02/2011; 35(6):1034-40. DOI:10.1111/j.1530-0277.2011.01435.x · 3.21 Impact Factor
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    Marc A Schuckit · Tom L Smith ·
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    ABSTRACT: Patterns of drinking and alcohol problems change with age. However, few studies use multiple data points and detailed history spanning early adulthood to middle age. This study reports such data from 373 men in the San Diego Prospective Study. Data were generated at baseline (T1) at ∼age 20, and through face-to-face followup interviews ∼every 5 years in >90% of these eligible Caucasian and relatively higher educated men. Subjects were placed into 4 groups regarding their course: 62.5% with no alcohol use disorder (AUD); 17.2% with AUD onset <age 30 and a chronic course; 6.7% with onset ≥age 30 and no recovery; and 13.7% with AUD onset <age 30 and maintained remission for >5 years before the 25-year followup. On a univariate level, low level of response (LR) to alcohol, family history of AUDs, and higher Novelty Seeking at ∼age 20 predicted AUDs with onset before age 30 (mean age∼25), but among these only LR predicted later onset (mean age 38) as well. Additional predictors of AUDs included demography (lower education), and greater involvement with alcohol, drugs, and nicotine prior to T1. Sustained remission from AUDs among alcoholics was predicted by lower T1 and T10 drinking frequencies, and being separated or divorced at T10, along with a trend for higher Reward Dependence. These data indicate that information available in ages of the late teens to early twenties can help predict the future onset and course of AUDs, and underscore the importance of longitudinal studies in substance use disorders.
    Drug and alcohol dependence 01/2011; 113(1):21-8. DOI:10.1016/j.drugalcdep.2010.06.017 · 3.42 Impact Factor
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    ABSTRACT: A low level of response to alcohol during an individual's early experience with alcohol is associated with an increase risk of alcoholism. A family-based genome-wide linkage analysis using sibling pairs that underwent an alcohol challenge where the level of response to alcohol was measured with the Subjective High Assessment Scale (SHAS) implicated the 10q terminal (10qter) region. CYP2E1, a gene known for its involvement with ethanol metabolism, maps to this region. Variance component multipoint linkage analysis was performed on a combined map of single-nucleotide polymorphism (SNP) and microsatellite data. To account for the heterogeneity evident in the dataset, a calculation assuming locus heterogeneity was made using the Heterogeneity Log of Odds (HLOD) score. Association between SNP marker allele counts and copy number and SHAS scores were evaluated using a logistic regression model. Linkage analysis detected significant linkage to CYP2E1, which was diminished because of apparent locus heterogeneity traced to a single family with extreme phenotypes. In retrospect, circumstances recorded during testing for this family suggest that their phenotype data are likely to be unreliable. Significant allelic associations were detected for several CYP2E1 polymorphisms and the SHAS score. DNA sequencing from families that contributed the greatest evidence for linkage did not detect any changes directly affecting the primary amino acid sequence. With the removal of a single family, combined evidence from microsatellites and SNPs offers significant linkage between the level of response to alcohol and the region on the end of chromosome 10. Combined linkage and association indicate that sequence changes in or near CYP2E1 affect the level of response to alcohol providing a predictor of risk of alcoholism. The absence of coding sequence changes indicates that regulatory sequences are responsible. Implicating CYP2E1 in the level of response to alcohol allows inferences to be made about how the brain perceives alcohol.
    Alcoholism Clinical and Experimental Research 10/2010; 35(1):10-8. DOI:10.1111/j.1530-0277.2010.01317.x · 3.21 Impact Factor
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    ABSTRACT: A low level of response (LR) to alcohol is an important endophenotype associated with an increased risk of alcoholism. However, little is known about how neural functioning may differ between individuals with low and high LRs to alcohol. This study examined whether LR group effects on neural activity varied as a function of acute alcohol consumption. A total of 30 matched high- and low-LR pairs (N = 60 healthy young adults) were recruited from the University of California, San Diego, and administered a structured diagnostic interview and laboratory alcohol challenge followed by two functional magnetic resonance imaging (fMRI) sessions under placebo and alcohol conditions, in randomized order. Task performance and blood oxygen level-dependent response contrast to high relative to low working memory load in an event-related visual working memory (VWM) task were examined across 120 fMRI sessions. Both LR groups performed similarly on the VWM task across conditions. A significant LR group by condition interaction effect was observed in inferior frontal and cingulate regions, such that alcohol attenuated the LR group differences found under placebo (p < 0.05). The LR group by condition effect remained even after controlling for cerebral blood flow, age, and typical drinking quantity. Alcohol had differential effects on brain activation for low- and high-LR individuals within frontal and cingulate regions. These findings represent an additional step in the search for physiological correlates of a low LR and identify brain regions that may be associated with the low LR response.
    Alcoholism Clinical and Experimental Research 07/2010; 34(7):1162-70. DOI:10.1111/j.1530-0277.2010.01193.x · 3.21 Impact Factor

Publication Stats

5k Citations
436.91 Total Impact Points


  • 1987-2015
    • University of California, San Diego
      • • Department of Psychiatry
      • • Department of Medicine
      San Diego, California, United States
    • Oregon Research Institute
      Eugene, Oregon, United States
  • 2006-2009
    • VA San Diego Healthcare System
      San Diego, California, United States
    • University of San Diego
      San Diego, California, United States
  • 2001-2009
    • National University (California)
      San Diego, California, United States
  • 1999-2009
    • CSU Mentor
      Long Beach, California, United States
  • 2005
    • National Institute on Alcohol Abuse and Alcoholism
      Maryland, United States
  • 2003
    • University of California, San Francisco
      • Department of Neurology
      San Francisco, California, United States
  • 2002
    • University of Iowa
      • Department of Psychiatry
      Iowa City, Iowa, United States
  • 1995-1998
    • San Diego State University
      • Department of Psychology
      San Diego, California, United States
  • 1992
    • United States Department of Veterans Affairs
      Бедфорд, Massachusetts, United States