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1.  Transitions In and Out of Alcohol Use Disorders: Their Associations with Conditional Changes in Quality of Life Over a 3-Year Follow-Up Interval† 
Aims: The aim of this study was to investigate longitudinal changes in quality of life (QOL) as a function of transitions in alcohol use disorders (AUD) over a 3-year follow-up of a general US population sample. Methods: The analysis is based on individuals who drank alcohol in the year preceding the Wave 1 National Epidemiologic Survey on Alcohol and Related Conditions and were reinterviewed at Wave 2 (n = 22,245). Using multiple linear regression models, changes in SF-12 QOL were estimated as a function of DSM-IV AUD transitions, controlling for baseline QOL and multiple potential confounders. Results: Onset and offset of AUD were strongly associated with changes in mental/psychological functioning, with significant decreases in mental component summary (NBMCS) scores among individuals who developed dependence and significant increases among those who achieved full and partial remission from dependence. The increases in overall NBMCS and its social functioning, role emotional and mental health components were equally great for abstinent and nonabstinent remission from dependence, but improvements in bodily pain and general health were associated with nonabstinent remission only. Onset of abuse was unrelated to changes in QOL, and the increase in NBMCS associated with nonabstinent remission from abuse only was slight. Individuals with abuse only or no AUD who stopped drinking had significant declines in QOL. Conclusions: These results suggest the possible importance of preventing and treating AUD for maintaining and/or improving QOL. They are also consistent with the sick quitter hypothesis and suggest that abuse is less a mental disorder than a maladaptive pattern of behavior.
doi:10.1093/alcalc/agn094
PMCID: PMC2605522  PMID: 19042925
2.  Consequences of an Adolescent Onset and Persistent Course of Alcohol Dependence in Men: Adolescent Risk Factors and Adult Outcomes 
Background
While there is an extensive literature on the correlates of alcohol use disorders (AUD; alcohol abuse and dependence), there are relatively few prospective studies of representative birth cohorts that have examined the unique effects of an adolescent onset and persistent course of AUD on a wide range of psychosocial variables.
Methods
A longitudinal, community-based sample of 530 men was used to examine the impact of an adolescent onset (AUD+ at age 17) and persistent course (AUD+ at age 29) of AUD on adolescent and adult functioning including substance use, antisocial behavior, mental health problems, overall psychosocial functioning, environmental risk and protective factors, and social outcomes such as peer and romantic relationships, marriage, educational and occupational attainment, and parenthood.
Results
An adolescent onset of AUD (n = 57) was associated with severe deficits across multiple domains of psychosocial functioning in adolescence. Measures of behavioral disinhibition in adolescence were strong predictors of a persistent course of AUD (n = 93). Nearly 40% of men with an adolescent onset were able to desist by age 29, and were similar, but not identical to men who never experienced an AUD in terms of adult functioning. Men with an adolescent onset and persistent course of AUD exhibited the most severe deficits in functioning.
Conclusion
Results emphasize the importance of examining developmental course to understand the etiology of AUD. Our findings are optimistic in that individuals who desist from AUD are able to achieve high levels of psychosocial functioning. Our findings suggest that future research on the persistence of AUD into adulthood should focus on the contributions of behavioral disinhibition and social environment variables including peer and romantic relationships.
doi:10.1111/j.1530-0277.2010.01154.x
PMCID: PMC2884045  PMID: 20184563
3.  Sociodemographic Correlates of Transitions from Alcohol Use to Disorders and Remission in the São Paulo Megacity Mental Health Survey, Brazil 
Aims: To evaluate sociodemographic correlates associated with transitions from alcohol use to disorders and remission in a Brazilian population. Methods: Data are from a probabilistic, multi-stage clustered sample of adult household residents in the São Paulo Metropolitan Area. Alcohol use, regular use (at least 12 drinks/year), DSM-IV abuse and dependence and remission from alcohol use disorders (AUDs) were assessed with the World Mental Health version of the Composite International Diagnostic Interview. Age of onset (AOO) distributions of the cumulative lifetime probability of each alcohol use stage were prepared with data obtained from 5037 subjects. Correlates of transitions were obtained from a subsample of 2942 respondents, whose time-dependent sociodemographic data were available. Results: Lifetime prevalences were 85.8% for alcohol use, 56.2% for regular use, 10.6% for abuse and 3.6% for dependence; 73.4 and 58.8% of respondents with lifetime abuse and dependence, respectively, had remitted. The number of sociodemographic correlates decreased from alcohol use to disorders. All transitions across alcohol use stages up to abuse were consistently associated with male gender, younger cohorts and lower education. Importantly, low education was a correlate for developing AUD and not remitting from dependence. Early AOO of first alcohol use was associated with the transition of regular use to abuse. Conclusion: The present study demonstrates that specific correlates differently contribute throughout alcohol use trajectory in a Brazilian population. It also reinforces the need of preventive programs focused on early initiation of alcohol use and high-risk individuals, in order to minimize the progression to dependence and improve remission from AUD.
doi:10.1093/alcalc/agr007
PMCID: PMC3080240  PMID: 21414952
4.  Diffusion Tensor Measures of the Corpus Callosum in Adolescents With Adolescent Onset Alcohol Use Disorders 
Background
In adults, myelination injury is associated with alcoholism. Maturation of the corpus callosum is prominent during adolescence. We hypothesized that subjects with adolescent-onset alcohol use disorders (AUD; defined as Diagnostic and Statistical Manual of Mental Disorders-IV alcohol dependence or abuse) would have myelination mircostructural differences compared to controls.
Methods
Adolescent subjects (25 males, 7 females) with an AUD (16.9 ± 1.2 years), who were recruited from substance abuse treatment programs and had co-morbid mental disorders, and 28 sociodemographically similar healthy controls (17 males, 11 females; 15.9 ± 1.1 years) underwent a 3.0 T MRI diffusion tensor imaging scan.
Results
Measures of rostral body fractional anisotropy (FA) were higher in the AUD group than in the control group. Compared to controls, mean diffusivity (MD) was lower, while FA was higher, in the AUD group in the isthmus region. Anterior corpus callosum mircostructural development differed in adolescents with AUD, as age was positively (not negatively) associated with rostrum MD and age was negatively (not positively) associated with rostrum FA. There were sex by group interactions in that control females had higher posterior midbody FA when com pared to female adolescents with AUD.
Conclusions
Lower MD and higher FA values in the AUD group suggest pre-morbid vulnerability for accelerated prefrontal and temporo-parietal myelin maturation that may enhance the risk for adolescent AUD. Significant (and opposite to developmentally expected) correlations were seen between anterior corpus callosum MD and FA measures and age in the AUD group, suggesting neurotoxic effects of alcohol on adolescent corpus callosum microstructure. As seen in adults, female adolescents with AUD may be especially vulnerable to corpus callosum mircostructural injury. Further diffusion tensor imaging studies of corpus callosum maturation in children at familial risk for alcoholism, and in those with AUD, need to be done to elucidate these mechanisms.
doi:10.1111/j.1530-0277.2007.00603.x
PMCID: PMC3566638  PMID: 18241319
Alcohol Use Disorders; Alcohol Abuse or Dependence; Diffusion Tensor Imaging; Adolescence; Corpus Callosum
5.  Environmental influences predominate in remission from alcohol use disorder in young adult twins 
Psychological medicine  2012;42(11):2421-2431.
Background
Familial influences on remission from alcohol use disorder (AUD) have been studied using family history of AUD rather than family history of remission. The current study used a remission phenotype in a twin sample to examine the relative contributions of genetic and environmental influences to remission
Method
The sample comprised 6183 twins with an average age of 30 years from the Australian Twin Registry. Lifetime history of alcohol abuse and dependence symptoms and symptom recency were assessed with a structured telephone interview. AUD was defined broadly and narrowly as history of two or more or three or more abuse or dependence symptoms. Remission was defined as absence of symptoms at time of interview among individuals with lifetime AUD. Standard bivariate genetic analyses were conducted to derive estimates of genetic and environmental influences on AUD and remission
Results
Environmental influences alone accounted for remission in males and for 89% of influences on remission in females, with 11% due to genetic influences shared with AUD, which decreased the likelihood of remission. For women, more than 80% of influences on remission were distinct from influences on AUD, and environmental influences were from individual experiences only. For men, just over 50% of influences on remission were distinct from those on AUD, and the influence of environments shared with the co-twin were substantial. The results for the broad and narrow phenotypes were similar
Conclusions
The current study establishes young adult remission as a phenotype distinct from AUD and highlights the importance of environmental influences on remission
doi:10.1017/S003329171200044X
PMCID: PMC3752317  PMID: 22423619
Alcohol dependence; alcohol use disorder; remission; twins
6.  Smoke-free policies in drinking venues predict transitions in alcohol use disorders in a longitudinal U.S. sample 
Drug and alcohol dependence  2012;128(3):214-221.
Background
Smoke-free legislation prohibiting smoking in indoor public venues, including bars and restaurants, is an effective means of reducing tobacco use and tobacco-related disease. Given the high comorbidity between heavy drinking and smoking, it is possible that the public health benefits of smoke-free policies extend to drinking behaviors. However, no prior study has examined whether tobacco legislation impacts the likelihood of alcohol use disorders (AUDs) over time. The current study addresses this gap in the literature using a large, prospective U.S. sample.
Method
Using data from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC), we utilized logistic regression to examine whether the implementation of state-wide smoke-free legislation in bars and restaurants between Waves I (2001–2002) and II (2004–2005) predicted changes in DSM-IV AUD status (remission, onset, recurrence) in current drinkers at Wave I (n = 19,763) and participants who drank in public ≥once per month (n = 5913).
Results
Individuals in states that implemented smoke-free legislation in drinking venues had a higher likelihood of AUD remission compared to participants in states without such legislation. Among public drinkers, smoke-free legislation was associated with a greater likelihood of AUD remission and a lower likelihood of AUD onset. These findings were especially pronounced among smokers, men, and younger age groups.
Discussion
These results demonstrated the protective effects of smoke-free bar and restaurant policies on the likelihood of AUDs; furthermore, these findings call attention to an innovative legislative approach to decrease the morbidity and mortality associated with AUDs.
doi:10.1016/j.drugalcdep.2012.08.028
PMCID: PMC4052952  PMID: 22999418
Smoke-free policies; Alcohol use disorders; Longitudinal
7.  Alcohol use disorder-related sick leave and mortality: a cohort study 
Background
Alcohol use disorders (AUDs) are associated with the highest all-cause mortality rates of all mental disorders. The majority of patients with AUDs never receive inpatient treatment for their AUD, and there is lack of data about their mortality risks despite their constituting the majority of those affected. Absenteeism from work (sick leave) due to an AUD likely signals worsening. In this study, we assessed whether AUD-related sick leave was associated with mortality in a cohort of workers in Germany.
Methods
128,001 workers with health insurance were followed for a mean of 6.4 years. We examined the associations between 1) AUD-related sick leave managed on an outpatient basis and 2) AUD-related psychiatric inpatient treatment, and mortality using survival analysis, and Cox proportional hazard regression models (separately by sex) adjusted for age, education, and job code classification. We also stratified analyses by sick leave related to three groups of alcohol-related conditions (all determined by International Classification of Diseases 9th ed. (ICD-9) codes): alcohol abuse and dependence; alcohol-induced mental disorder; and alcohol-induced medical conditions.
Results
Outpatient-managed AUD-related sick leave was significantly associated with higher mortality (hazard ratio (HR) 2.90 (95% Confidence interval (CI) 2.24-3.75) for men, HR 5.83 (CI 2.90-11.75) for women). The magnitude of the association was similar for receipt of AUD-related psychiatric inpatient treatment (HR 3.2 (CI 2.76-3.78) for men, HR 6.5 (CI 4.41-9.47) for women). Compared to those without the conditions, higher mortality was observed consistently for outpatients and inpatients across the three groups of alcohol-related conditions. Those with alcohol-related medical conditions who had AUD-related psychiatric inpatient treatment appeared to have the highest mortality.
Conclusions
Alcohol use disorder-related sick leave as documented in health insurance records is associated with higher mortality. Such sick leave does not necessarily lead to any specific AUD treatment. Therefore, AUD-related sick leave might be used as a trigger for insurers to intervene by offering AUD treatment to patients to try to reduce their risk of death.
doi:10.1186/1940-0640-8-3
PMCID: PMC3565982  PMID: 23363536
Workers; Alcohol; Mortality; Gender; Addiction; Outpatients; Inpatients
8.  DIFFERENCES IN THE PROFILES OF DSM-IV AND DSM-5 ALCOHOL USE DISORDERS: IMPLICATIONS FOR CLINICIANS 
Background
Existing information on consequences of the DSM-5 revision for diagnosis of alcohol use disorders (AUD) has gaps, including missing information critical to understanding implications of the revision for clinical practice.
Methods
Data from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions were used to compare AUD severity, alcohol consumption and treatment, sociodemographic and health characteristics and psychiatric comorbidity among individuals with DSM-IV abuse versus DSM-5 moderate AUD and DSM-IV dependence versus DSM-5 severe AUD. For each pair of disorders, we additionally compared three mutually exclusive groups: individuals positive solely for the DSM-IV disorder, those positive solely for the DSM-5 disorder and those positive for both.
Results
Whereas 80.5% of individuals positive for DSM-IV dependence were positive for DSM-5 severe AUD, only 58.0% of those positive for abuse were positive for moderate AUD. The profiles of individuals with DSM-IV dependence and DSM-5 severe AUD were almost identical. The only significant (p<.005) difference, more AUD criteria among the former, reflected the higher criterion threshold (≥4 vs. ≥3) for severe AUD relative to dependence. In contrast, the profiles of individuals with DSM-5 moderate AUD and DSM-IV abuse differed substantially. The former endorsed more AUD criteria, had higher rates of physiological dependence, were less likely to be White and male, had lower incomes, were less likely to have private and more likely to have public health insurance, and had higher levels of comorbid anxiety disorders than the latter.
Conclusions
Similarities between the profiles of DSM-IV and DSM-5 AUD far outweigh differences; however, clinicians may face some changes with respect to appropriate screening and referral for cases at the milder end of the AUD severity spectrum, and the mechanisms through which these will be reimbursed may shift slightly from the private to public sector.
doi:10.1111/j.1530-0277.2012.01930.x
PMCID: PMC3800556  PMID: 22974144
DSM-5; AUD; treatment; severity; clinical profile
9.  Perturbation of the Glutamate–Glutamine System in Alcohol Dependence and Remission 
Neuropsychopharmacology  2011;36(7):1359-1365.
As acute ethanol exposure inhibits N-methyl--aspartate glutamate (Glu) receptors, sudden withdrawal from chronic alcohol use may lead to an increased activation of these receptors with excitotoxic effects. In the longer term, brain levels of Glu and its metabolites, such as glutamine (Gln), are likely to be chronically altered by alcohol, possibly providing a measure of overall abnormal Glu–Gln cycling. However, few studies have assessed concentrations of these metabolites in clinical populations of individuals with alcohol use disorders. Glu and Gln levels were compared in groups of 17 healthy controls and in 13 participants with alcohol dependence. Within the alcohol-dependent group, seven participants had current alcohol use disorder (AUD), and six had AUD in remission for at least 1 year (AUD-R). Neurometabolite concentrations were measured with proton magnetic resonance spectroscopy (1H-MRS) in a predominantly gray matter voxel that included the bilateral anterior cingulate gyri. Tissue segmentation provided an assessment of the proportion of gray matter in the 1H-MRS voxel. The Drinker Inventory of Consequences (DrInC) and Form-90 were administered to all participants to quantify alcohol consequences and use. Glu level was lower and Gln level was higher in the AUD and AUD-R groups relative to the control group; creatine, choline, myo-inositol, and total N-acetyl groups, primarily N-acetylaspartate did not differ across groups. These results were not confounded by age, sex, or proportion of gray matter in the 1H-MRS voxel. Neurometabolite concentrations did not differ between AUD and AUD-R groups. Subsequent regressions in the combined clinical group, treating voxel gray matter proportion as a covariate, revealed that total score on the DrInC was positively correlated with Gln but negatively correlated with both Glu and gray matter proportion. Regression analyses, including DrInC scores and smoking variables, identified a marginal independent effect of smoking on Gln. The current findings of higher Gln and lower Glu in the combined AUD and AUD-R groups might indicate a perturbation of the Glu–Gln cycle in alcohol use disorders. The absence of differences in mean Glu and Gln between the AUD and AUD-R groups suggests that altered Glu–Gln metabolism may either predate the onset of abuse or persist during prolonged abstinence.
doi:10.1038/npp.2011.20
PMCID: PMC3096805  PMID: 21389979
magnetic resonance spectroscopy; alcohol use disorders; alcoholism; glutamate; glutamine; addiction & substance abuse; alcohol & alcoholism; glutamate; biological psychiatry; magnetic resonance spectroscopy
10.  Age and Ethnic Differences in the Onset, Persistence and Recurrence of Alcohol Use Disorder 
Addiction (Abingdon, England)  2012;107(4):756-765.
Aims
To estimate ethnic differences in three components of alcohol use disorder and alcohol dependence course (onset, persistence and recurrence) in a developmental framework.
Design
Longitudinal data from The National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), collected using face-to-face interviews.
Setting
Civilian non-institutionalized US population aged 18 years and older, with oversampling of Hispanics, Blacks and those aged 18–24.
Participants
Individuals who completed both NESARC assessments, were not lifelong abstainers, and were either White (n=17,458), Black (n=4995), US-born Hispanic (n=2810), or Hispanic-born outside the US (n=2389).
Measurements
Alcohol dependence (AD) and alcohol use disorder (AUD; abuse or dependence) onset, persistence and recurrence were examined using the Alcohol Use Disorders and Associated Disabilities Interview Schedule, DSM-IV version.
Findings
Among men: relative to Whites aged 18–29, AUD onset and persistence were elevated only in US-born Hispanics 40 and older; odds were reduced for all non-US born Hispanics, older Whites, most Blacks, and US-born Hispanics aged 30–39. For AD, onset risk was elevated for all younger minority men and only reduced among non-US born Hispanics 40 or older. For women: compared to young Whites, non-US born Hispanics were at decreased AUD and AD onset risk; AUD and AD onset and persistence were increased for older Blacks and US-born Hispanics.
Conclusions
Ethnic differences in alcohol disorder transitions (onset, persistence, and recurrence) vary across age, gender, and whether a broad (alcohol use disorder) or narrow (alcohol dependence) alcohol definition is used. Evidence of increased risk for some transitions in minority groups suggests that attention should be paid to the course of alcohol use disorders, and that differences in prevalence should not be assumed to reflect differences in specific transitions.
doi:10.1111/j.1360-0443.2011.03721.x
PMCID: PMC3290716  PMID: 22085024
11.  Alcohol-Use Disorders and Nonmedical Use of Prescription Drugs Among U.S. College Students* 
Objective
The purpose of this study was to examine the association between Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), alcohol-use disorders (AUDs) and nonmedical use of prescription drugs (NMPD) among U.S. college students. A secondary aim of this study was to identify individual-level and college-level characteristics associated with the co-occurrence of AUDs and NMPD.
Method
Data were collected from self-administered mail surveys, sent to a random sample of approximately 14,000 college students from a nationally representative sample of 119 U.S. colleges and universities.
Results
Among U.S. college students, those with AUDs represented approximately 75% of nonmedical users of prescription drugs. Multivariate logistic regression analyses indicated that college students with past-year DSM-IV alcohol abuse only (adjusted odds ratio [AOR] = 4.46, 95% confidence interval [CI] = 3.59-5.55) and students with past-year DSM-IV alcohol dependence (AOR = 9.17, 95% CI = 7.05-11.93) had significantly increased odds of NMPD in the past year compared with students without AUDs. The co-occurrence of AUDs and NMPD was more likely among college students who were male, white, earned lower grade point averages, and attended co-ed colleges and institutions located in Southern or Northeastern U.S. regions.
Conclusions
The findings provide evidence that NMPD is more prevalent among those college students with AUDs, especially individuals with past-year DSM-IV alcohol dependence. The assessment and treatment of AUDs among college students should account for other forms of drug use such as NMPD.
PMCID: PMC2377410  PMID: 17568959
12.  Long-Term Use of Benzodiazepines in Participants with Comorbid Anxiety and Alcohol Use Disorders 
Background
Although the only widely accepted role for benzodiazepines in alcohol dependence is the treatment of withdrawal syndromes, they are frequently prescribed outside of this clinical setting. There is little empirical evidence to guide the rational use of benzodiazepines in the common clinical situation where anxiety disorders are comorbid with alcohol use disorders (AUD). Since January 1989, the Harvard Anxiety Research Program has naturalistically monitored the prospective clinical course of people with anxiety disorders, some of whom had a history of AUD. Earlier research showed that the use of benzodiazepines was not significantly associated with the presence or absence of a history of an AUD over the first year of follow-up. This report extends that investigation.
Methods
Using standard parametric analytic methods, patterns of benzodiazepine use (routinely prescribed medication and as-needed [PRN] use) among participants receiving benzodiazepine treatment was prospectively examined over the course of 12 years. Differences in benzodiazepine usage patterns were examined in each year of follow-up between participants who did (n = 120) and did not (n = 425) have a new episode of AUD. Using proportional hazards regression analysis, benzodiazepine usage levels were examined as predictors of recovery and recurrence of AUD. Additionally, random-effects regression analyses were used to examine the patterns of benzodiazepine use before and after the onset of a prospectively observed episode of AUD.
Results
Benzodiazepine usage levels remained stable for the full sample over the course of the 12 years. Benzodiazepine use did not distinguish participants who had a new AUD from those who did not. Over the 12 years of follow-up, participants who had an AUD used more PRN medication in years five to eight. This difference reached statistical significance but was not clinically significant. Benzodiazepine usage levels did not predict recovery or recurrence in AUD subjects. Neither the total dose nor the PRN usage of benzodiazepines was significantly associated with the onset of AUD, but when combined into a measure of any benzodiazepine use, a relationship between increased use and the onset of AUD emerged.
Conclusions
For participants in the Harvard Anxiety Research Program with comorbid alcohol dependence and anxiety disorders, there was little association between the use of benzodiazepines and the occurrence of a new AUD. Neither was there a temporal relationship between the use of benzodiazepines and the onset of a new AUD. Whether or not this finding extends to a broader patient population or a group of people who present to addictions treatment awaits further investigation.
doi:10.1097/01.alc.0000175016.01790.f1
PMCID: PMC2548411  PMID: 16131848
Benzodiazepines; Alcohol Use Disorders; Harvard Anxiety Research Program; Anxiety; Comorbid Alcohol Dependence; Anxiety Disorders
13.  Diffusion Tensor Imaging of White Matter Networks in Individuals with Current and Remitted Alcohol Use Disorders and Comorbid Conditions 
Individuals with alcohol use disorders show white matter abnormality relative to normal samples, yet differences in white matter profiles have not yet been investigated as a function of abstinence. Individuals with current alcohol use disorders (AUD-C; n = 10), individuals with alcohol use disorders in remission for at least one year (AUD-R; n = 9), and healthy control participants (HC; n = 15) matched to alcohol groups on age and smoking status underwent magnetic resonance imaging (MRI). Diffusion tensor imaging (DTI) data were analyzed using tract-based spatial statistics (TBSS). Compared to HC, AUD-C showed reduced axial diffusivity in bilateral frontal and temporal white matter. In AUD-R, lower fractional anisotropy relative to HC was widespread in bilateral parietal regions. A combined AUD-C and AUD-R group had decreased fractional anisotropy primarily in the fornix and thalamus. In conclusion, AUD-R manifested damage in parietal regions integral to processing of visuospatial information and self-awareness, whereas AUD-C showed abnormal diffusivity in fronto-temporal regions that regulate impulsivity, attention, and memory. As a combined group, AUD individuals exhibited abnormality in subcortical areas associated with sensory processing and memory. White matter differences in individuals with AUD may be attributable to premorbid vulnerability or persisting effects of alcohol abuse, but the pattern of abnormality across groups suggests that these abnormalities may be secondary to alcohol use.
doi:10.1037/a0027168
PMCID: PMC3374918  PMID: 22352699
alcohol use disorder; tract-based spatial statistics; diffusion tensor imaging; axial diffusivity; radial diffusivity; fractional anisotropy
14.  Clinical Indices of Familial Alcohol Use Disorder 
Background
Alcohol use disorders (AUDs) are clinically heterogeneous and strongly influenced by familial/genetic factors. Can we identify specific clinical features of AUDs that index familial liability to illness?
Methods
In twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders meeting DSM-IV criteria for lifetime AUDs, we examined whether clinical features of AUDs, including individual DSM-IV criteria for alcohol dependence (AD) and alcohol abuse (AA), predicted risk for AUDs in cotwins and/or parents. Analyses of individual criterion were repeated controlling for the total number of endorsed criteria.
Results
Across these analyses, examining narrowly and broadly defined AUDs, risk of AUDs in relatives was more consistently predicted by abuse criteria than by dependence criteria, and by criteria reflecting negative psychosocial consequences rather than pharmacologic/biological criteria. Age at onset (AAO) poorly predicted risk in relatives. AUD associated legal problems, the one criterion slated for removal in DSM-5, was the most consistent single predictor of familial risk. Associations observed between individual criteria and risks of illness in relatives were generally stronger in monozygotic than dizygotic twin pairs, suggesting that these symptoms reflect a genetic risk for AUDs.
Conclusions
Individual DSM-IV criteria for AA and AD differ meaningfully in the degree to which they reflect the familial/genetic liability to AUDs. Contrary to expectation, the familial/genetic risk to AUDs was better reflected by symptoms of abuse and negative psychosocial consequences of AUD than by early AAO, or symptoms of tolerance and withdrawal.
doi:10.1111/j.1530-0277.2012.01844.x
PMCID: PMC3606908  PMID: 22978547
Alcohol Abuse; Alcohol Dependence; Twin Studies; Heritability; Symptoms
15.  The Relationships of the Level of Response to Alcohol and Additional Characteristics to Alcohol Use Disorders across Adulthood: A Discrete-Time Survival Analysis 
Background
A low level of response (LR) to alcohol has been shown to relate to a higher risk for alcohol use disorders (AUDs). However, no previous research has examined the association between LR and the development of AUDs in the context of additional robust risk factors for AUDs. This study evaluated whether LR and other related characteristics predicted the occurrence of AUDs across adulthood using discrete-time survival analysis (DTSA).
Methods
297 probands from the San Diego Prospective Study reported on the LR to alcohol, a family history (FH) of AUDs, the typical drinking quantity, the age of drinking onset, the body mass index and the age at the baseline (T1) assessment. Alcohol use disorders (AUDs) were evaluated at the 10-year (T10), T15, T20, and T25 follow-ups.
Results
A low LR to alcohol predicted AUD occurrence over the course of adulthood even after controlling for the effects of other robust risk factors. Interaction effects revealed that the impact of FH on AUDs was only observed for subjects with high T1 drinking levels, and probands with high T1 drinking were at high risk for AUDs regardless of their age of onset.
Conclusion
The findings illustrate that LR is a unique risk factor for AUDs across adulthood, and not simply a reflection of a broader range of risk factors. The continued investigation of how LR is related to AUD onset later in life will help inform treatment providers about this high-risk population, and future longitudinal evaluations will utilize DTSA to assess rates of AUD remission as well as the onset of drinking outcomes in adolescent samples.
doi:10.1111/j.1530-0277.2009.00984.x
PMCID: PMC2947374  PMID: 19485971
Level of Response; Alcoholism; Survival Analysis; Longitudinal; Family History; Drinking Onset
16.  Onset and Course of Alcoholism Over 25 Years in Middle Class Men 
Drug and alcohol dependence  2010;113(1):21-28.
Background
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.
Methods
Data were generated at baseline (T1) at ~age 20, and through face-to-face follow-up 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 5 years before the 25-year followup.
Results
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.
Conclusion
These data indicate that information available in the late teens to early 20’s can help predict the future onset and course of AUDs, and underscore the importance of longitudinal studies in substance use disorders.
doi:10.1016/j.drugalcdep.2010.06.017
PMCID: PMC3000869  PMID: 20727682
alcohol; sensitivity; alcoholism clinical course
17.  Social networks and alcohol use disorders: findings from a nationally representative sample 
Background
While some argue that social network ties of individuals with alcohol use disorders (AUD) are robust, there is evidence to suggest that individuals with AUDs have few social network ties, which are a known risk factor for health and wellness.
Objectives
Social network ties to friends, family, co-workers and communities of individuals are compared among individuals with a past-year diagnosis of alcohol dependence or alcohol abuse to individuals with no lifetime diagnosis of AUD.
Method
Respondents from Wave 2 of the National Epidemiologic Survey on Alcohol Related Conditions (NESARC) were assessed for the presence of past-year alcohol dependence or past-year alcohol abuse, social network ties, sociodemographics and clinical characteristics.
Results
Bivariate analyses showed that both social network size and social network diversity was significantly smaller among individuals with alcohol dependence, compared to individuals with alcohol abuse or no AUD. When social and clinical factors related to AUD status were controlled, multinomial logistic models showed that social network diversity remained a significant predictor of AUD status, while social network size did not differ among AUD groups.
Conclusion
Social networks of individuals with AUD may be different than individuals with no AUD, but this claim is dependent on specific AUD diagnosis and how social networks are measured.
doi:10.3109/00952990.2013.860984
PMCID: PMC4004646  PMID: 24405256
Alcohol use disorders; National Epidemiologic Survey on Alcohol Related Conditions (NESARC); social networks
18.  Longitudinal predictors of addictions treatment utilization in treatment-naïve adults with alcohol use disorders 
Drug and alcohol dependence  2010;113(2-3):215-221.
Background
Despite the substantial prevalence of alcohol use disorders (AUDs), prior research indicates that most people with AUDs never utilize either formal or informal treatment services. Several prior studies have examined the characteristics of individuals with AUDs who receive treatment; however, limited longitudinal data are available on the predictors of receiving AUD services in treatment-naive individuals with AUDs.
Methods
This study utilized data from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) to identify adults in Wave 1 who met criteria for an AUD within the last 12 months and reported no prior lifetime alcohol treatment (N=2,760). These individuals were surveyed again at Wave 2, approximately three to four years later (N=2,170). This study examined the Wave 1 demographic and psychiatric conditions that were associated with receipt of AUD treatment services between Wave 1 and Wave 2.
Results
In multivariable analyses, use of AUD treatment services between Waves 1 and 2 was significantly more likely among those who were male, non-Caucasian, younger, had lower income, and who had health insurance. Additionally, those who met criteria for a baseline drug use disorder, anxiety disorder or a personality disorder were more likely to receive AUD treatment.
Conclusions
Treatment was more often utilized in those who had more severe baseline psychopathology and in those with fewer economic resources. These findings highlight the need to broaden the types of care available to individuals with AUDs to increase the appeal of AUD services.
doi:10.1016/j.drugalcdep.2010.08.006
PMCID: PMC3005968  PMID: 20828944
Addictions treatment; service utilization; alcohol dependence; alcoholism
19.  Absence of P300 reduction in South African treatment-naïve adolescents with alcohol dependence 
Background
ERP studies show reduced P300 amplitudes in alcohol use disorders (AUDs). Alcohol exposure, genetic vulnerability to alcoholism, and comorbid psychopathology may contribute to this reduction. Most previous research has studied treated adult AUD samples, which have more severe alcoholism, a greater family history of AUDs, and more comorbidity than untreated samples. Untreated AUD samples tend to have little or no P300 amplitude reduction. We compared P300 between treatment-naïve alcohol-dependent (TNAD) adolescents with no diagnosable substance abuse or psychiatric comorbidity, and non-substance-abusing control (NSAC) adolescents.
Methods
Individuals between the ages of 13 and 18 years were recruited into either TNAD (n = 45) or NSAC (n = 64) groups. Alcohol-use variables, family history density of alcohol problems, and psychiatric symptom counts were assessed in a clinician-administered evaluation. EEGs were recorded during performance of a 3-condition visual target detection task.
Results
P300 amplitudes were of comparable size in TNAD adolescents and NSAC. Boys demonstrated larger P3a and P3b amplitudes than girls. Within TNAD, P3b amplitude was reduced in those who drank more frequently and P3a latency was more prolonged in subjects with higher internalizing symptom counts.
Conclusions
The P300 deficit was not present in TNAD adolescents without comorbidities. In comparison to results of reduced P300 in treated adolescent AUD samples, this finding likely reflects moderate alcohol exposure, lower genetic vulnerability to alcoholism, and lack of comorbidity in our sample. Further work is needed to determine the relative contributions of these factors to changes in the P300.
doi:10.1111/j.1530-0277.2012.01837.x
PMCID: PMC3491103  PMID: 22676302
Event-related potentials; P300; Alcoholism; Treatment-naïve; Adolescents
20.  The relationships of sociodemographic factors, medical, psychiatric and substance-misuse comorbidities to neurocognition in short-term abstinent alcohol dependent individuals 
Alcohol (Fayetteville, N.Y.)  2008;42(6):439-449.
Comorbidies that commonly accompany those afflicted with an alcohol use disorder (AUD) may promote variability in the pattern and magnitude of neurocognitive abnormalities demonstrated. The goal of this study was to investigate the influence of several common comorbid medical conditions (primarily hypertension and hepatitis C), psychiatric (primarily unipolar mood and anxiety disorders), and substance use (primarily psychostimulant and cannabis) disorders, and chronic cigarette smoking on the neurocognitive functioning in short-term abstinent, treatment-seeking individuals with AUD. Seventy-five alcohol dependent participants (ALC; 51 ± 9 years of age; 3 females) completed comprehensive neurocognitive testing after approximately one-month of abstinence. Multivariate multiple linear regression evaluated the relationships among neurocognitive variables and medical conditions, psychiatric and substance use disorders, controlling for sociodemographic factors. Sixty-four percent of ALC had at least one medical, psychiatric or substance abuse comorbidity (excluding smoking). Smoking status (smoker or non-smoker) and age were significant independent predictors of cognitive efficiency, general intelligence, postural stability, processing speed and visuospatial memory after age-normed adjustment and control for estimated premorbid verbal IQ, education, alcohol consumption, and medical, psychiatric, and substance misuse comorbidities. Results indicated that chronic smoking accounted for a significant portion of the variance in the neurocognitive performance of this middle-aged AUD cohort. The age-related findings for ALC suggest that alcohol dependence, per se, was associated with diminished neurocognitive functioning with increasing age. The study of participants who demonstrate common comorbidities observed in AUD is necessary to fully understand how AUD, as a clinical syndrome, affects neurocognition, brain neurobiology, and their changes with extended abstinence.
doi:10.1016/j.alcohol.2008.06.001
PMCID: PMC2597590  PMID: 18760713
alcohol use disorders; alcohol dependence; cigarette smoking; age effects; comorbidities
21.  DSM-IV alcohol abuse and dependence criteria characteristics for recent onset adolescent drinkers 
Drug and Alcohol Dependence  2012;124(1-2):88-94.
Background
Little is known about the psychometric properties of alcohol abuse and dependence criteria among recent-onset adolescent drinkers, particularly for those who consume alcohol infrequently. This study evaluated how well DSM-IV alcohol dependence criteria measure an alcohol use disorder (AUD) construct for recent onset adolescent drinkers at different levels of drinking frequency.
Method
Data were drawn from the National Survey on Drug Use and Health, a nationally representative sample of 9,356 recent-onset adolescent drinkers, aged 12–21, who began drinking within the past year. Multiple group item response theory analysis was conducted to assess the 11 DSM-IV alcohol abuse and dependence criteria.
Results
Criteria most likely to be endorsed at lower AUD severity included ““withdrawal,” “problems at home, school or work” and “tolerance.” The criteria “drinking larger amounts/longer period of time,” “unsuccessful efforts to cut down” and “continuing to drink despite related health problems” were more likely to be endorsed at higher AUD severity. Two criteria, “tolerance” and “time spent getting, using or recovering from alcohol” showed differential item functioning between drinking frequency groups (< 7 vs. ≥ 7 days in past month), with lower discrimination and severity for more frequent drinkers. DSM-IV criteria were most precise for intermediate levels of AUD severity.
Conclusions
All but two DSM-IV criteria had consistent psychometric properties across drinking frequency groups. Symptoms were most precise for a narrow, intermediate range of AUD severity. Those assessing AUD in recent onset adolescent drinkers might consider additional symptoms to capture the full AUD continuum.
doi:10.1016/j.drugalcdep.2011.12.013
PMCID: PMC3350753  PMID: 22236537
alcohol dependence; drinking frequency; item response theory; recent onset drinkers; adolescents
22.  Item Response Theory Analysis of Binge Drinking and its Relationship to Lifetime Alcohol Use Disorder Symptom Severity in an American Indian Community Sample 
Background
Item Response Theory (IRT) has been used to examine alcohol use disorder (AUD) symptoms and their psychometric properties but has not been previously applied to AUD symptoms from an American Indian sample.
Methods
Lifetime DSM-IV AUD symptoms and binge drinking (5+ drinks men/4+ drinks women) at ≥1, ≥4, ≥8, ≥15 days per month during the period of heaviest lifetime drinking criteria were assessed in 530 American Indian participants. Exploratory (EFA) factor analysis was used to examine the factor structure of the ten AUD symptoms and each alcohol consumption criterion. Two-parameter IRT models generated marginal maximum likelihood estimates for discrimination (a) and threshold (b) parameters for ten DSM-IV AUD symptoms and each consumption criterion. Differential Item Functioning (DIF) analysis was used to assess AUD symptom severity in groups defined by gender and age at interview.
Results
The AUD symptoms of “Withdrawal” and “Activities Given Up” were the most severe symptoms. “Tolerance” and “Social/Interpersonal Problems” were the least severe. All AUD symptoms fell on the moderate portion of the severity continuum, except “Withdrawal”, which fell at the lower end of the severe portion. The consumption criterion of 5+/4+ (male/female) at ≥8 times per month demarcated the portion of the severity continuum where AUD symptoms began to occur at a probability of 50%. DIF analysis showed significant gender and age at interview differences for “Hazardous Use,” “Tolerance,” and “Activities Given Up,” but not for the other AUD symptoms.
Conclusions
In this American Indian community sample, alcohol abuse and dependence did not represent distinct disorders. Only one AUD symptom was found outside the moderate portion of the underlying AUD severity continuum. Drinking 5+/4+ (male/female) drinks at a frequency of ≥8 times per month during the period of heaviest lifetime drinking was found to function well as both a risk and a diagnostic criterion for lifetime DSM-IV AUD. DSM-IV AUD symptom criteria, as currently assessed, may be limited in their ability to capture the full range of symptom severity of AUDs, at least in this high risk population.
doi:10.1111/j.1530-0277.2010.01429.x
PMCID: PMC3083452  PMID: 21314696
IRT; Binge Drinking; Alcohol Symptoms; Native American
23.  Correlates of alcohol abuse/dependence in early-onset alcohol-using women 
Background
Early-onset alcohol use is associated with increased vulnerability to subsequent alcohol abuse and dependence. However, not all early-onset alcohol users develop alcohol use disorders (AUDs). Using a sample of young women from the U.S., we identify correlates that contribute to a greater likelihood of AUDs in early-onset alcohol users.
Methods
Using interview and questionnaire data on participants of the Missouri Adolescent Female Twin Study (MOAFTS), we examine whether measures from domains including socio-demographic, pubertal development, religiosity, educational achievement, adverse life events, internalizing disorders, externalizing disorders and family history and discipline were associated with development of AUDs in 1,158 women who had their first drink of alcohol prior to age 16.
Results
Early-onset drinkers were 3.6 times more likely to meet criteria for AUDs than later onset drinkers. While univariate analyses revealed that a host of correlates were associated with likelihood of AUDs in early-onset drinkers, multivariate analyses suggested that, even after accounting for a particularly early age of onset of drinking, those with a history of physical abuse, co-twin alcohol problems, conduct disorder, regular smoking, older peers and peer substance use were considerably more likely to meet criteria for AUDs than early onset drinkers without a lifetime history of these correlates.
Conclusion
The progression from first drink to AUDs is complex, and while early age at first drink is a potent risk factor, other aspects of psychopathology, family history, conduct problems and peer affiliations can exacerbate or alleviate the risk of AUDs in these young female drinkers.
doi:10.1111/j.1521-0391.2011.00151.x
PMCID: PMC3571676  PMID: 21838841
alcohol; early-onset; alcohol abuse/dependence; female
24.  Comparative Performance of the AUDIT-C in Screening for DSM-IV and DSM-5 Alcohol Use Disorders* 
Drug and alcohol dependence  2012;126(3):384-388.
Objective
Under the proposed DSM-5 revision to the criteria for alcohol use disorder (AUD), a substantial proportion of DSM-IV AUD cases will be lost or shifted in terms of severity, with some new cases added. Accordingly, the performance of the AUDIT-C in screening for DSM-IV AUD cannot be assumed to extend to DSM-5 AUD. The objective of this paper is to compare the AUDIT-C in screening for DSM-IV and DSM-5 AUD.
Methods
Using a broad range of performance metrics, the AUDIT-C was tested and contrasted as a screener for DSM-IV AUD (any AUD, abuse and dependence) and DSM-5 AUD (any AUD, moderate AUD and severe AUD) in a representative sample of U.S. adults aged 21 and older and among past-year drinkers.
Results
Optimal AUDIT-C cutpoints were identical for DSM-IV and DSM-5 AUD: ≥4 for any AUD, ≥3 or ≥4 for abuse/moderate AUD and ≥4 or ≥5 for dependence/severe AUD. Screening performance was slightly better for DSM-5 severe AUD than DSM-IV dependence but did not differ for other diagnoses. At optimal screening cutpoints, positive predictive values were slightly higher for DSM-5 overall AUD and moderate AUD than for their DSM-IV counterparts. Sensitivities were slightly higher for DSM-5 severe AUD than DSM-IV dependence. Optimal screening cutpoints shifted upwards for past-year drinkers but continued to be identical for DSM-IV and DSM-5 disorders.
Conclusions
Clinicians should not face any major overhaul of their current screening procedures as a result of the DSM-5 revision and should benefit from fewer false positive screening results.
doi:10.1016/j.drugalcdep.2012.05.029
PMCID: PMC3469743  PMID: 22728044
AUDIT-C; screening; alcohol use disorder; DSM-IV; DSM-5
25.  Changes in Smoking for Adults with and without Alcohol and Drug Use Disorders: Longitudinal Evaluation in the U.S. Population 
Background
Little is known about the smoking cessation and smoking relapse behavior of adults with alcohol use disorders (AUDs) and drug use disorders (DUDs).
Objectives
The current study used longitudinal data from a representative sample of the U.S. adult population to examine changes in smoking over three years for men and women with and without AUD and DUD diagnoses.
Methods
Participants were current or former daily cigarette smokers at Wave 1 of the National Epidemiologic Survey on Alcohol and Related Conditions who completed the Wave 2 assessment three years later (n=11,973; 46% female). Analyses examined the main and gender-specific effects of AUD and DUD diagnoses on smoking cessation and smoking relapse.
Results
Wave 1 Current Daily Smokers with a Current AUD (OR=0.70, 95% CI=0.55, 0.89), Past AUD (OR=0.73, 95% CI=0.60, 0.89), Current DUD (OR=0.48, 95% CI=0.31, 0.76), and Past DUD (OR=0.62, 95% CI=0.49, 0.79) were less likely to have quit smoking at Wave 2 than those with no AUD or DUD diagnosis. Wave 1 Former Daily Smokers with a Current AUD (OR=2.26, 95% CI=1.36, 3.73), Current DUD (OR=7.97, 95% CI=2.51, 25.34), and Past DUD (OR=2.69, 95% CI=1.84, 3.95) were more likely to have relapsed to smoking at Wave 2 than those with no AUD or DUD diagnosis. The gender-by-diagnosis interactions were not significant.
Conclusion
Current and Past AUDs and DUDs were associated with a decreased likelihood of quitting smoking while Current AUDs, Current DUDs, and Past DUDs were associated with an increased likelihood of smoking relapse.
doi:10.3109/00952990.2013.785557
PMCID: PMC3696891  PMID: 23721534

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