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1.  Who Is Becoming Hallucinogen Dependent Soon After Hallucinogen Use Starts?1 
Drug and alcohol dependence  2006;87(0):153-163.
This study, based upon epidemiological survey data from the United States (U.S.) National Household Surveys on Drug Abuse (NHSDA) from 2000–2001, presents new estimates for the risk of developing a hallucinogen dependence syndrome within 24 months after first use of any hallucinogen (median elapsed time ~ 12 months). Subgroup variations in risk of becoming hallucinogen dependent also are explored. Estimates are derived from the NHSDA representative samples of non-institutionalized U.S. residents ages 12 and older (n = 114,241). A total of 2,035 respondents had used hallucinogens for the first time within 24 months prior to assessment. An estimated 2%–3% of these recent-onset hallucinogen users had become dependent on hallucinogens, according to the NHSDA DSM-IV computerized diagnostic algorithm. Controlling for sociodemographic and other drug use covariates, very early first use of hallucinogens (age 10–11 years) is associated with increased risk of hallucinogen dependence (p < 0.01). Excess risk of developing hallucinogen dependence was found in association with recent-onset use of mescaline; excess risk also was found for recent onset users of ecstasy and of PCP. This study’s evidence is consistent with prior evidence on a tangible but quite infrequent dependence syndrome soon after the start of hallucinogen use; it offers leads that can be confirmed or disconfirmed in future investigations.
PMCID: PMC4327824  PMID: 16987612
hallucinogen; dependence; logistic regression; epidemiology; recent-onset
2.  Extra-medical stimulant dependence among recent initiates 
Drug and alcohol dependence  2009;104(0):147-155.
New estimates for the risk of becoming stimulant dependent within 24 months after first extra-medical (EM) use of a stimulant drug compound are presented, with a focus on subgroup variations in this risk (e.g., alcohol dependence, male–female differences). The study estimates are derived from a representative sample of United States residents ages 12 and older (n = 166,737) obtained from the 2003 to 2005 National Surveys on Drug Use and Health. A total of 1700 respondents were found to have used stimulants extra-medically for the first time within 24 months prior to assessment. Approximately 5% of these recent-onset EM users had become stimulant dependent since onset of EM use. As hypothesized, alcohol dependence cases were found to have experienced an excess risk of becoming stimulant dependent soon after onset of stimulant drug use; there was no robust male–female difference in risk. Independently, initiates who had used multiple types of stimulants extra-medically, and methamphetamine users, were more likely to have become stimulant dependent soon after onset of use; by comparison, EM users of methylphenidate (Ritalin®) were less likely to have developed rapid-onset dependence. These epidemiologic findings help quantify a continuing public health burden associated with new onsets of extra-medical stimulant use in the 21st century.
PMCID: PMC4327814  PMID: 19515516
Stimulants; Dependence; Methylphenidate; Logistic regression; Epidemiology; Recent-onset
3.  Toward Primary Prevention of Extra-Medical OxyContin® Use Among Young People 
Preventive medicine  2013;57(3):244-246.
The prevention research context includes current epidemic levels of hazards associated with extra-medical use of OxyContin® (to get high or otherwise outside prescribed boundaries) among teenagers and young adults, and a recent OxyContin® reformulation with an intent to reduce these hazards, plus hope for possibly beneficial primary prevention impact. The aim is to create a benchmark of risk estimates for the years just prior to OxyContin® re-formulation in anticipation of potential public health benefit in future years, with a focus on teens and the youngest adults in the United States, and to compare two methods for estimating peak risk.
The data are from nationally representative probability sample surveys of 12–21 year olds, yielding estimates for incidence of extra-medical OxyContin® use. Samples are of the non-institutionalized United States population, recruited and assessed in National Surveys on Drug Use and Health (NSDUH), each year from 2004 through 2008. In aggregate, the sample includes 135,552 young people who had not used OxyContin® extra-medically prior to their year of survey assessment.
The main outcome was the estimated population-level age-specific incidence of extra-medical OxyContin® use, 2004–2008. We found that during the 2004–2008 interval the estimated risk accelerated from age 12 years, reached a peak value in mid-adolescence at roughly five newly incident users per 1000 persons per year (95% confidence intervals, 0.3%, 0.7%), and then declined. A meta-analysis approach to year-by-year data differentiated age patterns more clearly than a pooled estimation approach.
Studying young people in the United States, we have discovered that the risk of starting to use OxyContin® extra-medically rises to a peak by mid-adolescence and then declines. From a methods standpoint, the meta-analysis serves well in this context; there is no advantage to pooling survey data across years. We also discovered that during any given year a pediatrician might rarely see even one patient who has just started to use OxyContin® to get high or for other extra-medical purposes. Implications for screening are discussed.
PMCID: PMC3928689  PMID: 23701847
4.  The Relationship of Mental and Behavioral Disorders to All-Cause Mortality in a 27-Year Follow-up of 4 Epidemiologic Catchment Area Samples 
American Journal of Epidemiology  2013;178(9):1366-1377.
Subjects from the Epidemiologic Catchment Area Program, interviewed during 1979–1983, were linked to data in the National Death Index through 2007 to estimate the association of mental and behavioral disorders with death. There were more than 25 years of follow-up for 15,440 individuals, with 6,924 deaths amounting to 307,881 person-years of observation. Data were analyzed by using age as the time scale and parametric approaches to quantify the years of life lost due to disorders. Alcohol, drug use, and antisocial personality disorders were associated with increased risk of death, but there was no strong association with mood and anxiety disorders. Results of high- and low-quality matches with the National Death Index were similar. The 3 behavioral disorders were associated with 5–15 years of life lost, estimated along the life course via the generalized gamma model. Regression tree analyses showed that risk of death was associated with alcohol use disorders in nonblacks and with drug disorders in blacks. Phobia interacted with alcohol use disorders in nonblack women, and obsessive-compulsive disorder interacted with drug use disorders in black men. Both of these anxiety disorders were associated with lower risk of death early in life and higher risk of death later in life.
PMCID: PMC3813315  PMID: 24091891
anxiety disorders; generalized gamma distribution; mental disorder; mood disorders; mortality; personality disorders; proportional hazards model; substance-related disorders
5.  Embarrassment When Illness Strikes A Close Relative: A World Mental Health Survey Consortium Multi-Site Study 
Psychological medicine  2013;43(10):2191-2202.
This global study seeks to estimate the degree to which a family member might feel embarrassed when a close relative is suffering from an alcohol, drug, or mental health condition (ADMC) versus a general medical condition (GMC). To date, most studies have considered embarrassment and stigma in society and internalized by the afflicted individual, but have not assessed family embarrassment in a large scale study.
In 16 sites of the World Mental Health Surveys (WMHS), standardized assessments were completed including items on family embarrassment. Site matching was used to constrain local socially shared determinants of stigma-related feelings, enabling a conditional logistic regression model that estimates the embarrassment close relatives may hold in relation to family members affected by an ADMC, GMC, or both conditions.
There was a statistically robust association such that subgroups with an ADMC-affected relative were more likely to feel embarrassed as compared to subgroups with a relative affected by a GMC (p<0.001), even with covariate adjustments for age and sex.
The pattern of evidence from this research is consistent with conceptual models for interventions that target individual- and family-level stigma-related feelings of embarrassment as might be part of the obstacles to effective early intervention and treatment for ADMC conditions. Macro-level interventions are underway, but micro-level interventions also may be required among family members, along with care for each person with an ADMC.
PMCID: PMC4013530  PMID: 23298443
Family Embarrassment; Stigma; World Mental Health Surveys; Psychiatric Conditions
6.  Drinking Patterns and Alcohol Use Disorders in São Paulo, Brazil: The Role of Neighborhood Social Deprivation and Socioeconomic Status 
PLoS ONE  2014;9(10):e108355.
Research conducted in high-income countries has investigated influences of socioeconomic inequalities on drinking outcomes such as alcohol use disorders (AUD), however, associations between area-level neighborhood social deprivation (NSD) and individual socioeconomic status with these outcomes have not been explored in Brazil. Thus, we investigated the role of these factors on drink-related outcomes in a Brazilian population, attending to male-female variations.
A multi-stage area probability sample of adult household residents in the São Paulo Metropolitan Area was assessed using the WHO Composite International Diagnostic Interview (WMH-CIDI) (n = 5,037). Estimation focused on prevalence and correlates of past-year alcohol disturbances [heavy drinking of lower frequency (HDLF), heavy drinking of higher frequency (HDHF), abuse, dependence, and DMS-5 AUD] among regular users (RU); odds ratio (OR) were obtained.
Higher NSD, measured as an area-level variable with individual level variables held constant, showed an excess odds for most alcohol disturbances analyzed. Prevalence estimates for HDLF and HDHF among RU were 9% and 20%, respectively, with excess odds in higher NSD areas; schooling (inverse association) and low income were associated with male HDLF. The only individual-level association with female HDLF involved employment status. Prevalence estimates for abuse, dependence, and DSM-5 AUD among RU were 8%, 4%, and 8%, respectively, with excess odds of: dependence in higher NSD areas for males; abuse and AUD for females. Among RU, AUD was associated with unemployment, and low education with dependence and AUD.
Regular alcohol users with alcohol-related disturbances are more likely to be found where area-level neighborhood characteristics reflect social disadvantage. Although we cannot draw inferences about causal influence, the associations are strong enough to warrant future longitudinal alcohol studies to explore causal mechanisms related to the heterogeneous patterns of association and male-female variations observed herein. Hopefully, these findings may help guide future directions for public health.
PMCID: PMC4182710  PMID: 25272008
7.  Depressed Mood among Youth Reporting Alcohol Use: Associations with Subsequent Alcohol Involvement from Childhood through Young Adulthood 
Archives of general psychiatry  2008;65(6):702-712.
Despite prior evidence supporting cross-sectional associations of depression and alcohol use disorders, there is relatively little prospective data on the temporal relationship of depressed mood and maladaptive drinking, particularly across extended intervals.
Hypothesizing that depressed mood in childhood is associated with an increased risk for alcohol involvement among drinkers during adolescence and young adulthood, we used prospectively gathered data to assess these relationships by mood level, and by sex and race-ethnicity subgroup.
Cohort study of children followed during late childhood, early adolescence and young adulthood.
Setting and Participants
Two successive cohorts of students from 19 elementary schools in an urban mid-Atlantic region of the United States have been followed since entry into first grade (1985: cohort I, n=1196; 1986: cohort II, n=1115). The students were roughly equally divided by sex (48% female), and predominantly African-American (70%). Between 1989 and 1994, annual assessments were collected on students remaining in the public school system, and between 2000 and 2001, approximately 75% participated in a young adult interview (n=1692).
Among participants who reported having used alcohol, Cox and multinomial regression analyses were used to assess the association of childhood mood level, as measured by a depression symptom screener, with each alcohol outcome (incident alcohol intoxication, incident alcohol-related problems; DSM-IV alcohol abuse and alcohol dependence).
In adjusted regression analyses among drinkers, a high level of childhood depressed mood was associated with an earlier onset and increased risk for alcohol intoxication, and alcohol-related problems during late childhood and early adolescence, and for the development of DSM-IV alcohol dependence in young adulthood.
Early manifestations associated with possible depressive conditions in childhood helped predict and account for subsequent alcohol involvement, extending across life stages from childhood through young adulthood.
PMCID: PMC4151267  PMID: 18519828
alcohol; abuse; depression; mood; risk
8.  Smoking estimates from around the world: data from the first 17 participating countries in the World Mental Health Survey Consortium 
Tobacco control  2009;19(1):65-74.
To contribute new multinational findings on basic descriptive features of smoking and cessation, based upon standardised community surveys of adults residing in seven low-income and middle-income countries and 10 higher-income countries from all regions of the world.
Data were collected using standardised interviews and community probability sample survey methods conducted as part of the WHO World Mental Health Surveys Initiative. Demographic and socioeconomic correlates of smoking are studied using cross-tabulation and logistic regression approaches. Within-country sample weights were applied with variance estimation appropriate for complex sample survey designs.
Estimated prevalence of smoking experience (history of ever smoking) and current smoking varied across the countries under study. In all but four countries, one out of every four adults currently smoked. In higher-income countries, estimated proportions of former smokers (those who had quit) were roughly double the corresponding estimates for most low-income and middle-income countries. Characteristics of smokers varied within individual countries, and in relation to the World Bank's low-medium-high gradient of economic development. In stark contrast to a sturdy male-female difference in the uptake of smoking seen in each country, there is no consistent sex-associated pattern in the odds of remaining a smoker (versus quitting).
The World Mental Health Surveys estimates complement existing global tobacco monitoring efforts. The observed global diversity of associations with smoking and smoking cessation underscore reasons for implementation of the Framework Convention on Tobacco Control provisions and prompt local adaptation of prevention and control interventions.
PMCID: PMC4124902  PMID: 19965796
9.  Smoking quit success genotype score predicts quit success and distinct patterns of developmental involvement with common addictive substances 
Molecular psychiatry  2012;19(1):50-54.
Genotype scores that predict relevant clinical outcomes may detect other disease features and help direct prevention efforts. We report data that validate a previously-established v1.0 smoking cessation quit success genotype score and describe striking differences in the score in individuals who display differing developmental trajectories of use of common addictive substances. In a cessation study, v1.0 genotype scores predicted ability to quit with p = 0.00056 and area under ROC curve 0.66. About 43 vs 13% quit in the upper vs lower genotype score terciles. Latent class growth analyses of a developmentally-assessed sample identified three latent classes based on substance use. Higher v1.0 scores were associated with a) higher probabilities of participant membership in a latent class that displayed low use of common addictive substances during adolescence (p = 0.0004) and b) lower probabilities of membership in a class that reported escalating use (p = 0.001). These results suggest that: a) we have identified genetic predictors of smoking cessation success, b) genetic influences on quit success overlap with those that influence the rate at which addictive substance use is taken up during adolescence and c) individuals at genetic risk for both escalating use of addictive substances and poor abilities to quit may provide especially urgent focus for prevention efforts.
PMCID: PMC3922203  PMID: 23128154
genetic scores; complex genetics; smoking; development; cannabis; predictive validity
10.  A non-parametric approach for detecting gene-gene interactions associated with age-at-onset outcomes 
BMC Genetics  2014;15:79.
Cox-regression-based methods have been commonly used for the analyses of survival outcomes, such as age-at-disease-onset. These methods generally assume the hazard functions are proportional among various risk groups. However, such an assumption may not be valid in genetic association studies, especially when complex interactions are involved. In addition, genetic association studies commonly adopt case-control designs. Direct use of Cox regression to case-control data may yield biased estimators and incorrect statistical inference.
We propose a non-parametric approach, the weighted Nelson-Aalen (WNA) approach, for detecting genetic variants that are associated with age-dependent outcomes. The proposed approach can be directly applied to prospective cohort studies, and can be easily extended for population-based case-control studies. Moreover, it does not rely on any assumptions of the disease inheritance models, and is able to capture high-order gene-gene interactions. Through simulations, we show the proposed approach outperforms Cox-regression-based methods in various scenarios. We also conduct an empirical study of progression of nicotine dependence by applying the WNA approach to three independent datasets from the Study of Addiction: Genetics and Environment. In the initial dataset, two SNPs, rs6570989 and rs2930357, located in genes GRIK2 and CSMD1, are found to be significantly associated with the progression of nicotine dependence (ND). The joint association is further replicated in two independent datasets. Further analysis suggests that these two genes may interact and be associated with the progression of ND.
As demonstrated by the simulation studies and real data analysis, the proposed approach provides an efficient tool for detecting genetic interactions associated with age-at-onset outcomes.
PMCID: PMC4087128  PMID: 24986733
Weighted Nelson-Aalen; Cox regression; Progression of nicotine dependence; Joint association
11.  The epidemiological profile of alcohol and other drug use in metropolitan China 
There is evidence that alcohol, tobacco, and other drug use may be rising in China, but epidemiological studies that examine several drugs simultaneously and the transition from initial try to current use are limited. The present study provides an epidemiological profile of drug use in contemporary metropolitan China.
A multistage probability sampling method was used to select household-dwelling adults in Beijing and Shanghai. Standard face-to-face interviews with 5,201 participants were completed during 2002–2003.
An estimated 70–76% had used any type of drug: alcohol and tobacco were the most commonly used drugs (alcohol, 67%; tobacco, 39%). Regarding extra-medical use of internationally regulated drugs, sedatives and analgesics were most common and illegal drug use was rare. The majority of tobacco users used it recently (82.5%), especially young adults. Male–female differences were observed in lifetime tobacco use, but not for recent use. Concurrent use of alcohol and tobacco was very common.
Psychoactive drug use is common in metropolitan China. Public health policies and prevention initiatives may be needed to address associated problems that may increase following the country’s rapid socioeconomic change.
PMCID: PMC3992952  PMID: 20157758
Substance use; Epidemiology; China; Alcohol; Tobacco
12.  Disability associated with mental disorders in metropolitan China: An application of the quantile regression approach 
Psychiatry research  2012;199(3):212-219.
Recently active mental disorders are associated with substantial disability, but there is little research on residual disability once symptoms have subsided. The aim of this study is to estimate the degree to which recent disability might be due to recent or past history of mental disorders using a quantile regressions model that makes it possible to study the full range of disability. Data were from cross-sectional surveys of Chinese living in Beijing and Shanghai, China (n=1,628). The World Health Organization Disability Assessment Schedule and the WHO Composite International Diagnostic Interview was used to assess recent disability and common mental disorders, respectively. Recently active mental disorders are found to be associated with elevated levels of disability, especially for current substance use disorder. Anxiety disorders stand out with high levels of disability. Individuals at the higher disability levels show large variations in their disability levels. These epidemiological estimates from China add to the evidence base on the global burden of neuropsychiatric disorders, quantifying the hypothesized influence of recently active and past disorders with the novel quantile regression approach. In future studies, we hope to complete more detailed studies of the causal role of mental disorders in the development of disability.
PMCID: PMC3399993  PMID: 22494707
survey; epidemiology; methods; disability; substance use disorders; anxiety disorders
13.  An Updated Global Picture of Cigarette Smoking Persistence among Adults 
Cross-national variance in smoking prevalence is relatively well documented. The aim of this study is to estimate levels of smoking persistence across 21 countries with a hypothesized inverse relationship between country income level and smoking persistence.
Data from the World Health Organization World Mental Health Survey Initiative were used to estimate cross-national differences in smoking persistence–the proportion of adults who started to smoke and persisted in smoking by the date of the survey.
There is large variation in smoking persistence from 25% (Nigeria) to 85% (China), with a random-effects meta-analytic summary estimate of 55% with considerable cross-national variation. (Cochran's heterogeneity Q statistic=6,845; p<0.001). Meta-regressions indicated observed differences are not attributable to differences in country income level, age distribution of smokers, or how recent the onset of smoking began within each country.
While smoking should remain an important public health issue in any country where smokers are present, this report identifies several countries with higher levels of smoking persistence (namely, China and India).
PMCID: PMC3635135  PMID: 23626929
14.  Are early-onset cannabis smokers at an increased risk of depression spells? 
Journal of Affective Disorders  2012;138(1-2):54-62.
A recent research focus is a set of hypothesized adult-onset mental health disturbances possibly due to early-onset cannabis use (EOCU, onset <18 years). We seek to estimate the suspected EOCU-associated excess odds of experiencing an incident depression spell during adulthood, with comparisons to never cannabis smokers and those with delayed cannabis onset (i.e., not starting to smoke cannabis until adulthood).
The National Surveys on Drug Use and Health (NSDUH) assess non-institutionalized community-dwelling residents of the United States after probability sampling each year. In aggregate, the NSDUH analytical sample included 173,775 adult participants from survey years 2005–2009 (74–76% of designated respondents). Standardized computer-assisted interviews collected information on background determinants, age of first cannabis use, and depression spell onset. Logistic regression was used to estimate EOCU-depression spell associations in the form of odds ratios, with statistical adjustment for sex, age, race/ethnicity, years of cannabis involvement, tobacco cigarette onset, and alcohol onset.
About 1 in 10 experienced a depression spell during adulthood, and both early-onset and adult-onset cannabis smokers had a modest excess odds of a depression spell compared to never cannabis smokers, even with covariate adjustment (OR = 1.7 & 1.8, respectively; both p<0.001). Estimates for early- and adult-onset cannabis smokers did not statistically differ from one another.
Shared diathesis that might influence both EOCU and adult-onset depression spell is controlled no more than partially, as will be true until essentially all known early-life shared vulnerabilities are illuminated.
Cannabis smoking initiated at any age signals a modest increased risk of a spell of depression in adulthood, even when adjusted for suspected confounding variables studied here. Delaying cannabis onset until adulthood does not appear to diminish the cannabis-associated risk.
PMCID: PMC3351086  PMID: 22310034
cannabis; depression; early-onset; adult-onset; tobacco; alcohol
15.  Novel Phenotype Issues Raised in Cross-National Epidemiological Research on Drug Dependence 
Stage-transition models based on the American Diagnostic and Statistical Manual (DSM) generally are applied in epidemiology and genetics research on drug dependence syndromes associated with cannabis, cocaine, and other internationally regulated drugs (IRD). Difficulties with DSM stage-transition models have surfaced during cross-national research intended to provide a truly global perspective, such as the work of the World Mental Health Surveys (WMHS) Consortium. Alternative simpler dependence-related phenotypes are possible, including population-level count process models for steps early and before coalescence of clinical features into a coherent syndrome (e.g., zero-inflated Poisson regression). Selected findings are reviewed, based on ZIP modeling of alcohol, tobacco, and IRD count processes, with an illustration that may stimulate new research on genetic susceptibility traits. The annual National Surveys on Drug Use and Health can be readily modified for this purpose, along the lines of a truly anonymous research approach that can help make NSDUH-type cross-national epidemiological surveys more useful in the context of subsequent genome wide association (GWAS) research and post-GWAS investigations with a truly global health perspective.
PMCID: PMC3012560  PMID: 20201862
alcohol; tobacco; dependence; epidemiology; phenotype
16.  Behavioral Problems and the Occurrence of Tobacco, Cannabis, and Coca Paste Smoking in Chile: Evidence based on Multivariate Response Models for School Survey Data 
Drug and alcohol dependence  2009;104(1-2):50-55.
In this study we estimate suspected links between youthful behavioral problems and smoking of tobacco, cannabis, and coca paste.
In the Republic of Chile, school-attending youths were sampled from all 13 regions of the country, with sample size of 46,907 youths from 8th to 12th grades. A Generalized Estimating Equations (GEE) approach to multiple logistic regression was used to address three interdependent response variables, tobacco smoking, cannabis smoking, and coca paste smoking, and to estimate associations.
Drug-specific adjusted slope estimates indicate that youths at the highest levels of behavioral problems are an estimated 1.1 times more likely to have started smoking tobacco, an estimated 1.6 times more likely to have started cannabis smoking, and an estimated 2.0 times more likely to have started coca paste smoking, as compared to youths at the lowest level of behavioral problems (p< 0.01).
In Chile, there is an association linking behavioral problems with onsets of smoking tobacco and cannabis, as well as coca paste; strength of association is modestly greater for coca paste smoking.
PMCID: PMC2735105  PMID: 19446410
Adolescent behavior; tobacco smoking; marijuana smoking; coca paste smoking; Chilean students
17.  Longitudinal Effects of Prenatal Cocaine Use on Mother-Child Interactions at Ages 3 and 5 
To assess the effect of maternal prenatal and past-year cocaine use on mother-child interactions across the preschool years.
The sample is drawn from the Miami Prenatal Cocaine Study (MPCS), a longitudinal follow-up of prenatal cocaine exposure (PCE) in a large cohort of African-American infants prospectively enrolled at birth. Analyses are based on the 366 children (168 PCE and 198 NCE) in the care of their biological mothers and with completed mother-child interaction measures at the 3- and/or 5-year assessments. Videotaped interactions were coded using a modified Egeland Teaching Task scheme. GLM/GEE models were used to evaluate the effect of PCE on the overall quality of maternal-child interaction, measured by the Egeland total score at both study visits, and on the individual Egeland subscales at the 5-year visit, while adjusting for other suspected influences on interactions.
PCE dyads demonstrated less optimal overall mother-child interactions compared to NCE dyads. The estimated PCE-associated difference did not shift appreciably with statistical adjustment for child sex, child age at exam or other birth covariates. PCE dyads with past-year maternal cocaine use had significantly lower Egeland summary scores compared to children with neither exposure. In subscale analyses, PCE was most strongly associated with greater maternal intrusiveness and boundary dissolution at the 5-year visit.
Prenatal and past-year maternal cocaine use appear to be associated with poorer quality in mother-child interaction during early childhood. These dynamics should be considered when examining the association between prenatal cocaine exposure and child cognitive, behavioral, and academic outcomes.
PMCID: PMC3252426  PMID: 22157442
prenatal; cocaine; exposure; mother-child; interaction
18.  Childhood physical punishment and the onset of drinking problems: evidence from metropolitan China 
Drug and alcohol dependence  2011;118(1):31-39.
Evidence in support of a suspected causal association linking childhood physical punishment (CPP) and later alcoholic beverage-related disturbances has been found in metropolitan China. Here, the focus shifts to the CPP association with the estimated risk of starting to drink, having the first drinking problem, and transitioning from first drink to the first drinking problem.
Data are from the World Mental Health Surveys-metropolitan China study, with representative samples of adult household residents living in two metropolitan cities, Beijing and Shanghai. Recalled information was available for early life experiences (including CPP, other childhood adversities, and parental alcohol and drug problems), as well as the onset age of drinking and drinking problems. Survival analyses were used to estimate the hazard ratio. A structural equation modeling approach was used to control for other inter-correlated childhood adversities.
Cox proportional hazards modeling discloses statistically robust associations linking CPP with drinking and drinking problems, as well as more rapid transitions from first drink to first drinking problem, even after accounting for other childhood adversities and parental drinking problems. These associations cannot be attributed to a more general noxious family environment.
These results lay a foundation for future experimental studies on the possible causal relationship linking CPP with the onset of drinking problems and the transition from drinking to drinking problems.
PMCID: PMC3167011  PMID: 21474254
Alcohol use disorder; Childhood physical punishment; China; Epidemiology
19.  Children taking risks: The association with cocaine and other drug use by young adulthood 
Addictive behaviors  2008;33(9):1154-1161.
In this report from a longitudinal study, the main aim was to evaluate the long-term predictive strength of a novel cartoon-based risk-taking trait assessment, which might prove to have utility in future research on mechanisms leading toward illegal drug involvement. The study population originated as 2,311 first-graders entering 19 elementary schools during two successive school years. The assessments started when the children were midway through primary school in the same school system. The key response variable was participants’ use of cocaine by the time of a young adult assessment. We found that for each standard deviation increase in the risk-taking scale there was a two fold increase in the risk of becoming a cocaine user by young adulthood (estimated relative risk, RR = 1.9; 95% confidence interval, CI = 1.3, 2.7). Independently, onset of cannabis use by young adulthood also was predicted by risk-taking scale values, but use of legal drugs (alcohol and tobacco) was not. These long-span associations provide support for new research on very early risk-taking mechanisms that lead toward illegal drug involvement.
PMCID: PMC2533157  PMID: 18550295
risk-taking; cocaine; cannabis; children; longitudinal; drug initiation
20.  Childhood predictors of first chance to use and use of cannabis by young adulthood 
Drug and alcohol dependence  2011;117(1):7-15.
To prospectively examine the linkage between childhood antecedents and progression to early cannabis involvement as manifest in first chance to try it and then first onset of cannabis use.
Two consecutive cohorts of children entering first grade of a public school system of a large mid-Atlantic city in the mid 1980s (n=2311) were assessed (mean age 6.5 years) and then followed into young adulthood (15 years later, mean age 21) when first chance to try and first use were assessed for 75% (n=1698) of the original sample. Assessments obtained at school included standardized readiness scores (reading; math) and teacher ratings of behavioral problems. Regression and time to event models included covariates for sex, race, and family disadvantage.
Early classroom misconduct, better reading readiness, and better math readiness predicted either occurrence or timing of first chance to try cannabis, first use, or both. Higher levels of childhood concentration problems and lower social connectedness were not predictive.
Childhood school readiness and behavioral problems may influence the risk for cannabis smoking indirectly via an increased likelihood of first chance to use. Prevention efforts that seek to shield youths from having a chance to try cannabis might benefit from attention to early predictive behavioral and school readiness characteristics. When a youth’s chance to try cannabis is discovered, there are new windows of opportunity for prevention and intervention.
PMCID: PMC3128694  PMID: 21288658
marijuana abuse/epidemiology; sex factors; child behavior; academic readiness
21.  Genome-Environmental Risk Assessment of Cocaine Dependence 
Cocaine-associated biomedical and psychosocial problems are substantial twenty-first century global burdens of disease. This burden is largely driven by a cocaine dependence process that becomes engaged with increasing occasions of cocaine product use. For this reason, the development of a risk-prediction model for cocaine dependence may be of special value. Ultimately, success in building such a risk-prediction model may help promote personalized cocaine dependence prediction, prevention, and treatment approaches not presently available. As an initial step toward this goal, we conducted a genome-environmental risk-prediction study for cocaine dependence, simultaneously considering 948,658 single nucleotide polymorphisms (SNPs), six potentially cocaine-related facets of environment, and three personal characteristics. In this study, a novel statistical approach was applied to 1045 case-control samples from the Family Study of Cocaine Dependence. The results identify 330 low- to medium-effect size SNPs (i.e., those with a single-locus p-value of less than 10−4) that made a substantial contribution to cocaine dependence risk prediction (AUC = 0.718). Inclusion of six facets of environment and three personal characteristics yielded greater accuracy (AUC = 0.809). Of special importance was the joint effect of childhood abuse (CA) among trauma experiences and the GBE1 gene in cocaine dependence risk prediction. Genome-environmental risk-prediction models may become more promising in future risk-prediction research, once a more substantial array of environmental facets are taken into account, sometimes with model improvement when gene-by-environment product terms are included as part of these risk predication models.
PMCID: PMC3355331  PMID: 22629285
cocaine dependence; genome-environmental risk prediction; childhood abuse; GBE1 gene; tree-assembling ROC
22.  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.
PMCID: PMC3080240  PMID: 21414952
23.  Estimated Effect of Prenatal Cocaine Exposure on Examiner-Rated Behavior at Age 7 Years 
Neurotoxicology and teratology  2011;33(3):370-378.
Prenatal cocaine exposure has been linked to increased child behavior difficulties in some studies but not others.
The primary aim was to estimate the relationship between in utero cocaine exposure and child behavioral functioning at age 7 years with ratings made by blinded examiners during a structured testing session. A second aim was to examine whether caregiver drug use and psychological problems might mediate suspected relationships between prenatal cocaine exposure and aspects of examiner-rated behavior.
407 children (212 cocaine-exposed, 195 non-exposed) participating in the longitudinal Miami Prenatal Cocaine Study (MPCS) were rated with regard to their behavior during a neuropsychological assessment conducted at age 7 years. Raters were trained research psychometricians blinded to drug exposure. Individual behavioral items were summarized and the cocaine-behavior relationship was estimated within the context of latent variable modeling, using Mplus software.
Two latent variables, Behavioral Regulation and Sociability, were derived via exploratory latent structure analysis with promax rotation. Prenatal cocaine exposure, statistically controlling for child sex, test age, and prenatal exposure to alcohol, tobacco, and marijuana, was associated with Behavioral Regulation (estimated slope ß = -0.25; 95% CI = -0.48, -0.02; p = 0.04) but not Sociability (estimated slope ß = -0.03; 95% CI = -0.26, 0.20; p = 0.79). Neither postnatal drug use by caregivers nor the severity of their psychological problems at age 5 follow-up predicted levels of child Behavioral Regulation or Sociability at age 7 years (p>0.10).
Examiner ratings of child behavior at age 7 revealed less optimal behavioral regulation for prenatally cocaine-exposed compared to non-exposed children, in contrast with what had been previously found from parent-report data. This evidence highlights the potential value of trained observers in assessing behavioral outcomes of children exposed in utero to drugs and other toxicants.
PMCID: PMC3138213  PMID: 21640292
prenatal cocaine exposure; behavior; examiner ratings; caregiver drug use; caregiver psychological functioning; behavioral regulation
24.  Willingness to treat drug dependence and depression: comparisons of future health professionals 
Stigma-related feelings, including degree of enthusiasm and willingness to work with alcohol, drug, and mental disorder (ADM) patients, as well as anticipated success in such work, will be required for the United States to be successful in its new initiatives for ADM screening, brief intervention, and effective referral to treatment and rehabilitation services (SBIRT). This study investigates students of medicine and social work with respect to their stigma-related feelings and degree of enthusiasm or willingness to treat patients affected by alcohol dependence, nicotine dependence, or major depression. Inference is strengthened by an anonymous online survey approach, with use of randomized reinforcers to gain at least partial experimental control of nonparticipation biases that otherwise are present in student survey data.
Material and methods
All students on required course rosters were asked to participate in a two-part in-class and online assessment; 222 participated, with a gradient of participation induced via randomly drawn reinforcers for online survey participation. Between-group comparisons were made with a multivariate generalized linear model and generalized estimating equations approach that adjusts for covariates.
Medical and social work students did not differ from each other with respect to their willingness to treat patients affected by major depression, alcohol dependence, or nicotine dependence, but together were less willing to treat nicotine and alcohol dependence-affected patients as compared to depression-affected patients. Personal history was not associated with the students' willingness to treat, but men were less willing to treat. Drawing strength from the randomized reinforcer experimental design nested within this survey approach, the study evidence suggests potential nonparticipation bias in standard surveys on this topic.
These results indicate that future health professionals may prefer to treat depression as opposed to drug dependence conditions. For SBIRT success, curriculum change with educational interventions may be needed to increase willingness to treat patients with neuropsychiatric conditions such as drug dependence. Future research requires attention to a possible problem of nonparticipation bias in surveys of this type.
PMCID: PMC3124145  PMID: 21731413
alcohol dependence; nicotine dependence; depression; health professionals; stigma
25.  Mental Disorders in Megacities: Findings from the São Paulo Megacity Mental Health Survey, Brazil 
PLoS ONE  2012;7(2):e31879.
World population growth is projected to be concentrated in megacities, with increases in social inequality and urbanization-associated stress. São Paulo Metropolitan Area (SPMA) provides a forewarning of the burden of mental disorders in urban settings in developing world. The aim of this study is to estimate prevalence, severity, and treatment of recently active DSM-IV mental disorders. We examined socio-demographic correlates, aspects of urban living such as internal migration, exposure to violence, and neighborhood-level social deprivation with 12-month mental disorders.
Methods and Results
A representative cross-sectional household sample of 5,037 adults was interviewed face-to-face using the WHO Composite International Diagnostic Interview (CIDI), to generate diagnoses of DSM-IV mental disorders within 12 months of interview, disorder severity, and treatment. Administrative data on neighborhood social deprivation were gathered. Multiple logistic regression was used to evaluate individual and contextual correlates of disorders, severity, and treatment. Around thirty percent of respondents reported a 12-month disorder, with an even distribution across severity levels. Anxiety disorders were the most common disorders (affecting 19.9%), followed by mood (11%), impulse-control (4.3%), and substance use (3.6%) disorders. Exposure to crime was associated with all four types of disorder. Migrants had low prevalence of all four types compared to stable residents. High urbanicity was associated with impulse-control disorders and high social deprivation with substance use disorders. Vulnerable subgroups were observed: women and migrant men living in most deprived areas. Only one-third of serious cases had received treatment in the previous year.
Adults living in São Paulo megacity had prevalence of mental disorders at greater levels than similar surveys conducted in other areas of the world. Integration of mental health promotion and care into the rapidly expanding Brazilian primary health system should be strengthened. This strategy might become a model for poorly resourced and highly populated developing countries.
PMCID: PMC3279422  PMID: 22348135

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