Illicit Drug Dependence Research Articles

Sintomatología frontal y trastornos de personalidad en usuarios de drogas ilícitas

La dependencia a sustancias ilícitas es un problema del ámbito mundial, que afecta a la población independientemente de la edad, sexo, cultura o estrato social; algunos de los factores que mantienen el consumo de sustancias son los trastornos de personalidad y los daños en los lóbulos frontales, a su vez, estos últimos podrían ser un elemento que explica las alteraciones en los patrones de personalidad. El objetivo de este artículo, en primer lugar, es determinar la influencia de la dependencia a sustancias sobre los trastornos de personalidad y la sintomatología frontal y en segundo lugar, relacionar la sintomatología frontal y los trastornos de personalidad en personas dependientes a sustancias. En la investigación de la que parte este texto, participaron 110 personas, 55 dependientes a sustancias y 55 de población no clínica, quienes llenaron las escalas ISP y MCMI-III. Dentro de los resultados se halló que las personas dependientes a sustancias presentan mayor daño en los lóbulos pre-frontales y alta probabilidad de desarrollar trastornos de personalidad, además existen relaciones significativas entre los trastornos de personalidad y las dificultades en las actividades cotidianas relacionadas con las funciones del lóbulo prefrontal. Los trastornos que más se presentan en la población clínica son el Antisocial, Evitativo y Depresivo, éstos se asocian al deterioro en el lóbulo frontal del cerebro, principalmente en las áreas que atañen a las capacidades de control emocional, y en las funciones ejecutivas. Se concluye que los daños en el lóbulo frontal y la tendencia al desarrollo de trastornos de personalidad se ven influenciados por la dependencia a sustancias, existiendo a su vez correlaciones altamente significativas entre ambas variables.

Logistic Regression to Assess Risk Factors in Offspring from Brazilian Families with Alcohol and Drug Problems

Background: The correlations between protective and risk factors in Brazilian families with substance misuse problems were investigated in this study. Methods: A case-control study was conducted with a convenience sample; the participants were paired by sex and age. Three hundred five families with children and adolescents (4-18 years of age) were evaluated; 60% (n=183) were in the study group, and 40% (n=122) were in the control group. In the study group, 73% (n=133) of the families had fathers with drinking problems and 27% (n=50) had fathers with illicit poly-drug addiction. Results: Parents with illicit drug dependence problems showed a greater number of clinical aspects to their children’s psychological development than parents with alcohol addiction, as the proportion of this group was (CBCL: withdrawn (59%); somatic complaints (24.5%); social problems (29%); thought problems (12%); delinquent behavior (24,5%); externalizing (55%); and total problems (55%)). However, both substances are equally harmful and can trigger mental health risks in children, especially younger children. Regarding the risk of mental health problems, the findings indicate that 39% (n=115) of the children demonstrated externalizing problems and 33% (n=97) demonstrated internalizing

Parental Separation and Offspring Alcohol Involvement: Findings from Offspring of Alcoholic and Drug Dependent Twin Fathers.

We examined associations between parental separation during childhood and offspring alcohol involvement, adjusting for genetic and environmental risks specific to parental alcohol (AD) and cannabis/other illicit drug dependence (DD). The sample consisted of 1,828 offspring of male twins from the Vietnam Era Twin (VET) Registry, who completed a telephone diagnostic interview. Cox proportional hazards regression analyses were conducted predicting onset of first use, transition from first use to first AD symptom, and transition from first use to AD diagnosis from paternal and avuncular AD and DD history, parental separation, and offspring and family background characteristics. Paternal/avuncular DD/AD was based on the DSM-III-R; offspring and maternal AD were based on DSM-IV criteria. Paternal DD/AD predicted increased offspring risk for all transitions, with genetic effects suggested on rate of transitioning to AD diagnosis. Parental separation was predictive of increased risk for early alcohol use, but a reduced rate of transition to both AD symptom onset and onset of AD. No interactions between separation and familial risk (indexed by paternal or avuncular DD/AD) were found. Findings highlight the contribution of both parental separation and paternal substance dependence in predicting timing of offspring alcohol initiation and problems across adolescence into early adulthood.

Predictors of start of different antidepressants in patient charts among patients with depression.

In usual psychiatric care, antidepressant treatments are selected based on physician and patient preferences rather than being randomly allocated, resulting in spurious associations between these treatments and outcome studies. To identify factors recorded in electronic medical chart progress notes predictive of antidepressant selection among patients who had received a depression diagnosis. This retrospective study sample consisted of 556 randomly selected Veterans Health Administration patients diagnosed with depression from April 1, 1999, to September 30, 2004, stratified by the antidepressant agent, geographic region, gender, and year of depression cohort entry. Predictors were obtained from administrative data, and additional variables were abstracted from electronic medical chart notes in the year prior to the start of the antidepressant in 5 categories: clinical symptoms and diagnoses, substance use, life stressors, behavioral/ideation measures (e.g., suicide attempts), and treatments received. Multinomial logistic regression analysis was used to assess the predictors associated with different antidepressant prescribing, and adjusted relative risk ratios (RRR) were reported. Of the administrative data-based variables, gender, age, illicit drug abuse or dependence, and number of psychiatric medications in the prior year were significantly associated with antidepressant selection. After adjusting for administrative data-based variables, sleep problems (relative risk ratio [RRR] = 2.47) or marital issues (RRR = 2.64) identified in the charts were significantly associated with prescribing mirtazapine rather than sertraline; however, no other chart-based variables showed a significant association or an association with a large magnitude. Some chart data-based variables were predictive of antidepressant selection, but we neither found many nor found them highly predictive of antidepressant selection in patients treated for depression.

Examining the role of common genetic variants on alcohol, tobacco, cannabis and illicit drug dependence: genetics of vulnerability to drug dependence.

Twin and family studies suggest that genetic influences are shared across substances of abuse. However, despite evidence of heritability, genome-wide association and candidate gene studies have indicated numerous markers of limited effects, suggesting that much of the heritability remains missing. We estimated (1) the aggregate effect of common single nucleotide polymorphisms (SNPs) on multiple indicators of comorbid drug problems that are typically employed across community and population-based samples, and (2) the genetic covariance across these measures. A total of 2596 unrelated subjects from the Study of Addiction: Genetics and Environment provided information on alcohol, tobacco, cocaine, cannabis and other illicit substance dependence. Phenotypic measures included: (1) a factor score based on DSM-IV drug dependence diagnoses (DD), (2) a factor score based on problem use (PU; i.e. 1+ DSM-IV symptoms) and (3) dependence vulnerability (DV; a ratio of DSM-IV symptoms to the number of substances used). Univariate and bivariate genome-wide complex trait analyses of this selected sample indicated that common SNPs explained 25-36% of the variance across measures, with DD and DV having the largest effects [h(2) SNP (standard error) = 0.36 (0.13) and 0.33 (0.13), respectively; PU = 0.25 (0.13)]. Genetic effects were shared across the three phenotypic measures of comorbid drug problems [rDD-PU = 0.92 (0.08), rDD-DV = 0.97 (0.08) and rPU-DV = 0.96 (0.07)]. At least 20% of the variance in the generalized vulnerability to substance dependence is attributable to common single nucleotide polymorphisms. The additive effect of common single nucleotide polymorphisms is shared across important indicators of comorbid drug problems.

Genes Associated With Alcohol Outcomes Show Enrichment of Effects With Broad Externalizing and Impulsivity Phenotypes in an Independent Sample

The purpose of this study was to evaluate evidence for association with a panel of genes previously associated with alcohol-related traits in a new sample of adolescent and young adult individuals (N = 2,128; 51% female) collected as part of the Collaborative Study on the Genetics of Alcoholism (COGA). We tested for association with phenotypes related to externalizing behavior, including diagnostic symptom counts for disorders on the externalizing spectrum (alcohol dependence, conduct disorder, adult antisocial personality disorder, and illicit drug dependence), and related behavioral/personality traits (Achenbach Externalizing, NEO Extraversion, NEO Conscientiousness, Zuckerman's Sensation Seeking, and the Barratt Impulsivity Scale) based on the substantial literature suggesting that these behaviors may be alternate manifestations of a shared genetic liability. We tested for overall enrichment of the set of 215 genotyped single-nucleotide polymorphisms (SNPs) for each of the phenotypes. We conducted secondary analyses comparing results for sensation seeking with results for the other phenotypes. For all phenotypes, there was significant enrichment of association results (p < .05) compared with chance expectations. The greatest number of significant results was observed with the phenotype Sensation Seeking. Secondary analyses indicated that the number of SNPs yielding p < .05 with Sensation Seeking was significantly greater than that observed for each of the other phenotypes. We find evidence for enrichment of association results across a spectrum of externalizing phenotypes with a panel of candidate genes/SNPs selected based on previous suggestion of association with alcohol-related outcomes. In particular, we find significant enrichment of effects with sensation seeking, suggesting that this may be a particularly salient behavior associated with risk for alcohol-related problems.

Genes Associated With Alcohol Outcomes Show Enrichment of Effects With Broad Externalizing and Impulsivity Phenotypes in an Independent Sample

Objective: The purpose of this study was to evaluate evidence for association with a panel of genes previously associated with alcohol-related traits in a new sample of adolescent and young adult in- dividuals (N = 2,128; 51% female) collected as part of the Collaborative Study on the Genetics of Alcoholism (COGA). We tested for association with phenotypes related to externalizing behavior, including diagnostic symptom counts for disorders on the externalizing spectrum (alcohol dependence, conduct disorder, adult antisocial personality disorder, and illicit drug dependence), and related behavioral/personality traits (Achenbach Externalizing, NEO Extraversion, NEO Conscientiousness, Zuckerman's Sensation Seeking, and the Barratt Impulsivity Scale) based on the substantial literature suggesting that these behaviors may be alternate manifestations of a shared genetic liability. Method: We tested for overall enrichment of the set of 215 genotyped single-nucleotide polymorphisms (SNPs) for each of the phenotypes. We conducted secondary analyses comparing results for sensation seeking with results for the other phenotypes. Results: For all phenotypes, there was signifi - cant enrichment of association results (p < .05) compared with chance expectations. The greatest number of signifi cant results was observed with the phenotype Sensation Seeking. Secondary analyses indicated that the number of SNPs yielding p < .05 with Sensation Seeking was signifi cantly greater than that observed for each of the other phenotypes. Conclusions: We fi nd evidence for enrichment of association results across a spectrum of externalizing phenotypes with a panel of candidate genes/SNPs selected based on previous suggestion of association with alcohol-related outcomes. In particular, we fisignifi cant enrichment of effects with sensation seeking, suggesting that this may be a particularly salient behavior associated with risk for alcohol-related problems. (J. Stud. Alcohol Drugs, 76, 38-46, 2015)

Association between DRD2/ANKK1 TaqIA polymorphism and common illicit drug dependence: Evidence from a meta-analysis

BackgroundGrowing evidence indicated conflicting results about the dopamine receptor D2 (DRD2)/kinase domain containing 1 gene (ANKK1) TaqIA single nucleotide polymorphism (rs1800497) and common illicit drug dependence risk including stimulants, opioid and marijuana. We conducted a meta-analysis to evaluate the association between the polymorphism and common illicit drug dependence risk. MethodA total of 25 available studies (26 subgroups) testing the association between the polymorphism and common illicit drug dependence were examined through Oct 2013. Pooled odds ratios (ORs) and 95% confidence intervals (CI) were estimated using fixed- and random-effects models when appropriate. Heterogeneity and publication bias were evaluated. ResultsWe found the DRD2/ANKK1 TaqIA polymorphism was significantly associated with increased risk of opioid dependence under homozygote, dominant, and recessive genetic model, respectively (homozygote: OR=1.546, 95%CI=1.279–1.87; dominant: OR=1.265, 95%CI=1.055–1.516; recessive: OR=1.409, 95%CI=1.182–1.680). Subgroup analyses were similar to the results of the total population by ethnicity and quality score. Besides, we also found that Caucasian and low-quality studies were major sources of heterogeneity for opioid dependence. We failed to find any significant association between the polymorphism and stimulants or marijuana neither in total population nor subgroup analyses under any genetic model. ConclusionsThe current meta-analysis suggested that DRD2/ANKK1 TaqIA polymorphism might be associated with opioid dependence risk, but not associated with stimulants or marijuana dependence.

Treatment use, perceived need, and barriers to seeking treatment for substance abuse and mental health problems among older adults compared to younger adults

BackgroundThis study examined age group differences in and correlates of treatment use and perceived treatment need for substance use disorders (SUD) and mental health (MH) problems as well as self-reported barriers to treatment among people 65+ years old vs. 26–34, 35–49, and 50–64 years old. MethodsData are from the 2008 to 2012 National Survey on Drug Use and Health (NSDUH) (N=96,966). Age group differences were examined using descriptive bivariate analyses and binary logistic regression analyses. ResultsThe 65+ age group was least likely to use treatment and perceive treatment need, but the 50–64 age group was more similar to the younger age groups than the 65+ age group. Controlling for age, other predisposing, and enabling factors, alcohol and illicit drug dependence and comorbid SUD and MH problems increased the odds of SUD treatment use. Of MH problems, anxiety disorder had the largest odds for MH treatment use. Bivariate analyses showed that lack of readiness to stop using and cost/limited insurance were the most frequent barriers to SUD and MH treatment, respectively, among older adults, and they were less likely than younger age groups to report stigma/confidentiality concerns for MH treatment. ConclusionsOlder adults will become a larger portion of the total U.S. population with SUD and/or MH problems. Healthcare providers should be alert to the need to help older adults with SUD and/or MH problems obtain treatment.

Gene-environment interplay between parent-child relationship problems and externalizing disorders in adolescence and young adulthood.

Previous studies have shown that genetic risk for externalizing (EXT) disorders is greater in the context of adverse family environments during adolescence, but it is unclear whether these effects are long lasting. The current study evaluated developmental changes in gene-environment interplay in the concurrent and prospective associations between parent-child relationship problems and EXT at ages 18 and 25 years. The sample included 1382 twin pairs (48% male) from the Minnesota Twin Family Study, participating in assessments at ages 18 years (mean = 17.8, s.d. = 0.69 years) and 25 years (mean = 25.0, s.d. = 0.90 years). Perceptions of parent-child relationship problems were assessed using questionnaires. Structured interviews were used to assess symptoms of adult antisocial behavior and nicotine, alcohol and illicit drug dependence. We detected a gene-environment interaction at age 18 years, such that the genetic influence on EXT was greater in the context of more parent-child relationship problems. This moderation effect was not present at age 25 years, nor did parent-relationship problems at age 18 years moderate genetic influence on EXT at age 25 years. Rather, common genetic influences accounted for this longitudinal association. Gene-environment interaction evident in the relationship between adolescent parent-child relationship problems and EXT is both proximal and developmentally limited. Common genetic influence, rather than a gene-environment interaction, accounts for the long-term association between parent-child relationship problems at age 18 years and EXT at age 25 years. These results are consistent with a relatively pervasive importance of gene-environmental correlation in the transition from late adolescence to young adulthood.

Integration of substance use disorder services with primary care: health center surveys and qualitative interviews

BackgroundEach year, nearly 20 million Americans with alcohol or illicit drug dependence do not receive treatment. The Affordable Care Act and parity laws are expected to result in increased access to treatment through integration of substance use disorder (SUD) services with primary care. However, relatively little research exists on the integration of SUD services into primary care settings. Our goal was to assess SUD service integration in California primary care settings and to identify the practice and policy facilitators and barriers encountered by providers who have attempted to integrate these services.MethodsPrimary survey and qualitative interview data were collected from the population of federally qualified health centers (FQHCs) in five California counties known to be engaged in SUD integration efforts was surveyed. From among the organizations that responded to the survey (78% response rate), four were purposively sampled based on their level of integration. Interviews were conducted with management, staff, and patients (n = 18) from these organizations to collect further qualitative information on the barriers and facilitators of integration.ResultsCompared to mental health services, there was a trend for SUD services to be less integrated with primary care, and SUD services were rated significantly less effective. The perceived difference in effectiveness appeared to be due to provider training. Policy suggestions included expanding the SUD workforce that can bill Medicaid, allowing same-day billing of two services, facilitating easier reimbursement for medications, developing the workforce, and increasing community SUD specialty care capacity.ConclusionsEfforts to integrate SUD services with primary care face significant barriers, many of which arise at the policy level and are addressable.

The Global Burden of Disease projects: What have we learned about illicit drug use and dependence and their contribution to the global burden of disease?

The Global Burden of Disease (GBD) 2010 study updated the findings of earlier exercises. It provided regional and global estimates of the burden of disease attributable to diseases, injuries and risk factors. Here we provide a brief summary of the work for illicit drug use. Systematic reviews were undertaken to estimate the major epidemiological parameters (incidence, prevalence, duration/remission and mortality) for each drug. Reviews evaluated the nature and quality of evidence for illicit drug use as a risk factor for many health outcomes, for the comparative risk assessment (CRA) exercise. Substantial gaps existed in basic epidemiological parameters. Following modelling and imputation of missing data, it was estimated that opioid and amphetamine dependence were the most common forms of illicit drug dependence in 2010; opioid dependence was responsible for the greatest burden. Few putative consequences of illicit drug use had the quality or quantity of data required to be included in the CRA. Estimates of the extent and distribution of disease burden are likely to shape global and regional health policy development. The GBD exercise will be repeated on an annual basis; GBD 2010 clearly demonstrated that although the illicit drug field is generating more and better epidemiological data on the health risks of drug use, there is still much work to be done to generate defensible estimates of the magnitude of risk, particularly for impactful and prevalent outcomes, such as injuries, violence and mental health complications. Until then, burden of disease attributable to illicit drugs will be underestimated.

The Global Epidemiology and Contribution of Cannabis Use and Dependence to the Global Burden of Disease: Results from the GBD 2010 Study

AimsEstimate the prevalence of cannabis dependence and its contribution to the global burden of disease.MethodsSystematic reviews of epidemiological data on cannabis dependence (1990-2008) were conducted in line with PRISMA and meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Culling and data extraction followed protocols, with cross-checking and consistency checks. DisMod-MR, the latest version of generic disease modelling system, redesigned as a Bayesian meta-regression tool, imputed prevalence by age, year and sex for 187 countries and 21 regions. The disability weight associated with cannabis dependence was estimated through population surveys and multiplied by prevalence data to calculate the years of life lived with disability (YLDs) and disability-adjusted life years (DALYs). YLDs and DALYs attributed to regular cannabis use as a risk factor for schizophrenia were also estimated.ResultsThere were an estimated 13.1 million cannabis dependent people globally in 2010 (point prevalence0.19% (95% uncertainty: 0.17-0.21%)). Prevalence peaked between 20-24 yrs, was higher in males (0.23% (0.2-0.27%)) than females (0.14% (0.12-0.16%)) and in high income regions. Cannabis dependence accounted for 2 million DALYs globally (0.08%; 0.05-0.12%) in 2010; a 22% increase in crude DALYs since 1990 largely due to population growth. Countries with statistically higher age-standardised DALY rates included the United States, Canada, Australia, New Zealand and Western European countries such as the United Kingdom; those with lower DALY rates were from Sub-Saharan Africa-West and Latin America. Regular cannabis use as a risk factor for schizophrenia accounted for an estimated 7,000 DALYs globally.ConclusionCannabis dependence is a disorder primarily experienced by young adults, especially in higher income countries. It has not been shown to increase mortality as opioid and other forms of illicit drug dependence do. Our estimates suggest that cannabis use as a risk factor for schizophrenia is not a major contributor to population-level disease burden.

Vulnerability to Smokeless Tobacco Use Among Those Dependent on Alcohol or Illicit Drugs

Individuals dependent on alcohol or illicit drugs are vulnerable to cigarette smoking and related adverse health outcomes. Less research has been conducted regarding whether these same groups are vulnerable to smokeless tobacco (ST) use. The goal of this study is to examine vulnerability to ST use among individuals with other drug dependence. Utilizing the most recent (2011) National Survey on Drug Use and Health (NDSUH), we determined odds ratios (ORs) for current cigarette smoking and ST use among those with current alcohol, cocaine, heroin, and marijuana dependence, adjusting for relevant sociodemographic characteristics. Vulnerability to cigarette smoking was assessed to confirm that alcohol and illicit drug dependence were associated with increased smoking in these data sets, as shown in prior studies. Identical analyses were completed in the 2009 and 2010 NSDUH to assess generality. Odds for current cigarette smoking were increased for each category of dependence (p < .0005): alcohol (OR with 99% CI = 3.30 [2.58, 4.21]), cocaine (OR = 4.50 [1.53, 13.20]), heroin (OR = 7.84 [1.92, 32.03]), and marijuana (OR = 3.55 [2.59, 4.88]). Odds for current ST use were also increased among those with alcohol dependence (OR = 1.56 [1.06, 2.30], p = .003) but not illicit drug dependence. Generality of the findings was confirmed in the 2009 and 2010 NSDUH. Consistent with earlier reports, alcohol and illicit drug dependence are associated with robust increases in risk for cigarette smoking. In the case of alcohol dependence, but not illicit drug dependence, this vulnerability also extends to ST use.

Recreational Drugs of Abuse

The use of recreational drugs of abuse continues to expand without limitations to national boundaries, social status, race, or education. Beyond the prevalence of illicit drug use and dependence, their contribution to the global burden of disease and death are large and troubling. All medical providers should be aware of the evolving drugs of abuse and their medical and social consequences. In addition to heroin and stimulants such as cocaine and methamphetamine, new designer stimulants called "bath salts" and cannabinoids called "spice," along with the abuse of prescription drugs and volatile substances, are now widely recognized problems in many societies. The wide variety and continuingly expanding clinical manifestations of toxicity of recreational drugs of abuse is not widely appreciated by clinicians. This edition attempts to summarize six major classes of drugs of abuse and their clinical effects with special emphasis on their immunological and respiratory effects.

Depression and substance abuse and dependency in relation to current smoking status and frequency of smoking among nondaily and daily smokers

Daily smoking rates are decreasing while intermittent or nondaily smoking rates are increasing. Little is known about the association of depression, alcohol abuse and dependence, and illicit drug abuse and dependence with different patterns of smoking, particularly nondaily smoking. Thus, we examined these relationships among current smokers versus nonsmokers and among those who smoke daily versus less frequently. We conducted a secondary analysis of 37,897 adults who participated in the 2008 National Survey on Drug Use and Health. We developed logistic regression models examining predictors of (i) current smoking and (ii) number of days smoking per month (1-10 days, 11-29 days, and ≥30 days) among current smokers, focusing on past-year major depression, alcohol abuse and dependence, and illicit drug abuse and dependence. Compared to nonsmokers, current smokers more frequently reported a major depressive episode (p < .001), alcohol dependence (p < .001) and abuse (p < .001), and illicit drug dependence (p < .001) and abuse (p < .001), controlling for sociodemographics. Among current smokers, greater smoking frequency was associated with illicit drug dependence (p = .004), but lower likelihood of alcohol dependence (p = .01), alcohol abuse (p = .01), and illicit drug abuse (p = .01). Although depression and substance use were associated with greater likelihood of smoking, most measures were inversely associated with frequency of smoking. Thus, it is important to examine underlying mechanisms contributing to these counterintuitive findings in order to inform intervention approaches. With increased rates of nondaily smoking, developing a greater understanding about the mental health correlates related to this pattern of smoking is critical.

Childhood sexual abuse and adult developmental outcomes: Findings from a 30-year longitudinal study in New Zealand

ObjectivesChildhood sexual abuse (CSA) has been associated with many adverse medical, psychological, behavioral and socioeconomic outcomes in adulthood. This study aims to examine the linkages between CSA and a wide range of developmental outcomes over a protracted time period to age 30. MethodsData from over 900 members of the New Zealand birth cohort the Christchurch Health and Development Study were examined. CSA prior to age 16 was assessed at ages 18 and 21 years, in addition to: mental health, psychological wellbeing, sexual risk-taking behaviors, physical health and socioeconomic outcomes to age 30. ResultsAfter statistical adjustment for confounding by 10 covariates spanning socio-demographic, family functioning and child factors, extent of exposure to CSA was associated with increased rates of (B, SE, p): major depression (0.426, 0.094, <.001); anxiety disorder (0.364, 0.089, <.001); suicidal ideation (0.395, 0.089, <.001); suicide attempt (1.863, 0.403, <.001); alcohol dependence (0.374, 0.118, <.002); and illicit drug dependence (0.425, 0.113, <.001). In addition, at age 30 CSA was associated with higher rates of PTSD symptoms (0.120, 0.051, .017); decreased self-esteem (−0.371, 0.181, .041); and decreased life satisfaction (−0.510, 0.189, .007). Childhood sexual abuse was also associated with decreased age of onset of sexual activity (−0.381, 0.091, <.001), increased number of sexual partners (0.175, 0.035, <.001); increased medical contacts for physical health problems (0.105, 0.023, <.001); and welfare dependence (0.310, 0.099, .002). Effect sizes (Cohen's d) for the significant outcomes from all domains ranged from .14 to .53, while the attributable risks for the mental health outcomes ranged from 5.7% to 16.6%. ConclusionsCSA is a traumatic childhood life event in which the negative consequences increase with increasing severity of abuse. CSA adversely influences a number of adult developmental outcomes that span: mental disorders, psychological wellbeing, sexual risk-taking, physical health and socioeconomic wellbeing. While the individual effect sizes for CSA typically range from small to moderate, it is clear that accumulative adverse effects on adult developmental outcomes are substantial.

Prospective effects of adolescent indicators of behavioral disinhibition on DSM-IV alcohol, tobacco, and illicit drug dependence in young adulthood

ObjectiveTo identify robust predictors of drug dependence. MethodsThis longitudinal study included 2361 male and female twins from an ongoing longitudinal study at the Center for Antisocial Drug Dependence (CADD) at the University of Colorado Boulder and Denver campuses. Twins were recruited for the CADD project while they were between the ages of 12 and 18. Participants in the current study were on average approximately 15years of age during the first wave of assessment and approximately 20years of age at the second wave of assessment. The average time between assessments was five years. A structured interview was administered at each assessment to determine patterns of substance use and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; Fourth Edition) attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), and drug dependence symptoms. Cloninger's Tridimensional Personality Questionnaire was also used to assess novelty seeking tendencies (NS). At the second wave of assessment, DSM-IV dependence symptoms were reassessed using the same interview. Path analyses were used to examine direct and indirect mechanisms linking psychopathology and drug outcomes. ResultsAdolescent substance use, CD, and NS predicted young adult substance dependence, whereas the predictive effects of ADHD were few and inconsistent. Furthermore, CD and NS effects were partially mediated by adolescent substance use. ConclusionsAdolescent conduct problems, novelty seeking, and drug use are important indices of future drug problems. The strongest predictor was novelty seeking.

How phenotype and developmental stage affect the genes we find: GABRA2 and impulsivity.

The detection and replication of genes involved in psychiatric outcome has been notoriously difficult. Phenotypic measurement has been offered as one explanation, although most of this discussion has focused on problems with binary diagnoses. This article focuses on two additional components of phenotypic measurement that deserve further consideration in evaluating genetic associations: (1) the measure used to reflect the outcome of interest, and (2) the developmental stage of the study population. We focus our discussion of these issues around the construct of impulsivity and externalizing disorders, and the association of these measures with a specific gene, GABRA2. Data were analyzed from the Collaborative Study on the Genetics of Alcoholism Phase IV assessment of adolescents and young adults (ages 12-26; N = 2,128). Alcohol dependence, illicit drug dependence, childhood conduct disorder, and adult antisocial personality disorder symptoms were measured by psychiatric interview; Achenbach youth/adult self-report externalizing scale; Zuckerman Sensation-Seeking scale; Barratt Impulsivity scale; NEO extraversion and consciousness. GABRA2 was associated with subclinical levels of externalizing behavior as measured by the Achenbach in both the adolescent and young adult samples. Contrary to previous associations in adult samples, it was not associated with clinical-level DSM symptom counts of any externalizing disorders in these younger samples. There was also association with sensation-seeking and extraversion, but only in the adolescent sample. There was no association with the Barratt impulsivity scale or conscientiousness. Our results suggest that the pathway by which GABRA2 initially confers risk for eventual alcohol problems begins with a predisposition to sensation-seeking early in adolescence. The findings support the heterogeneous nature of impulsivity and demonstrate that both the measure used to assess a construct of interest and the age of the participants can have profound implications for the detection of genetic associations.

ANKK1, TTC12, and NCAM1 Polymorphisms and Heroin Dependence

The genetic contribution to liability for opioid dependence is well established; identification of the responsible genes has proved challenging. To examine association of 1430 candidate gene single-nucleotide polymorphisms (SNPs) with heroin dependence, reporting here only the 71 SNPs in the chromosome 11 gene cluster (NCAM1, TTC12, ANKK1, DRD2) that include the strongest observed associations. Case-control genetic association study that included 2 control groups (lacking an established optimal control group). Semistructured psychiatric interviews. A total of 1459 Australian cases ascertained from opioid replacement therapy clinics, 531 neighborhood controls ascertained from economically disadvantaged areas near opioid replacement therapy clinics, and 1495 unrelated Australian Twin Registry controls not dependent on alcohol or illicit drugs selected from a twin and family sample. Lifetime heroin dependence. Comparison of cases with Australian Twin Registry controls found minimal evidence of association for all chromosome 11 cluster SNPs (P ≥ .01); a similar comparison with neighborhood controls revealed greater differences (P ≥ 1.8 × 10(-4)). Comparing cases (n = 1459) with the subgroup of neighborhood controls not dependent on illicit drugs (n = 340), 3 SNPs were significantly associated (correcting for multiple testing): ANKK1 SNP rs877138 (most strongly associated; odds ratio = 1.59; 95% CI, 1.32-1.92; P = 9.7 × 10(-7)), ANKK1 SNP rs4938013, and TTC12 SNP rs7130431. A similar pattern of association was observed when comparing illicit drug-dependent (n = 191) and nondependent (n = 340) neighborhood controls, suggesting that liability likely extends to nonopioid illicit drug dependence. Aggregate heroin dependence risk associated with 2 SNPs, rs877138 and rs4492854 (located in NCAM1), varied more than 4-fold (P = 2.7 × 10(-9) for the risk-associated linear trend). Our results provide further evidence of association for chromosome 11 gene cluster SNPs with substance dependence, including extension of liability to illicit drug dependence. Our findings highlight the necessity of considering drug exposure history when selecting control groups for genetic investigations of illicit drug dependence.