Illicit Drug Dependence Research Articles

HUMAN GENETIC STUDY: Association analysis of genes encoding the nociceptin receptor (OPRL1) and its endogenous ligand (PNOC) with alcohol or illicit drug dependence

Recent studies in animal models have shown that the nociceptin system, comprising nociceptin (or OFQ/N, encoded by PNOC) and the nociceptin receptor (an opioid receptor-like protein encoded by OPRL1), may be involved in alcohol and other drug reward pathways. To determine whether the nociceptin system is associated with alcohol or illicit drug dependence in humans, we analyzed 10 single nucleotide polymorphisms (SNPs) in OPRL1 and 15 SNPs in PNOC in a sample of 1923 European Americans from 219 multiplex alcohol dependent families ascertained by the Collaborative Study on the Genetics of Alcoholism. The SNPs spanned both genes and several kb of their flanking sequences, and were in high linkage disequilibrium. Neither gene was associated with alcohol or illicit drug dependence, although two SNPs in PNOC showed marginal association with alcoholism and one with illicit drug dependence (P = 0.04-0.05). Secondary analyses suggested that two adjacent SNPs in intron 1 of OPRL1 were marginally associated with opioid dependence (P = 0.05); none of the SNPs in PNOC were associated with opioid dependence.

The Sensitivity of Variance Component Estimates to Underreporting: Method and Application to Substance Abuse Data

Many studies of human behavior and psychological constructs rely on subjects' willingness to disclose information about themselves. This is problematic for phenotypes that require the disclosure of sensitive information, such as sexual behavior or illicit drug use, which are likely to be underreported. We describe a method for evaluating how sensitive variance component estimates are to underreporting. The method involves estimating, by maximum likelihood, the original population proportions of the response classes, and adjusting them for a set of hypothesized underreporting parameters. If the true values of the underreporting parameters were known, the researcher could estimate the variance components based on these values. Usually, underreporting levels are not known with certainty. However, it is possible to assume a specific value for the underreporting rate, obtain response pattern proportions adjusted for this rate, and then to conduct the analyses on these revised estimates. By repeating the procedure across the range of plausible underreporting values, the researcher can assess how sensitive the variance component estimates are to variation in underreporting. We apply this method to a sample of male-male twin pairs who reported on themselves and their co-twins for illicit drug abuse and dependence (DAD). We show how underreporting influences estimates of additive genetic, common environment, and specific environment variance components (A, C, and E) obtained for DAD in a classical twin design.

Substance Use Disorders and Overweight/Obesity in Bipolar I Disorder

This investigation was undertaken to explore the relationship between alcohol/illicit drug dependence and overweight/obesity in individuals with bipolar I disorder. The data for this analysis were procured from the Canadian Community Health Survey-Mental Health and Well-Being (CCHS) conducted by Statistics Canada in 2002. Bipolar I disorder was defined as persons screening positive for a lifetime manic episode using the World Mental Health 2000 version of the Composite International Diagnostic Interview (WMH-CIDI). Substance abuse and illicit drug dependence were determined using criteria commensurate with the DSM-IV-TR. Overweight and obesity were defined as a body mass index of 25.0 to 29.9 and greater than or equal to 30.0 kg/m(2), respectively. The total sample comprised 36,984 individuals (>or= 15 years old) screening positive for a lifetime manic episode. Subgroup analysis indicated that overweight/obese bipolar individuals had a significantly lower rate of substance dependence than the normal weight sample (13% vs. 21%, p < .01). Conversely, bipolar individuals who screened positive for substance dependence had a lower rate of overweight/obesity when compared with non-substance-dependent bipolar respondents (39% vs. 54%, p< .01). The inverse association between the presence of these 2 co-morbid conditions in bipolar I disorder continued to be statistically significant in multivariate analysis (OR = 0.57, 95% CI = 0.34 to 0.95, p < .05). An inverse relationship between the presence of comorbid overweight/obesity and substance use disorders was observed in bipolar I disorder. These results suggest that comorbid addictive disorders (i.e., substance use and compulsive overeating) may compete for the same brain reward systems.

Pharmacotherapy for Anxiety Disorders in Children and Adolescents: An Evidence-Based Medicine Review

&lt;p&gt;Childhood-onset anxiety disorders are among the most common problems affecting children and adolescents, with an estimated prevalence of greater than 10%. Although common, childhood-onset anxiety disorders are not benign. Anxiety in children and adolescents can range from mild worries to incapacitating symptoms, which can significantly interfere with functioning. Children with anxiety disorders are at increased risk for later anxiety, depression, illicit drug dependence, educational underachievement, suicide attempts, and psychiatric hospitalization. Over the past three decades, researchers have investigated a variety of psychopharmacologic agents for the treatment of these disorders.&lt;/p&gt; &lt;h4&gt;ABOUT THE AUTHORS&lt;/h4&gt; &lt;p&gt;Scott N. Compton, PhD, and John S. March, MD, are with Duke University Medical Center, Durham, North Carolina. Christopher J. Kratochvil, MD, is with University of Nebraska Medical Center, Omaha, Nebraska.&lt;/p&gt; &lt;p&gt;Address correspondence to: Scott N. Compton, PhD, Pediatric Psychiatry, Duke University Medical Center, DUMC Box 3527, Durham, NC 27710; fax 919-416-2420; or e-mail &lt;a href="mailto:scompton@duke.edu"&gt;scompton@duke.edu&lt;/a&gt;.&lt;/p&gt; &lt;p&gt;Dr. Compton has disclosed no relevant financial relationships. Dr. Kratochvil has disclosed the following relevant financial relationships: Abbott Laboratories, Eli Lilly, and Cephalon: Consultant; AstraZeneca and Pfizer: Data Safety Monitoring Board; Abbott Laboratories, Cephalon, Eli Lilly, McNeil, Shire: Research Grant Recipient; and Eli Lilly: Member of Speakers&amp;#146; Bureau. Dr. March has disclosed the following relevant financial relationships: MedAvante: Stockholder; Eli Lilly, GlaxoSmithKline, Pfizer, and Wyeth: Scientific Consulting; Eli Lilly and Pfizer: Scientific Advisor; Eli Lilly: Research Support (Primary Investigator/Investigator); AstraZeneca, Johnson and Johnson, and Organon: Data Safety Monitoring Board; Eli Lilly and Pfizer: Drug Supplied for National Institutes of Health Study; Child/Adolescent Anxiety Multimodal Study (CAMS), Child and Adolescent Psychiatry Trails Network (CAPTN), K 24, Pediatric Obsessive-Compuslive Disorder (OCD) Treatment Study (POTS I and POTS II), Treatment of Adolescents who Made a Recent Suicide Attempt (TASA), and Treatment for Adolescents with Depression Study (TADS): Federal Study Participant; and Multidimensional Anxiety Scale for Children (MultiHealth Systems): Other.&lt;/p&gt;

Alcohol dependence with comorbid drug dependence: genetic and phenotypic associations suggest a more severe form of the disorder with stronger genetic contribution to risk*

Twin data suggest that alcohol dependence comorbid with illicit drug dependence represents a more heritable form of the disorder. In the Collaborative Study on the Genetics of Alcoholism sample, approximately half the alcohol-dependent individuals also meet diagnostic criteria for illicit drug dependence. In this study, we tested for heterogeneity in the association between the muscarinic acetylcholine M2 receptor gene (CHRM2) and alcohol dependence, reported previously in the full sample, among the subgroups of alcohol-dependent individuals with and without comorbid drug dependence. Family-based association tests were conducted separately (a) in individuals with alcohol dependence with comorbid drug dependence (n = 477) and (b) in individuals with alcohol dependence without comorbid drug dependence (n = 433). These subgroups were subsequently compared on other phenotypic characteristics. The evidence for association between CHRM2 and alcohol dependence came entirely from the subgroup of individuals with comorbid drug dependence. There was no evidence of association with CHRM2 among the alcohol-dependent individuals without drug dependence. Subsequent phenotypic analyses suggest that the subgroup of alcohol-dependent individuals with comorbid drug dependence differ on a number of other phenotypic characteristics, including several measures of the severity of their alcohol problems, personality traits and comorbid psychiatric disorders. These analyses provide specific genetic evidence suggesting that alcohol dependence with comorbid drug dependence represents a particularly severe form of the disorder, with higher genetic contribution to vulnerability.

Impact of Intimate Partner Violence on Unmet Need for Mental Health Care: Results From the NSDUH

Impact of Intimate Partner Violence on Unmet Need for Mental Health Care: Results From the NSDUH

Eating Disorders and Substance Abuse in Canadian Men and Women: A National Study

The objective of this study was to examine the co-morbidity between eating disorders and substance use in a large nationally representative sample of Canadian women and men while including varied measures of substance consumption and a wide range of substance classes. The research was based on secondary analyses of data collected, using multistage stratified probability sampling, by Statistics Canada in the Mental Health and Well-being cycle 1.2 of the Canadian Community Health Survey (CCHS). Data were collected mostly in face to face interviews using the Computer Assisted Personal Interviewing method. Data included the Eating Attitude Test (EAT-26), and modules of the short form of the Composite International Diagnostic Interview (CIDI-SF) to assess alcohol and drug use, dependence and interference. Alcohol interference and amphetamine use were associated with the risk for an eating disorder in both women and men. In the women sample only, risk for an eating disorder was associated with illicit drug use, dependence and interference, as well as with the number of substance classes used. The study findings support the importance of developing assessment instruments and treatment strategies that address the co-occurrence of eating disorders and substance use for both women and men.

The opioid system in alcohol and drug dependence: Family‐based association study

Opioid receptors and their endogenous peptide ligands play important roles in neurotransmission and neuromodulation in response to addictive drugs such as heroin, cocaine, and alcohol. In an earlier study, we reported that variation in the genes encoding the kappa-opioid receptor (OPRK1) and its peptide ligand (PDYN) were associated with the risk for alcoholism. We continued our investigation of the role of the opioid system in alcohol dependence by analyzing the genes encoding the micro- and delta-opioid receptors and their peptide ligands. We analyzed 18 OPRM1 SNPs, 18 OPRD1 SNPs, 7 PENK SNPs, and 7 POMC SNPs in a sample of 1923 European Americans from 219 multiplex alcohol dependent families. Employing a family-based test of association, we found no evidence that these four genes were significantly associated with alcohol dependence. We also did not find association between these genes and illicit drug dependence. Secondary analyses employing the narrower phenotype of opioid dependence (83 affected individuals) demonstrated association with SNPs in PENK and POMC, but not in OPRM1 or OPRD1. Haplotype analyses provided further support for the association of PENK and POMC with opioid dependence. Therefore, our data provide no support for the idea that variations in OPRM1, OPRD1, PENK and POMC are associated with alcohol dependence or general illicit drug dependence, but variations in PENK and POMC appear to be associated with the narrower phenotype of opioid dependence in these families.

Psychometric properties of DSM assessments of illicit drug abuse and dependence: results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC)

DSM-IV criteria for illicit drug abuse and dependence are largely based on criteria developed for alcohol use disorders and there is a lack of research evidence on the psychometric properties of these symptoms when applied to illicit drugs. This study utilizes data on abuse/dependence criteria for cannabis, cocaine, stimulants, sedatives, tranquilizers, opiates, hallucinogens and inhalants from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC, n=43 093). Analyses included factor analysis to explore the dimensionality of illicit drug abuse and dependence criteria, calculation of item difficulty and discrimination within an item response framework and a descriptive analysis of 'diagnostic orphans': individuals meeting criteria for 1-2 dependence symptoms but not abuse. Rates of psychiatric disorders were compared across groups. Results favor a uni-dimensional construct for abuse/dependence on each of the eight drug classes. Factor loadings, item difficulty and discrimination were remarkably consistent across drug categories. For each drug category, between 29% and 51% of all individuals meeting criteria for at least one symptom did not receive a formal diagnosis of either abuse or dependence and were therefore classified as 'orphans'. Mean rates of disorder in these individuals suggested that illicit drug use disorders may be more adequately described along a spectrum of severity. While there were remarkable similarities across categories of illicit drugs, consideration of item difficulty suggested that some alterations to DSM regarding the relevant severity of specific abuse and dependence criteria may be warranted.

Problem gambling in bipolar disorder: Results from the Canadian Community Health Survey

Objective This investigation was undertaken to explore the prevalence and associated features of problem gambling amongst individuals with bipolar I disorder. Methods The data for this analysis were procured from the Canadian Community Health Survey: Mental Health and Well-being (CCHS 1.2) conducted by Statistics Canada. Individuals screening positive for a lifetime (World Mental Health- Composite International Diagnostic Interview) WMH-CIDI-defined manic episode (i.e. bipolar I disorder) or depressive episode (i.e. major depressive disorder) and current (i.e. past 12-month) problem gambling were compared to the general population without these disorders. Past year problem gambling was operationalized with the Canadian Problem Gambling Index (CPGI). Results The sample consisted of 36,984 individuals (≥ 15 years old); the weighted prevalence of problem gambling was significantly higher (6.3%) amongst the population with bipolar disorder as compared to the general population (2.0%, p < 0.001) and those with major depressive disorder (2.5%, p < 0.01). Compared to those without bipolar disorder, the odds of problem gambling for bipolar individuals were over twice as high (OR = 2.3; 95% CI 1.4–3.7), even when controlling for potential confounders. Males also had higher odds of problem gambling (OR = 1.8; 95% CI 1.4–2.3), as did individuals without post-secondary education (OR = 1.4; 95% CI 1.1–1.8). Persons who were married/cohabiting had lowered odds of problem gambling, compared with those who were unmarried (OR = 0.6; 95% CI 0.5–0.8). Comorbid alcohol dependence (OR = 3.4; 95% CI 2.3–5.0) and illicit drug dependence (OR = 2.6; 95% CI 1.1–6.2) each conferred an increased risk for problem gambling. Physical activity level (moderate to active) was associated with a decreased risk for problem gambling (OR = 0.8; 95% CI 0.6–0.9). Conclusions Individuals with bipolar I disorder are differentially affected by problem gambling. Opportunistic screening for problem gambling is warranted, particularly in persons with comorbid alcohol or substance dependence.

Eating disorders and substance abuse in Canadian women: a national study

This study aimed to examine the comorbidity between eating disorders and substance use in a large nationally representative sample of Canadian adult women. Recent as well as life-time measures of substance use were used. The research was based on secondary analyses of data collected, using multi-stage stratified probability sampling, by Statistics Canada in the Mental Health and Well-being cycle 1.2 of the Canadian Community Health Survey (CCHS). The Eating Attitude Test (EAT-26) was used to measure risk of eating disorders. Alcohol use, dependence and interference, and illicit drug use, dependence and interference were measured using relevant modules from the short form of the Composite International Diagnostic Interview (CIDI-SF). Data on a nationally representative sample of Canadian adult women, grouped into three age groups, were used for this research. Alcohol dependence and alcohol interference were associated significantly with the risk for an eating disorder in the three adult age groups. Significant associations were also found in the three age groups between risk for an eating disorder and the life-time abuse of and dependence on illicit drugs. Significant associations were found in the 15-24 and 25-44-year age groups when the 12-month time-frame was used. The study findings support the call for the development of short screening instruments for adult women with eating disorders and substance abuse, as well as for the development of treatment strategies that address the co-occurrence of eating disorders and substance use

The Inclusion of Measured Covariates in the Neale and Kendler Model Fitting Approach

Neale and Kendler (1995, Am J Hum Genet 57:935-953) described 13 comorbidity models, providing the most comprehensive set of alternative hypotheses regarding the possible causes of comorbidity to date. This research note describes an extension of the Neale and Kendler model fitting approach that permits the inclusion of measured covariates. An example of 13 models examining the comorbidity between alcohol dependence and illicit drug dependence is presented.

Heroin and Cocaine Dependence and the Risk of Accidental Non-Fatal Drug Overdose

The relation between illicit drug dependence and the likelihood of drug overdose is unclear. We recruited 1,066 habitual drug users for this analysis through street-based outreach in New York City. In this sample, 99.3% of respondents used heroin in the past year and 87.1% of respondents used cocaine; 819 (77.5%) heroin users and 735 (79.2%) cocaine users were severely dependent on either drug, respectively. In multivariable models, among heroin users, persons who were severely heroin dependent were less likely (OR = 0.6; 95% CI = 0.4-0.9) to have overdosed on any drug in the past year; among cocaine users, those who were severely cocaine dependent were more likely (OR = 1.6; 95% CI = 1.0-2.6) to have overdosed in the past year. The relation between illicit drug dependence and risk of overdose may vary for different patterns of drug dependence. These observations suggest that overdose prevention interventions, perhaps even those specifically targeting opiate overdose, may be more efficiently directed at individuals exhibiting cocaine dependence.

The role of conduct disorder in explaining the comorbidity between alcohol and illicit drug dependence in adolescence

Background Conduct disorder (CD), alcohol dependence (AD), and illicit drug dependence (IDD) frequently co-occur. This paper describes the result of an investigation of the extent to which comorbid alcohol and illicit drug dependence in adolescents are explained by etiological factors in common with conduct disorder. Methods Participants were 645 MZ twin pairs, 702 DZ twin pairs, 429 biological sibling pairs, and 96 adoptive sibling pairs, aged 12–18 years, from a community based sample. Conduct disorder was measured using the Diagnostic Interview Schedule for Children-IV. Alcohol and illicit drug dependence were assessed using the Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM). For each outcome, subjects were categorized into those with no symptoms, those with one or more symptoms but no diagnosis, and those with a diagnosis. Results The heritability estimates for CD, AD, and IDD were 58, 66, and 36%, respectively. The genetic correlation between AD and IDD was partially explained by the genetic risk they both share with conduct disorder. Conclusions We conclude that conduct disorder in adolescents explains, in part, the co-occurrence of alcohol and illicit drug dependence. Specifically, the genetic contribution to their covariation is explained partially by the genetic contribution in common with conduct disorder.

Co-morbid health conditions at mid-life in the Iowa adoptees

Adverse health effects due to alcohol and illicit drug abuse and dependence have been well documented. This study examines the effect of substance misuse on five major groups of health conditions using a sample of well characterized adoptees. The sample consisted of 742 adoptees interviewed in the last wave of the Iowa Adoption Studies. Death rate analyses included an additional 34 participants who had died prior to the last follow-up. Substance use patterns and medical history were assessed using the SSAGA-II (Bucholz, K. K., Cadoret, R. J., Cloninger, C. R., Dinwiddie, S. H., Hesselbrock, V. M., Nurnberger, J. L., Jr., et al. (1994). A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA. Journal of Studies on Alcohol, 55 (2), 149–158). Subjects were divided into three groups according to DSM-IV diagnostic criteria, controls, alcohol abuse or dependence only (alcohol only), and the Alcohol–Drug group (abuse or dependence diagnosis on at least one illicit substance with or without alcohol diagnosis). Incidence rates of various diseases were measured using logistic regression. Survival analyses were used to examine whether substance abusers developed cardiovascular or metabolic disease at an earlier age than control subjects. Diagnostic grouping made no difference in the incidence rates or age of onset of health conditions. The amount of alcohol consumed by males significantly predicted higher number of overall health complaints as well as higher incidence rates of cardiovascular disease. The amount of illicit drug exposure did not predict an earlier age of diagnosis for cardiovascular or metabolic disease. Individuals in the Alcohol–Drug group had an increased incidence of deaths than either the alconly or the control groups.

Lifetime illicit drug use and drug dependence are common by the age of 25 in New Zealand

Lifetime illicit drug use and drug dependence are common by the age of 25 in New Zealand

Association of GABRA2 with Drug Dependence in the Collaborative Study of the Genetics of Alcoholism Sample

Results from twin studies suggest that overlapping genetic factors influence alcohol dependence and illicit drug dependence. Using data from the Collaborative Study on the Genetics of Alcoholism (COGA), we examined the association between 69 SNPs in the GABAA receptor gene cluster on chromosome 4 and marijuana and illicit drug dependence, individually, and as co-occurring phenotypes with alcohol dependence. Results suggested association between marijuana dependence and illicit drug dependence with SNPs in the GABRA2 gene. Interestingly, the evidence for association previously observed with alcohol dependence came only from individuals with comorbid illicit drug dependence. There was no association with other genes in the GABAA cluster on chromosome 4 with illicit drug dependence.

Illicit Drug use and Dependence in a New Zealand Birth Cohort

To describe the patterns of illicit drug use in a birth cohort studied to the age of 25 years. The data were gathered during the Christchurch Health and Development Study. In this study a cohort of 1265 children born in the Christchurch, New Zealand urban region in mid-1977 have been studied to the age of 25 years. Information was gathered on patterns of illicit drug use and dependence during the period 15-25 years. By age 25 years, 76.7% of the cohort had used cannabis, while 43.5% had used other illicit drugs on at least one occasion. In addition, 12.5% of the cohort met DSM-IV criteria for dependence on cannabis, and 3.6% of the cohort met criteria for dependence on other illicit drugs at some time by age 25. There was also evidence of substantial poly-drug use among the cohort, with hallucinogens and amphetamines being the most commonly used illicit drugs (excluding cannabis). Illicit drug use and dependence was higher in males, in Māori, and in those leaving school without qualifications. Key risk factors for illicit drug use and dependence included adolescent risk-taking behaviours including cigarette smoking and alcohol consumption, affiliation with substance-using peers, novelty-seeking, and conduct problems in adolescence. Other key risk factors included parental history of illicit drug use and childhood sexual abuse. Levels of cumulative illicit drug use in this cohort were relatively high, with the majority of respondents having tried illicit drugs by age 25. For the majority of illicit drug users, drug use did not lead to problems of dependence. Nonetheless, nearly 15% of the cohort showed symptoms of illicit drug dependence by the age of 25 years, with cannabis dependence accounting for the majority of illicit drug dependence.

Illicit drug use and dependence in a New Zealand birth cohort

Illicit drug use and dependence in a New Zealand birth cohort

Comorbidity between alcohol dependence and illicit drug dependence in adolescents with antisocial behavior and matched controls

Background Knowledge regarding the causes of comorbidity among substance use disorders can have significant impact on future research examining the etiology of these disorders. Unfortunately, the conclusions of past studies examining the comorbidity among substance use disorders are conflicting; some studies emphasize familial influences common to multiple substances, while others emphasize substance-specific influences. Discrepancies in results may reflect different analytical approaches or differences in the samples. Here, we examine the causes of comorbidity between alcohol dependence and illicit drug dependence in adolescents. Methods We ascertained a clinical sample of adolescents treated for antisocial behavior and substance use disorders and their siblings and a matched control sample. A model fitting approach was used to test 13 alternative hypotheses for the causes of comorbidity. Results The best supported hypothesis for the comorbidity between alcohol dependence and illicit drug dependence was a model hypothesizing that comorbid disorders are alternate forms of a single underlying liability. The next best fitting models were two of the correlated liabilities models (correlated risk factors and reciprocal causation). Discussion The results suggest that the best hypotheses explaining the comorbidity between alcohol and illicit drug dependence in adolescents are that alcohol dependence and illicit drug dependence are manifestations of a single general liability to develop substance dependence or that there are separate liabilities that are highly correlated.