Origins and Pathways to Drug Abuse

Research Findings from September, 2004 Director's Report

This section lists selected summaries from NIDA funded research projects that investigate the origins and pathways to drug abuse. The summaries provided were selected from recent issues of the Director's Report to the National Advisory Council on Drug Abuse. For a more comprehensive listing of NIDA funded projects see the Director's Report.

Environmental Enrichment During Rearing Selectively Affects Dopamine Transport in the Prefrontal Cortex

In preclinical studies, early environmental enrichment (EC) affects subsequent behavioral responsivity to drugs of abuse such as amphetamine. For example, EC rats show an attenuated amphetamine-induced sensitization and a decrease in self-administration of this drug. EC also induces structural changes in neurons of the cortex and striatum. These structural changes may affect synaptic transmission in brain dopamine systems that give rise to behavioral effects of psychostimulants. Recently, NIDA-funded investigators at the University of Kentucky performed a kinetic analysis of dopamine transporter (DAT) function in the medial prefrontal cortex (mPFC), striatum and nucleus accumbens (NAS) of rats reared in EC conditions or in isolation (IC). Initially the investigators administered the selective DAT inhibitor, GBR 12935, to assess behavioral effects on the locomotor activity of EC and IC groups. Although EC animals had a lower basal level of behavioral activity, GBR increased activity to a greater extent in this group than in the IC group, when given acutely (dose range: 1.0-10.0 mg/kg). Surprisingly, when 3.0 or 5.6 mg/kg was given repeatedly, only the EC group developed a behavioral sensitization to the locomotor activating effects of GBR. The authors note that this contrasts with previous observations from repeated amphetamine administration, but behavioral differences may be accounted for by different neurochemical mechanisms of action in central dopamine neurons. Subsequent DAT analysis revealed no differences in Ki values of [3H]dopamine uptake between groups for any brain area. However, EC significantly decreased (36%) Vmax in the mPFC, in comparison to the IC condition. This difference was evident for the mPFC only, with no between group differences for subcortical areas. HPLC measures of the DA metabolite DOPAC also revealed a significant difference between groups for the mPFC only. The observation that EC selectively decreases DAT function and DA metabolism in the mPFC suggests that the environment can modulate the activity of central DA systems that participate in chronic neuroadaptations that give rise to psychostimulant craving and relapse. Zhu, J., Green, T., Bardo, M.T. and Dwoskin, L.P. Environmental Enrichment Enhances Sensitization to GBR 12935-induced Activity and Decreases Dopamine Transporter Function in the Medial Prefrontal Cortex. Behavioral Brain Research, 148, pp. 107-117, 2004.

Factors Associated with Cessation of Smoking in Young Adults

As part of a longitudinal study of psychopathology and smoking in a school-based sample, 242 daily smokers provided complete data on factors associated with successful smoking cessation. Factors positively associated with successful cessation included being married and having higher household income; those negatively associated included lifetime major depressive disorder, antisocial personality symptoms, family history of drug and alcohol use disorder, and nicotine dependence (for women). In a multivariate analysis, marital status, nicotine dependence (for women), and male gender were significant, and major depression approached significance. Of note, factors associated with successful cessation in young adulthood differed from those predicting smoking initiation and progression; while all Axis I psychiatric diagnoses were associated with uptake and progression, only depression and antisocial behavior had some association (negatively) with cessation in this age group. Thus, factors that predict onset of nicotine use and dependence should not be used to predict cessation, which has implications for intervention programs. Rohde, P., Kahler, C.W., Lewinsohn, P.M., and Brown, R.A. Psychiatric Disorders, Familial Factors, and Cigarette Smoking: III. Associations with Cessation by Young Adulthood Among Daily Smokers. Nicotine & Tobacco Research, 6, pp. 509-522, 2004.

Neighborhood Environment and Opportunity to Try Methamphetamine ("Ice") and Marijuana: Evidence from Guam in the Western Pacific Region of Micronesia

This study examines the occurrence of youthful drug involvement among youths living in village and metropolitan regions of Guam during 1998. A probability sample of 776 high school students living in Guam, Micronesia, completed a self-report anonymous survey, one that assessed their village and metropolitan neighborhood environments as well as drug involvement. Results indicate that higher levels of neighborhood disadvantage were associated with youths being more likely to have been offered a chance to try drugs. This study adds new evidence on the potential importance of environmental and psychosocial contexts of neighborhood environment that might help account for the nonrandom distribution of youthful drug involvement. Storr, C.L., Arria, A.M., Workman, Z.R. and Anthony, J.C. Substance Use and Misuse, 39(2), pp. 253-276, 2004.

Relationship Between Early Experiences with Tobacco and Early Experiences with Alcohol

Prior research indicates that smoking and alcohol use are highly comorbid, animal studies indicate cross-sensitivity, and genetic correlates of nicotine and alcohol dependence overlap. Given these background findings, this study examined the association between retrospectively-reported responses to tobacco and alcohol in current smokers (n=111) and never-smokers (n=86). Results indicated that early smoking experiences were correlated with comparable responses to alcohol in smokers, and to a lesser extent, in never-smokers. Both pleasurable early experiences with nicotine and pleasurable experiences with alcohol predicted current alcohol intake, and pleasurable early experiences with alcohol predicted alcohol dependence. Neither pleasurable nor displeasurable experiences with either substance predicted current amount smoked or degree of nicotine dependence. These preliminary findings may have implications for understanding the mechanisms underlying the smoking-alcohol link. Pomerleau, C.S., Marks, J.L., Pomerleau, O.F. and Snedecor, S.M. Addictive Behaviors, 29(6), pp. 1245-1251, 2004.

Early Childhood Misbehavior and the Estimated Risk of Becoming Tobacco-Dependent

In this study, the authors focused on signs of early childhood misbehavior that might be linked to the risk of becoming tobacco-dependent. Standardized teacher ratings of misbehavior were obtained for an epidemiologic sample of first graders entering an urban mid-Atlantic public school system in 1985 and 1986. Fifteen years later, 1,692 of the students were reassessed (nearly 75% of the original sample). As adults, 962 participants indicated that they had tried tobacco at least once; 66% of the 962 had become daily users. Latent class analysis of items on the Fagerstrom Test for Nicotine Dependence gave evidence of three classes pertinent to tobacco dependence syndrome in smokers by young adulthood: one nondependent class of smokers (50% of smokers), a class of smokers experiencing a moderate number of dependence features (31%), and a third class that was more severely affected (19%), as manifest in the need to smoke immediately after waking and smoking when ill. With or without adjustment for covariates, higher levels of teacher-rated childhood misbehavior at entry into primary school were associated with a modest excess risk of becoming tobacco-dependent by young adulthood (risk ratio = 1.6, 95% confidence interval: 1.1, 2.5). These findings suggest that interventions that seek to improve childhood behavior might reduce early onset tobacco smoking and risk of tobacco dependence among smokers. Storr, C.L., Reboussin, B.A. and Anthony, J.C. American Journal of Epidemiology, 160(2), pp. 126-130, 2004.

Family Attention and Tobacco Smoking Among Adolescents

This study examined the association between family attention and tobacco use among 5549 adolescent students in five Central American countries, Panama, and the Dominican Republic who participated in a survey of drug use in 1994. Drug use and other variables were assessed using an adapted version of the Drug Use Screening Inventory (DUSI) in Spanish. Students with the highest level of family attention had a lower occurrence of tobacco smoking than students with the lowest level of family attention. Country-specific analyses show similar associations. These findings underscore the need to understand tobacco use in Central America and neighboring countries and to test whether interventions aimed at enhancing parentalÑchild attention, communication, and monitoring reduce the incidence of tobacco use among youths. Gosebruch, G., Sanchez, M., Delva, J., Wagner, F., and Anthony, J.C. Family Attention and Tobacco Smoking Among Adolescents in Central America, Panama, and the Dominican Republic. Substance Use Misuse 38(8), pp. 1037-1106, 2003.

Anxiety and Risk for Substance Use Disorders Among Late Adolescents/Young Adults

This study examined the relation between comorbid and pure (non-comorbid) anxiety disorders and both substance dependence and substance use problems in a community sample of 1,751 young adults ages 18-23. Results indicate that collectively anxiety disorders, both pure and comorbid with other psychiatric diagnoses are predictive of substance dependence. When temporal order was controlled, anxiety disorders generally preceded the onset of substance dependence. However, in analyses in which PTSD was excluded, anxiety disorders were no longer predictive of substance dependence, suggesting that the increased risk associated with anxiety disorders is largely if not wholly attributable to PTSD. Finally, comorbid and pure anxiety disorders were found to be predictive of the number of alcohol and drug use problems. Lopez, B., Turner, R.J., and Saavedra, L.M. Anxiety and Risk for Substance Use Disorders Among Late Adolescents/Young Adults. Journal of Anxiety Disorders. Corrected proof available online 10 May 2004.

Correlates of Aggression in African American and Puerto Rican Children

This cross-sectional study examines the interrelationship of psychosocial domains as they relate to aggression in a sample of African American and English-speaking Puerto Rican children living in New York City. The sample included 80 biological children of African American and Puerto Rican young adults who have participated in the authors ongoing longitudinal study and 77 mothers or mother substitutes (rearing mothers) of those children. Hierarchical multiple regression analysis was performed, with childhood aggression as the dependent variable and the following domains as independent variables: child and maternal personality attributes; mother-child relationship; ethnic identification and discrimination; and the partner/marital relationship. The results indicated that: (a) the child's personality and maternal attributes were significantly related to the child's aggression, despite control on all the other domains; (b) the ethnic identification and discrimination domain was no longer related to the child's aggression with control on the mother-child relationship domain or the child's personality domain. The findings have implications for clinical practice and public policy, and provide significant insights into childhood risk factors that need to be altered to reduce physical aggression. Brook, J.S., Rosenberg, G., Brook, D.W., Balka, E.B. and Meade, M. Correlates of Aggression in African American and Puerto Rican Children. Journal of Genetic Psychology, 165(2), pp. 185-202, 2004.

Illicit Drug Use and Risky Sexual Behavior Among African American and Puerto Rican Urban Adolescents: The Longitudinal Links

This study assessed whether (a) early illicit drug use predicts later risky sexual activity; (b) early risky sex predicts later illicit drug use; and (c) common factors affect both risky sex and illicit drug use. African American and Puerto Rican youth completed questionnaires in their classrooms at Time 1 (T1) and face-to-face interviews five years later at Time 2 (T2). Logistic regression analyses showed the association between T1 illicit drug use and T2 risky sexual activity and between T1 risky sexual behavior and T2 illicit drug use. With few exceptions, T1 illicit drug use was associated with all of the T2 risky sexual behaviors. After controlling for demographic factors, multiple sex partners at T1 was not related to illicit drug use at T2. Condom use at T1 was related to illicit drug use at T2, whereas sexually transmitted diseases and early pregnancy were not. The findings indicated that assessments of and treatments for substance use should focus on the risky sexual behaviors that seem to accompany illicit drug use. Brook, J.S., Adams, R.E., Balka, E.B., Whiteman, M., Zhang, C. and Sugerman, R. Illicit Drug Use and Risky Sexual Behavior Among African American and Puerto Rican Urban Adolescents: The Longitudinal Links. Journal of Genetic Psychology, 165(2), pp. 203-220, 2004.

Risk-Taking Behaviors Among African American Adolescents

This study explores the relationship between peer status, peer groups' social influence and risk-taking behavior in an urban sample of 647 African American seventh grade students. Highest rates of problem behaviors were seen in those youth who were both highly liked and highly disliked by other youth. Findings also revealed contrasting patterns of peer group leadership. The more controversial the youth the more likely the involvement in deviant peer groups. Results highlight the importance of controversial status students as key influence agents during early adolescence, and implications for prevention interventions to reduce adolescent problem behaviors. Miller-Johnson, S., Costanzo, P.R., Cole, J.D., Rose, M.R., Browne, D.C., and Johnson, C. Peer Social Structure and Risk-Taking Behaviors Among African American Early Adolescents. Journal of Youth and Adolescence, 32(5), pp. 375-384, 2003.

Classroom Environment Influences On Aggression, Peer Relations and Academic Focus

Peers provide models of behavior, and consequently classrooms containing high numbers of students with poor academic skills or behavioral problems are likely to promote bad behavior in individual students. This study examined the extent to which variations in social and academic classroom composition as well as the larger school context affected behavior in a normative sample of children over a 2-year period. Teachers provided ratings of individual students, which were then aggregated to form teacher-based measures of classroom environment. Concurrent and longitudinal effects of classroom and school environments on individual behaviors were examined for students in 65 classrooms in 17 schools. Poorer classroom environments were associated with higher levels of student aggression, poor peer relations, and lack of academic focus. Changes in student behavior over time can be explained by the classroom environment. Barth, J.M., Dunlap, S.I., Dane, H., Lochman, J.E. and Wells, K.C. Journal of School Psychology, 42(2), pp. 115-133, 2004.

Educational Resilience among Youth at Risk

Educational experts and others recognize the importance of early school experiences on later educational outcomes. Following a sample of youth based on 692 files from low-income, single parent families from one urban school district from 1898-90 to 1996-97, the authors apply event history analytic techniques to examine the relationship between first grade retention and high school completion. The findings indicate that being retained in first grade increases the risk of dropping out of high school years later. However, there is a link between retention, extracurricular activity participation and high school completion such that those students who were retained but were involved in extracurricular activities had drop out rates that were lower than the retained uninvolved students. Thus educational trajectories can be redirected such that positive educational outcomes can occur. Randoph, K.A., Fraser, M.W. and Orthner, D.K. Educational Resilience among Youth at Risk: Substance Use and Misuse 39, pp. 747-767, 2004.

Psychosocial Factors Related to Drinking Among Rural Adolescents

This study examined the relationship of psychosocial factors to alcohol use for adolescent boys and girls residing in rural Iowa. Seventh graders (n=1673) self-reported alcohol use, peer drinking norms, adult drinking norms, drug refusal assertiveness, drug refusal techniques, life skills, pro-drinking attitudes, risk-taking tendency, and perceived family management practices. Multiple regressions indicated that peers' drinking norms, drug refusal assertiveness, drug refusal techniques, life skills, pro-drinking attitudes, and risk taking tendency were related to drinking measures. Perceived family management skills and drug refusal techniques were associated with drinking for girls but not boys. Risk-taking tendency was related to drinking for boys but not girls. Epstein, J.A., Botvin, G.J. and Spoth, R. Which Psychosocial Factors are Related to Drinking Among Rural Adolescents? Journal of Child and Adolescent Substance Abuse, 13(1), pp. 19-35, 2003.

Aggressive Juvenile Offenders Transitioning into Emerging Adulthood: Factors Discriminating Persistors and Desistors

As part of a randomized clinical trial comparing Multisystemic Therapy to usual community services, researchers tracked juvenile offenders through early adulthood to assess psychosocial factors that were associated with success in treatment. Of the 115 adolescents participating in the original study, 80 completed multiple assessments in young adulthood, about 5 years later. Of these 80 participants, 55 were classified as "persistors", having engaged in crimes related to property or aggression in young adulthood based on self-reports and official law enforcement records; 25 were classified as "desistors", having no such self-reported or officially reported criminal behavior. In adolescence, those who became desistors in young adulthood showed less aggressive behavior than persistors, and behaved more positively toward peers. At young adulthood, desistors reported better psychosocial adjustment overall, including more emotional support, higher job satisfaction, closer peer relationships, and fewer psychiatric problems. Differences between desistors and persistors at young adulthood remained significant even after controlling for initial differences during adolescence. These results identify several targets for prevention and treatment interventions that could impact the long-term functioning of juvenile offenders as they transition to adulthood. Clingempeel, W.G. and Henggeler, S.W. American Journal of Orthopsychiatry, 73, pp. 310-323, 2003.

A Randomized Controlled Trial of Pemoline for Attention-Deficit/Hyperactivity Disorder in Substance-Abusing Adolescents

In adolescents with substance use disorder (SUD), comorbid attention-deficit/hyperactivity disorder (ADHD) is associated with greater severity of substance abuse, conduct problems, and worse treatment outcomes. Although many controlled trials have established the efficacy of psychostimulants, including pemoline, for ADHD in children and adolescents, none have been conducted in adolescents with SUD. This randomized, placebo-controlled trial, conducted between 1996 and 2000, evaluated the safety and efficacy of pemoline on substance abuse and conduct problems. Sixty-nine adolescents (aged 13-19) with conduct disorder (CD), SUD, and ADHD were recruited from the community and randomly assigned to a 12-week clinical trial of pemoline (n = 35) or placebo (n = 34), titrated over 4 weeks to a single morning dose of 75 to 112.5 mg as tolerated. Results showed that pemoline had greater efficacy than placebo for ADHD as determined by significantly more Clinician's Global Impression-Improvement (CGI-I) ratings of 1 (very much improved) or 2 (much improved) at the study endpoint (n = 69; p <.05). There was also greater reduction in ADHD severity on the parent-rated Conners Hyperactivity-Impulsivity scale in pemoline-treated study completers compared to placebo-treated completers (pemoline, n = 17; placebo, n = 16; p <.01), but no difference between groups in the intent-to-treat analysis (n = 68; p <.13). Substance use did not decline in either group, and there was no difference between groups in baseline to study endpoint change in substance use or CD symptoms. Overall, pemoline was well tolerated, demonstrating a good safety profile and no elevation in liver enzyme levels. The results suggest that pemoline was efficacious for ADHD but did not have an impact on CD or substance abuse in the absence of specific treatment for SUD. Riggs, P.D., Hall, S.K., Mikulich-Gilbertson, S.K., Lohman, M., and Kayser, A. A Randomized Controlled Trial of Pemoline for Attention-Deficit/Hyperactivity Disorder in Substance-abusing Adolescents. J. Am. Acad. Child Adolesc. Psychiatry, 43, pp. 420-429, 2004.

Abuse Experiences in a Community Sample of Young Adults: Relations with Psychiatric Disorders, Sexual Risk Behaviors, and Sexually Transmitted Diseases

This study documents significant associations among lifetime abuse experiences, psychiatric diagnoses, and sexual risk behaviors in a multiethnic community sample of young men and women (N = 1803) in South Florida. Self-report data were collected via structured interviews as part of a longitudinal follow-up of a larger school-based study. Participants were grouped according to extent of lifetime abuse experiences. Cumulative lifetime abuse experiences were associated with increased risk for a broad range of individual lifetime psychiatric disorders, as well as cumulative lifetime psychiatric disorders. Both cumulative abuse experiences and cumulative psychiatric disorders were independently associated with (a) higher levels of sexual risk behaviors and (b) higher risk for lifetime sexually transmitted diseases (STDs). Implications for selective prevention of sexual risk behaviors and STDs among young adults with histories of abuse and psychiatric disorders are discussed. Tubman, J.G., Montgomery, M.J., Gil, A.G., and Wagner, E.F. Abuse Experiences in a Community Sample of Young Adults: Relations with Psychiatric Disorders, Sexual Risk Behaviors, and Sexually Transmitted Diseases. American Journal of Community Psychology. 34(1/2), pp. 147-162, September 2004.

Chronic Marijuana Use Associated With Dropping Out of School

This paper explores the relationship between adolescent marijuana use and school attendance. Data were pooled from the 1997 and 1998 National Household Surveys on Drug Abuse to form a sample of 15,168 adolescents, aged 12Ñ18 years, who had not yet complete high school. The analysis determined the role of marijuana use in adolescent school dropout and, conditional on being enrolled, estimated the number of days truant. The potential endogeneity of marijuana use was tested in all specifications. The results indicate that any marijuana use was positively associated with school dropout and truancy in all models. However, when chronic marijuana use (weekly or more frequent) was distinguished from non-chronic marijuana use (less frequent than weekly), chronic marijuana use was found to be the dominant factor in these relationships. The results have important implications for educators, substance abuse treatment providers, and policymakers. Roebuck, M.C., French, M.T. and Dennis, M.L. Chronic Marijuana Use Associated With Dropping Out of School. Economics of Education Review, 23, pp. 133Ñ141, 2004.

Elevated Post Treatment Relapse Rates Among Recovering Youth with ADHD

Researchers used a sample of 220 adolescent drug abusers in treatment to estimate the degree to which probable ADHD status increases the odds of post treatment alcohol, marijuana, and other drug relapse during the first 6 months following discharge. Drug abusing youth with probable ADHD status exhibited 2.5 times the risk of post treatment alcohol relapse when compared to youth without probable ADHD status, while controlling for demographics, pretreatment conduct-disordered behavior, pretreatment alcohol use frequency, and treatment factors. A significant crude association between probable ADHD status and other drug relapse was not maintained when adjusted for pretreatment conduct-disordered behavior, pretreatment other drug use frequency, or treatment factors. The findings suggest that standard treatment approaches that do not directly address comorbid disorders may result in elevated post treatment relapse rates among recovering youth with ADHD. Latimer, W.W., Ernst, J., Hennessey, J., Stinchfield, R.D. and Winters, K.C. Relapse Among Adolescent Drug Abusers Following Treatment: The Role of Probable ADHD Status. Journal of Child and Adolescent Substance Abuse, 13, pp. 1-16, 2004.

Alcohol and Marijuana Use in Early and Late Adolescence

This study examined alcohol and marijuana use over a 9-year period between ages 11-12 and ages 19-21 using a community based dataset collected prospectively as part of the evaluation of Project DARE. Because the DARE intervention was found to have no effects on any program targets, this dataset provides an appropriate community sample for investigating developmental changes in drug use over time. 481 participants (50.17% male, 79.2% Caucasian) were interviewed once a year in the sixth through tenth grades and again at age 20. A growth mixture model approach was used to analyze interview data from 6 time points in an attempt to empirically identify subgroups of alcohol and marijuana users over time. Three subgroups were identified for both alcohol use and marijuana use: a group that initiated substance use in early adolescence (age 11-12), a group that initiated use in late adolescence/early adulthood (age 15-16), and an abstainer group. Several variables measured in early adolescence including school and church involvement, self-esteem, peer pressure resistance, sensation seeking, expectancies, and conduct problems significantly differentiated the alcohol and marijuana subgroups. The subgroups also differed significantly on young adult outcomes, including alcohol and marijuana dependence, antisocial personality disorder symptoms, and number of arrests. For alcohol use, the early-onset group was more dysfunctional in terms of early psychosocial risk factors and later deleterious outcomes whereas the late-onset and nonuser groups were better adjusted. In contrast, for marijuana, the early- and late-onset groups were both more dysfunctional than the nonuser group. Flory, K., Lynam, D., Milich, R., Leukefeld, C. and Clayton, R. Early Adolescent through Young Adult Alcohol and Marijuana Use Trajectories: Early Predictors, Young Adult Outcomes, and Predictive Utility. Development and Psychopathology, 16, pp. 93-213, 2004.

Gender Identity, Ethnicity, Acculturation and Drug Use

This article presents the findings of a survey completed by 1351 predominantly Mexican American middle school students residing in a large urban center in the U.S. Southwest. The study explores possible associations between drug use attitudes and behaviors and biological sex, gender identity, ethnicity, and acculturation status. Based on the concepts of "machismo" and "marianismo" that have been used to describe Mexican populations, four dimensions of gender identity were measured: aggressive masculinity, assertive masculinity, affective femininity, and submissive femininity. In explaining a variety of indicators of drug use behaviors and anti-drug norms, gender alone had limited explanatory power, while gender identityÑoften regardless of genderÑwas a better predictor. Aggressive masculinity was generally associated with higher risk of drug use, while the other three gender identity measures had selected protective effects. The impact of gender identity was strongly mediated by acculturation: less acculturated Mexican American students reported lower aggressive masculinity scores than non-Latinos; less acculturated Mexican American girls reported both the lowest aggressive masculinity scores and the highest submissive femininity scores; more acculturated Mexican American students, along with the less acculturated Mexican American boys, did not appear to be polarized by gender identity. The findings suggest that some aspects of culturally prescribed gender roles can have a protective effect against drug use behaviors and attitudes, possibly for both girls and boys. Kulis, S., Marsiglia, F.F. and Hurdle, D. Gender Identity, Ethnicity, Acculturation, and Drug Use: Exploring Differences Among Adolescents in the Southwest. Journal of Community Psychology, 31(2), pp.167-188, 2003.

Family and Peers Influence Severity of Alcohol and Drug Problems in Adolescents

To examine how parental limit setting, family conflict, and perception of family experience influence severity of alcohol and drug problems, and important gender differences in these relationships, the researchers interviewed consecutive intakes, aged 12 to 18 years, at 4 chemical dependency programs of a large group-model nonprofit health maintenance organization (HMO) (n=419). The Family Conflict, Limit Setting, and Positive Family Experience scales correlated with substance dependence (p<0.01, p<0.01, p<0.05, respectively). Depression also correlated with family conflict (p<0.01), absence of limit setting (p<0.01), poor family experience (p<0.01) and dependence symptoms (p<0.01). Number of substance-using friends correlated with number of dependence symptoms (p<0.01). Gender differences included the following: (1) girls scoring higher in family conflict (p=0.0002), negative perceptions of family experience (p<0.0017), and lower in absence of limit setting (p<0.0001); (2) how family environment predicted problem severity: absence of limit setting was significant for boys and girls but family conflict for boys only; (3) girls had more dependence symptoms (p=<0.0001), psychiatric diagnoses (e.g., depression (p<0.0003), anxiety (p<0.0002), conduct disorder (p=0.07)), and substance-abusing family members (53 % versus 39%; p=0.006). To conclude, family and peers influence severity of alcohol and drug problems in adolescents. Wu, N., Lu, Y., Sterling, S., and Weisner, C. Family Environment Factors and Substance Abuse Severity in an HMO Adolescent Treatment Population. Clinical Pediatrics, 43(4), pp. 323-333, 2004.