Director's Report to Council - Research Findings Excerpts

May, 2007

Basic Neurosciences Research

Rat Prenatal or Adolescent THC Exposure is Associated with Greater Heroin Intake in Adulthood

Brain cannabinoid and opioid systems are intimately connected. Cannabinoids stimulate release of enkephalin in the nucleus accumbens (NAS). They also stimulate PENK - the precursor gene for this endogenous opioid. Cannabinoid and opioid mu receptors are found on the same VTA neurons. Dr. Yasmin Hurd and colleagues have been conducting NIDA-supported studies to model (1) prenatal effects of clinically relevant gestational THC exposure and (2) adolescent marijuana abuse, to determine effects on the vulnerability for opiate self-administration in adulthood. In the prenatal study, rats were implanted for i.v. THC administration and then bred. THC was administered (.15 mg/kg) from gestational day 5 to postnatal day (PND) two (corresponding to mid-gestation in the human). Results showed that THC rats administered more drug and emitted more responses after stress, and had more drug-seeking behavior during extinction, but resembled controls on reinstatement tests with a heroin "prime" (return to bar-pressing on the drug-associated lever). Other groups were used to measure opioid peptide mRNA expression. The authors report that PENK mRNA in the NAS core and medial shell, and in the amygdala, was significantly increased in THC exposed animals at PND 62, suggesting a hyperactivity of the mesocorticolimbic enkaphalinergic system that may mediate greater sensitivity for heroin reinforcement seen on some measures of these behavioral paradigms. Spano, M.S, Allgren, M., Wang, X. and Hurd, Y.L. Prenatal Cannabis Exposure Increases Heroin Seeking with Allostatic Changes in Limbic Enkephalin Systems in Adulthood. Biological Psychiatry, 61, pp. 554-563, 2007. In the adolescent study, THC exposed adolescents took significantly more opiate (greater number of infusions on the active lever, with no differences on an inactive lever) than adults. During dose response testing, they also self-administered significantly more heroin at this dose, and at 60 g/kg/inf. Interestingly, THC treated animals did not exhibit more drug-seeking behavior during extinction. In a separate group sacrificed at PND 57, THC treatment was associated with significant increases of PENK mRNA expression in the NAC shell. There was also a significant positive correlation between the heroin self-administration and DAMGO-stimulated [35S]GTP S binding in the shell suggesting that THC increases opiate receptors in this region, and a significant correlation between heroin self-administration and CB-1 (cannabinoid receptor) binding in the substantia nigra. Ellgren, M., Spano, S.M. and Hurd, Y.L. Adolescent Cannabis Exposure Alters Opiate Intake and Opioid Limbic Neuronal Populations in Adult Rats. Neuropsychopharmacology, (Epub ahead of print) May 22, 2006, pp. 1-9. Findings from these studies suggest that developmental exposure to the active pharmacological ingredient in marijuana, THC, may enhance subsequent vulnerability for opiate abuse, and shed light on potential neurobiological mechanisms responsible for this effect.

Prenatal Marijuana Exposure and Marijuana Use at Age 14

In this longitudinal study conducted at the University of Pittsburgh, a cohort was recruited during the fourth prenatal month, and the mothers and their offspring were assessed at multiple ages from that time on. The assessments involved maternal psychological, social, and environmental factors, demographic status and substance use, and offspring cognitive, behavioral, psychological, and physical development. This report focuses on the association between prenatal marijuana exposure and marijuana use by the offspring at age 14 years. The analyses in this report are based on 563 offspring-mother pairs (74% of the original sample). The sample was half African American, half Caucasian, and mostly of lower socioeconomic status. Overall, at age 14 years, 30% of the adolescents reported using marijuana in the past year, and 7.5% reported using marijuana regularly (i.e., at least three to four times per week). Thirteen additional adolescents had initiated marijuana use but did not report use in the past year. Based on multivariate models of analysis, the authors conclude that prenatal marijuana exposure (i.e., average daily joints), in addition to other factors, predicts marijuana use at age 14 years. Specifically, they report a marginally significant association between prenatal marijuana exposure and age of onset of marijuana use, and a significant association between prenatal marijuana exposure and frequency of marijuana use at age 14 years. Variables controlled in these analyses include child's current alcohol and tobacco use, pubertal stage, delinquency, peer drug use, family history of drug use, and parental depression, current drug use, and strictness/supervision. Prenatal marijuana use did not predict age of onset or frequency of use for either alcohol or tobacco. The investigators discuss possible mechanisms by which prenatal marijuana exposure may predict marijuana use at age 14, and also discuss limitations on generalizability of the findings. Day, N.L., Goldschmidt, L., and Thomas, C.A. Prenatal Marijuana Exposure Contributes to the Prediction of Marijuana Use at Age 14. Addiction, 101, pp. 1313-1322, 2006.

Prenatal Cocaine Exposure and Child Behavior Outcomes through Age 7 Years

Investigators from the Maternal Lifestyle Study, a multi-site longitudinal cohort study of development following prenatal exposure to cocaine and other substances, have reported on child behavior problems at ages 3, 5, and 7 years. The Child Behavior Checklist (CBCL) was administered to caregivers at all three ages, and data were reported for internalizing (e.g., social withdrawal, somatic complaints, anxiety), externalizing (e.g., delinquent and aggressive behaviors), and total behavior problems. Between 752 and 917 children were included in data analyses depending on the score category and the assessment age. Longitudinal hierarchical linear models were utilized to investigate relationships between prenatal cocaine exposure and behavior problem trajectories from 3 to 7 years. Statistical analyses included adjusting for a number of other prenatal exposures, and for time-varying covariates such as ongoing caregiver use of substances, demographic factors, family violence, and caregiver psychological distress. The authors report that high prenatal cocaine exposure was associated with trajectories of behavior problems (high exposure was defined as use > 3 times per week in the first trimester), independent of, and less than the significant combined effect of prenatal and postnatal tobacco and alcohol exposures. Caregiver depression and family violence were found to have independent negative association with all behavior outcomes. The investigators note that although the analyses are an important step in examining relationships between prenatal cocaine exposure and behavior outcomes, causality is far from being established. In addition, they point out that the findings highlight a need not only for continued prevention and treatment programs directed toward illegal drug use, but also for increased effort toward prevention and treatment of tobacco and alcohol use. Bada, H.M., Das, A., Bauer, C.R. et al. Impact of Prenatal Cocaine Exposure on Child Behavior Problems through School Age. Pediatrics, 119, pp. e348-e359, 2007.

Maternal Depression, Prenatal Cocaine Use, and Infant Neurobehavior

Infant neurobehavior was assessed for 1053 infants at 1 month of age, and was studied in relation to prenatal cocaine use and postpartum maternal depression. The NICU Network Neurobehavioral Scale (NNNS) was used to measure infant neurobehavior, and the Addiction Severity Index (ASI) was used to assess present and past psychiatric history. These analyses were carried out within the context of the Maternal Lifestyle Study, a multi-site longitudinal cohort study of development following prenatal exposure to cocaine and other substances. Four groups were derived based on combinations of prenatal cocaine exposure/no prenatal cocaine exposure and current postpartum depression/no current postpartum depression. Analysis of covariance (with covariates birthweight, maternal age, SES, research site, and prenatal nicotine, marijuana, and alcohol) was utilized to examine infant neurobehavior in the four groups. Prenatal cocaine exposure by postpartum depression interactions were significant. A postpartum depression association was found for the non-cocaine-exposed infants (poorer self-regulation and more stress signs, excitability, and arousal than infants in the other groups). The combined prenatal cocaine exposure/current postpartum depression group did not differ on any of the neurobehavioral measures from the no-prenatal cocaine exposure/no current postpartum depression group. The investigators suggest that prenatal cocaine exposure may buffer or alter the relationship between postpartum depression and infant neurobehavior, with one possible explanation being prenatal cocaine exposure influences on developing monoamine systems. While cautioning that these analyses cannot determine if the observed depression effects are related solely to postpartum depression or if prenatal depression contributes to this relationship, the authors note that the findings do suggest the importance of considering maternal mood in studies of prenatal substance exposure. Salisbury, A.L., Lester, B.M., Seifer, R. et al. Prenatal Cocaine Use and Maternal Depression: Effects on Infant Neurobehavior. Neurotoxicology and Teratology, epub ahead of print, December 2006.

Prenatal Cocaine Exposure and Infant Regulation at 7 Months of Age

Using heart rate (HR) and respiratory sinus arrhythmia (RSA) as indices of reactivity and regulation during infancy, Drs. Schuetze, Eiden, and Coles report on assessments at 7 months of age in a sample of 154 infants (79 prenatally-exposed to cocaine and 75 not prenatally-exposed to cocaine). Data were collected during baseline and during tasks designed to elicit positive and negative affect. Analyses of covariance were carried out to examine group differences in change scores, with maternal alcohol and cigarette use during pregnancy, maternal age, measures of fetal growth, and gestational age as covariates. The investigators report that there was a significant suppression of RSA during the negative affect task for the non-exposed group but not for the exposed group. The response pattern of RSA suppression from baseline to environmental challenge is noted by the authors as being associated with more optimal state regulation in infancy, decreased behavior problems in preschool aged children, and more adaptive behavior during attention and affect eliciting tasks in preschool and school aged children. Based on their RSA suppression finding and other results, the authors conclude that their findings provide additional support for an association between prenatal cocaine exposure and dysregulation during infancy. Schuetze, P., Eiden, R.D., and Coles, C.D. Prenatal Cocaine and Other Substance Exposure: Effects on Infant Autonomic Regulation at 7 Months of Age. Developmental Psychobiology, 49, pp. 276-289, 2007.

Types of Violence, Protective Factors, Psychopathology, and Behaviors in Drug-Exposed Youth at 11 Years of Age

In this examination of violence and resilience among youth exposed to cocaine and other substances during pregnancy, four types of violence (community, domestic, violent friends, history of child abuse) were studied relative to the occurrence of several outcomes (delinquency, early drug use, symptoms of depression, diagnosis of conduct disorder or oppositional defiant disorder, diagnosis of ADHD) for 517 children at 11 years of age. Measurement of protective factors involved seven indicators of positive relationships and prosocial behavior to teachers, parents, friends, and peers, as well as indicators of effortful control (inhibitory control and attentional focusing). This work was conducted in the context of the Maternal Lifestyle Study, a multi-site longitudinal study of the development of children prenatally-exposed to cocaine and other substances. Mixed model regression analysis was used for each outcome, and all models were adjusted for research site effects. The results show various patterns of associations between specific types of violence and specific outcomes. For example, all forms of delinquency were associated with having violent friends, symptoms of depression were related to history of abuse, CD/ODD was more likely if exposed to domestic violence, and ADHD was not associated with any type of violence. Associations with protective factors also showed variation by outcome. For example, reduced occurrence of CD/ODD was associated with positive relatedness to others and with effortful control, while reduced school delinquency and reduced depression were related to positive relatedness. The authors conclude that the study provides new evidence on violence and protective factors relative to disruptive forms of psychopathology and behavior, and they comment on implications of the findings for interventions. Lagasse, L.L., Hammond, J., Liu, J., et al. Violence and Delinquency, Early Onset Drug Use, and Psychopathology in Drug-Exposed Youth at 11 Years. Annals of the New York Academy of Science, 1094, pp. 313-318, 2006.

Models of Genetic Co-morbidity for Cannabis and Other Illicit Drugs

The authors investigated the co-morbidity between cannabis use (experimentation, early and repeated use, and problems) and experimentation and problems with other illicit drugs (OID) using genetic models proposed by Neale and Kendler. Using data from a sample of 4152 same-sex male and female adult Australian twins, they fit 13 genetically informative models of co-morbidity to data on experimentation, early use, repeated use of cannabis and co-morbid OID experimentation, and to abuse/dependence (A/D) problems with cannabis and OIDs. Model-fitting results suggest that common genetic, shared and unique environmental factors are responsible for the association between cannabis experimentation, early use, repeated use and A/D problems and OID experimentation or problems. causation model, which is a reduced form of the correlated vulnerabilities model, also fit very well. In women, authors found evidence for high-risk cannabis experimenters and repeated users to be at increased risk for OID experimentation, despite being below the risk threshold on the liability distribution for OID experimentation. The authors conclude that co-morbid cannabis and OID use and misuse are due partly to a common predisposition to substance use disorders, but causal effects could not be ruled out. These models warrant further research, so that features of the correlated vulnerabilities model and the gateway models can be studied jointly. Agrawal, A., Lynskey, M., Bucholz, K., Martin, N., Madden, P., and Heath, A. Contrasting Models of Genetic Co-morbidity for Cannabis and Other Illicit Drugs in Adult Australian Twins. Psychol Med, 37(1), pp. 49-60, 2007.

Convergence of HIV Seroprevalence among Injecting and Non-injecting Drug Users in New York City

HIV infection has historically been higher among injecting drug users because the virus is efficiently transmitted through the sharing of drug-injecting equipment. In this study, researchers sought to compare HIV prevalence among injecting and non-injecting heroin and cocaine users in New York City by analyzing data from 2 separate cross-sectional surveys, both with HIV counseling and testing and drug use and HIV risk behavior questionnaires. Participants included injecting and non-injecting heroin and cocaine users recruited at detoxification and methadone maintenance treatment from 2001-2004 (n = 2121) and through respondent-driven sampling from a research storefront in 2004 (n = 448). In both studies, HIV prevalence was nearly identical among current injectors (injected in the last 6 months) and heroin and cocaine users who had never injected: 13% [95% confidence interval (CI), 12-15%] among current injectors and 12% (95% CI, 9-16%) among never-injectors in the drug treatment program study, and 15% (95% CI, 11-19%) among current injectors and 17% (95% CI, 12-21%) among never injectors in the respondent driven sampling storefront study. The 95% CIs overlapped in all gender and race/ethnicity subgroup comparisons of HIV prevalence in both studies. These findings indicate that the very large HIV epidemic among drug users in New York City may be entering a new phase, in which sexual transmission is increasingly important. Additional prevention programs are needed to address this transition. Des Jarlais, D., Arasteh, K., Perlis, T., Hagan, H., Abdul-Quader, A., Heckathorn, D., McKnight, C., Bramson, H., Nemeth, C., Torian, L., and Friedman, S. Convergence of HIV Seroprevalence Among Injecting and Non-injecting Drug Users in New York City. AIDS, 21(2), pp. 231-235, 2007.

Grandmother and Parent Influences on Child Self-Esteem

This study tests a model of intergenerational influences on childhood self-esteem that proposes paths from grandmothers' drug problems to grandchildren's self-esteem via parents' drug problems and parental adaptive child rearing and from grandmothers' maternal acceptance to grandchildren's self-esteem via parents' unconventionality and adaptive child rearing. This longitudinal study uses data obtained from interviews with a New York City sample of black and Puerto Rican children (N = 149) and 1 of their parents and from mailed questionnaires or comparable interviews with those parents' mothers. Structural equation modeling was used to test the proposed model. The LISREL analysis found that, with 3 exceptions, all of the hypothesized paths were significant. The total effects analysis indicated that parents' adaptive child rearing was the strongest latent construct, a finding that was consistent with this construct's proximal position in the model. This study suggests that mothers' drug problems are not just near-term risks for their children, but also pose long-term risks for their children's future functioning as parents and thereby for their grandchildren. The authors conclude that the relative strength of parents' adaptive child rearing in this intergenerational model indicates that this area should be the focus of therapeutic intervention efforts, but addressing future grandmothers' drug problems may have positive effects on multiple generations. Brook, J., Ning, Y., Balka, E., Brook, D., Lubliner, E., and Rosenberg, G. Grandmother and Parent Influences on Child Self-Esteem. Pediatrics, 119(2), pp. 444-451, 2007.

Women Who Gave Birth as Unmarried Adolescents: Trends in Substance Use from Adolescence to Adulthood

The purpose of this study was to determine whether adolescent childbearing mothers "mature out" of substance use as they transition into adulthood; how their substance use compares to that of typical young women of the same ages; and whether there are different patterns of substance use evident in this vulnerable population. The data come from an ongoing longitudinal study of 240 young women who were unmarried, pregnant, and under age 18 at enrollment. They have been interviewed regularly from pregnancy through 11.5 years postpartum. The data are based on self-reported substance use verified by random urinalysis for drug metabolites. Substance use did not decline during the transition to adulthood nor into early adulthood. With the exception of alcohol, the prevalence of substance use was higher than that of a nationally representative sample of same-aged women. Three distinct patterns of substance use were identified: licit users (cigarettes and/or alcohol), marijuana users, and "hard" drug users. Based on these findings, the authors suggest that clinicians should routinely assess substance use among young mothers who bore children as teenagers, and make referrals for appropriate treatment. Cigarette smoking is especially a cause for concern, given its widespread use and harmful effects for both mothers and their children. Although only a small proportion (about 5%) of young mothers used hard drugs consistently over time, this group will likely require comprehensive interventions that address multiple issues such as mental health and contextual factors to be effective. Future research should address reasons for continued substance use in this population. Gillmore, M., Gilchrist, L., Lee, J., and Oxford, M. Women who Gave Birth as Unmarried Adolescents: Trends in Substance Use from Adolescence to Adulthood. J Adolesc Health, 39(2), pp. 237-243, 2006.

Maternal Cigarette Smoking During Pregnancy and Child Aggressive Behavior

This study's objective was to examine the association between maternal smoking during pregnancy and childhood aggressive behavior in African-American and Puerto Rican children, as well as the relationship between maternal unconventional behavior, low maternal affection, and offspring aggression. Participants consisted of African-American and Puerto Rican children (N = 203; mean age = 8.6, SD = 0.87) and their mothers living in an inner city community. An interview consisting of a structured questionnaire was administered to the mothers and their children. Scales with adequate psychometric properties were adapted from previous validated measures. They included maternal smoking during pregnancy, maternal education, unconventionality, and warmth. Controlling for demographic factors, maternal unconventional behavior, and low maternal warmth, maternal smoking during pregnancy was associated with having offspring who were aggressive. Maternal unconventionality and warmth were independently related to childhood aggression. The authors suggest that although causal limitations are noted, it may be that a decrease in smoking during pregnancy is associated with a reduction in aggression in the offspring. Brook, D., Zhang, C., Rosenberg, G., and Brook, J. Maternal Cigarette Smoking during Pregnancy and Child Aggressive Behavior. Am J Addict, 15(6), pp. 450-456, 2006.

Between Parental and Offspring Psychiatric Disorders

The present study was conducted to investigate the specificity of the association between parental and offspring psychiatric disorders using epidemiological data from a series of parent and offspring interviews. A community-based sample of 593 mothers and their offspring from upstate New York were interviewed during the adolescence and early adulthood of the offspring. The children of parents with generalized anxiety disorder were at specifically elevated risk for anxiety disorders when co-occurring psychiatric disorders were controlled. The associations between parental and offspring antisocial, conduct, depressive, and substance use disorders were characterized by modest specificity. Children of parents with externalizing disorders were nearly as likely to develop internalizing disorders as they were to develop externalizing disorders. Children of parents with internalizing disorders were somewhat, but not significantly, more likely to develop internalizing disorders. These findings support the inference that children of parents with generalized anxiety disorder may be more likely to develop anxiety disorders than they are to develop other psychiatric disorders. However, when co-occurring psychiatric disorders are accounted for, the children of parents with depressive, disruptive, and substance use disorders may be as likely to develop other disorders as they are to develop the same type of disorder that their parents have had. Johnson, J., Cohen, P., Kasen, S., and Brook, J. A Multiwave Multi-Informant Study of the Specificity of the Association between Parental and Offspring Psychiatric Disorders. Compr Psychiatry, 47(3), pp. 169-177, 2006.

Prescription Drug Abuse and Diversion among Adolescents

The aims of this study were to determine the prevalence of medical use of 4 classes of prescription medications relative to nonmedical use (illicit use) and to assess whether gender differences exist in the trading, selling, loaning, or giving away of medications. A Web-based survey was administered to 7th- to 12th-grade students residing in 1 ethnically diverse school district in 2005. There were 1086 secondary students, including 586 girls, 498 boys, 484 black students, and 565 white students. Students were asked about their medical and nonmedical use of sleeping, sedative or anxiety, stimulant, and pain medications. Diversion of prescription medication was assessed by determining who asked the student to divert his or her prescription and who received it. Thirty-six percent of students reported having a recent prescription for 1 of the 4 drug classes. A higher percentage of girls reported giving away their medications than boys (27.5% vs. 17.4%, respectively; chi(2)(1) = 6.7; P = .01); girls were significantly more likely than boys to divert to female friends (64.0% vs. 21.2%, respectively; chi(2)(1) = 17.5; P<.001) whereas boys were more likely than girls to divert to male friends (45.5% vs. 25.6%, respectively; chi(2)(1) = 4.4; P = .04). Ten percent diverted their drugs to parents. These findings provide evidence of the need for physicians to discuss the proper use of prescription medications with their patients and their patients' families. Boyd, C., McCabe, S., Cranford, J., and Young, A. Prescription Drug Abuse and Diversion among Adolescents in a Southeast Michigan School District. Arch Pediatr Adolesc Med, 161(3), pp. 276-281, 2007.

Predictors of Unprotected Sex with Non-cohabitating Primary Partners among Sheltered and Low-income Housed Women in Los Angeles County

This study investigated cross-sectional associations of substance use, relationship abuse and HIV self-protective behavior with unprotected sex among 290 impoverished women with a non-cohabitating primary partner. Unprotected sex was associated with having a physically or psychologically abusive partner among low-income housed women, and having an abusive partner who also drank to intoxication among women living in shelters. Indicators of HIV self-protective behavior were associated with less frequent unprotected sex among sheltered women, even after accounting for abuse and substance use within the relationship. Results suggest the need for HIV-prevention interventions to address the problems of partner substance use and relationship abuse. Tucker, J., Wenzel, S., Elliott, M., and Hambarsoomian, K. Predictors of Unprotected Sex with Non-Cohabitating Primary Partners among Sheltered and Low-Income Housed Women in Los Angeles County. J Health Psychol, 11(5), pp. 697-710, 2006.

Psychological Correlates of Trading Sex for Money among African American Crack Cocaine Smokers

This article compares demographic characteristics, sexual practices, and psychosocial status among 193 African American female crack cocaine users who currently, previously, or never traded sex for money. Current traders were less likely to have a main sexual partner, more likely to have a casual sexual partner, and more likely to smoke larger quantities of crack. There was a significant trend towards current traders reporting lower self-esteem, greater depression and anxiety, poorer decision-making confidence, more hostility, less social conformity, greater risk taking behaviors, and more problems growing up, compared to previous and never traders. These differences suggest that interventions should address self-esteem, risk-taking practices, depression and anxiety as well as other psychosocial factors. Risser, J., Timpson, S., McCurdy, S., Ross, M., and Williams, M. Psychological Correlates of Trading Sex for Money among African American Crack Cocaine Smokers. Am J Drug Alcohol Abuse, 32(4), pp. 645-653, 2006.

Assortative Mating Explains Spousal Similarity in Cigarette and Alcohol Use and Dependence

Non-random mating affects population variation for substance use and dependence. Developmentally, mate selection leading to positive spousal correlations for genetic similarity may result in increased risk for substance use and misuse in offspring. Mate selection varies by cohort and thus, assortative mating in one generation may produce marked changes in rates of substance use in the next. This team of researchers used data from female twins and their male spouses to clarify the mechanisms contributing to spousal similarity for cigarette smoking and alcohol consumption. They found that assortative mating significantly influenced regular smoking, regular alcohol use, nicotine dependence and alcohol dependence. The bivariate models for cigarette smoking and alcohol consumption also highlighted the importance of primary assortative mating on all stages of cigarette smoking and alcohol consumption, with additional evidence for assortative mating across the two stages of alcohol consumption. They concluded that women who regularly used, and subsequently were dependent on cigarettes or alcohol were more likely to marry men with similar behaviors. After mate selection had occurred, one partner's cigarette or alcohol involvement did not significantly modify the other partner's involvement with these psychoactive substances. Agrawal, A., Heath, A., Grant, J., Pergadia, M., Statham, D., Bucholz, K., Martin, N., and Madden, P. Assortative Mating for Cigarette Smoking and for Alcohol Consumption in Female Australian Twins and their Spouses. Behav Genet, 36(4), pp. 553-566, 2006.

Prevention Research

Multidimensional Treatment Foster Care For Girls in the Juvenile Justice System: Two Year Follow-Up of a Randomized Clinical Trial

This study is a 2-year follow-up of girls with serious and chronic delinquency who were enrolled in a randomized clinical trial conducted from 1997 to 2002 comparing multidimensional treatment foster care (MTFC) and group care (N = 81). Girls were referred by juvenile court judges and had an average of over 11 criminal referrals when they entered the study. A latent variable analysis of covariance model controlling for initial status demonstrated maintenance of effects for MTFC in preventing delinquency at the 2-year assessment, as measured by days in locked settings, number of criminal referrals, and self-reported delinquency. A latent variable growth model focusing on variance in individual trajectories across the course of the study also demonstrated the efficacy of MTFC. Older girls exhibited less delinquency over time relative to younger girls in both conditions. Implications for gender-sensitive programming for youths referred from juvenile justice are discussed. Chamberlain, P., Leve, L., and Degarmo, D. Multidimensional Treatment Foster Care for Girls in the Juvenile Justice System: 2-Year Follow-up of a Randomized Clinical Trial. J Consult Clin Psychol, 75(1), pp. 187-193, 2007.

Neighborhood Effects on Prevention Program Efficacy

This study examines how neighborhood characteristics affect program efficacy through an analysis of data from a randomized prevention trial. The prevention program, called "Keepin' it REAL", was administered to a predominantly Mexican American sample of 4,622 middle school students in Phoenix, Arizona, beginning in 1998. The program was designed to extend evidence-based resistance and life-skills prevention approaches to incorporate ethnically appropriate traditional values and practices that promote protection against drug use. Thirty-five middle schools were randomized to one of two culturally grounded prevention conditions or a control condition. Prior research supports the overall efficacy of the prevention program. However, among less linguistically accultured Latinos, living in poorer neighborhoods and in single-mother families decreased program effectiveness in reducing alcohol use. High neighborhood immigrant composition increased program effectiveness. Unexpectedly, the program was also more effective in neighborhoods with higher rates of crime. Yabiku, S., Kulis, S., Marsiglia, F.F., Lewin, B., Nieri, T., and Hussaini, S. Neighborhood Effects on the Efficacy of a Program to Prevent Youth Alcohol Use. Subst Use Misuse, 42, pp. 65-87, 2007.

Adolescent Predictors of Emerging Adult Sexual Patterns

This study estimates the percentages of young adults who fall into three groups based on the context of sexual transition: (1) those who had vaginal intercourse before marriage (Premaritals), (2) those who postponed sex until after marriage (Postponers), and (3) those who have never had vaginal intercourse (Virgins). The second purpose was to determine adolescent biopsychosocial factors that predict membership in these adult groups. Analyses are based on 11,407 respondents ages 18-27 years who participated in Waves I and III of the National Longitudinal Study of Adolescent Health. Adolescent indicators reflecting sociodemographic, biosocial, experiential, and contextual factors were used to predict young adult sexual status using multinomial logistic regression models. About 8% of the sample were virgins and 2% were virgins until marriage. Almost 90% had sex before marriage (Premaritals--referent group). Most predictors of status were similar for males and females. Compared with Premaritals, Virgins were younger, non-Black, not advanced in physical maturity relative to peers in adolescence, had higher body mass indexes, were more religious, and perceived parental disapproval of sex during adolescence. Postponers were also more religious than Premaritals but were older. Female Postponers were non-Black and perceived parental disapproval of sex during adolescence. Male Postponers were less likely to have same-gender attractions or no sexual attractions. Findings document premarital sexual activity as the almost universal sexual trajectory into young adulthood for these cohorts and underscore the roles of biosocial factors and conventional institutions in emerging sexual patterns. Halpern, C., Waller, M., Spriggs, A., and Hallfors, D. Adolescent Predictors of Emerging Adult Sexual Patterns. J Adolesc Health, 39(6), pp. e1-e10, 2006.

Drug Abuse Risk and Protective Factors among Black Urban Adolescent Girls: A Group-randomized Trial of Computer-delivered Mother-daughter Intervention

A group-randomized design tested a mother-daughter intervention in which researchers aimed to increase protective factors in a community sample of Black urban adolescent girls. Girls and their mothers at 2 community agencies were pretested and, by agency, were randomized to either an intervention arm or a control arm. Intervention arm girls and their mothers received a program for improving mother- daughter rapport. Posttest data collected 3 weeks after program delivery revealed that intervention arm mothers and daughters improved more than did control arm mothers and daughters on measures of communication and closeness. At 3-month follow-up, intervention arm mothers, relative to control arm mothers, continued to report better communication with and closeness to their daughters. Girls and mothers in the intervention arm rated the computer program favorably on parameters of enjoyment, comfort, relevance, usefulness of information, improvements to their relationship with one another, and whether they would recommend the computer program to friends. Schinke, S., Di Noia, J., Schwinn, T., and Cole, K. Drug Abuse Risk and Protective Factors among Black Urban Adolescent Girls: A Group-Randomized Trial of Computer-Delivered Mother-Daughter Intervention. Psychol Addict Behav, 20(4), pp. 496-500, 2006.

Perceived Smoking Environment and Smoking Initiation Among Multi-ethnic Urban Girls

The purpose of this study was to examine associations between the perceived smoking environment and smoking initiation among urban multi-ethnic adolescent girls in New York City. Self-report surveys completed in grades 7, 8, and 9 assessed girls '' (n = 858) smoking initiation, and perceived smoking environment (family smoking, friends' smoking, smoking norms, and cigarette availability). Carbon monoxide breath samples were collected from girls using a variation of the bogus pipeline procedure. Differences were found in smoking prevalence with white girls reporting the highest prevalence of smoking at baseline and greatest increase in smoking prevalence from seventh to eighth grade. Black girls reported an initial increase in smoking prevalence from seventh to eighth grade followed by a decrease from eighth to ninth grade. Family smoking, friends' smoking, smoking norms, and cigarette availability were all associated with smoking initiation at eighth grade but only friends' smoking was associated with smoking initiation at ninth grade. Few ethnic differences were found in risk factors at baseline and racial/ethnic group did not modify associations between risk and smoking initiation. Urban adolescent girls of different racial/ethnic backgrounds had similar perceptions of the smoking environment. Despite the similarity of risk factors across racial/ethnic groups, urban white girls are at increased risk to initiate smoking. Preventive interventions that target girls' perceived smoking environment during early adolescence should be effective across ethnic groups. Nichols, T., Birnbaum, A., Birnel, S., and Botvin, G. Perceived Smoking Environment and Smoking Initiation among Multi-Ethnic Urban Girls. J Adolesc Health, 38(4), pp. 369-375, 2006.

Perceived Physical Maturity, Age of Romantic Partner, and Adolescent Risk Behavior

Early pubertal timing and advanced physical maturity for age confer elevated risk for problem behaviors for both boys and girls. However, examinations of possible biological and social mediators have been limited. Using more than 4,000 adolescents under age 15 who participated in Waves I and II of the National Longitudinal Study of Adolescent Health (Add Health), authors examined the relationship between perceived physical maturity and membership in risk behavior clusters, and tested whether having a romantic partner mediates the maturity/risk behavior relationship. Results of multinomial regression models indicated that for both boys and girls, advanced physical maturity was associated with membership in higher risk clusters, and that having a romantic partner plays an important mediating role in this association. For females, the additional impact of having an older partner, versus any partner at all, was substantial and particularly important for the highest risk clusters. The role of partner age could not be tested for males. Because romantic partners elevate risk for young adolescent males and females, there is a need to identify and understand facets and developmental functions of adolescent romantic relationships that play a role in substance use and sexual decisions. Halpern, C., Kaestle, C., and Hallfors, D. Perceived Physical Maturity, Age of Romantic Partner, and Adolescent Risk Behavior. Prevention Science, 8(1), pp. 1-10, 2006.

Adolescent Girls Offending and Health-Risking Sexual Behavior: The Predictive Role of Trauma

Several studies have highlighted high levels of risk for girls who have been exposed to traumatic experiences, but little is known about the exact relationship between traumatic experiences and problems with delinquency and health-risking sexual behavior (e.g., precipitory and/or exacerbatory roles). However, numerous short- and long-term detrimental effects have been linked to trauma, delinquency, and health-risking sexual behavior. The utility of diagnostic and experiential trauma measures in predicting the greatest risk for poor outcomes for delinquent girls was examined in this study. Results indicate that the experiential measures of trauma (cumulative and composite trauma scores) significantly predicted adolescent offending and adolescent health-risking sexual behavior, whereas the diagnostic measures of trauma (full and partial diagnostic criteria) did not. Smith, D., Leve, L.D., and Chamberlain, P. Adolescent Girls' Offending and Health-Risking Sexual Behavior: The Predictive Role of Trauma. Child Maltreat, 11, pp. 346-353, 2006.

The Relationship between Cultural Practices and Commonly Used Markers of Acculturation

The current study was conducted to ascertain the validity of two commonly used markers of acculturation (nativity and years in the receiving culture). Relationships between these markers and a bidimensional measure of acculturation were examined in a convenience sample of Hispanic immigrant adolescents and their caregivers in Miami. Nativity was examined using adolescent-reported data; approximately half of the youth were U.S.-born and half foreign-born, but all of the caregivers were foreign-born. Years in the receiving culture was examined using both adolescent and caregiver data. Results indicated that nativity was significantly associated with adoption of receiving-culture practices, with a small to moderate effect size. Years in the receiving culture was significantly associated with adoption of receiving-culture practices only for adolescent girls and for female caregivers who immigrated as youth. Neither nativity nor years in the receiving culture explained even moderate amounts of variance in retention or loss of culture-of-origin practices. Schwartz, S.J., Pantin, H. and Sullivan, S. Nativity and Years in the Receiving Culture as Markers of Acculturation in Ethnic Enclaves. J Cross Cult Psychol, 37(3), pp. 345-353, 2006.

Research on the Caretaking of Children of Incarcerated Parents: Findings and Their Service Delivery Implications

This paper reviews research findings on caretaking-related problems associated with the absence of parents from the home following incarceration. It focuses on the impact of incarceration on the welfare and adjustment of urban African American children and on the assumption of caretaking responsibilities by other caretakers, principally maternal grandmothers. Noting the complex situational difficulties involved and the potential burdens associated with surrogate parenting in general, and with this population in particular, the service-provider implications of this parenting arrangement are considered in this review. Findings indicate that problems associated with incarceration of parents tend to be intergenerational and vary considerably in complexity and severity. To the extent that they impact the children involved, these issues should be addressed in coordinated service delivery focusing on prevention. Hanlon, T.E., Carswell, S.B., and Rose, M. Research on the Caretaking of Children of Incarcerated Parents: Findings and Their Service Delivery Implications. Child and Youth Services Review, 29(3), pp. 348-362, 2006.

Sex Differences in Overt Aggression and Delinquency

Given the recent debate over whether differential pathways to overt aggression and delinquency exist between boys and girls, this study examined sex differences in overt aggressive and delinquent acts along with potential differences in precursors (anger, self-control, family disruption) to antisocial behaviors among a sample of urban minority adolescents (N = 1559). Overall the sample was 54% girls, 47% African American, 27% Latino/Hispanic, 5% Asian American, 7% Caucasian, and 13% biracial or other race/ethnicity. Almost all of the students (85%) attended public schools. Using a longitudinal design with data from 6th to 7th grade, results showed that girls had greater increases in rates of aggression relative to boys. Delinquency increased over time for both boys and girls, with boys consistently engaging in more delinquency. Girls and boys did not differ on the level of risk factors experienced except for a greater increase in anger over time for girls relative to boys. Across sex, anger and self-control predicted increases in both overt aggression and delinquency; family disruption also predicted increases in delinquency. Implications for subsequent studies on developmental process and preventive interventions are discussed. Nichols, T.R., Graber, J.A., Brooks-Gunn, J., and Botvin, G.J. Sex Differences in Overt Aggression and Delinquency among Urban Minority Middle School Students. Applied Developmental Psychology, 27, pp. 78-91, 2006.

Latino Students Perceptions of School Environment

This study describes results from an investigation of Latino students attending a Hispanic Education Summit (HES) in North Carolina. Findings from data gathered from 275 middle and high school students are presented (n= 142 female; n = 121 male). Self-report data assessed level of acculturation, as well as students' perceptions with regard to a variety of issues, including school programs, barriers to participation in programs, problems in the school environment, and academic aspirations. Results revealed that students reported few perceived barriers to school and aspirations. However, there was a significant relationship between acculturation level and the frequency with which students reported selected barriers and future life goals. Results indicated that low-acculturated students more often reported language-related problems as barriers to school involvement. Also reported by those students in the low-acculturation group were perceived discrimination, parental lack of time as a barrier, and low or no community involvement. These results indicate that high acculturation provides some students with a greater sense of belonging to their community and fewer barriers, including perceived discrimination. Gender differences were found with regard to acculturation level, perception of barriers, and academic aspirations. Specifically, with the exception of lack of interest, females reported more barriers than males and were rated as low in acculturation more frequently than males. Females also reported higher levels of academic aspirations, desires to do well in school, and a desire to be successful more frequently than males. Being female seems to promote resiliency with regard to academic aspirations for Latinos/as. These results lend support to previous research findings that females' higher value of academic achievement is related to being less acculturated or less vulnerable to assimilation of adversarial attitudes and behaviors responsible for academic failure. Overall this study suggests that there is not a linear relationship between acculturation and academic aspirations but, rather, this relationship may be mediated by a variety of factors including students' beliefs and attitudes, family cohesion, parental monitoring, parental attitudes concerning education, cultural identity, perceived stereotypes, and discrimination. Future studies examining acculturation would benefit from a framework that clearly captures the complex dynamics of acculturation and how this phenomenon affects academic achievement and the overall adjustment of Latino immigrant students into their environment. Valencia, E.Y., and Johnson, V. Latino Students in North Carolina: Acculturation, Perceptions of School Environment, and Academic Aspirations. Hispanic Journal of Behavioral Sciences, 28(3), pp. 350-367, 2006.

Adding MEMS Feedback to Behavioral Smoking Cessation Therapy Increases Compliance with Bupropion: A Replication and Extension Study

This study was conducted to replicate and extend initial positive findings on the usefulness of a Medication Event Monitoring System (MEMS) to assess pill-taking behavior and enhance compliance with Bupropion for smoking cessation. Participants were 55 women aged 20-65, smoking a minimum of 10 cigarettes per day. All participants received MEMS bottles containing Bupropion-SR (150 mg) to be taken twice daily for 7 weeks, then randomized into one of two conditions, Usual Care (UC) or Enhanced Therapy (ET). In the UC condition, participants received individual cognitive behavioral therapy for smoking cessation. In the ET condition, weekly smoking cessation therapy sessions included additional 10 min of MEMS feedback and counseling using CBT techniques. Compliance outcomes included total doses taken and number of doses taken within the prescribed time interval. Results indicated significantly higher compliance over time for the Enhanced Therapy group. Smoking abstinence rates did not differ between the two groups, but pooled sample analysis showed a significant association between level of medication compliance and abstinence status at treatment weeks 3 and 6. Findings recommend incorporating MEMS-based compliance interventions into smoking pharmacotherapy trials. Mooney, M.E., Sayre, S.L., Hokanson, P.S., Stotts, A.L., and Schmitz, J.M., Addictive Behaviors, 32, pp. 875-880, 2007.

Attrition in a Multi-Component Smoking Cessation Study for Females

Attrition is a major challenge faced by researchers when implementing clinical trials. Investigators conducted this study to determine which baseline smoking-related, demographic and psychological participant characteristics were associated with attrition. Data were from a clinical trial evaluating exercise as an adjunctive treatment for nicotine gum among female smokers (N=246). There were a number of significant demographic predictors of attrition. Participants with at least one child living at home were at increased risk of both early and late dropout. Non-Whites were at increased risk of early dropout, while not having a college degree put one at increased risk of late dropout. Age was found to be a protective factor in that the older a participant was, the less likely she was to drop out in the early stages of the trial. With respect to psychological variables, weight concerns and guilt increased risk of attrition. In terms of smoking-related variables, mean cigarettes per day was not a significant predictor of attrition, although length of longest prior quit attempt was a significant predictor of early dropout when age was removed from the regression. Leeman, R.F., Quiles, Z.N., Molinelli, L.A., Medaglia Terwal, D., Nordstrom, B.L., Garvey, A.J. and Kinnunen, T. Tobacco Induced Diseases, 3, pp. 59-71, 2006.

Research on Pharmacotherapies for Drug Abuse

Mood Disorders Affect Drug Treatment Success of Drug-dependent Pregnant Women

This study examined the impact of co-occurring Axis I disorders on drug treatment outcomes of drug-dependent pregnant women. Participants (N =106) were women who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for opioid dependence and were receiving methadone. Based on DSM-IV Axis I criteria, participants were categorized into three groups: (1) absence of mood/anxiety disorder (ND, n = 29), (2) primary mood disorder (MD, n = 39), or (3) primary anxiety disorder (AD, n = 38). Demographically, the groups were similar. The MD group was significantly more likely to be positive for drugs while in treatment compared with both the ND and AD groups. The MD and AD groups had more psychosocial impairment and higher incidence of suicidal ideation compared with the ND group. Interestingly, the AD group spent more days in treatment compared with the ND or MD group. These findings highlight the need to treat co-occurring Axis I disorders, particularly given the higher relapse risk for those with mood disorders. Fitzsimons, H.E., Tuten, M., Vaidya, V., and Jones, HE. Mood Disorders Affect Drug Treatment Success of drug-dependent pregnant women. J Subst Abuse Treat. 32(1), pp. 19-25, 2007. Epub 2006 October 13, 2006.

Research on Medical Consequences of Drug Abuse And Co-Occurring Infections (HIV/AIDS, HCV)

Needle Exchange Program Utilization and Entry into Drug User Treatment: Is There a Long-Term Connection in Baltimore, Maryland?

This study examined the relationship between Needle Exchange Program (NEP) utilization and treatment entry in Baltimore, Maryland. The sample was composed of 440 drug injectors with disadvantaged backgrounds. Face-to-face interviews, focusing on HIV risk behaviors, drug use, and health, were conducted between June 1997 and June 2002. Multivariate logistic analyses revealed that entering treatment was associated with NEP utilization, being female, and being HIV-positive. Cocaine sniffers/snorters were less likely to enter treatment. These findings highlight the importance of NEPs in linking injectors to treatment. They also suggest that treatment programs should be prepared and capable of addressing co-occurring problems, like HIV and mental illness. Study limitations are noted. Latkin, C., Davey, M., and Hua, W. Needle Exchange Program Utilization and Entry into Drug User Treatment: Is There a Long-Term Connection in Baltimore, Maryland? Subst Use Misuse, 41(14), pp. 1991-2001, 2006.

Clinical Trials Network Research

Substance Abuse Treatment Entry, Retention, and Outcome in Women: A Review of the Literature

A search of the English language literature from 1975 to 2005 using Medline and PsycInfo databases found 280 relevant articles. Ninety percent of the studies investigating gender differences in substance abuse treatment outcomes were published since 1990, and of those, over 40% were published since the year 2000. Only 11.8% of these studies were randomized clinical trials. A convergence of evidence suggests that women with substance use disorders are less likely, over the lifetime, to enter treatment compared to their male counterparts. Once in treatment, however, gender is not a significant predictor of treatment retention, completion, or outcome. Gender-specific predictors of outcome do exist, and individual characteristics and treatment approaches can differentially affect outcomes by gender. While women-only treatment is not necessarily more effective than mixed-gender treatment, some greater effectiveness has been demonstrated by treatments that address problems more common to substance-abusing women or that are designed for specific subgroups of this population. There is a need to develop and test effective treatments for specific subgroups such as older women with substance use disorders, as well as those with co-occurring substance use and psychiatric disorders such as eating disorders. Future research on effectiveness and cost-effectiveness of gender-specific versus standard treatments, as well as identification of the characteristics of women and men who can benefit from mixed-gender versus single-gender treatments, would advance the field. Greenfield, S.F., Brooks, A.J., Gordon, S.M., Green, C.A., Kropp, F., McHugh, R.K., Lincoln, M., Hien, D., and Miele, G.M. Substance Abuse Treatment Entry, Retention, and Outcome in Women: A Review of the Literature. Drug Alcohol Depend., 86(1), pp. 1-21, 2007. Epub June 8, 2006.

International Research

Naltrexone With or Without Fluoxetine for Preventing Relapse to Heroin Addiction in St. Petersburg, Russia

INVEST Fellow: Anton Bespalov, Russia, 1994-1995
This randomized placebo-controlled trial tested the efficacy of oral naltrexone with or without fluoxetine for preventing relapse to heroin addiction and for reducing HIV risk, psychiatric symptoms, and outcome. All patients received drug counseling with parental or significant-other involvement to encourage adherence. Patients totaling 414 were approached, 343 gave informed consent, and 280 were randomized (mean age, 23.6 +/- 0.4 years). At 6 months, two to three times as many naltrexone patients as naltrexone placebo patients remained in treatment and had not relapsed, odds ratio (OR) = 3.5 (1.96-6.12), p < .0001. Overall, adding fluoxetine did not improve outcomes, OR = 1.35 (0.68-2.66), p = .49; however, women receiving naltrexone and fluoxetine showed a trend toward a statistically significant advantage when compared to women receiving naltrexone and fluoxetine placebo, OR = 2.4 (0.88-6.59), p = .08. HIV risk, psychiatric symptoms, and overall adjustment were markedly improved among all patients who remained on treatment and did not relapse, regardless of group assignment. More widespread use of naltrexone could be an important addition to addiction treatment and HIV prevention in Russia. Krupitsky, E.M., Zvartau, E.E., Masalov, D.V., Tsoy, M.V., Burakov, A.M., Egorova, V.Y., Didenko, T.Y., Romanova, T.N., Ivanova, E.B., Bespalov, A.Y., Verbitskaya, E.V., Neznanov, N.G., Grinenko, A.Y., O'Brien, C.P. and Woody, G.E. J Subst Abuse Treat., 31(4), pp. 319-328, 2006. Epub July 24, 2006.

Former Hubert H. Humphrey Drug Abuse Research Fellows

Predictors of HIV Sero-status Among Drug Injectors at Three Ukraine Sites

HHH Fellow: Sergey Dvoryak, Ukraine, 1999-2000
The objective of this study was to assess the HIV serostatus of injection drug users (IDU) in Ukraine, as well as associations between serostatus and selected demographic and risk factors. IDU were recruited from the streets in Kiev, Odessa and Makeevka/Donesk. Participants were interviewed using an HIV risk behavior assessment and tested for HIV with a finger-stick rapid test. Multiple logistic regression was used to identify determinants of HIV infection. Of the 891 IDUs surveyed, one-third came from each site and 22% were female. Their mean age was 29 years and on average they had been injecting for slightly more than 10 years. Seven hundred and seventy-eight of the total sample did not know their HIV status when first interviewed; they are the participants in this investigation. Overall, 33% tested positive for HIV, including 34% in Kiev, 51% in Odessa and 17% in Makeevka/Donesk. Independent predictors of HIV included injecting a sedative/opiate mixture, female sex, having sex with a person who was HIV positive or whose HIV status was unknown and injecting daily. HIV-negative IDU were significantly younger than those infected, they were more likely to be from Makeevka/Donesk and they were more likely to have been sexually active. Rates of HIV infection among IDU vary considerably across Ukraine, although even in the site with the lowest rate nearly one in five was infected. The extent of drug and sex-related risk behaviors calls for interventions to reduce the spread of HIV and other infectious diseases. Booth, R.E., Kwiatkowski, C.F., Brewster, J.T., Sinitsyna, L. and Dvoryak, S. AIDS. 20(17), pp. 2217-2223, 2006.

Obstetric and Neonatal Outcomes in Women Who Live in an Urban Resettlement Area of Delhi, India: A Cohort Study

HHH Fellow: Arun Kumar Sharma, India, 2004-2005
The aim of the present research was to study the pregnancy outcome, namely mode and place of delivery, attendant at birth and perinatal mortality in an urban resettlement area of Delhi, India, and to determine factors that affect the outcome. Methods: All the pregnant women (n = 909) in the area were enrolled and followed until 7 days after delivery. The authors calculated the crude and adjusted odds ratios for predictors of pregnancy related obstetric and neonatal outcomes, using logistic regression analysis. A total of 884 (97.3%) women could be followed up. Approximately two-thirds of deliveries took place at home. Primigravida, more educated mothers and mothers with non-cephalic presentation or complications were more likely to deliver in a health facility (P < 0.05). Most deliveries (97%) were vaginal, 2.5% were cesarean and 0.5% forceps deliveries. Primigravida mothers, mothers with short stature, mothers with non-cephalic presentation or complications had cesarean and forceps delivery more often (P < 0.05). A perinatal mortality rate of 74.5 per 1000 live births was observed. Presentation of the fetus and complications in the mother remained important factors. The authors conclude that the majority of deliveries in the under-privileged sections in urban Delhi take place at home and the perinatal mortality remains high. Chhabra, P., Sharma, A.K. and Tupil, K.A. J Obstet Gynaecol Res. 32(6), pp. 567-573, 2006.