Director's Report to Council - Research Findings Excerpts

September, 2006

Basic Neurosciences Research

Uterine Anandamide Levels and Pregnancy

Anandamide, an endogenous cannabinoid, plays an important role in implantation of the fertilized ovum. Uterine implantation requires a reciprocal interaction between a blastocyst and a receptive uterus. NIDA supported research in mice has illuminated anandamide's role in mediating this interaction. During early pregnancy, anandamide is at lower levels in both the receptive uterus and at the implantation site. However, the mechanism by which differential uterine anandamide gradients are established is not clearly understood. NIDA researchers Dr. Dey and his associates have recently demonstrated that uterine anandamide levels are primarily regulated by Nape-Pld, the gene encoding N-acylphosphatidyl-ethanolamine-hydrolyzing phospholipase D (NAPE-PLD) that generates anandamide. This suggests that aberrant uterine NAPE-PLD activity may cause implantation failure or defective implantation. These findings may be relevant to human abuse of cannabinoids, since elevated anandamide is associated with spontaneous pregnancy failure. Guo, Y., Wang, H., Okamoto, Y., Ueda, N., Kingsley, P.J., Marnett, L.J., Schmid, H.H.O., Das, S.K., and Dey S.K., N-Acylphosphatidylethanolamine-hydrolyzing Phospholipase D Is an Important Determinant of Uterine Anandamide Levels during Implantation. Journal of Biological Chemistry, 280, pp. 23429-23432, 2005.

Basic Behavioral Research

Rats Given Prolonged Access to Nicotine Display Age, But Not Gender, Differences

In a recent study by NIDA grantee Dr. B. M. Sharp, adolescent rats were housed in operant chambers allowing 23 hr access to self-administered nicotine via lever-pressing on one of two available levers (one active, one inactive). During acquisition of self-administration behavior, males displayed greater variation in responding on the active lever, but there were no significant gender differences in acquisition. Thus, both genders rapidly learned to self-administer nicotine and there were no gender differences in sensitivity to dose. However, adult female rats acquired nicotine self-administration at a slower rate than adolescent females and the adult females self-administered significantly less drug than their adolescent counterparts. (Adult male rats were not tested in this phase of the study). The procedure used by Dr. Sharp and his colleagues differs from those previously employed to establish nicotine self-administration in that animals were not food restricted (which may affect growth, especially in animals that are continuing to develop). This experimental paradigm more closely mimics the conditions under which humans self-administer nicotine. Additionally, since the "adolescent" phase of development is short in rats, this model allows for rapid acquisition of the self-administration behavior for study. Chen, H., Matta, S.G. and Sharp, B.M. Acquisition of Nicotine Self-Administration in Adolescent Rats Given Prolonged Access to the Drug. Neuropsychopharmacology, 32(3), 700-709, 2007.

Sex Difference in Visual Cue Enhancement of Nicotine Reinforcement

Human laboratory studies have shown that sensitivity to nicotine is lower in females than in males but that sensitivity to nonpharmacological stimuli associated with cigarette use is higher in females than in males. The importance of stimuli associated with nicotine to the reinforcing effects of nicotine has been established by researchers at the University of Pittsburg. That research was conducted previously in male rats and the researchers have now extended this work to female rats and have observed sex differences in this effect. Following acquisition of i.v. self-administration of either 0.03, 0.06, or 0.15 mg/kg nicotine and stable responding, nicotine deliveries were subsequently paired with a visual cue. In the absence of the visual cue, nicotine alone functioned as a reinforcer in both males and females at the .06 and 0.15 mg/kg doses, but not the 0.03 mg/kg dose. Addition of the visual cue produced a robust enhancement of nicotine reinforcement (response rate, infusions earned, and nicotine intake) in both males and females at the lower doses, and this enhancement at the 0.06 mg/kg dose was greater in females than males. The authors suggest possible explanations for this greater enhancement in females, including a greater synergistic interaction between nicotine and the visual cue and sex differences in limbic responses to nicotine and nicotine cues. This sex difference in visual cue enhancement of nicotine reinforcement could have implications for the use of pharmacologic versus non-pharmacologic strategies for nicotine cessation in males versus females. Chaudhri, N., Cagguila, A.R., Donny, E.C., Booth, S., Gharib, M.A., Craven, L.A., Shannon, S.A., Alan, F.S., and Perkins, K.A. Sex Differences in the Contribution of Nicotine and Nonpharmacological Stimuli to Nicotine Self-Administration in Rats. Psychopharmacology, 180, pp. 258-266, 2005.

Behavioral and Brain Development Research

Prenatal Smoking and Disruptive Behavior in Early Development

An association between prenatal smoking and disruptive behaviors in children has been documented in the research literature, but little is known about the possible emergence of these behaviors in early development. Dr. Lauren Wakschlag and colleagues investigated very early precursors to disruptive behavior problems, examining behaviors of prenatally-exposed children and non-exposed children at 12, 18, and 24 months of age. Maternal reports were recorded at 12, 18, and 24 months, and behavioral observations were carried out at 24 months. Analyses took into account multiple covariates (e.g., other substances used during pregnancy, parenting practices, and cumulative family risk, which included demographic, psychiatric, and psychosocial factors). The investigators report that exposed toddlers exhibited higher levels of behavior problems from 12 to 24 months, and that virtually all of the toddlers with clinically significant problems at age 2 years had been exposed. They also report that exposure was associated with social, rather than emotional aspects of early problem behaviors. Those exposed were more likely to exhibit stubbornly defiant and aggressive behavior, and lower social engagement. The two groups did not differ on difficulty regulating negative emotion. While pointing out that the data do not prove a causal relationship, the researchers do note that the findings allow generating ideas concerning which areas of the brain may be affected by exposure, and highlight a potential window of opportunity for early interventions aimed at altering disruptive behavior pathways before they become serious clinical patterns. Wakschlag, L.S., Leventhal, B.L., Pine, D.S., Pickett, K.E., and Carter, A.S. Elucidating Early Mechanisms of Developmental Psychopathology: The Case of Prenatal Smoking and Disruptive Behavior. Child Development, 77, pp. 893-906, 2006.

Postnatal Cocaine Use and Parental Behavior During Mother-Infant Interactions

Within a broader conceptual model for maternal behavior among polydrug cocaine-using mothers, this study investigated the relationship between maternal cocaine use (prenatal and postnatal) and maternal behavior during mother-infant interactions. Specifically, behaviors were observed in a feeding context between 4 and 8 weeks of infant age. The categories of maternal behaviors analyzed were maternal insensitivity (e.g., position without support, misses infant cues) and maternal warmth (e.g., talks to infant, pleasure toward infant). The conceptual model used by Dr. Eiden and her colleagues included prenatal and postnatal polydrug use, maternal psychopathology, maternal childhood history, and infant birth weight. There were no group differences in maternal warmth or between maternal psychological functioning and maternal warmth. Results of conceptual model testing indicated that only postnatal cocaine use was a significant and unique predictor of maternal insensitivity during feeding. Maternal depression/anxiety was marginally associated with maternal insensitivity. The investigators point out that the results add to a growing body of evidence that indicates the importance of examining postnatal caregiving as a predictor of child outcome among children exposed to substances in the prenatal period. Eiden, R.D., Stevens, A., Schuetze, P., and Dombkowski, L.E. A Conceptual Model for Maternal Behavior Among Polydrug Cocaine-Using Mothers: The Role of Postnatal Cocaine Use and Maternal Depression. Psychology of Addictive Behaviors, 20, pp. 1-10, 2006.

Prediction of Parenting Stress and Perception of Infant Temperament

This investigation was conducted from the perspective that prenatal cocaine exposure is a marker of developmental risk, and the risk may involve a range of social, environmental, and biological factors. The researchers note that two factors likely to mark heightened risk are the degree to which mothers perceive their parental role as highly stressful and the degree to which they perceive their infant as temperamentally difficult. Therefore, the goal of this study was to understand processes that may heighten or attenuate levels of parenting stress and perceptions of infant temperament for infants prenatally-exposed to cocaine. Neonatal behavior, infant temperament, parenting stress, and maternal psychopathology were assessed in a large sample of mother-infant dyads (394 prenatally-exposed infants and 590 comparison infants). The sample was drawn from the multi-site longitudinal Maternal Lifestyle Study, and infants were selected for inclusion if they were in the care of their biological mother. Neonatal behavior was observed at 1 month corrected age, and other assessments were carried out at 4 months corrected age. Results indicated that neonatal behavioral characteristics and certain maternal psychological characteristics interacted to predict maternal ratings of infant temperament, and maternal self-reports of parenting stress. Results were not related to drug exposure history. The researchers conclude that for mothers of at risk infants, with or without prenatal cocaine exposure, psychological distress affects the degree to which infant behavioral characteristics are experienced as stressful or difficult. The researchers also discuss implications of the findings for interventions. Sheinkopf, S.J., Lester, B.M., LaGasse. L.L., et al. Interactions Between Maternal Characteristics and Neonatal Behavior in the Prediction of Parenting Stress and Perception of Infant Temperament. Journal of Pediatric Psychology, 31, pp. 27-40, 2006.

Predicting Caregiver-Reported Behavior Problems in Cocaine-Exposed Children

The purpose of this study was to investigate predictors of caregiver-reported behavior problems in a sample of 3-year-old children. The children were either in a group exposed to cocaine prenatally, or in a comparison group. Two measures of behavior problems were used: the Conners' Parent Report Scale, and the Eyberg Child Behavior Inventory. The Conners' Scale has scales assessing conduct problems and impulsive/hyperactive behaviors. The Eyberg Inventory was designed to assess disruptive behaviors, especially those associated with oppositional-defiant and conduct disorders. Concurrent maternal/caregiver depression as measured by the Center for Epidemiologic Studies-Depression (CES-D) Scale was the only significant predictor of reported child behavior problems in a model that included prenatal drug exposure, child sex, and the quality of the child's environment. Comparisons involving maternal and non-maternal caregivers relative to depression scores and child behavior ratings are also provided in the report. The researchers discuss implications of the findings for clinical care and for future research on behavioral functioning of prenatally exposed children. Warner, T.D., Behnke, M., Hou, W., et al. Predicting Caregiver-Reported Behavior Problems in Cocaine-Exposed Children at 3 Years. Journal of Developmental and Behavioral Pediatrics, 27, pp. 83-92, 2006.

Behavioral Reactivity and Regulation in Preschoolers Prenatally-Exposed to Cocaine

Based on concerns in the literature that prenatal exposure to cocaine may increase risk for problems related to reactivity and regulation in infancy and childhood, this study examined whether cocaine-exposed children show such difficulties during the preschool period, a time of increased social and cognitive demands, and a time of rapid changes in reactivity and regulation. The procedure involved observing reactivity and regulation during a frustrating problem-solving task at 4.5 years of age. Frustration reactivity was measured by latency to show frustration and number of disruptive behaviors. Regulation was measured by latency to approach and attempt the problem-solving task and by the number of problem-solving behaviors. Results indicated that cocaine-exposed children took longer to engage in the problem-solving task, and that cocaine-exposed boys showed the most difficulties. The cocaine-exposed boys expressed frustration more rapidly and had a larger number of disruptive behaviors compared to non-exposed children and cocaine-exposed girls. The researchers make note that the effect sizes were relatively small, and feel that the results indicate both resilience and vulnerabilities. They also comment on implications for intervention and prevention. Dennis, T., Bendersky, M., Ramsay, D., and Lewis, M. Reactivity and Regulation in Children Prenatally Exposed to Cocaine. Developmental Psychology, 42, pp. 688-697, 2006.

Neuroimaging and Prenatal Drug Exposure

This article is a summary report of a symposium that brought together researchers who are investigating effects of prenatal substance abuse in humans and primates, and who are utilizing neuroimaging techniques in their studies. The purpose of the symposium was to assess strengths and weaknesses of the neuroimaging and data processing techniques, and to discuss strategies that may facilitate collection of imaging data in exposed and comparison children. Various imaging techniques were discussed, i.e., magnetic resonance imaging (MRI), positron emission tomography (PET), diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), and molecular imaging. Papers were presented by five groups, and are provided in this article. While the findings in this report are very preliminary, they emphasize the potential that neuroimaging methodologies have for understanding how drug exposure may affect brain development. Dow-Edwards, D.L., Benveniste, H., Behnke, M., et al. Neuroimaging of Prenatal Drug Exposure. Neurotoxicology and Teratology, 28, pp. 386-402, 2006.

Depression, Sensation Seeking, and Maternal Smoking as Predictors of Adolescent Cigarette Smoking

This study examined maternal and adolescent depression, maternal and teen sensation seeking, and maternal smoking, and their associations with adolescent smoking. Data were collected from a sample of 47 male and 66 female adolescents (ages 11-18 years) and their mothers from three different health clinics. The findings indicate that maternal sensation seeking was linked indirectly with adolescent smoking through teen sensation seeking, both of which were significantly associated with teen smoking (beta = 0.29, p < 0.001 and beta = 0.32, p < 0.001, respectively). Teen depression was associated positively with teen smoking (beta = 0.24, p < 0.01) when controlling for sensation seeking behaviors. Maternal smoking was also directly linked to adolescent smoking (beta = 0.20, p < 0.05). These findings underscore a potentially important role of sensation seeking in the origins of adolescent smoking, and clarify pathways of influence with regard to maternal attitudes and behaviors in subsequent teenage nicotine use. van de Venne, J., Bradford, K., Martin, C., Cox, M., and Omar, H.A. Depression, Sensation Seeking, and Maternal Smoking as Predictors of Adolescent Cigarette Smoking. Scientific World Journal, 6, pp. 643-652, 2006.

Clinical Neuroscience Research

Affect Modulates Appetite-Related Brain Activity To Images Of Food

DeborahYugelun-Todd and colleagues used fMRI to determine whether affect ratings predicted regional brain responses to high and low-calorie foods in healthy individuals. Thirteen normal-weight adult women viewed photographs of high and low-calorie foods during BOLD functional magnetic resonance imaging (fMRI). Positive and negative affect had different effects on several important appetite-related regions depending on the calorie content of the food images. When viewing high-calorie foods, positive affect was associated with increased activity in satiety-related regions of the lateral orbitofrontal cortex, but when viewing low calorie foods, positive affect was associated with increased activity in hunger-related regions including the medial orbitofrontal and insular cortex. The opposite pattern of activity was observed for negative affect. These findings describe the neurobiologic substrates involved in the commonly reported increase in cravings for calorie-dense foods during heightened negative emotions. Killgore, W.D.S., and Yurgelun-Todd, D.A. Affect Modulates Appetite-related Brain Activity to Images of Food. International Journal of Eating Disorders, 39, pp. 357-363, 2006.

Gender Differences Among Recreational Gamblers: Association With the Frequency of Alcohol Use

Marc Potenza and colleagues at Yale School of Medicine investigated the interactive effects of alcohol use and gender on health and gambling attitudes and behaviors in recreational gamblers. The Gambling Impact and Behavior Study surveyed by telephone 2,417 adults targeted to be representative of the U.S. adult population. Male and female recreational gamblers (n = 1,471) were stratified by frequency of alcohol use on measures of health and gambling. Significant Gender x Alcohol Use group interactions were observed such that moderate-to-high frequency alcohol consumption correlated with heavier gambling in men than in women, whereas such an association did not exist among abstinent or low frequency drinkers. There were few gender differences in the correlations between alcohol consumption and health. Future research should consider gender-related influences when examining alcohol use and gambling behaviors. Desai, R.A., Maciejewski, P.K., Pantalon, M.V., and Potenza, M.N. Gender Differences Among Recreational Gamblers: Association With the Frequency of Alcohol Use. Psychology of Addictive Behaviors, 20, pp. 145-153, 2006.

Cognitive Deficits Were Found In Non-Clinically-Referred College Women Who Were Sexually Abused Prior To Age 18

Clinically-reported sexual abuse is associated with several disorders appearing in adutlthood including drug abuse. Teicher and colleagues at Mclean Hospital assessed cognitive effects in community-based subjects recruited by advertisement and assessed college women who endorsed at least three episodes of "forced contact sexual abuse" and were physically healthy on a number of cognitive tests. Some of the subjects had either current or past diagnoses of Major Depressive Disorder, Post-Traumatic Stress Disorder, or General Anxiety Disorder. Results showed that there were a constellation of deficits in some but not all tests. In particular, the abused group had a diminished capacity on a test requiring response inhibition, performed less well on the Math SAT tests (in spite of normal level verbal scores), and demonstrated memory deficits as a function of abuse duration. Navalta, C.P., Polcari, A., Webster, D.M., Boghossian, A., and Teicher, M.H. Effects of Childhood Sexual Abuse on Neuropsychological and Cognitive Function in College Women. Journal of Neuropsychiatry and Clinical Neuroscience, 18(1), pp. 45-53, 2006.

Genes Contributed to the Covariance between Conduct Disorder and Dependence Vulnerability

Stallings and Hewitt in Crowley's group at Boulder's Institute for Behavioral Genetics examined the genetic, shared and non-shared environmental factors contributing to both conduct disorders and dependence vulnerability or to dependence vulnerability alone. The subjects were nearly 900 twin pairs encompassing all five groups--monozygotic males and females, dizygotic males and female, and dizygotic male/female pairs. Symptoms of both disorders were significantly heritable and all three factors contributed to the co-variation: genes contributed 35% of the phenotypic covariance, shared environment contributed 46%, and non-shared environment contributed the remaining 19%. Finally, it was noted that the etiology of the comorbidity was similar in males and females. Button, T.M.M., Hewitt, J.K., Rhee, S.H., Young, S.E., Corley, R.P., Stallings, M.C. Examination of the Causes of Covariation Between Conduct Disorder symptoms and Vulnerability to Drug Dependence. Twin Research and Human Genetics, 9(1), pp. 38-45, 2006.

Epidemiology and Etiology Research

Is Prenatal Smoking Associated with a Developmental Pattern of Conduct Problems in Young Boys?

Prenatal smoking is robustly associated with increased risk of conduct problems in offspring. This study used a developmental framework to examine the association of exposure with (1) oppositional defiant disorder and attention-deficit/hyperactivity disorder in young boys and (2) the pattern of delinquent behavior at adolescence. Using diagnostic measures and repeated measures of delinquency, the researchers compare exposed and non-exposed boys from the youngest cohort of the Pittsburgh Youth Study (N = 448). Exposed boys were significantly more likely to (1) develop oppositional defiant disorder and comorbid oppositional defiant disorder-attention-deficit/hyperactivity disorder but not attention-deficit/hyperactivity disorder alone and (2) to have an earlier onset of significant delinquent behavior. The early emergence and developmental coherence of exposure-related conduct problems is striking and is consistent with a behavioral teratological model. Phenotypically, exposure-related conduct problems appear to be characterized by socially resistant and impulsively aggressive behavior. Whether prenatal smoking plays an etiological role in or is a risk marker for the development of conduct problems, exposed offspring are at increased risk of an early-starter pathway to conduct problems. Wakschlag, L., Pickett, K., Kasza, K., and Loeber, R. Is Prenatal Smoking Associated with a Developmental Pattern of Conduct Problems in Young Boys? J Am Acad Child Adolesc Psychiatry, 45(4), pp. 461-470, 2006.

The Growth in Marijuana Use among American Youths During the 1990s and the Extent of Blunt Smoking

Marijuana use among American youths and young adults increased substantially during the 1990s. This paper reviews that trend using data collected 1979-2003 by the National Survey on Drug Use and Health (NSDUH). The data suggest that the increase in marijuana use started first among persons age 12-20. Among 18-20 year-olds, the increase started earlier among whites and blacks than Hispanics, among males before females, and surprisingly in areas that are not part of an MSA as opposed to those with a population in excess of a million. Much of the increase in marijuana use could have been attributable to the growing popularity of blunts. Starting in 2000, the NSDUH explicitly asked youth's age 12-17 (but not older respondents) about smoking blunts. Of the 9% of youths who reported past-30-day use of marijuana 2000-03, more than half reported smoking blunts. On the other hand, the data also indicate that blunts have not fully supplanted other ways that youths consume marijuana. Blunts were more common among youths that were black, older, male, and from metropolitan areas. Many blunt smokers reported they had not used marijuana, which suggests that they did not define smoking blunts as marijuana use. Even fewer reported that they had used cigars, suggesting they did not define smoking blunts as cigar use. Golub, A., Johnson, B., and Dunlap, E. The Growth in Marijuana Use Among American Youths During the 1990s and the Extent of Blunt Smoking. J Ethn Subst Abuse, 4(3-4), pp. 1-21, 2005.

Childhood and Adolescent Antecedents of Drug and Alcohol Problems: A Longitudinal Study

Despite the serious health and economic consequences of drug and alcohol abuse and dependence, few studies have prospectively examined the etiology of this problem in non-clinical populations. This longitudinal study examines childhood and adolescent antecedents of drug and alcohol problems in adulthood among an African American cohort (n=1242; 51% female) from Woodlawn, a neighborhood in Chicago. The participants were followed from age 6 to 32 years, and data were collected in first grade, adolescence, and adulthood. Structural equation modeling showed that, for both males and females, educational attainment was directly associated with a reduced risk for substance use problems. For males, first grade shyness was directly associated with a reduced risk of substance use problems, and adolescent substance use was directly associated with an increased risk. First grade aggression, low family socioeconomic status (SES), and low school bonds were indirectly associated with substance use problems for both males and females. For males, first grade underachievement had an indirect effect, and, for females, first grade shyness and strong parental supervision had indirect effects. This study is among the first to identify life course trajectories to substance use problems among an African American, community-based population. These results help to identify the targets and timing of interventions that may help to reduce the risk of drug and alcohol problems in adulthood. Fothergill, K., and Ensminger, M. Childhood and Adolescent Antecedents of Drug and Alcohol Problems: A Longitudinal Study. Drug Alcohol Depend, 82(1), pp. 61-76, 2006.

Estimates of IDU at the National and Local Level in Developing and Transitional Countries, and Gender and Age Distribution

This study sought to update available national and sub national estimates of IDUs in developing/transitional countries, and provide indicative estimates of gender and age distribution. Literature reviews were conducted of both "grey" and published literature, including updates from previously reported estimates, on estimates of IDU population and data sources giving age and gender breakdowns. The scope area was developing/transitional countries and the reference period was 1998-2005. Estimates of IDU numbers were available in 105 countries and 243 sub national areas. The largest IDU populations were reported from Brazil, China, India, and Russia. Sub national areas with the largest IDU populations (35,000-79,000) were: Warsaw (Poland); Barnadul, Irtkustk, Nizhny-Novgorod, Penza, Voronez, St. Petersburg, and Volgograd (Russia); New Delhi and Mumbai (India); Jakarta (Indonesia), and Bangkok (Thailand). By region, Eastern Europe and Central Asia have the largest IDU prevalence, followed by Asia and Pacific. In the Middle East and Africa the median value equals 0.2% and in Latin America and the Caribbean, 0.12%. Greater dispersion of national IDU prevalence's was observed in Eastern Europe and Central Asia, and Asia and Pacific. Sub national areas with the highest IDU prevalence among adults (8-14.9%) were Shymkent (Kazakhstan), Balti (Moldova), Astrakhan, Barnadul, Irtkustk, Khabarovsk, Kaliningrad, Naberezhnyje Chelny, Penza, Togliatti, Volgograd, Voronez, and Yaroslavl (Russia), Dushanbe (Tajikistan), Ashgabad (Turkmenistan), Ivano-Frankivsk and Pavlograd (Ukraine) and Imphal, Manipur (India). Data on the IDU age/gender distributions are scarce or unavailable for many countries. The proportion of IDU men was 70%-90% in Eastern Europe and Central Asia, and there was a marked absence of data on women outside this region. In conclusion, data on IDU prevalence available to national and international policymakers are of an unknown and probably yet to be tested quality. This study provides baseline figures, but steps need to be taken to improve the reporting and assessment of these critical data. Aceijas, C., Friedman, S., Cooper, H., Wiessing, L., Stimson, G., and Hickman, M. Estimates of Injecting Drug Users at the National and Local Level in Developing and Transitional Countries, and Gender and Age Distribution. Sex Transm Infect, 82(3), pp. 10-17, 2006.

Impact of Marriage on HIV Risk Behaviors

Studies among normative samples generally demonstrate a positive impact of marriage on health behaviors and other related attitudes. This study used a multilevel latent variable approach to examine the impact of marriage on HIV/AIDS risk behaviors and attitudes among impoverished, highly stressed, homeless couples, many with severe substance abuse problems. A multilevel analysis of 368 high-risk sexually intimate married and unmarried heterosexual couples assessed individual and couple-level effects on social support, substance use problems, HIV/AIDS knowledge, perceived HIV/AIDS risk, needle sharing, condom use, multiple sex partners, and HIV/AIDS testing. More variance was explained in the protective and risk variables by couple-level latent variable predictors than by individual latent variable predictors, although some gender effects were found (e.g., more alcohol problems among men). The couple-level variable of marriage predicted lower perceived risk, less deviant social support, and fewer sex partners but predicted more needle sharing. Stein, Nyamathi, Ullman, and Bentler. Impact of Marriage on HIV/AIDS Risk Behaviors Among Impoverished, At-Risk Couples: A Multilevel Latent Variable Approach. AIDS Behav, 11(1), pp. 87-98, 2007.

Estimated Numbers of Men and Women Infected with HIV/AIDS in Tijuana, Mexico

Tijuana, Mexico, just south of San Diego, California, is located by the busiest land border crossing in the world. Although UNAIDS considers Mexico to be a country of "low prevalence, high risk," recent surveillance data among sentinel populations in Tijuana suggests HIV prevalence is increasing. The aim of this study was to estimate the number of men and women aged 15 to 49 years infected with HIV in Tijuana. Gender and age-specific estimates of the Tijuana population were obtained from the 2000 Mexican census. Population and HIV prevalence estimates for at-risk groups were obtained from published reports, community based studies, and data from the Centro Nacional para la Prevencion y Control del VIH/SIDA (CENSIDA). Age-specific fertility rates for Mexico were used to derive the number of low and high-risk pregnant women. Numbers of HIV-positive men and women were estimated for each at-risk group and then aggregated. A high growth scenario based on current HIV prevalence and a conservative, low growth estimate was determined. A total of 686,600 men and women in Tijuana were aged 15 to 49 years at the time of the 2000 census. Considering both scenarios, the number of infected persons ranged from 1,803 to 5,472 (HIV prevalence: 0.26 to 0.80%). The majority of these persons were men (>70%). The largest number of infected persons were MSM (N = 1,146 to 3,300) and IDUs (N = 147 to 650). Data from this study suggest that up to one in every 125 persons aged 15-49 years in Tijuana is HIV-infected. Interventions to reduce ongoing spread of HIV are urgently needed. Brouwer, K., Strathdee, S., Magis-Rodriguez, C., Bravo-Garcia, E., Gayet, C., Patterson, T., Bertozzi, S., and Hogg, R. Estimated Numbers of Men and Women Infected with HIV/AIDS in Tijuana, Mexico. J Urban Health, 83(2), pp. 299-307, 2006.

Psychiatric Disorders and Their Correlates among Young Adult MDMA Users in Ohio

This study describes the lifetime prevalence, correlates, and age of onset of selected psychiatric disorders among a community sample of MDMA users (n = 402), aged 18 to 30, in Ohio. Participants responded to interviewer-administered questionnaires, including sections of the computerized Diagnostic Interview Schedule for DSM-IV. Fifty-five percent of the sample had at least one lifetime disorder, with major depression (35.3%) and antisocial personality disorder (ASPD) (25.4%) the most common. Proportionately more women were diagnosed with depression, generalized anxiety disorder, and posttraumatic stress disorder (PTSD), while proportionately more men were diagnosed with ASPD. Proportionately more non-White participants had attention deficit/hyperactivity disorder (AD/HD). Higher levels of education were associated with proportionately less PTSD, ASPD, and AD/HD. Higher frequencies of MDMA use were associated with proportionately more ASPD and AD/HD. Comparing the age of first MDMA use with the age of onset for selected psychiatric disorders revealed that for most participants disorders preceded use. Multivariate analysis revealed participants with more than a high school education were less likely to have experienced a lifetime disorder, while those who had used MDMA more than 50 times were more likely. Variations in the prevalence of psychiatric disorders have practical implications for drug abuse prevention and treatment programs. Falck, R., Carlson, R., Wang, J., and Siegal, H. Psychiatric Disorders and Their Correlates Among Young Adult MDMA Users in Ohio. J Psychoactive Drugs, 38(1), pp. 19-29, 2006.

Correlates of Rural Methamphetamine and Cocaine Users: Results from a Multi-state Community Study

Use and production of methamphetamine (MA) has dramatically increased in the United States, especially in rural areas, with concomitant burdens on the treatment and criminal justice systems. However, cocaine is also widely used in many rural areas. The purpose of this article is to contrast MA and cocaine users in three geographically distinct rural areas of the US. Participants were recent not-in-treatment adult cocaine and MA users living in rural Ohio, Arkansas, and Kentucky, who were recruited by a referral recruitment method for sampling hidden community populations. Participants were interviewed for demographics, drug and alcohol use, criminal justice involvement, and psychological distress (Brief Symptom Inventory). The sample of 706 comprised 29% nonwhite and 38% female participants; the average age was 32.6 years; 58% had a high school education or higher, and 32% were employed. In the past 6 months, they had used either MA only (13%), cocaine only (52%), or both (35%). MA users were seldom (8.2%) nonwhite, but type of stimulant use did not vary by gender. Combined MA/cocaine users reported significantly greater use of alcohol and other drugs, including marijuana and non-prescribed opiates and tranquilizers, and reported significantly higher psychological distress. MA users (with or without cocaine use) had greater odds of recent criminal justice involvement compared with cocaine-only users. There is a clear need for accessible substance-use treatment and prevention services in rural areas of the United States, including services that can address MA, cocaine, poly-drug use, and mental health needs. There is a particular need of these services for poly-drug users. Booth, B., Leukefeld, C., Falck, R., Wang, J., and Carlson, R. Correlates of Rural Methamphetamine and Cocaine users: Results from a Multi-state Community Study. J Stud Alcohol, 67(4), pp. 493-501, 2006.

Sexual Risk Behaviors among Adolescent Mothers in an HIV Prevention Program

The purpose of this study was to determine the following: (1) whether adolescent mothers in a human immunodeficiency virus (HIV) prevention program had significantly greater perceived self-efficacy and perceived behavioral control to use condoms, and more favorable outcome expectancies and subjective norms regarding condom use than those in a health education control group, 3 months after intervention; and (2) the impact of the 3-month post-intervention theoretical variables on intentions to use condoms at 3 months and sexual risk behaviors at 6 months. Structural equation modeling with latent variables was used to assess the influence of theoretical variables and treatment condition using data from 496 participants (78% Latinas, 18% African-Americans) who completed questionnaires at baseline and at 3- and 6-month follow-up evaluations. Substantial improvements were shown by both groups, with a slight advantage for the HIV prevention group, on all theoretical variables between pretest and the follow-up evaluations. In the predictive model, the intervention group reported significantly fewer sex partners. By using intentions to use condoms as a mediator, greater self-efficacy, hedonistic beliefs, positive subjective norms, and less unprotected sex predicted intentions to use condoms, which, in turn, predicted less unprotected sex. Lower subjective norms modestly predicted multiple partners. Significant indirect paths mediated through intentions to use condoms were observed. These data support a relationship among several constructs from social cognitive theory and the theory of reasoned action, and subsequent sexual risk behaviors. HIV-prevention programs for adolescent mothers should be designed to include these theoretical constructs and to address contextual factors influencing their lives. Koniak-Griffin, D., and Stein, J. Predictors of Sexual Risk Behaviors Among Adolescent Mothers in a Human Immunodeficiency Virus Prevention Program. J Adolesc Health, 38(3), pp. 297-311, 2006.

The Role of Coping and Problem Drinking in Men's Abuse of Female Partners

This article examines the relationship of coping and problem drinking to men's abusive behavior towards female partners. While previous research has demonstrated a consistent association between problem drinking and male abuse of intimate partners, virtually no studies have assessed the role of coping in relation to men's violence. An ethnically diverse sample of 147 men in a court-mandated program for domestic violence offenders completed questionnaires at the first session. Path modeling was conducted to test the extent to which coping and problem drinking predicted both physical and psychological abuse. In addition, the relationships of problem drinking and physical abuse to injury of the men's female partners were examined. Results indicated that both the use of avoidance and problem-solving coping to deal with relationship problems were related indirectly to abusive behavior through problem drinking. Greater use of avoidance coping strategies was more likely among problem drinkers. By contrast, men who used higher levels of problem-solving coping were less likely to be problem drinkers. Avoidance, but not problem-solving coping also was directly and positively related to physical and psychological abuse. Men identified as problem drinkers were more likely to use both physical and psychological abuse. Finally, greater use of physical violence was strongly related to higher levels of injury among female partners, and served to mediate the relationship between problem drinking and injury. Snow, D., Sullivan, T., Swan, S., Tate, D., and Klein, I. The Role of Coping and Problem Drinking in Men's Abuse of Female Partners: Test of a Path Model. Violence Vict, 21(3), pp. 267-285, 2006.

Partner Concurrency among Drug Users with Large Numbers of Partners

The objective of this study was to measure the nature of concurrent sex partnering in two samples of drug users having large numbers of sex partners, and in which some or all participants were trading sex-for-money. The two samples included drug-using male sex workers (MSW) and male and female crack cocaine smokers (CS) having vaginal sex. Three measures were used to reflect the quality of concurrent partnering: the proportion of the samples having concurrent partners; the proportions of the samples having intimate, casual, and sex-for-money of partners; and overlap in concurrent partners. Proportions of each sample having concurrent partners were essentially the same. However, the kinds of concurrent partners and overlap in concurrent partners were significantly different. Concurrent partners in the MSW sample were mostly sex-for-money or sex-for-drugs partners. Most concurrent partners in the CS sample were initimate or casual sex partners. Overlap in concurrent partners was also significantly different. The measure of overlap for the CS sample was three times higher than that of the MSW sample. These data suggest that concurrent sex partnering in the two samples, beyond the proportion having concurrent partners, was different. The patterns of concurrent sex partners in each sample may reflect different reasons for engaging in concurrent partnering, and may be reflected in different overlap scores between the two samples. Efforts should be made in future studies to better capture the complexities of concurrent partnering and to examine the implications of these for disease spread and control. Williams, M., Ross, M., Atkinson, J., Bowen, A., Klovdahl, A., and Timpson, S. An Investigation of Concurrent Sex Partnering in Two Samples of Drug Users Having Large Numbers of Sex Partners. Int J STD AIDS, 17(5), pp. 309-314, 2006.

Drug Use, Drug Severity, and Help-seeking Behaviors of Lesbian and Bisexual Women

Illicit substance use and abuse may be an important contributor to behavioral health problems of lesbian and bisexual women. This paper describes the nature and extent of self-reported illicit and licit drug use, associated severity, and substance use-related help-seeking behaviors in an urban/metropolitan community sample of sexual minority women in California. Self-administered questionnaire data from 2011 lesbian and bisexual women recruited through multiple strategies were used. Multiple logistic regression was employed to describe patterns of reported drug use and to compare lifetime severity of drug use with demographic characteristics, recent drug use, indicators of current social and emotional problems, and help-seeking behaviors. Drug use, especially marijuana (33% used in the past year), was fairly common. Overall, 16.2% of the women in the study reported lifetime drug use that was associated with self-reported severity of substance use, and another 10.8% indicated moderate-risk use. Extent of lifetime drug use was positively correlated with self-reported recent drug use as well as current life problems. Of the respondents who evidenced more problematic drug use, 41.5% indicated that they had received professional help for a substance use problem, and 16.3% wanted but had not received such help. The women in this study reported elevated rates of illicit drug use that were frequently associated with impairment and specific life problems. A significant proportion wanted and had not received professional treatment for their drug use problems, suggesting an important need to examine pathways by which lesbians and bisexual women can obtain referrals and treatment for substance use problems. Corliss, H., Grella, C., Mays, V., and Cochran, S. Drug Use, Drug Severity, and Help-Seeking Behaviors of Lesbian and Bisexual Women. J Womens Health (Larchmt), 15(5), pp. 556-568, 2006.

Prevalence and Correlates of Current Depressive Symptomatology among a Community Sample of MDMA Users in Ohio

Research suggests that MDMA can cause serotonin depletion as well as serotonergic neurodegradation that may result in depression among users of the drug. Several small-scale studies have used various editions of the Beck Depression Inventory (BDI) to quantify depressive symptomatology among MDMA users. This study represents the largest application of the BDI to date to explore symptoms of current depression among a community sample of young adult MDMA users (n = 402). Internal consistency testing of the BDI-II with this sample revealed Cronbach's alpha = .92. Results show a mean BDI-II score of 9.8, suggesting low levels of depressive symptomatology among study participants. Two-thirds of the sample had scores that placed them in the non-depressed/minimal depression category, while 4.7% had scores indicative of severe depression. Logistic regression analysis revealed that men were significantly less likely than women and people who used opioids were significantly more likely than non-users to have higher levels of depressive symptomatology. Higher lifetime occasions of MDMA use were marginally related to symptoms of serious depression. Falck, R., Wang, J., Carlson, R., and Siegal, H. Prevalence and Correlates of Current Depressive Symptomatology among a Community Sample of MDMA Users in Ohio. Addict Behav, 31(1), pp. 90-101, 2006.

Factors Associated with Buying and Selling Syringes among IDUs in a Setting of one of North America's Largest Syringe Exchange Programs

Researchers performed analyses of syringe buying and syringe selling among Vancouver injection drug users, recruited from May 1996 and followed up between November 2002 and August 2003, in the context of one of North America's largest syringe exchange programs (SEPs). An interviewer-administered questionnaire, approximately 45 minutes in duration, was used to collect information regarding risk factors for HIV infection and sources of sterile syringes. Seventy participants (15%) reported syringe selling and 122 (26%) reported syringe buying. Syringe sellers were more likely to be female, reside in unstable housing, need help injecting, and have visited the SEP at least once weekly. Syringe buyers were more likely to need help injecting, have difficulty finding new syringes, have binged on drugs, and have visited the SEP at least once weekly. Syringe buying most frequently occurred when the SEP was closed. Kuyper, L., Kerr, T., Li, K., Hogg, R., Tyndall, M., Montaner, J., and Wood, E. Factors Associated with Buying and Selling Syringes Among Injection Drug Users in a Setting of one of North America's Largest Syringe Exchange Programs. Subst Use Misuse, 41(6-7), pp. 883-899, 2006.

Factors Associated With Non-IDUs Having IDU Sex Partners

This study examined factors associated with non-injectors having 1 or more IDUs as sex partners. Data were collected as part of the Self-Help in Eliminating Life Threatening Diseases study, a network-oriented experimental HIV prevention intervention. All eligible participants were administered a detailed face-to-face interview on their socio-demographic background, patterns of drug use, HIV prevention and risk behaviors, and social networks. The sample for these analyses consisted of 863 non-injectors, 97 of whom had 1 or more injection drug-using sex partners. The study found that the factors associated with an increased odds of having 1 or more IDU sex partners were long-term unemployment, increasing proportion of women in network (among male non-injectors), increasing number of recent sex partners (among former injectors), increasing number of injecting non-sex partners in the network, and increasing network size above 15. These findings indicate that there are specific network characteristics associated with non-injectors having injecting sex partners. Howard, D., and Latkin, C. A Bridge Over Troubled Waters: Factors Associated With Non-Injection Drug Users Having Injection Drug-using Sex Partners. J Acquir Immune Defic Syndr, 42(3), pp. 325-330, 2006.

Substance Use among Adolescent Children with Drug Abusing Fathers

This longitudinal study examined paternal, perceived maternal, and youth risk factors at Time 1 (T1) (e.g., substance use, violent victimization, parental rules) as predictors of the stage of substance use in the adolescent child at Time 2 (T2). Participants (N = 296) consisted of drug-abusing fathers and one of their adolescent children, aged 12 to 20 years. Fathers and youths were each administered structured interviews separately and in private. Adolescents were re-interviewed approximately one year later. Pearson correlation analyses showed that the paternal, perceived maternal, and youth risk factors were significantly related to adolescent stage of substance use at T2. With an increase in risk factors, there was an increase in T2 stage of substance use in the child. Findings imply that father-oriented treatment programs should focus on how paternal behaviors, such as illegal drug use, inadequate parenting skills, and a poor father-child relationship contribute to youth problem behaviors, including alcohol, tobacco, and illicit drug use. Castro, F., Brook, J., Brook, D., and Rubenstone, E. Paternal, Perceived Maternal, and Youth Risk Factors as Predictors of Youth Stage of Substance Use A Longitudinal Study. J Addict Dis, 25(2), pp. 65-75, 2006.

Parent Drug Use and Personality Attributes: Child Rearing in African-American and Puerto Rican Young Adults

This study assessed the effect of the interrelationship of mothers' and fathers' tobacco and marijuana use with their personality attributes on some of their child rearing behaviors. A longitudinal design was used to analyze the data of 258 males and females who were seen four times over a 13-year period from early adolescence through young adult parenthood. Thirty-one percent of the multiple regression analyses revealed significant interactions between the effect of tobacco or marijuana use and a personality attribute on child rearing. The majority of these significant interactions suggested that protective personality characteristics were offset by substance use risks resulting in less adequate child rearing. If these results are substantiated in an experimental intervention, it suggests that having resilient personality attributes does not protect against the negative effects of tobacco or marijuana use on child rearing. Brook, Balka, Fei, and Whiteman. The Effects of Parental Tobacco and Marijuana Use and Personality Attributes on Child Rearing in African-American and Puerto Rican Young Adults. J Child Fam Stud, 15(2), pp. 153-164, 2006.

Contextual Determinants of Condom Use Among Female Sex Exchangers in East Harlem, NYC: An Event Analysis

Recent studies have identified a variety of contexts involving HIV risk behaviors among women who exchange sex for money or drugs. Event analysis was used to identify the individual, relationship, and contextual factors that contribute to these high-risk sex exchange practices. Analyses were conducted on data obtained from 155 drug-using women who reported details of their most recent sex exchange event with male clients. The majority of sex exchange encounters (78%) involved consistent condom use. In multivariable analysis, protective behavior was associated primarily with situational and relationship variables, such as exchange location, substance use, sexual practices, and respondent/client discussion and control. To inform HIV prevention programs targeted to women sex exchangers, research should focus on the contextual determinants of risk, especially with regard to condom-use negotiation and factors involving substance use that adversely affect women's ability to manage protective behavior in the context of sex exchange. McMahon, Tortu, Pouget, Hamid, and Neaigus. Contextual Determinants of Condom Use Among Female Sex Exchangers in East Harlem, NYC: An Event Analysis. AIDS Behav, 10(6), pp. 731-741, 2006.

Borderline Personality and Substance Use in Women

The association between borderline personality disorder (BPD) and substance use disorder (SUD) was examined in a predominantly psychiatric (77.6%) sample of 232 women. BPD proved to be a significant predictor of a lifetime diagnosis of SUD across four different categories: any SUD (including alcohol); alcohol use; drug use; and heroin, cocaine, or poly-substance use. BPD continued to be a predictor of SUD even when the effects of other cluster B and all cluster C PDs were controlled statistically. Antisocial personality disorder generally yielded larger odds ratios than BPD and emerged as a partial mediator of the relation between BPD and SUD. Histrionic PD was the only other PD that showed meaningful relations with SUD. Feske, U., Tarter, R., Kirisci, L., and Pilkonis, P. Borderline Personality and Substance Use in Women. Am J Addict, 15(2), pp. 131-137, 2006.

Prenatal Cocaine Exposure not Linked to Child Behavior Problems at Age 7

This study examined the relationship between prenatal cocaine exposure and parent-reported child behavior problems at age 7 years. Data were from 407 African-American children (210 cocaine-exposed, 197 non-cocaine-exposed) enrolled prospectively at birth in a longitudinal study on the neurodevelopmental consequences of in utero exposure to cocaine. Prenatal cocaine exposure was assessed at delivery through maternal self-report and bioassays (maternal and infant urine and infant meconium). The Achenbach Child Behavior Checklist (CBCL), a parent report measure of childhood externalizing and internalizing behavior problems, was completed by the child's current primary caregiver during an assessment visit scheduled when the child was seven years old. Structural equation and GLM/GEE models disclosed no association linking prenatal cocaine exposure status or level of cocaine exposure to child behavior (CBCL Externalizing and Internalizing scores or the eight CBCL subscale scores). This evidence, based on standardized ratings by the current primary caregiver, fails to support hypothesized cocaine-associated behavioral problems in school-aged children with in utero cocaine exposure. A next step in this line of research is to secure standardized ratings from other informants (e.g., teachers, youth self-report). Accornero, V., Anthony, J., Morrow, C., Xue, L., and Bandstra, E. Prenatal Cocaine Exposure: An Examination of Childhood Externalizing and Internalizing Behavior Problems at Age 7 Years. Epidemiol Psychiatr Soc, 15(1), pp. 20-29, 2006.

Psychiatric Disorders among Parents/Caretakers of American Indian Early Adolescents in the Midwest

This study reports prevalence and comorbidty of five DSM-III-R diagnoses (alcohol abuse, alcohol dependence, drug abuse, major depressive episode, and generalized anxiety disorder) among American Indian and Canadian First Nations parents/caretakers of children aged 10-12 years from the Northern Midwest United States and Canada. Lifetime prevalence rates were compared to adults in the National Comorbidity Survey (NCS) and Southwest and Northern Plains cultures from the AI-SUPERPFP study. Native interviewers used computer-assisted personal interviews to administer the University of Michigan Composite International Diagnostic Interview (UM-CIDI) to 861 tribally enrolled parents and caretakers (625 females; 236 males) of 741 tribally enrolled children aged 10-12 years. Fathers/male caretakers ranged in age from 21 years to 68 years with an average age of 41 years; mothers/female caretakers ranged in age from 17 years to 77 years with an average of 39 years. About three-fourths (74.6%) of the adults met lifetime criteria for one of the five disorders; approximately one-third (31.6%) met lifetime criteria for two or more of the five disorders. Prevalence of the substance use disorders was higher than those in the general population (NCS); prevalence of internalizing disorders (major depressive disorder and generalized anxiety disorder) was very similar to those in the general population. Prevalence rates for alcohol abuse among the Northern Midwest adults were higher than those reported for Southwest and Northern Plains Tribes, but rates of alcohol dependency were very similar across cultures. The higher prevalence rates for some mental disorders found for the Northern Midwest are discussed in terms of potential method variance. The Northern Midwest results reflect unique patterns of psychiatric disorders in the ubiquity of substance abuse disorders and the co-occurrence of substance abuse disorders with internalizing disorders. Reducing lifetime occurrences of substance abuse disorders would have an enormous positive impact on the mental health of this population. Whitbeck, Hoyt, Johnson, and Chen. Mental Disorders among Parents/caretakers of American Indian Early Adolescents in the Northern Midwest. Soc Psychiatry Psychiatr Epidemiol, 41(8), 2006.

Drug Use Related to Suicide Ideation in Midwestern American Indian Youth

This study examined correlates of suicidal ideation among 212 American Indian youth who lived on or near three reservations in the upper Midwestern United States. The youths were, on average, 12 years old, and 9.5% reported current thoughts about killing themselves. Females were over 2 times more likely than males to think about suicide. Multivariate logistic regression results indicated that gender, enculturation, negative life events, perceived discrimination, self-esteem, and drug use were related to the likelihood of thinking about suicide. Drug use was the strongest correlate of suicidal ideation, and both enculturation and perceived discrimination emerged as important culturally specific variables. It was suggested that suicide prevention programs should draw on the strengths of American Indian culture. Yoder, K., Whitbeck, L., Hoyt, D., and Lafromboise, T. Suicidal Ideation among American Indian Youths. Arch Suicide Res, 10(2), pp. 177-190, 2006.

Prevention Research

Results of Two Methods of Delivery of Life Skills Training

The study reported here assessed two methods of delivery of a prevention program called Life Skills Training (LST), implemented in nine rural disadvantaged school districts. This study tested the effectiveness of both standard LST curriculum, which is usually taught by one or two teachers in classes dedicated to substance abuse prevention), and the infused LST (I-LST) condition, which integrates LST and alcohol, tobacco and other drug information into the existing grade-level subject curricula, taught by the regular teachers for these subject areas. The results indicate that neither standard LST nor an infused LST delivery methods were effective for the entire sample, although some encouraging results were found for the females in the study. This study, conducted by researchers independent of the original LST program, is useful for school decision makers in determining what programs are most effective with which groups. It included all students with parental permission, controlling for prior use levels, unlike some previous LST studies. The results of the program, as implemented by regular classroom teachers, reflect many issues relevant to recruitment, training, implementation, adaptation, and institutionalization of prevention programming. Vicary, J., Smith, E., Swisher, J., Hopkins, A., Elek, E., Bechtel, L., and Henry, K. Results of a 3-year Study of Two Methods of Delivery of Life Skills Training. Health Educ Behav, 33(3), pp. 325-339, 2006.

Prenatal Care Providers' Role in Reducing Risk for Smoking, Alcohol Use, Illicit Drug Use and Domestic Violence during Pregnancy

This qualitative study explored prenatal care providers' methods for identifying and counseling pregnant women to reduce or stop 4 high risk behaviors: smoking, alcohol use, illicit drug use, and the risk of domestic violence. Six focus groups were conducted (five with OB/Gyn physicians, one with nurse practitioners and certified nurse midwives), with 49 care providers, using open-ended questions that assessed: providers' specific issues or interests in preventing the risk behaviors; providers'' reactions and opinions to ACOG recommendations for handling the risk behaviors and whether providers feel they can have a positive impact on the risk behaviors; providers' challenges with assessing and counseling patients; providers' opinions about whether pregnancy is an opportune time to effect behavior change; whether providers should counsel patients about risk behaviors; best ways for providers to ask about the risky behaviors; and specific strategies providers have found effective for the risky behaviors. Three major themes emerged: (1) specific risk-prevention tactics or strategies exist that are useful during pregnancy; (2) some providers address patients' isolation or depression; and (3) providers can adopt a policy of "just chipping away" at risks. Specific tactics included normalizing risk prevention, using specific assessment techniques and counseling strategies, employing a patient-centered style of smoking reduction, and involving the family. Providers generally agreed that addressing behavioral risks in pregnant patients is challenging, and that patient-centered techniques and awareness of patients' social contexts help patients disclose and discuss risks. Herzig, K., Danley, D., Jackson, R., Petersen, R., Chamberlain, L., and Gerbert, B. Seizing the 9-month Moment: Addressing Behavioral Risks in Prenatal Patients. Patient Educ Couns, 61(2), pp. 228-235, 2006.

HIV Risk is Common Among Older (Age 49-60) Substance Users, Particularly Men

Gender differences and other factors associated with current heroin and cocaine use were assessed among middle-aged drug users in New York City. Baseline data were merged from 2 studies of men and women with or at risk for HIV infection, and those age 49-60 years who had ever used heroin or cocaine were selected for analysis. HIV-antibody status, drug-use history, and psychosocial and sociodemographic data were examined. Logistic regression models were used to assess factors independently associated with current heroin and cocaine use. Of 627 persons who ever had used heroin and/or cocaine, 250 (39.9%) reported using these drugs within 6 months of the study interview. Men were more likely to be using drugs currently, compared with women (42.3% vs. 28.2%; p = .007). In multivariate analysis, men, unemployed persons, and HIV-seronegative persons were more likely to be using heroin or cocaine at the time of the interview. In addition, current marijuana users, persons drinking alcohol on a daily basis, and persons who had been homeless in the 6 months before the interview were also more likely to be using these drugs. It appears that a relatively high proportion of middle-aged substance users with or at risk for HIV infection, especially men, may continue to use illicit drugs into the sixth decade of life. Special attention needs to be given to aging and gender issues in framing HIV-prevention and drug-treatment programs. Hartel, D.M., Schoenbaum, E.E., Lo, Y., and Klein, R.S. Gender Differences in Illicit Substance Use Among Middle-Aged Drug Users with or at Risk for HIV Infection. Clin Infect Dis, 43(4), pp. 525-531, 2006.

In India Sixth Graders Use More Tobacco Than Eight Graders

The epidemic of tobacco use is shifting from developed to developing countries, including India, where increased use is expected to result in a large disease burden in the future. Changes in prevalence of tobacco use in adolescents are important to monitor, since increased use by young people might be a precursor to increased rates in the population. A survey of 11,642 students in the sixth and eighth grades in 32 schools in Delhi and Chennai, India about their tobacco use and psychosocial factors related to onset of tobacco use was conducted. Schools were representative of the range of types of school in these cities. Students who were in government schools, male, older, and in sixth grade were more likely to use tobacco than students who were in private schools, female, younger, and in eighth grade. Students in sixth grade were, overall, two to four times more likely to use tobacco than those in eighth grade. 24.8% (1529 of 6165) of sixth-grade students and 9.3% (509 of 5477) of eighth-grade students had ever used tobacco; 6.7% (413 of 6165) and 2.9% (159 of 5477), respectively, were current users. Psychosocial risk factors were greater in sixth-grade than in eighth-grade students. The increase in tobacco use by age within each grade was larger in sixth grade than in eighth grade in government schools, with older sixth-grade students at especially high risk. The finding that sixth-grade students use significantly more tobacco than eighth-grade students is unusual, and might indicate a new wave of increased tobacco use in urban India that warrants confirmation and early intervention. Reddy, K., Perry, C., Stigler, M., and Arora, M. Differences in Tobacco use Among Young People in Urban India by Sex, Socioeconomic Status, Age, and School Grade: Assessment of Baseline Survey Data. Lancet, 367(9510), pp. 589-594, 2006.

Direct and Mediated Effects of Aggressive Marital Conflict on Child Aggressive-Disruptive Behavior

Direct associations between aggressive marital conflict and child aggressive-disruptive behavior at home and school were explored in this cross-sectional study of 360 kindergarten children. In addition, mediated pathways linking aggressive marital conflict to maternal harsh punishment to child aggressive-disruptive behavior were examined. Moderation analyses explored how the overall frequency of marital disagreement might buffer or exacerbate the impact of aggressive marital conflict on maternal harsh punishment and child aggressive-disruptive behavior. Participants were a sub-sample of the normative and high risk groups in the Fast Track Project, and were included in this analysis if the biological mother of the study child was married and living with a spouse, and if the mother completed the measure of aggressive marital conflict during the child's kindergarten year. The Hierarchical regressions revealed direct pathways linking aggressive marital conflict to child aggressive-disruptive behavior at home and school, and maternal harsh punishment partially mediated the pathway linking aggressive marital conflict to child aggressive-disruptive behavior at home. Further analyses revealed that rates of marital disagreement moderated the association between aggressive marital conflict and child aggressive-disruptive behavior at home, with an attenuated association at high rates of marital disagreement as compared with low rates of marital disagreement. These preliminary findings suggest that marital conflict may be another important target for the prevention of child conduct problems and related high-risk trajectories. Erath, S., Bierman, K., and Bierman, K.C. Aggressive Marital Conflict, Maternal Harsh Punishment, and Child Aggressive-disruptive Behavior: Evidence for Direct and Mediated Relations. J Fam Psychol, 20(2), pp. 217-226, 2006.

Influences of Social Norms on Early Adolescent Substance Use

Social norms play an important role in adolescent substance use. Norm focus theory (Cialdini et al., 1990) distinguishes three types of norms: injunctive, descriptive, and personal. This study examines the relative influence of these three norms, as well as the moderating effects of gender and ethnicity, on the concurrent substance use of 2,245 Mexican or Mexican-American students, 676 other Latino students, 756 non-Hispanic White students, and 353 African-American students. Personal norms appear to be the strongest significant predictor of substance use. Descriptive, parental injunctive, and friend injunctive norms also demonstrate significant, though weaker influences. Controlling for intentions reduces the predictive ability of each type of norm, especially personal norms. Gender moderates the relationship between norms and substance use with the relationships generally stronger for males. Personal norms act as stronger predictors of some types of substance use for Mexican/Mexican Americans. Elek, E., Miller-Day, M., and Hecht, M.L. Influences of Personal, Injunctive, and Descriptive Norms on Early Adolescent Substance Use. Journal of Drug Issues, 36(1), pp. 147-171, 2006.

Victimization and Health Among Indigent Young Women in the Transition to Adulthood: A Portrait of Need

To understand victimization by physical and sexual violence and its association with physical and behavioral health in a probability sample of sheltered homeless and low-income-housed young women in the transition to adulthood (ages 18 through 25). Participants were 224 women ages 18 through 25 who were selected by means of a stratified random sample from 51 temporary shelter facilities (N = 94) and 66 Section 8 private project-based Housing and Urban Development (HUD)-subsidized apartment buildings (N = 130) in Los Angeles County, California. Women completed structured interviews. Forty-one percent of the sample had been physically or sexually victimized as children and 51% had been victimized since turning 18. Young women who experienced victimization were significantly (p < .05) more likely than non-victimized women to have a sexually-transmitted disease (STD) other than HIV/AIDS or Hepatitis B or C, vaginal discharge or bleeding and pelvic pain in the past 6 months, and past-12 month screening diagnoses of drug abuse/dependence and depression. Victimized women were also significantly more likely to use alcohol to intoxication and drugs, including crack and amphetamines, during the past 6 months, and to have experienced psychological distress and poor self-esteem. This study highlights striking rates of victimization and its association with physical and behavioral health problems among indigent young women during the period of emerging adulthood. This portrait of need communicates an urgency to develop multifaceted programs for such women to help them successfully navigate the transition to adulthood and realize their full potential as adults. Wenzel, S., Hambarsoomian, K., D 'Amico, E., Ellison, M., and Tucker, J. Victimization and Health Among Indigent Young Women in the Transition to Adulthood: A Portrait of Need. J Adolesc Health, 38(5), pp. 536-543, 2006.

HIV Infection is a Significant Risk Factor for Human Papillomavirus (HPV) Among Drug Using Women

A total of 230 female former and current drug users in New York City were prospectively studied at 6 month intervals. Each assessment included interviews, HIV testing, and cervicovaginal lavage sampling for human papillomavirus (HPV). Incidence rates of and factors associated with HPV infections of all types and high-risk types were analyzed. Baseline median age was 40 years (range 24-65); 62% of women were Hispanic, 20% black, and 16% white; 54 (24%) were HIV seropositive; 172 (75%) were without detectable HPV; 58 (25%) had only low-risk or untypeable HPV. The incidence rate for any HPV 9.5/100 person-years type and for high-risk types was 4.8/100 person-years. HIV-seropositive women had a significantly increased hazard rate for any HPV (HRadj: 3.4; 95% CI: 1.4 to 8.0) and for high-risk HPV (HRadj 3.0; 95% CI: 1.4 to 6.6), adjusted for race, sexual behaviors, condom use, and history of other sexually transmitted infections. HIV infection was independently associated with a substantial and significantly increased risk for any and for high-risk genital HPV infection and was the most important risk factor found. Dev, D., Lo, Y., Ho, G.Y., Burk, R.D., and Klein, R.S. Incidence of and Risk Factors for Genital Human Papillomavirus Infection in Women Drug Users. J Acquir Immune Defic Syndr, 41(4), pp. 527-529, 2006.

Research on Behavioral & Combined Treatments for Drug Abuse

Characterizing Nicotine Withdrawal in Pregnant Cigarette Smokers

The aim of this study was to characterize nicotine withdrawal and craving in pregnant cigarette smokers. These data were collected as part of prospective clinical trials assessing the efficacy of voucher-based incentives to promote abstinence from cigarette smoking during pregnancy and postpartum. Results from 27 abstainers and 21 smokers during the first 5 days of a cessation attempt were examined. Abstinent pregnant smokers reported more impatience, anger and difficulty concentrating than did smokers. The results also suggest that pregnant smokers generally may have elevated baseline levels of withdrawal, which need to be considered in the design and analysis of future studies. Heil, S.H., Higgins, S.T., Mongeon, J.A., Badger, G.J., and Bernstein, I.M. Characterizing Nicotine Withdrawal in Pregnant Cigarette Smokers. Experimental and Clinical Psychopharmacology, 14, pp. 165-170, 2006.

Research on Pharmacotherapies for Drug Abuse

Cognitive Deficits Predict Low Treatment Retention in Cocaine Dependent Patients

Impaired cognition predicted treatment dropout from cognitive behavioral therapy (CBT) in a small sample of cocaine dependent patients. To further address the role of impaired cognition in retention and treatment outcome of cocaine-dependent patients in CBT, the P.I. expanded a previous investigation to a larger sample, added depressed cocaine patients, and added an additional cognitive assessment. Fifty-six cocaine dependent patients receiving CBT in outpatient clinical trials were assessed for cognitive performance at treatment entry with the computerized MicroCog (MC) and the Wisconsin Card Sort Test (WCST). Treatment completion was defined as 12 or more weeks. Treatment dropouts had significantly lower MC scores (poorer cognitive functioning) than completers on attention, memory, spatial ability, speed, accuracy, global functioning, and cognitive proficiency, with effect sizes in the moderate to large range. These findings were not affected by depression, demographics (age, gender, race, sex, marital status) or drug use (years of cocaine use or average weekly cocaine expenditure in the prior 30 days). In contrast, patients' performance on the WCST was in the average or near-average range, and WCST scores did not differentiate between completers and dropouts. Consistent with previous research, results suggest that mild cognitive impairments (< or =1 S.D. below the mean) negatively affect retention in outpatient CBT treatment for cocaine dependence. Future studies should examine whether there are specific effects of different executive functioning abilities on treatment outcome. Modified behavioral and pharmacologic interventions should be considered to target mild cognitive impairments to improve substance treatment outcome. Aharonovich, E., Hasin, D. S., Brooks, A. C., Liu, X., Bisaga, A., & Nunes, E. V. Cognitive Deficits Predict Low Treatment Retention in Cocaine Dependent Patients. Drug Alcohol Depend., 81, pp. 313-322, 2006.

Preliminary Observations of Paranoia in a Human Laboratory Study of Cocaine

Cocaine-induced paranoia (CIP) has recently shown a relationship to genetic factors that may moderate disulfiram treatment response in cocaine-dependent individuals. However, little research has examined CIP under controlled laboratory conditions. This study examined subjective and physiological responses to a 0.4 mg/kg dose of smoked cocaine in a human laboratory setting with 23 male and 21 female cocaine users. Twenty-nine of 44 participants (67%) reported feeling Paranoid/Suspicious in response to cocaine. Those who reported feeling Paranoid/Suspicious were more likely to be older and male. Further studies are warranted to investigate the mechanisms of gender influence on CIP, and CIP in pharmacotherapy development for cocaine-dependent individuals. Mooney, M., Sofuoglu, M., Dudish-Poulsen, S., and Hatsukami, D.K. Preliminary Observations of Paranoia in a Human Laboratory Study of Cocaine. Addict. Behav., 31, pp. 1245-1251, 2006.

Research on Medical Consequences of Drug Abuse and Infections

Comorbid Medical and Psychiatric Conditions and Substance Abuse in HCV Infected Persons on Dialysis

The burden of comorbidity in the Hepatitis C virus (HCV) infected persons on dialysis is unknown. Authors identified all HCV infected and uninfected subjects in the United States Renal Data System in the years 1997-1998 using ICD-9 codes. Controls were matched on the date of first dialysis. ICD-9 codes and claims data was used to identify medical and psychiatric comorbidities. Authors identified 5,737 HCV infected persons and 11,228 HCV uninfected subjects. HCV infected subjects were younger, more likely to be black race and male and more likely to have the following comorbidities: hypertension; hepatitis B; cirrhosis; wasting; anemia; human immunodeficiency virus (HIV) infection; major depression; mild depression; bipolar disorder; schizophrenia; post-traumatic stress disorder; drug use; alcohol use; smoking and less likely to have the following comorbidities: coronary artery disease; stroke; peripheral vascular disease; diabetes; cancer; erythropoietin use. After adjusting for age, gender and race, HCV infected subjects were more likely to have hypertension, hepatitis B, cirrhosis, wasting, anemia and HIV infection and less likely to have coronary artery disease and stroke. Authors concluded that HCV infected persons on dialysis are more likely to have psychiatric comorbidities and substance abuse, as well as certain medical comorbidities. These factors should be considered when developing future intervention strategies. Butt, A.A., Evans, R., Skanderson, M., and Shakil, A.O. Comorbid Medical and Psychiatric Conditions and Substance Abuse in HCV Infected Persons on Dialysis. J Hepatol., 44(5), pp. 864-868, 2006.

(C2) Saliva, Breast Milk, and Mucosal Fluids in HIV Transmission

The oral environment has received various amounts of attention in association with HIV infection and pathogenesis. Since HIV infection occurs through mucosal tissue, oral factors-including tissue, fluids, and compartments-are of interest in furthering our understanding of the diagnosis, infectivity, transmission, and pathogenesis of disease. This report reviews: (1) HIV testing and diagnoses with oral fluids; (2) post-natal acquisition of HIV in association with breast-feeding from HIV-positive mothers; and (3) oral sex and HIV transmission. In the first, authors examine how oral fluids are used to detect HIV infection and review current consensus on the role of salivary molecules as markers for immunosuppression. Second, lactation-associated HIV acquisition is reviewed, with special consideration of emerging issues associated with the impact of anti-retroviral therapies. Last, authors consider current data on the risk of HIV infection in association with oral sex. Investigation of these diverse topics has a common goal: understanding how HIV presents in the oral environment, with an aim to rapid and accessible HIV diagnosis, and improved prevention and treatment of infection. Page-Shafer, K., Sweet, S., Kassaye, S., and Ssali, C. (C2) Saliva, Breast Milk, and Mucosal Fluids in HIV Transmission. Adv Dent Res., 19, pp. 152-157, 2006.

Cardiovascular Function in Multi-Ethnic Study of Atherosclerosis: Normal Values by Age, Sex, and Ethnicity

MRI provides accurate and high-resolution measurements of cardiac anatomy and function. The purpose of this study was to describe the imaging protocol and normal values of left ventricular (LV) function and mass in the Multi-Ethnic Study of Atherosclerosis (MESA). Eight hundred participants (400 men, 400 women) in four age strata (45-54, 55-64, 65-74, 75-84 years) were chosen at random. Participants with the following known cardiovascular risk factors were excluded: current smoker, systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, fasting glucose > 110 mg/dL, total cholesterol > 240 mg/dL, and high-density lipoprotein (HDL) cholesterol < 40 mg/dL. Cardiac MR images were analyzed using MASS software (version 4.2). Mean values, SDs, and correlation coefficients in relationship to patient age were calculated. There were significant differences in LV volumes and mass between men and women. LV volumes were inversely associated with age (p < 0.05) for both sexes except for the LV end-systolic volume index. For men, LV mass was inversely associated with age (slope = -0.72 g/year, p =0.0021), but LV mass index was not associated with age (slope = -0.179 g/m2/year, p = 0.075). For women, LV mass (slope = -0.15 g/year, p = 0.30) and LV mass index (slope = 0.0044 g/m2/year, p = 0.95) were not associated with age. LV mass was the largest in the African-American group (men, 181.6 +/- 35.8 [SD] g; women, 128.8 +/- 28.1 g) and was smallest in the Asian-American group (men, 129.1 +/- 20.0 g; women, 89.4 +/- 13.3 g). The normal LV differs in volume and mass between sexes and among certain ethnic groups. When indexed by body surface area, LV mass was independent of age for both sexes. Studies that assess cardiovascular risk factors in relationship to cardiac function and structure need to account for these normal variations in the population. Natori, S., Lai, S., Finn, J.P., Gomes, A.S., Hundley, W.G., Jerosch-Herold, M., Pearson, G., Sinha, S., Arai, A., Lima, J.A., and Bluemke, D.A. Cardiovascular Function in Multi-Ethnic Study of Atherosclerosis: Normal Values by Age, Sex, and Ethnicity. AJR Am J Roentgenol, 186(6 Suppl 2):S357-365, 2006.

Caffeine Metabolites in Umbilical Cord Blood, Cytochrome P-450 1A2 Activity, and Intrauterine Growth Restriction

Studies investigating antenatal caffeine consumption and reproductive outcomes show conflicting results, and most studies have used maternal self-reported caffeine consumption to estimate fetal exposure. This study (n=1,606) was specifically designed to test the association of caffeine and its primary metabolites in umbilical cord blood with intrauterine growth restriction (IUGR). Pregnant women were recruited from 56 obstetric practices and 15 clinics affiliated with six hospitals in Connecticut and Massachusetts between September 1996 and January 2000. In an adjusted model including caffeine only, levels in all quartiles were associated with reduced risk of IUGR. In adjusted analyses including paraxanthine and caffeine, serum paraxanthine levels in the highest quartile were associated with increased risk of IUGR (adjusted odds ratio=3.29, 95% confidence interval: 1.17, 9.22); caffeine remained protective. These conflicting findings suggest that cytochrome P-450 1A2 (CYP1A2) metabolic activity may be associated with IUGR, so the ratio of paraxanthine to caffeine was then modeled. The likelihood of IUGR increased 21% for every one standard deviation change in the ratio (adjusted odds ratio=1.21, 95% confidence interval: 1.07, 1.37), suggesting that CYP1A2 activity, and not the absolute levels of paraxanthine, influences fetal growth. No associations were observed between caffeine or any metabolites and preterm delivery. Grosso, L.M., Triche, E.W., Belanger, K., Benowitz, N.L., Holford, T.R., and Bracken, M.B. Caffeine Metabolites in Umbilical Cord Blood, Cytochrome P-450 1A2 Activity, and Intrauterine Growth Restriction. Am J Epidemiol., 163(11), pp. 1035-1041, 2006.

Caffeine Metabolism, Genetics, and Perinatal Outcomes: A Review of Exposure Assessment Considerations During Pregnancy

The purpose of this study was to review the methodologic issues complicating caffeine exposure assessment during pregnancy; to discuss maternal and fetal caffeine metabolism, including genetic polymorphisms affecting caffeine metabolism; and to discuss the endogenous and exogenous risk factors known to influence caffeine metabolism. Methods consisted of a review of the relevant literature. Results indicated that there is wide inter-individual variation in caffeine metabolism, primarily due to variations in CYP1A2 enzyme activity. Some variability in CYP1A2 activity is due to genetic polymorphisms in the CYP1A2 gene that can cause increased or decreased inducibility of the enzyme. Considerable evidence exists that maternal caffeine metabolism is influenced by a variety of endogenous and exogenous factors and studying the genetic polymorphisms may improve understanding of the potential effects of caffeine and its metabolites on perinatal outcomes. There is substantial evidence that measurement of maternal, fetal, and neonatal caffeine metabolites may allow for a more precise measure of fetal caffeine exposure. Authors conclude that research on the genetic polymorphisms affecting caffeine metabolism may further explain the potential effects of caffeine and its metabolites on perinatal outcomes. Grosso, L.M. and Bracken, M.B. Caffeine Metabolism, Genetics, and Perinatal Outcomes: A Review of Exposure Assessment Considerations During Pregnancy. Ann Epidemiol., 15(6), pp. 460-466, 2005.

Services Research

Survival Benefits of AIDS Treatment

As widespread adoption of potent combination antiretroviral therapy (ART) reaches its tenth year, the objective of this study was to quantify the cumulative survival benefits of acquired immunodeficiency syndrome (AIDS) care in the United States. Eras were defined that corresponded to advances in standards of human immunodeficiency virus (HIV) disease care, including opportunistic infection prophylaxis, treatment with ART, and the prevention of mother-to-child transmission (pMTCT) of HIV. Per-person survival benefits for each era were determined using a mathematical simulation model. Published estimates provided the number of adult patients with new diagnoses of AIDS who were receiving care in the United States from 1989 to 2003. Compared with survival associated with untreated HIV disease, per-person survival increased 0.26 years with Pneumocystis jiroveci pneumonia prophylaxis alone. Four eras of increasingly effective ART in addition to prophylaxis resulted in per-person survival increases of 7.81, 11.05, 11.57, and 13.33 years, compared with the absence of treatment. Treatment for patients with AIDS in care in the United States since 1989 yielded a total survival benefit of 2.8 million years. pMTCT averted nearly 2900 infant infections, equivalent to 137,000 additional years of survival benefit. In conclusion, at least 3.0 million years of life have been saved in the United States as a direct result of care of patients with AIDS, highlighting the significant advances made in HIV disease treatment. Walensky, R., Paltiel, A., Losina, E., Mercincavage, L., Schackman, B., Sax, P., Weinstein, M., and Freedberg, K. The Survival Benefits of AIDS Treatment in the United States. J Infect Dis, 194(1), pp. 11-19, 2006.

Prevalence of DSM/ICD-Defined Nicotine Dependence

In this study techniques of systematic review were used to estimate for adults (1) the lifetime and current prevalence of DSM/ICD-defined nicotine dependence and (2) the prevalence of individual DSM/ICD dependence criteria. Systematic computer searches and other methods located eleven population-based surveys of adults (>/=18 year olds) and two of young adults (18-30 year olds). In the USA and Germany, about 25% of adults had been dependent on nicotine in their lifetime, including 15% who were currently dependent. Similar or higher rates were seen in Asian men but <5% of Asian women had been dependent. About a third of ever-smokers and half of current smokers either had been or were currently dependent on nicotine and this did not consistently differ by age, country or sex. Impaired control over tobacco use was the most commonly endorsed criteria and giving up activities to use and spending lots of time with nicotine were the least commonly endorsed. This study is consistent with others that show that nicotine dependence is one of the most common mental disorders; however, about half of current smokers do not meet DSM/ICD dependence criterion, perhaps because they have not tried to stop, nicotine is more legal than other drugs of dependence, and nicotine causes fewer behavioral disturbances than other drugs of abuse. However none of these possible explanations have been empirically tested as yet. Hughes, J.R., Helzer, J.E., and Lindberg, S.A. Prevalence of DSM/ICD-defined Nicotine Dependence. Drug Alcohol Depend, 85(2), pp. 91-102, 2006.

Utilization of Medicaid Substance Abuse Services Among Adolescents

This study examined race and gender disparities in utilization of substance abuse treatment among adolescents enrolled in Medicaid in Tennessee. By using Medicaid enrollment, encounter, and claims data, utilization of substance abuse services for the population of adolescents enrolled in TennCare was examined in two ways. The first utilization measure considered annual utilization rates and probability of use of substance abuse services for the statewide population of enrolled adolescents (approximately 170,000 per year). The second examined the age at which the first substance abuse service was received for the 8,473 youths who had that service paid for by TennCare during state fiscal years 1997 to 2001. Proportionally, among adolescents, more whites than blacks and more males than females used substance abuse services. The disparities were greater than differences in prevalence rates explain. Black females had the greatest disparity in service utilization. Whites and females received their first substance abuse service at a younger age than blacks or males in this Medicaid population. However, the age difference may not be clinically significant. The low utilization rates, in general, and the disparities in service use by race and gender raise questions about the identification of substance use problems at both provider and system levels. Heflinger, C., Chatman, J., and Saunders, R. Racial and Gender Differences in Utilization of Medicaid Substance Abuse Services among Adolescents. Psychiatr Serv, 57(4), pp. 504-511, 2006.

Gender Differences in the Prediction of Condom Use Among Incarcerated Juvenile Offenders

This study seeks to predict condom-protected vaginal intercourse among incarcerated youth using the Information-Motivation-Behavioral skills (IMB) model as the theoretical framework. The IMB model is a three-factor conceptualization of HIV preventive behavior including information on HIV/AIDS transmission and prevention methods, motivation to act on the knowledge and change risky behavior, and behavioral skills in performing the specific prevention act. Data was collected from youth held in a detention center located in a Southern city. Adolescents 13 years of age or older and recently incarcerated (within 3 days of booking) were eligible for the study. The study sample included 523 adolescents (328 male and 195 female. Participants were predominately African-American (90%), with an average age of 15, and average level of highest education was 9th grade. Survey data was collected for a self-report measure of AIDS knowledge, pre-condom peer influence, risk perception, condom attitudes, condom use self-efficacy, frequency of vaginal intercourse, and frequency of condom-protected vaginal intercourse. Results revealed that being male, peer influence, positive condom attitudes, and condom self-efficacy significantly predicted condom use. Separate gender analyses revealed that condom use among males was predicted by peer influence and positive condom attitudes, whereas condom use among females was predicted by peer influence, self-efficacy, and condom attitudes. Compared with males, females reported significantly greater knowledge, less peer influence, higher perceived risk for infection, more positive condom attitudes, and more self-efficacy. Despite these findings, females reported less condom use than males. The authors conclude that females find it difficult to use condoms consistently despite their awareness. They suggest that power imbalances and other dynamics operating within relationships between boys and girls need to be explored further in developing effective HIV prevention interventions. Robertson, A.A., Stein, J.A., and Baird-Thomas, C. Gender Differences in the Reduction of Condom Use among Incarcerated Juvenile Offenders: Testing the Information-motivation-behavior Skills (IMB) Model. J Adolesc Health, 38(2006), pp. 18-25, 2006.

Pregnant Women Treated in Women-only Versus Mixed-gender Programs Receive More Services

This study-compared characteristics of pregnant women treated in women-only (WO) and mixed-gender (MG) substance abuse treatment programs and compared services provided by these two types of programs. Participants were 407 pregnant women who were admitted to 7 WO programs and 29 MG programs in 13 counties across California during 2000-2002. Pregnant women treated in WO programs demonstrated greater severity in drug use, legal problems, and psychiatric problems than those treated in the MG programs. They were also less likely to be employed and more likely to be homeless. Women-only programs were more likely to offer childcare, children's psychological services, and HIV testing. The greater problem severity of pregnant women treated in WO programs suggests that these specialized services are filling an important gap in addiction services, although further expansion is warranted in psychiatric, legal, and employment services. Hser, Y., and Niv, N. Pregnant Women in Women-Only and Mixed-Gender Substance Abuse Treatment Programs: A Comparison of Client Characteristics and Program Services. J Behav Health Serv Res, 33(4), pp. 431-442, 2006.

Exposure to Transphobia and HIV Risk Behavior Among Transgendered Women

This study examined the relationship between exposure to transphobia -societal discrimination and stigma of individuals who do not conform to traditional notions of gender--and risk for engaging in unprotected receptive anal intercourse (URAI) among 327 transgendered women of color. Overall, 24% of participants had engaged in URAI at least once in the past 30 days. Individuals who self-identified as pre-operative transsexual/transgendered women were significantly more likely than self-identified females to have engaged in URAI. Although exposure to transphobia was not independently related to URAI, an interaction between age and experiencing discrimination was observed. Among transgendered women 18-25 years old, those reporting higher levels of exposure to transphobia had a 3.2 times higher risk for engaging in URAI compared to those reporting lower levels. Findings from this study corroborate the importance of exposure to transphobia on HIV risk, particularly among transgendered young adults. Sugano, E., Nemoto, T., and Operario, D. The Impact of Exposure to Transphobia on HIV Risk Behavior in a Sample of Transgendered Women of Color in San Francisco. AIDS Behav, 10(2), pp. 217-225, 2006.

International Research

Alumni of the NIDA International Program research training and exchange programs authored or coauthored the following articles indexed by PubMed:

Prevalence and Correlates of Drug Use Disorders in Mexico

The objective of this study was to describe the prevalence of drug use disorders, the correlates of drug use, and the utilization of specialized treatment services for drug users among the Mexican urban population 18-65 years old. The data were collected in 2001 and 2002 in the Mexican National Comorbidity Survey. The sample design was stratified probabilistically for six geographical areas of the country in a multistage process for census count areas, city blocks, groups of households, and individuals. The data were weighted, taking into account the probability of selection and the response rate. The information was collected using a computerized version of the World Mental Health Survey edition of the Composite International Diagnostic Interview. The weighted response rate for individuals was 76.6%. Overall, 2.3% of the population reported any illicit use of drugs in the preceding 12 months; marijuana and cocaine were the substances most often used. Low levels of education were significantly associated with use, abuse, and dependence. Use of any drug was significantly more common among those who were in the youngest age group (18-29 years), were male, or were living in the Northwest region of the country. Overall, 1.4% had a lifetime history of drug abuse or dependence, with this being much more common for men (2.9%) than for women (0.2%). The 12-month prevalence of drug abuse or dependence was 0.4% overall (0.9% for men, and 0.0% for women). The rate of treatment during the preceding 12 months for those with the 12-month criteria for abuse or dependence was 17.1%; 14.8% were seen in specialized treatment centers; 2.8% reported having attended self-help groups. A noticeable number of Mexicans have a drug use disorder, but demand for treatment is limited, in part due to stigma. These results indicate that there is an urgent need to organize the specialized services for persons with a substance abuse disorder according to the prevalence of dependence on different substances and the variation in prevalence in the different regions of the country. Medina-Mora, M.E., Borges, G., Fleiz, C., Benjet, C., Rojas, E., Zambrano, J., Villatoro, J., and Aguilar-Gaxiola, S. Rev Panam Salud Publica. 19(4), pp. 265-276, April 2006. INVEST Fellow: Guilherme Borges, Mexico, 1997-1998.

Leber's Hereditary Optic Neuroretinopathy (LHON) Associated with Mitochondrial DNA Point Mutation G11778A in Two Croatian Families

Leber's hereditary optic neuroretinopathy (LHON) is manifested as a bilateral acute or subacute loss of central vision due to optic atrophy. It is linked to point mutations of mitochondrial DNA, which is inherited maternally. The most common mitochondrial DNA point mutations associated with LHON are G3460A, G11778A and T14484C. These mutations are linked with the defects of subunits of the complex I (NADH-dehydrogenase-ubiquinone reductase) in mitochondria. The G11778A mitochondrial DNA point mutation is manifested by a severe visual impairment. In this paper two Croatian families with the LHON G11778A mutation are presented. Three LHON patients from two families were younger males who had the visual acuity of 0.1 or below, the ophthalmoscopy revealed telangiectatic microangiopathy and papilloedema, while Goldmann kinetic perimetry showed a central scotoma. The mothers and female relatives were LHON mutants without symptoms, whereas their sons suffered from a severe visual impairment. Molecular diagnosis helps to explain the cause of LHON disease. Martin-Kleiner, I., Gabrilovac, J., Bradvica, M., Vidovic, T., Cerovski, B., Fumic, K., and Boranic, M. Coll Antropol. 30(1), pp. 171-174, March 2006. INVEST Fellow: Irena Martin-Kleiner, Croatia, 1995-1996.

Former Hubert H. Humphrey Drug Abuse Research Fellows

Assessing Prescribing and Patient Care Indicators for Children Under Five Years Old With Malaria and Other Disease Conditions in Public Primary Health Care Facilities

A prospective descriptive observational study using WHO indicator forms and questionnaire was carried out in Kibaha district public primary health care facilities. Authors assessed knowledge about drugs in mothers/guardians of sick children under age five years immediately after consulting clinicians and after receiving drugs from the dispenser. The questionnaires had closed- and open-ended questions. Interviews were administered by trained nurses and the authors. The prescribing, dispensing practices, including drug labeling and instructions given to mothers/guardians on how to use drugs at home, in these health facilities which are under the Essential Drugs Program (EDP), was assessed. A total of 652 prescriptions from mothers/ guardians with sick children under age five years were observed, recorded and analyzed. Prescribing indicators were used as stipulated by the WHO/DAP/93.1 how to investigate drug use in health facilities. The diagnosis for malaria cases made by the clinicians on average per facility were as follows: malaria alone 25, diarrhea alone 3, pneumonia alone 3, malaria and diarrhea 4 cases, malaria and pneumonia 2 cases and malaria and other conditions 14 cases. The average number of drugs per prescription in these facilities was 2.3 and the percentage generic prescribing was 87.0, antibiotics 30.5, and injections 26.2, with 93.5 % of all prescribed drugs being within the Essential Drugs List (EDL). The overall average dispensing time was 1.4 minutes per patient, of the drugs prescribed, 54.7 % were dispensed, whereas 21.4 % of drugs dispensed to mothers/guardians were adequately labeled, and 37.2 % of mothers knew how to administer drugs correctly to their sick children after receiving the drugs from the dispenser. These results suggest the need for educational intervention for prescribers (health care providers) on rational prescribing of drugs, such as antimalarials, antibiotics, injections, proper dispensing, and adequate labeling drugs in packets, while the dispensing time for drugs was too short. It is necessary to correct these malpractices of irrational prescribing and dispensing drugs for treatment of malaria and other childhood illnesses in public primary health care facilities (PHC). Furthermore, inadequate physical examination and short consultation time needs to be improved. There is a need to advise the Ministry of Health to develop health education programs on a regular basis for all health care providers in the country and mothers/guardians of children in general public/rural communities on how to use/administer antimalarials and other drugs at home. All these can be achieved through well planned health education training programs. Nsimba, S.E. Southeast Asian J Trop Med Public Health. 37(1):206-214, January 2006. HHH Fellow: Stephen Nsimba, Tanzania, 2005-2006.

Poor Educational Attainment and Sexually Transmitted Infections Associated with Positive HIV Serostatus Among Female In-Patient Substance Abusers in Trinidad and Tobago

Female crack cocaine users are at high risk for HIV infection. Data from 121 female substance abusers admitted to an all-female rehabilitation center in Trinidad and Tobago between 1996 and 2002 were reviewed retrospectively to determine human immunodeficiency virus (HIV) seroprevalence and associated risk factors. HIV seroprevalence was 19.8%, which is six times higher than in the general population. The univariate analysis identified the following factors associated with HIV infection: poor educational attainment, history of a sexually transmitted infection (STI), and use of crack cocaine. In the multivariate analysis, only poor educational attainment and history of an STI were independently associated with HIV seroprevalence. Female substance abusers, especially female crack cocaine users, are at high risk of acquiring and transmitting the HIV virus. To reduce risk of HIV infection, rehabilitation programs should address risky sexual behaviors and screen for STIs, and they also should improve educational attainment, develop skills, and provide vocational training. Reid, S.D. Drug Alcohol Depend. 82 Suppl 1, pp. S81-84, April 2006. HHH Fellow: Sandra Reid, Trinidad and Tobago, 1992-1993.

Intramural Research

Treatment Section, Clinical Pharmacology and Therapeutics Research Branch

Adverse Events Among Patients in a Behavioral Treatment Trial for Heroin and Cocaine Dependence: Effects of Age, Race, and Gender

Safety monitoring is a critical element of clinical trials evaluating treatment for substance dependence, but is complicated by participants' high levels of medical and psychiatric comorbidity. This paper describes AEs reported in a large (N = 286), 29-week outpatient study of behavioral interventions for heroin and cocaine dependence in methadone-maintained outpatients. A total of 884 AEs were reported (3.1 per patient, 0.12 per patient-week), the most common being infections (26.8%), gastrointestinal (20.5%), musculoskeletal (12.3%), and general (10%) disorders. Serious AEs were uncommon (1.6% of total). Female participants reported significantly higher rates of AEs (incidence density ratio, IDR = 1.38, p < 0.0001); lower rates of AEs were reported by African Americans (IDR = 0.73, p < 0.0001) and participants over age 40 reported lower rates of AEs (IDR = 0.84, p = 0.0095). AE incidence was not associated with the study intervention or with psychiatric comorbidity. Further work is needed to adapt AE coding systems for behavioral trials for substance dependence; the standard Medical Dictionary for Regulatory Activities, International Federation of Pharmaceutical Manufacturers Associations (MedDRA) coding system used in this report did not contain a separate category for one of the most common types of AE, dental problems. Nonetheless, the data reported here should help provide a context in which investigators and IRBs can interpret the patterns of AEs they encounter. Schroeder, J.R., Schmittner, J.P., Epstein, D.H., and Preston, K.L. Drug and Alcohol Dependence, 80, pp. 45-51, 2005.

Menstrual Cycle Length during Methadone Maintenance

While the menstrual disruption of heroin has been demonstrated, there are few published data concerning methadone maintenance and menstrual function. This study was conducted to evaluate whether cycle length was more regular during methadone maintenance. A total of 191 heroin and cocaine-using women who were maintained on methadone therapy (70-100 mg/day) in two clinical trials, lasting 25-29 weeks. Start/end dates of each menses were collected weekly. Menstrual patterns were classified as regular, irregular, transient amenorrhea, persistent amenorrhea or cycle restart. Repeated-measures regression modeling determined correlates of cycle length and predictors of long cycles (> 40 days) and short cycles (< 20 days). Bleeding episodes were defined as 1 or more bleeding days, bound by at least 2 non-bleeding days. Correlates/predictors examined were body mass index, drug use, methadone dose and race. In the 133 women for whom menstrual patterns could be determined, cycle-length irregularity was common: irregular, 62 (46.7%); regular, 37 (27.8%); cycle restart, 16 (12%); persistent amenorrhea, 11 (8.3%); transient amenorrhea, seven (5.3%). Each additional week on methadone maintenance was associated with decreased risk of long (OR = 0.96, P < 0.01 and short (OR = 0.92, P < 0.01) cycles. Of 27 women with secondary amenorrhea pre-study, 16 (59%) restarted menses. Positivity for opioids or cocaine was not significantly associated with short or long cycles. Cycle length begins to normalize during methadone maintenance. Menses resumption may occur. Methadone maintenance, despite interfering with menstrual function in an absolute sense, may interfere less than illicit heroin abuse. Schmittner, J., Schroeder, J.R., Epstein, D.H., and Preston, K.L. Addiction, 100, pp. 829-836, 2005.