Director's Report to Council - Research Findings Excerpts

May, 2004

Basic Research

Gestational Nicotine Exposure Attenuates Nicotine-Stimulated Dopamine Release in the Nucleus Accumbens Shell of Adolescent Lewis Rats

The effects of chronic gestational exposure to nicotine on the nucleus accumbens dopamine response to acute nicotine were determined during adolescence (postnatal day 2936) in cross-fostered and noncross-fostered Lewis rats. In both males and females, gestational nicotine exposure diminished the adolescent nucleus accumbens dopamine response to 0.07 mg/kg nicotine i.v. However, dopamine responses to 0.105 mg/kg nicotine were unaffected by gestational nicotine treatment and were similar in both genders. Furthermore, in both female and male gestational nicotine and control groups, the dopamine response to nicotine (0.105) was the same as that observed to the lower dose of nicotine in gestational controls. Thus, in adolescent male and female Lewis rats, gestational nicotine exposure attenuated nucleus accumbens dopamine release to a maximally stimulative dose of nicotine. Unexpectedly, in female gestational controls cross fostering per se reduced nucleus accumbens dopamine secretion to 0.07 mg/kg nicotine. These investigations suggest that gestational nicotine exposure could modify the acute reinforcing effects of nicotine in adolescent rats, whereas early postnatal stressors, (e.g., cross-fostering) may affect nicotine-induced reinforcement in female but not male adolescents. Kane, V.B., Fu, Y., Matta, S.G. and Sharp, B.M. Gestational Nicotine Exposure Attenuates Nicotine-Stimulated Dopamine Release in the Nucleus Accumbens Shell of Adolescent Lewis Rats. JPET, 308(2), pp. 521-528, 2004.

Behavioral Research

Early Life Events Increase Susceptibility for Cocaine Self-Administration: The Identification of 'Sensitive Periods' in Development

Individual differences in susceptibility to drug abuse and addiction are influenced by both genetic and environmental factors, such as early life stressors and maternal care. In this study, the investigators compared the effects of manipulations during week 1 vs. week 2 of life on subsequent propensity to self-administer cocaine. Pups received daily subcutaneous saline injections, were handled briefly, or remained undisturbed during their respective treatment periods. The rats were then given the opportunity to self-administer cocaine when they were 70 days old. Only animals manipulated during the second week of life acquired drug-taking behavior. These effects were both stimulus- and gender-specific: Females handled during the second week of life acquired cocaine self-administration at the lowest dose, and females injected during the second week of life acquired at the intermediate dose. Males injected during the second week of life showed a similar, but more variable, drug-taking pattern. In addition, females that were either handled or saline injected during the first week of life were the most resistant to acquiring self-administration. The authors conclude that the second week of life represents a sensitive period in this preclinical model of environmental manipulations, for influencing the vulnerability to acquire cocaine self-administration, especially in females. The observed gender difference is consistent with findings from many other studies comparing vulnerability for self-administration in male versus female subjects. The results also support previous observations that increased maternal attention following stressful events during early development can confers protective effects for subsequent drug taking behaviors. This study makes a valuable contribution to understanding how early life events alter neurobiological substrates that may confer differential susceptibility to drugs of abuse in adolescents and adults. Flagel, S.B., Vazquez, D.M. and Robinson T.E. Manipulations During the Second, but not the First, Week of Life Increase Susceptibility to Cocaine Self-Administration in Female Rats. Neuropsychopharmacology, 28, pp. 1741-1751, 2003.

Estrogen Enhances Stimulant-Induced Behavioral Activity in Female Rats

It is well established that locomotor activating effects of cocaine are greater in female than male rats. Several observations suggest that this sex difference is mediated by estrogen: For example, these sex differences emerge after puberty; cocaine-induced locomotion is greater during proestrus (when estrogen is highest) and estrous, than during diestrus; and cocaine-induced locomotion in ovariectomized rats is enhanced by the chronic administration of estrogen. Drs. Kathryn Cunningham, Mary Thomas and colleagues at the University of Texas Medical Branch have found evidence that the locomotor hyperactivity induced by 3,4methylenedioxymeth-amphetamine (MDMA, ecstasy) is also greater in female than male rats. They previously reported greater locomotor hyperactivity in female than male rats in response to 4 mg/kg doses of (+)-MDMA (Bubar, Thomas, & Cunningham, 2001). In a follow-up study, these researchers compared locomotor activity induced by either (+)-MDMA or cocaine, in rats that were ovariectomized (OVX) and in rats that were ovariectomized plus given a 17_-estradiol (E2) implant (OVX+E2). Locomotor activity was examined for two hours following (+)-MDMA (1, 2, 4 mg/kg ip) or cocaine (5, 10, 20 mg/kg ip). During initial habituation to the open field activity chambers, activity declined from Day 1 to Day 3. The investigators observed that the OVX+E2 group displayed retarded habituation of vertical and horizontal activity relative to the OVX group, although this difference did not achieve statistical significance. Both MDMA and cocaine administration dose-dependently increased locomotor activity. Both horizontal and vertical activity were elevated in the OVX+E2 group relative to the OVX group at the highest MDMA dose (4 mg/kg) and at the highest two cocaine doses (10 and 20 mg/kg), indicating E2 enhancement of MDMA-induced and cocaine-induced locomotor activation at those doses. Examination of the time course of locomotor activation indicated differential effects of MDMA and cocaine. Within 5-min of cocaine administration, both OVX and OVX+E rats exhibited hyperactivity followed by a decline over the 2-hr session. In contrast, MDMA activity increased only slightly in the first 20 min followed by hyperactivity between 20 and 40 min following injection. These differences appear in part to be related to the pharmacokinetic profiles of MDMA and cocaine. Although both drugs potentiate efflux of dopamine (DA) and 5-hydroxytryptamine (5-HT, serotonin), the drugs have different time courses for this potentiation -- MDMA produces an immediate increase in 5-HT, but a delayed increase in DA, whereas cocaine produces an immediate increase in both 5-HT and DA. Thus, the present data suggest that E2 may play a greater role in altering DA activity than 5-HT activity. Zhou, W., Cunningham, K.A., and Thomas, M.L. Estrogen Effects on the Hyperactivity Induced by (+)-MDMA and Cocaine in Female Rats. Behavioral Neuroscience, 117, pp. 84-94, 2003.

Sex-Dependent Effects of _9-tetrahydrocannabinol on Locomotor Activity in Mice

Prior research on the locomotor-altering effects of _9-tetrahydrocannabinol in rodents has shown suppressive effects at higher doses, facilitation at lower doses, and tolerance to the suppressive effects with repeated dosing. In the present study, Dr. Jenny Wiley of the Virginia Commonwealth University examined sex differences in _9-tetrahydrocannabinol's locomotor effects in mice. A range of single-injection doses, 1  30 mg/kg ip, was delivered to separate groups of mice on two separate test days. On Day 1, males did not exhibit increased locomotor activity compared to vehicle at any dose. Females, on the other hand, exhibited elevated locomotion at 1, 3, and 10 mg/kg. The enhancement at 1 and 10 mg/kg were each statistically higher than vehicle effects, and statistically higher than effects seen in males. Following 3 days of daily injections of 10 mg/kg (two injection on Days 2 and 3 and one injection on Day 4), on Day 5, the dose-response curve was re-determined. Again, males did not exhibit increased locomotor activity compared to vehicle at any dose. Females, however, exhibited statistically significantly increased locomotor activity with the 3, 10, and 30 mg/kg dose. However, at the 1mg/kg dose, no enhancement of locomotor activity was observed, suggesting the development of tolerance. At none of the doses was activity-suppression observed in either males or females. _9-tetrahydrocannabinol's activity-inducing effects in females, but not in males, observed in the present study is consistent with prior observations from rats showing greater female sensitivity to _9-tetrahydrocannabinol's locomotor-suppressive effects, antinociceptive effects, and cataleptic effects. Wiley, J.L. Sex-Dependent Effects of _9-tetrahydrocannabinol on Locomotor Activity in Mice. Neuroscience Letters, 352, pp. 77-80, 2003.

Treatment Research and Development

Smoking Among Female Prisoners: An Ignored Public Health Epidemic

The Mississippi Department of Corrections surveyed 866 female prisoners about tobacco use and interest in a smoking cessation program with a 27-item questionnaire. The majority of female inmates (73.9%) were current tobacco users with a mean of 14.6 cigarettes per day. Approximately 12.5% of current smokers reported a tobacco-related medical problem. Most (60.6%) had made at least one attempt to quit smoking and only 24.5% felt very confident that they could quit if they made an attempt. Overall, 64.2% of the smokers reported interest in participating in the smoking cessation program, with heavier smokers (71.4 %) reporting the most interest in enrolling in the program. The high percentage of current tobacco users, high level of interest in smoking cessation, and presence of smoking-related health problems indicate a tremendous public and correctional health problem that is being ignored. Cropsey, K., Eldridge, G.D., and Ladner, T. Addictive Behaviors, 29, pp. 425-431, 2004.

Psychiatric Co-morbidity Among Adolescent Substance Abusers Effects Response to Behavioral Treatment

Dr. Cindy Rowe of the University of Miami and colleagues continue their work to clarify the connection between psychiatric co-morbidity and treatment of adolescent substance abuse. Building on previous work highlighting the importance of both externalizing and internalizing disorders among adolescent substance abusers, this newest study examined whether adolescents with different psychiatric co-morbidities differed in clinical presentation and treatment response. Among 182 adolescent drug abusers in a randomized clinical trial comparing family and individual cognitive-behavioral therapy, more severe co-morbidity was associated with greater family dysfunction and being female and younger at intake. Regarding treatment response, adolescents with mixed externalizing and internalizing co-morbidities initially responded to treatment but returned to intake levels of substance use by 1 year post-discharge. Rowe, C.L., Liddle, H.A., Greenbaum, P.E. and Henderson, C. Impact of Psychiatric Comorbidity on Treatment Outcomes of Adolescent Drug Abusers. Journal of Substance Abuse Treatment, 26, pp. 1-12, 2004.

Mothers Entering Drug Treatment Appear to be Successful at Maintaining or Re-establishing Co-residency with their Children

Dr. Danica Knight and colleagues at Texas Christian University conducted a study of the degree to which mothers who enter residential drug treatment are successful in maintaining or re-establishing their role as parents during the course of treatment. The sample included 152 female clients admitted to a residential drug treatment program for women with dependent children. Among the 152 women in the study, there was a significant increase in child co-residency from admission to follow-up. Women who entered treatment with all children, or who were reunited with children previously in others' care at admission, were over five times more likely to co-reside with all children at follow-up. At follow-up, mothers who reported complete co-residence were more likely to be 30 years old or younger, live independently, and have fewer than two parenting challenges. This study documents the status of child co-residence prior to, during, and following treatment, which may have implications for the practice of providing child care and family residency options in drug abuse treatment. Knight, D.K. and Wallace, G. Where Are the Children? An Examination of Children's Living Arrangements when Mothers Enter Residential Drug Treatment. Journal of Drug Issues, 33(2), pp. 305-324, 2003.

HIV-Risk Behaviors Appear to be Connected to Violence and Clinical Depression Among Some Female Drug Users

Drs. Johnson, Cunningham-Williams, and Cottler recently published a paper describing the connection between sexual HIV-risk behaviors and exposure to violence and/or depression among 420 African-American out-of-treatment female drug users. Sexual risk behaviors were compared for women in mutually exclusive groups based on exposure to violence and the presence of clinical depression. Results showed that women with a history of sexually transmitted diseases were more likely to experience violence and depression, both alone and jointly. Women who had two or more sexual partners in the last 30 days and women who had an early onset of alcohol use were at an increased risk for having drug use, violence and depression. Never being married was a protective factor for drug use, violence and depression. As expected, more risk factors were found among women who had the full tripartite than among women with one or two of the factors. Johnson, S., Cunningham-Williams, R.M. and Cottler, L.B. A Tripartite of HIV-risk for African-American Women: The Intersection of Drug Use, Violence, and Depression. Drug and Alcohol Dependence, 70(2), pp. 169-175, 2003.

Improving Parenting and Drug Use Among Drug-Dependent Mothers

Dr. Suchman of Yale University and colleagues developed and tested a 12-week parenting intervention for drug-dependent mothers. The investigators compared 20 mothers receiving Emotionally-Responsive Parenting (ERP) to a historical control group of 23 mothers that received standard treatment. Mothers receiving ERP mothers had better weekly attendance, and completion rates, and were more compliant with clinical advice. At post-treatment, 83% of women receiving ERP vs. 70% of comparison mothers were abstinent, but this difference was non-significant. Importantly, ERP mothers' capacity to acknowledge their own and their children's cognitive and affective states also improved significantly. This pilot study suggests that a parenting intervention focused on increasing parents' emotional availability to children can be effective in contributing both to abstinence and to emotional responsiveness. Suchman, N. E., Altomare, M., Moller, F., Slade, A., & Mayes, L. Emotionally Responsive Parenting: A New Parenting Intervention for Drug Dependent Mothers. Invited poster presentation, College on Problems of Drug Dependence Annual Meeting, Bal Harbour, FL, June 2003.

Social Relationships Appear to be Integral to Successful Treatment for Women in Drug Abuse Treatment

Dr. Danica Knight and colleagues at Texas Christian University presented a paper on the role of social relationships for women in drug abuse treatment. Findings documented significant associations between interpersonal relationship measures and key treatment process indicators among 152 women in long-term residential drug abuse treatment. For example, clients who were motivated at treatment entry were more likely to develop healthy relationships with fellow clients during treatment, and those who reported healthier family relationships were more likely to complete treatment requirements. Relationships with peers were important in the development of counselor rapport, and in perceived support for treatment. Relationships with family members impacted psychosocial functioning and completion, and relationships with counselors facilitated compliance, longer retention, and completion. This study provides additional evidence for the importance of building and maintaining positive social networks during the course of treatment. Knight, D.K., Joe, G.W, and Simpson, D.D. Is the Treatment Process Different for Women in Residential Treatment? Presented at the annual meeting of the American Psychological Association, Toronto, Canada, August 2003.

Genetic and Environmental Influences on Substance Initiation, Use, and Problem Use in Adolescents

Dr. Thomas Crowley and colleagues at the University of Colorado conducted a sibling/twin/adoption study of substance initiation, use, and problem use, estimating the relative contribution of genetic and environmental influences on these phenotypes in adolescents. The participants were 345 monozygotic twin pairs, 337 dizygotic twin pairs, 306 biological sibling pairs, and 74 adoptive sibling pairs. Results showed that there were moderate to substantial genetic influences, with the exception of alcohol use and any drug use, and modest to moderate shared environmental influences on substance initiation, use, and problem use. For alcohol and any drug, heritability was higher and the magnitude of shared environmental influences was lower for problem use than for initiation or use. Environmental influences shared only by twin pairs had a significant effect on tobacco initiation, alcohol use, and any drug use. For tobacco use, tobacco problem use, and marijuana initiation, heritability was higher and the magnitude of shared environmental influences was lower in female than in male adolescents. There was no evidence for sex-specific genetic or shared environmental influences on any variable. The moderate to substantial heritabilities found for adolescents in the present study are comparable to those found in twin studies of adult substance use and substance use disorders. The finding that problem use is more heritable than initiation and use is also consistent with the results of adult twin studies. The significance of environmental influences shared only by twin pairs on tobacco initiation, alcohol use, and any drug use suggests the influences of peers, accessibility of substances, and sibling interaction. Soo Hyun Rhee, S.H, Hewitt, J.K, Young, S.E., Corley, R.P., Crowley, T.J. and Stallings, M.C. Archives of General Psychiatry, 60, pp. 1256-1264, 2003.

Sex Differences in rCBF Induced by Cue-induced Craving

Using verbal scripts to induce craving in patients with cocaine dependence (most, but not all who were in treatment), Kilts and colleagues at Emory University found, using PET, rCBF increases in the superior temporal gyrus, dorsal anterior and posterior cingulate cortex, nucleus accumbens area, and the central sulcus. However, in comparison to an identical study in men, women showed less activation of the amygdala, insula, orbitofrontal cortex, and ventral cingulate cortex but greater activation of the central sulcus and widely distributed frontal cortical areas. These findings suggest sex differences in the functional anatomy associated with cue-induced cocaine craving. Whether these differences are physiological or perceptual or both cannot be determined but once characterized may have implications for treatment. Kilts, C.D., Gross, R.E., Ely, T.D. and Drexler, K.P.G. American Journal of Psychiatry, 161(2), pp. 233-241, 2004.

Research on AIDS and Other Medical Consequences of Drug Abuse

AIDS Research

Sex Work and Drug Use in a Subculture of Violence

In this paper, researchers examine the subculture of violence thesis as it relates to female street sex workers in Miami. Interview and focus group methods were used to study the intersection of childhood trauma, drug use, and violent victimization among 325 women. Using targeted sampling, crack- and heroin-using sex workers were recruited through street outreach into an HIV-prevention research program. Interviews used standard instrumentation and focused on drug-related and sexual risk for HIV, sex work, violence, childhood trauma, and health status. Past drug use among the women was found to be substantial, and large percentages reported high levels of substance use in the past month, including use of alcohol. Nearly half of the respondents reported physical (44.9%) and/or sexual (50.5%) abuse as children, and over 40% experienced violence from clients in the prior year: 24.9% were beaten, 12.9% were raped, and 13.8% were threatened with weapons. Consistent relationships between historical and current victimization suggest that female sex workers experience a continuing cycle of violence throughout their lives. Surratt, H., Inciardi, J., Kurtz, S. and Kiley, M. Sex Work and Drug Use in a Subculture of Violence. Crime and Delinquency, 50(1), pp. 43-59, 2004.

Methamphetamine Dependence Increases Risk of Neuropsychological Impairment in HIV Infected Persons

HIV infection and methamphetamine (METH) dependence can each be associated with brain dysfunction. Little is known, however, about the cognitive effects of co-occurring HIV infection and METH dependence. NIDA researchers studied four groups of 200 participants: HIV+/METH, HIV-/METH, HIV+/No METH, and HIV-/ No METH. The groups were similar in age, education, and ethnicity, although there were significantly more females in the HIV-/No METH group. A comprehensive, demographically corrected neuropsychological battery was administered yielding a global performance score and scores for seven neuro-behavioral domains. Rates of global impairment were higher in the HIV+/METH (58%), HIV-/METH (40%) and HIV+/No METH (38%) groups compared to the HIV-/No METH (18%) group. A significant monotonic trend for global cognitive status was seen across groups, with the least impairment in the HIV-/No METH group and highest in the HIV+/METH+ group. The results indicate that HIV infection and METH dependence are each associated with neuropsychological deficits, which suggests that these factors in combination are associated with additive deleterious cognitive effects. This additivity may reflect common pathways to neural injury involving both cytotoxic and apoptotic mechanisms. Rippeth, J.D., Heaton, R.K., Carey, C.L., Marcotte, T.D., Moore, J.D., Gonzalez, R. and Wolfson, I.G., The HNRC Group. Methamphetamine Dependence Increases Risk of Neuropsychological Impairment in HIV Infected Persons. Journal of the International Neuropsychological Society. 10(1), pp.1-14, January 2004.

Sharing of Non-Injection Drug Use Implements as a Risk Factor for Hepatitis C

Researchers examined sharing of non-injection drug implements as a risk factor for hepatitis C (HCV) infection among women drug users (n=123) with no history of drug injection. Participants were street-recruited from East Harlem, New York City, between October 1997 and June 1999. They were administered a survey measuring risk factors for HCV. Prevalence of HCV and HIV infections was 19.5% and 14.6%, respectively. Multiple logistic regression determined significant associations between sharing non-injection drug use implements and HCV infection. Ever shared both oral and intranasal non-injection drug implements was independently associated with HCV infection (OR 2.83, CI 1.04, 7.72; p=0.04); ever shared non-injected heroin implements with an injector was a trend (OR 3.06, CI .85, 10.79; p=0.08). The strongest association between sharing non-injection drug use implements and HCV infection was found among HIV positive individuals (chi square=8.8, p<0.01). The strong association between HIV and HCV seropositivity among women reporting no history of injecting drugs indicates that HIV may facilitate the transmission of HCV through non-injecting routes. These findings suggest that sharing non-injection drug implements, either for intranasal or oral drug use, may be a risk factor for HCV and may explain the higher than expected prevalence of HCV infection observed in this sample. Tortu, S., McMahon, J., Pouget, E. and Hamid, R. Sharing of Non-Injection Drug Use Implements as a Risk Factor for Hepatitis C. Subst Use & Misuse, 39(2), pp. 211-224, 2004.

Research on AIDS and Other Medical Consequences of Drug Abuse

Non-AIDS Research

Relation of Coronary Artery Calcium to Left Ventricular Mass in African-Americans

Both coronary artery calcium (CAC) deposits and increased ventricular (LV) mass are important risk factors for coronary heart disease, but the relation between these two factors has rarely been studied. The investigators (Dr. Shenghan Lai and his colleagues at Johns Hopkins) examined the correlation of coronary artery calcium and left ventricular mass in 159 young to middle-aged African-Americans, and found that the average left ventricular mass indices were bigger in the CAC-positive groups than in CAC-negative groups in both genders [p=0.0004 in men and p=0.08 in women]. Studies are in progress to examine if drug abuse (e.g., cocaine) has an impact on cardiovascular disease (coronary artery calcium/ventricular function) in African-Americans. Tong, W., Lima, J.A., Lai, H., Celentano, D.D., Dai, S. and Lai, S. Am J. Cardiol., 93, pp. 490-492, 2004.

Severity of Prenatal Cocaine Exposure and Child Language through Age 7 Years

Results of data analyses from a longitudinal cohort study at the University of Miami suggest that greater severity of prenatal cocaine exposure is associated with increased (although modest) deficits in aptitude for language performance, but not with a trajectory of language development through 7 years of age. Within the framework of the latent growth curve analysis utilized, the intercept of the language growth curve was interpreted as reflecting a relatively time-invariant aptitude for language performance, and the slope was interpreted as indicating a time-varying trajectory of language performance. Language was assessed at ages 3, 5, and 7 years. The observed association was independent of multiple other possible sources of variation in language development, including the child's intellectual functioning and language stimulation in the home. Severity of prenatal cocaine exposure was characterized using a construct combining maternal self-report of cocaine use during pregnancy with maternal and infant bioassays. The statistical analytical model included gender, and prenatal alcohol, tobacco, and marijuana among the covariates. The researchers note that although the study has many strengths, the sample is relatively homogeneous (e.g., full-term, relatively healthy African-American children residing in socially disadvantaged inner-city neighborhoods), and caution should be exerted in generalizing the cocaine-language estimate to other populations or settings. Furthermore, they call for further investigation in other scientifically rigorous studies with sufficient sample sizes, in order to understand mechanisms by which prenatal cocaine exposure may affect child language functioning. Bandstra, E.S., Vogel, A.L., Morrow, C.E., Xue, L., and Anthony, J.C. Severity of Prenatal Cocaine Exposure and Child Language Functioning Through Age Seven Years: A Longitudinal Latent Growth Curve Analysis. Substance Use and Misuse, 39(1), pp. 25-59, 2004.

Epidemiology, Etiology and Prevention Research

Status Variations in Stress Exposure Among Young Adults: Implications for the Interpretation of Prior Research

Life Events checklists have been the predominant method for estimating variations in stress exposure. It is unknown, however, whether such inventories are equally meaningful for estimating differences in exposure between men and women, African-Americans and Whites, and those in lower and higher SES categories. In this paper, we employ a wider range of measures of stress  recent life events, chronic stressors, lifetime major events and discrimination stress  to examine the extent to which these dimensions collectively yield conclusions about status variations in stress exposure that are similar to or different from estimates based only on a life events checklist. Our analyses of data collected from 899 young men and women of African American and non-Hispanic White ancestry suggest that status differences in exposure to stress vary considerably by the measure of stress that is employed. Although women are more exposed to recent life events than men, males report more major events and discrimination stress than females. Our results also reveal that life event measures tend to substantially under-estimate differences between African-Americans and non-Hispanic Whites in exposure to stress. A similar pattern also holds for SES. When stress is more comprehensively estimated, level of exposure profoundly affects ethnic differences in depressive symptomatology, accounts for almost half of the difference by SES but contributes little to the explanation of the gender difference in distress. The implications of these findings for the debate over the relative mental health significance of exposure and vulnerability to stress are discussed. Turner, R.J., and William A. Journal of Health and Social Behavior, 44, pp. 488-505, 2003.

Substance Use Disorders Related to Attempted Suicide in Adolescents

This study examined the effects of psychiatric disorders on attempted suicide among adolescents with substance use disorders (SUD). Age of onset for psychiatric disorders, age of first suicide attempt, and the relationship of psychiatric disorder with attempted suicide were investigated in a sample of 503 adolescents with DSM-IV defined SUD (age range: 12.2-19.0 years). Results indicated that males who attempted suicide had a significantly earlier onset of alcohol use disorders (AUD) and significantly more mood, AUD, and disruptive behavior disorder symptoms compared to non-attempting males. Females who attempted suicide had a significantly earlier onset and higher counts of mood disorders and SUD symptoms compared to non-attempting females. Hazard analysis revealed that mood disorders represent the highest psychiatric risk for attempted suicide in both the genders. Attention deficit-hyperactivity disorder (ADHD) increased the risk for attempted suicide among males. The interaction of mood disorder and AUD increased the risk for attempted suicide among females. The investigators conclude that clinicians should closely monitor SUD adolescents for suicide risk and be aware of gender differences for suicidal behavior based on course and severity of psychiatric disorder in this population. Kelly, T.M., Cornelius, J.R. and Clark, D.B. Psychiatric Disorders and Attempted Suicide Among Adolescents with Substance Use Disorders. Drug And Alcohol Dependence, 73(1), pp. 87-97, 2004.

Review of Twin and Adoption Studies of Adolescent Substance Use

This paper reviews studies of adolescent substance use and abuse with twin and adoption studies. Results were presented by design, sample, and stage of drug use. Of 19 studies that used adolescent samples, 18 examined initiation or use of substances and 1 examined abuse. Of the 7 retrospective studies using adult samples, 6 examined problematic behaviors such as substance dependence. Genetic and shared environmental influences on adolescent substance use appear to be moderated by the specific substance, age, gender, specific contexts, religiousness, and region. There is some evidence for a common genetic influence on substance use across substances. Genetic influences on adolescent substance use may act through an influence on disinhibited behavior. Shared environment contributed to adolescent substance use consistently across all adolescent samples and common shared environmental factors influenced initiation into tobacco and alcohol use. While parental alcohol use had a small influence on adolescent shared environment, sibling influences were substantial. In summary, twin and adoption studies have increased our understanding of genetic and environmental influences on adolescent substance use and its initiation, although more studies focusing on clinical syndromes of abuse and dependence are needed. Hopfer, C.J., Crowley, T.J., and Hewitt, J.K. Review of Twin and Adoption Studies of Adolescent Substance Use. Journal of the American Academy of Child and Adolescent Psychiatry, 42, pp. 710-719, 2003.

Substance Use Among Adults 35 Years of Age: Prevalence, Adulthood Predictors, and Impact of Adolescent Substance Use

Using national longitudinal panel data from the Monitoring the Future study, this study examines the prevalence of substance use among American adults aged 35 years, and assesses the impact of adolescent substance use and adulthood predictors. Logistic regressions were conducted to assess the impact of demographics, life experiences, and adolescent substance use on smoking, heavy drinking, prescription drug misuse, marijuana use, and cocaine use at 35 years of age. Results indicate that factors related to increased likelihood of substance use include high school use, unemployment, and non-custodial parenthood. Lower use was associated with being female, a college graduate, a professional, married, or a custodial parent. Among those aged 35 years, substance use was still fairly prevalent and was a function of adulthood roles, experiences, and previous use. Merline A.C., O'Malley P.M., Schulenberg J.E., Bachman J.G. and Johnston L.D. Substance Use Among Adults 35 Years of Age: Prevalence, Adulthood Predictors, and Impact of Adolescent Substance Use. American Journal of Public Health, 94(1), pp. 96-102, 2004.

Cumulative Adversity and Drug Dependence in Young Adults: Racial/Ethnic Contrasts

This study assesses the effects of cumulative exposure to stressors as a risk factor for drug dependence, and evaluates whether race/ethnic differences in exposure to stressful events contributes to race/ethnic differences in prevalence of drug dependence. Data were analyzed cross-sectionally from a community survey of lifetime adverse experiences and substance and psychiatric disorders among young adults. Data were collected between 1997-2000 in Miami-Dade County, Florida. The sample size is 1,803 former Miami-Dade Public School students, 93% of whom were between ages 19 and 21 when interviewed. Males and females of Cuban origin, other Caribbean basin Hispanics, African-Americans, and non-Hispanic Whites are equally represented. Drug dependence disorder was assessed by DSM-IV criteria using the Composite International Diagnostic Interview, and a 41-item checklist of lifetime exposure to major and potentially traumatic experiences was used to measure cumulative adversity. Both measures include age at time of first occurrence. The lifetime rate of drug dependence disorder (total 14.3%) did not vary significantly (p>.05) by socioeconomic group. The rate for males (17.6%) was significantly greater than female rate (10.9%). The African-American rate (6.5%) was dramatically lower than non-Hispanic White (17.0%), Cuban (18.1%) and non-Cuban Hispanic (16.0%) rates despite their dramatically higher exposure to adversity. Twenty eight of 33 individual adversities were associated with the subsequent onset of drug dependence (p<.05). Cumulative lifetime exposure was greatest for males and for African-Americans, and was inversely associated with socioeconomic level. Multivariate discrete-time event history analysis revealed significant independent effects of distal (>1 year earlier) and proximal (previous year) exposure to adverse events (p<.05), controlling for childhood conduct disorder, ADHD, and prior psychiatric disorder. Lifetime cumulative exposure to distant as well as more recent adversity predicts risk of subsequent drug dependence, though it does not explain ethnic group differences in risk. Implications are that distal and proximal stressful events should both be included when measuring stress exposure. Turner, R.J., and Lloyd, D. Cumulative Adversity and Drug Dependence in Young Adults: Racial/Ethnic Contrasts. Addiction, 98, pp. 305-315, 2003.

Childhood Compelled Sex and Its Relationship to Structural Disadvantage, Subcultural Norms, Violence, and Illicit Drug Use in Inner City Households

There are a number of studies that have linked child sexual abuse to various adverse outcomes, including substance abuse. This study is a retrospective, qualitative study that seeks to understand the etiology, significance, and response to early compelled sex within the social context of poor, inner-city, predominantly African-American households (approximately 72 households) in New York City. Adult sexual contact with girls was widespread, even the norm in many impoverished households, although it is not accepted behavior by everyone living in the inner city. 61% of female subjects reported having compelled sex by age 13. Typically this activity took place regularly over time and fit within the young girl's sexual development pathway leading to independent sexuality. Many adults do not regard compelled sex as a major problem, and compelled sex is consistent with other subcultural behaviors, including violence and the ever-present threat of violence. The primacy of drug use in the lives of many inner-city residents also supports the acceptance of these subcultural norms and the commodification of sexual behavior (exchange of sex for food, rent money, drugs). Dunlap, E., Golub, A. and Johnson, B. Girls' Sexual Development in the Inner City: From Compelled Childhood Sexual Contact to Sex-for-Things Exchanges. Journal of Child Sexual Abuse, 12(2), pp. 73-96, 2003.

Smoking Progression and Physical Activity

This study examined the association between changes in physical activity and changes in smoking among adolescents. Smoking progression, physical activity, demographic factors, and covariates were assessed in 978 high school students participating in a longitudinal cohort study of the predictors of smoking adoption. Analyses used latent growth modeling with the parallel processes smoking progression and physical activity as our method, with smoking progression measured as an ordered categorical variable. Results indicated that higher levels of physical activity reduced the odds of progressing to smoking or a higher level of smoking by nearly 1.5. Although no race differences were found, being male increased the odds of smoking progression by 1.32. These findings indicate that higher levels of physical activity may reduce the risk of smoking during adolescence, and that youth smoking prevention initiatives should consider incorporating strategies to promote physical activity to prevent smoking experimentation and escalation. Audrain-McGovern, J., Rodriguez, D., and Moss, H.B. Smoking Progression and Physical Activity. Cancer Epidemiology, Biomarkers, and Prevention, 12, pp. 1121-1129, 2003.

Antisocial Behavior, Depressive Symptoms, and Partner Violence

This study examined the extent to which antisocial behavior and depressive symptoms were associated between romantic partners, and whether the partner's antisocial behavior and depressive symptoms affected the individual's aggression toward the partner. Questions were examined concurrently and longitudinally for 79 couples from a young, at-risk sample. There were reliable associations between partners' antisocial behavior and depressive symptoms. Women's antisocial behavior and depressive symptoms were significantly related to concurrent levels of men's physical and psychological aggression. Women's depressive symptoms remained significant in predicting men's psychological aggression over time. Overall, men's risk factors had little effect on their partners' aggression. Findings suggest that interventions to reduce partner violence need to consider the potential influence of partner, as well as perpetrator characteristics. Kim, H.K., and Capaldi, D.M. The Association of Antisocial Behavior and Depressive Symptoms between Partners and Risk for Aggression in Romantic Relationships. Journal of Family Psychology, 18, pp. 82-96, 2004.

Prevention Research

An Acute Post-Rape Intervention to Prevent Substance Use and Abuse

Rape trauma frequently is associated with extreme acute distress increasing the risk of developing psychopathology and substance use or abuse post-rape, with the degree of internal distress positively predicting future problems. The nature of post-rape forensic evidence collection procedures may exacerbate initial distress, thus potentiating post-rape negative emotional sequelae. Substance use may increase in an effort to reduce this distress. To address this outcome, a two-part video intervention was develop for use in acute post-rape time frames with two goals: to minimize anxiety during forensic rape examinations, thereby reducing risk of future emotional problems; and to prevent increased post-rape substance use and abuse. Pilot data with 124 rape victims who completed a police report and were brought for medical care immediately following such a report and who completed a 6-week post-rape assessment are included in this article. Half the women saw a 17-minute video immediately prior to the forensic examination. The data indicated that the low-cost, easily administered intervention was effective in reducing risk of marijuana abuse at six weeks. Trends also were noted in favor of the intervention in the subgroup of women who were actively using substances pre-rape (among pre-rape alcohol users, 28% of viewers versus 43% nonviewers met criteria for post-rape alcohol abuse; among pre-rape marijuana users, the rates of post-marijuana use were 17% and 43% respectively). While still preliminary, these data support the use of immediate, brief intervention via the video to target substance abuse within a vulnerable population. Acierno, R., Resnick, H.S., Flood, A. and Holmes, M. An Acute Post-Rape Intervention to Prevent Substance Use and Abuse. Addictive Behaviors, 28, pp. 1701-1715, 2003.

Maternal Influences on Urban Adolescent Girls' Smoking Intentions

Prior research has shown that parents who smoke are more likely to have children who smoke. Moreover, adolescents have been found to overestimate the number of adults and teenagers who smoke. This overestimation produces an expectation of smoking as normative and has been associated with an increase use of cigarettes among adolescents. This study examined maternal social influences on cigarette usage among urban minority girls with interview data from 450 mother-daughter dyads recruited from 30 New York City public and parochial middle schools. Girls in this sample ranged in age from 11 to 15 years and reported smoking rates of about 18% and smoking intention rates of 24%. Most of the sample was either Black or Latina, with smaller percentages of other groups (White, Native American, Asian). Neither mothers' reports of their own smoking nor maternal attitudes toward children's smoking were predictive of girls' experimental smoking and intentions to smoke in the next year. However, girls who perceived their mothers to be smokers were more likely to have tried smoking and to say that they intend to try smoking compared to girls who perceived their mothers to be nonsmokers. Compared to girls with low normative expectations of adult smoking, girls with high normative expectations were 2.89 times more likely to have tried cigarettes and 2.32 times more likely to intend to smoke. These findings suggest that preventive interventions aimed at correcting normative expectations of smoking among parents and youth may be helpful in deterring smoking among children. Nichols, T.R., Graber, J.A., Brooks-Gunn, J., and Botvin, G.J. Maternal Influences on Smoking Initiation Among Urban Adolescent Girls. Journal of Research on Adolescence, 14, pp. 73-97, 2004.

Effects of the Early Risers Program on Young Aggressive Children's Peer Relations

Peer nominations for behavioral reputation, likeability, and friendship were examined after 4 years of an ongoing randomized, controlled prevention trial designed to interrupt the developmental trajectory of young aggressive children by improving peer relations. Participants included 125 moderately to highly aggressive children (program and control) and 1,489 of their 4th-grade classmates. Results indicated that program children (compared to controls) obtained higher reputation scores on leadership and social etiquette and chose friends with lower aggression. Self-reported quality of friendship also differed between groups, with program children reporting more companionship and recreation, program girls reporting more validation and caring, and severely aggressive program children reporting less aggression toward others than their control counterparts. These findings provide evidence for the generalization of program effects to a natural peer setting. Four Years of the Early Risers Early-Age-Targeted Preventive Intervention: Effects on Aggressive Children's Peer Relations. August, G.J., Egan, E.A., Realmuto, G.M., and Hektner, J.M. Behavior Therapy, 34(4), pp. 453-470, 2003.

Services Research

Women More Vulnerable than Men to Relapse Because of Substance-Using Partners

Gender differences in the characteristics of individuals entering drug treatment and their post-treatment substance use were examined among 904 individuals, the majority of whom were female (63%) and predominantly African American (93%), who were admitted into the Chicago Target Cities Project. Bivariate relationships were examined in background characteristics, addiction and treatment career parameters, family and social relationships, psychosocial functioning, and treatment/social interventions received. Path analysis was used to determine the predictors of drug/alcohol use at 6- and 24-months following intake at a central referral agency, by developing separate path models for males and females. Drug/alcohol use was significantly reduced for men and women at 6- and 24-months, dropping by about 50% for both. Women had more episodes of subsequent treatment and men had higher rates of incarceration during the follow-up periods. The path analyses showed that at 6-months following intake, living with someone with a drug/alcohol problem was related to higher rates of drug/alcohol use for women, but not for men. For both men and women, psychological distress was related to higher levels of substance use at the 6-month follow-up, whereas having an improved living situation and participating in 12-step groups were related to lower levels of use at both follow-up points. The findings suggest that, although there are some similarities in the factors related to recovery for both men and women, women are more vulnerable to relapse because of having substance-using partners. Grella, C.E., Scott, C.K., Foss, M.A., Joshi, V. and Hser, Y. Gender Differences in Drug Treatment Outcomes Among Participants in the Chicago Target Cities Study. Evaluation and Program Planning, 26, pp. 297-310, 2003.

Methamphetamine Use Behaviors and Gender Difference

This analysis describes methamphetamine (MA) use behaviors in a broad cross-section of (N = 350) former clients from a large publicly funded treatment system and examines differences between males and females in drug use history, MA initiation and motivators, MA-related problems, acquisition, distribution, manufacture, and treatment characteristics. Results describe the prevalence of polydrug use, prolonged MA use before treatment, initiation primarily through friends, common sensation-seeking motivators (to have fun, get high, and experiment), numerous problems related to MA use (including paranoia, violent behavior, hallucinations, financial problems, and legal and work problems), and a majority who have sold MA. Gender differences appear in selected aspects of motivators and routes of initiation, access to MA, use patterns, and MA-related problems. Males were more likely than females to report work problems (70% vs. 48%) and high blood pressure (31% vs. 16%), and females were more likely to report skin problems (47% vs. 27%). Such description of behaviors and gender differences can provide a basis for development of treatment strategies and points of departure for future research. Brecht, M.L., O'Brien, A., von Mayrhauser, C. and Anglin, M.D. Addictive Behaviors, 29(1), pp. 89-106, 2004.

Epidemiology of Substance Use Disorders in Women

This article reviews the current epidemiology and patterns of substance use, abuse, and dependence, and the course, medical consequences, and treatment-related issues of substance disorders in women of all ages. There are approximately 15.1 million individuals who abuse or depend on alcohol in the United States; approximately 4.6 million (nearly one third) of these individuals are women. In 2001, an estimated 15.9 million Americans aged 12 years or older were current illicit drug users, and more than a third were women. In 1999, almost 4% of pregnant women were past-month users of illicit drugs. Research suggests that women are more susceptible than men to substance-related interpersonal difficulties, trauma, and medical consequences, heightening their risk of morbidity and mortality. In an early study of 100 alcohol-dependent women, 31% were dead at the 11-year follow-up, with most deceased from alcohol-related causes. The lifespan of these alcohol-dependent women was shortened by an average of more than 15 years. In a more recent study, heavily drinking women (> 4 standard alcoholic drinks/day) died significantly earlier compared with non-alcohol-dependent women (consume <4 standard alcoholic drinks/day), and there was also a trend toward earlier mortality rates compared with the heavily drinking men (>8 standard alcoholic drinks/day). In addition to these data on alcohol disorders, other studies indicate a broad range of health-related consequences in women with substance use disorders. For example, in 1986, mortality for lung cancer in women surpassed breast cancer mortality to become the leading cause of cancer death for women in the United States. These and other illnesses and accidents that can be attributed to substance use and abuse in women accounted for $68 billion in health care costs in 1995 (12.3% of the total health care expenditure for women). Despite these statistics, women are underrepresented in traditional substance abuse treatment settings. This may be partly because women tend to pursue avenues of treatment other than traditional substance abuse programs, such as mental health or primary care services. One study of obstetrics and gynecology practices found that 12% to 16% of patients had an alcohol disorder. The obstetrician gynecologist (OB-GYN) may be the only clinician and primary care provider for many women through the life cycle. Many of these women come for a myriad of problems that may or may not be related to their substance abuse, including routine physical examinations, prenatal care, and sexual problems. Discussions about infertility, pregnancy, or birth control provide the OB-GYN with an opportunity to assess and advise patients about their alcohol or drug use. From a public health and clinical perspective, this presents an enormous opportunity to detect and counsel these patients and refer them to appropriate treatment as indicated. Greenfield, S.F., Manwani, S.G. and Nargiso, J.E. Epidemiology of Substance Use Disorders in Women. Obstetrics and Gynecology Clinics of North America, 30(3), pp. 413, 2003.

HIV Testing For Homeless Women Indicated

This study describes the prevalence and predictors of HIV testing in a probability cluster sample of urban homeless women. Researchers analyzed data from the University of California Los Angeles-RAND Access to Health Care for Homeless Women of Reproductive Age Study, a survey conducted in six waves from January 1997 through November 1997 at shelters and soup kitchens in Los Angeles (LA) County. The sampling unit consists of homeless woman-visits, and data were collected using structured face-to-face interviews for which respondents were paid $10. Each sampling unit was weighted to account for the frequency with which respondents used shelters or meal programs. The main outcome measure was receipt of HIV test in the past year. With a response rate of 83%, the final sample size was 970. Sixty-eight percent reported receiving an HIV test in the past year, and 1.6% reported ever being diagnosed with HIV. HIV testing in the past year was most strongly associated with pregnancy in the past year and with having a regular source of care. Approximately 25% of homeless women with indications for HIV testing had not been tested in the past year. The reported HIV seroprevalence of greater than 1% suggests that providers should offer and encourage HIV testing for all homeless women in LA County. These data, which show a high rate of testing and few statistically significant independent predictors, indicate that this may be what is happening in practice. Herndon, B., Asch, S.M., Kilbourne, A.M., Wang, M., Lee, M., Wenzel, S.L., Andersen, R. and Gelberg, L. Prevalence and Predictors of HIV Testing Among a Probability Sample of Homeless Women in Los Angeles County. Public Health Rep., 118(3), pp. 261-269, 2003.

Similarities and Differences in Rural and Urban Substance Abuse Treatment

Using three waves of longitudinal data from a nationally representative sample of 450 privately-funded substance abuse treatment centers, this research found that rural and urban centers were similar in their increasing provision of inpatient psychiatric levels of care and their decreasing provision of more intensive services for chemical dependency between 1995 and 2001. Rural and urban centers were increasingly likely to offer specialty treatment tracks for women, adolescents, clients with HIV/AIDS, and relapsing clients over time, but rural centers were less likely to offer a treatment track tailored to substance-abusing women. The use of treatment innovations was similar at rural and urban treatment centers with the exception of lesser use of acupuncture at rural centers. Rural and urban centers did not differ in their average charges for treatment services. Knudsen, H.K., Johnson, J.A., Roman, P.M. and Oser, C.B. Rural and Urban Similarities and Differences in Private Substance Abuse Treatment Centers. Journal of Psychoactive Drugs, 35, pp. 511-518, 2003.

Posttraumatic Stress Disorder Among Minority Drug Users

This study explores cocaine abuse/dependence with physiological dependence and posttraumatic stress disorder diagnosis differences between out-of-treatment Hispanic and African American adults, in order to identify cultural differences in how experiences and attitudes affect cocaine use behaviors. Data was collected between February and November 2000, as part of a three-year longitudinal study. A cohort of 347 out-of-treatment, Hispanic and African American cocaine-using adults from the Houston metropolitan area were interviewed to measure differences between cocaine users who are dually diagnosed and those that are not. For the dual diagnoses categories, 102 (29%) participants met the requirements. Logistic regression models were used with age, race, gender, and income as the independent variables. Results indicate that individuals with higher income have a greater probability of developing a diagnosis. Results also indicate that being female increases the likelihood of developing both types of dual diagnoses. However, being an older female decreases the probability that an individual would develop these dual diagnoses. No differences were found for race/ethnicity among the dually diagnosed Hispanics and African Americans, however, gender differences were found. Treating high-risk substance abusers who are members of minority groups may require varied protocols depending on differences among minority groups. Montoya, I.D., Covarrubias, L.D., Patek, J.A., and Graves, J.A. Posttraumatic Stress Disorder among Hispanic and African-American Drug Users. American Journal of Drug and Alcohol Abuse, 29 (4), pp. 729-741, 2003.

Predictors of Self-Reported HIV Infection Among Drug Injectors in Ukraine

The spread of HIV infection in Eastern Europe has been most intense in Ukraine where the number of cases has grown from 1,500 in 1994 to over 230,000 in 2002. Much of this rise in infection has been attributed to injection drug use. Researchers interviewed 212 IDUs (mean age = 29 years; 28% female) from Makeevka/Donetsk, Kiev, and Odessa. Responses indicated that 89% had injected drugs within the past 30 days, and that most respondents engaged in unsafe needle use. No gender differences were found. HIV positive respondents reported increased safe sex behavior, but were more likely to engage in unsafe needle use. Less than 25% reported receiving information about AIDS or risk reduction. Injection with others was common regardless of HIV status. Results suggest that HIV infection in Ukraine will continue to grow fueled to a large extent by unsafe injection drug use. Booth, R.E., Mikulich-Gilbertson, S.K., Brewster, J.T., Salomonsen-Sautek, S. and Semerik, O. Predictors of Self-Reported HIV Infection Among Drug Injectors in Ukraine. Epidemiology and Social Science, 35(1), pp. 82-88, 2004.

Burden of Medical Illness in Drug and Alcohol Dependent Persons without Primary Care

Little is known about the frequency, severity and risk factors for disease in drug and alcohol dependent persons without primary medical care. This article assesses the burden of medical illness and identifies patient and substance dependence characteristics associated with worse physical health in order to compare measures of illness burden in this population. Researchers conducted a cross-sectional study among alcohol, heroin or cocaine dependent persons without primary medical care admitted to an urban inpatient detoxification unit (mean age = 35.7 years; 76% male; 46% Black). Forty-five percent reported being diagnosed with a chronic illness, and 80% had prior medical hospitalizations. The mean age-adjusted SF-36 Physical Component Summary (PCS) score was significantly lower than the general U.S. population norm (44.1 vs. 50.1). In multivariable analysis, the following factors were associated with worse health: female gender, problem use of hallucinogens, heroin, other opiates, living alone, having medical insurance, and older age. Alcohol and drug dependent persons without primary medical care have a substantial burden of medical illness compared to age and gender matched U.S. population controls. While the optimal measure of medical illness burden in this population is unclear, a variety of health measures document this medical illness burden in addicted persons. De Alba, I., Samet, J.H. and Saitz, R. Burden of Medical Illness in Drug and Alcohol Dependent Persons without Primary Ccare. American Journal of Addiction, 13, pp. 33-45, 2004.