Director's Report to Council - Research Findings Excerpts

February, 2008

Basic Neurosciences Research

Sex Differences in THC's Effects on Spatial Learning in Adult and Adolescent Rats

In 2006 Dr. Scott Swartzwelder and colleagues at Duke University reported effects of 2.5, 5.0, and 10.0mg/kg THC on learning in male adolescent and adult rats in the Morris water maze (Cha et al., 2006). The researchers found that THC disrupts both spatial and non-spatial learning more powerfully in adolescent rats than in adults at all dose levels. Dr. Swartzwelder and his colleagues have now published results from three studies that extend findings of this initial report. In the first study, effects of 5.0 mg/kg THC on spatial learning in the Morris Water maze were studied in male and female adolescent and adult rats over 5 daily test sessions. In males, spatial learning was impaired in adolescents on all test days, but was not impaired on any of the test days in adults. Among females, adolescents exhibited impairment on all test days, but adults were impaired only during the first two sessions. Thus, THC impairment was more potent in adolescents than adults and more potent in adult females than adult males. To assess the effects of chronic THC on subsequent learning, in a second experiment, separate groups of male and female adolescent and adults rats were treated with 5.0 mg//kg THC for 21 days and tested 28 days later in the Morris Water maze. Chronic THC treatment did not produce learning deficits in any of the groups. The third experiment was a THC dose-response study (2.5, 5.0, and 10.0mg/kg THC) using adolescent and adult female rats, conducted to parallel the initial experiment in males (Cha et al., 2006). Each dose was tested for 5 days. Consistent with the earlier outcome in males, THC produced a dose-response impairment in spatial learning. Although there was no overall age effect on spatial learning, there were differences in the dose-response function between adolescents and adults, suggesting a greater dose sensitivity in adolescents. Additionally, assessment of spatial memory indicated impairment in adolescents but not adults. These outcomes have important implications for future research on THC and other abused drugs. Animal model research in drug abuse has largely been conducted on adult males. The results of the present study join a growing body of drug abuse research showing that outcomes observed in adult males do not always generalize to females and to adolescents, highlighting the limitations of research conducted with only adult male subjects. Cha, Y.M., Jones, K.H., Kuhn, C.M., Wilson, W.A., and Swartzwelder, H.S. Sex Differences in the Effects of Delta (9)-tetrahydrocannabinol on Spatial Learning in Adolescent and Adult Rats. Behavioral Pharmacol. 18, pp. 563-569, 2007.

Sex Chromosome Complement Regulates Habit Formation

Gonadal hormones can cause sex differences via their brain organization effects during development and via their activational effects in puberty and adulthood. Other sex differences, however, are not due to gonadal hormones, but rather the direct action of the chromosome complement. Recent development of the 'four core genotype' mouse model permits dissociation of gonadal sex and chromosomal sex by comparison of males and females that are gonadally and chromosomally either congruent or incongruent. The two incongruent cases are (1) chromosomal XY males with deletion of the testis-determining Sry gene and are therefore gonadally female and (2) chromosomal XX females with insertion of the Sry gene and are therefore gonadally male. Dr. Jane Taylor and colleagues at Yale and UCLA have used this four core genotype mouse model to study the role of chromosomal sex versus gonadal sex on habit formation. In the first phase of their study, mice were trained to nose-poke in one of three apertures for a food pellet delivery. Following either moderate training (9 days) or extended training (15 days), food pellets were devalued in a conditioned taste aversion procedure in which food pellets were paired with injections of the emetic lithium chloride. The mice were then retested in the instrumental procedure. In past studies using this habit formation procedure, devaluation decreases instrumental performance prior to habit formation, but after habit formation, instrumental performance is unaffected by devaluation. Dr. Taylor and her colleagues found that XX mice that previously received moderate instrumental training, showed operant performance following devaluation that was insensitive to changes in reinforcer value, indicating formation of a habit. XY mice subjected to devaluation, however, exhibited poorer performance than those not subjected to devaluation of the reinforcer, indicating that XY mice had not yet acquired habit formation. This outcome was independent of gonadal phenotype and was independent of gonadectomy vs. sham-operated status, indicating that the effects did not depend on organizational or activational functions of gonadal hormones. Following extended instrumental training, XX mice exhibited better instrumental performance (more correct nose-pokes) than XY mice. After devaluation, XX and XY mice were equally insensitive to changes in reward value of the reinforcer, indicating that with extended training, all mice had developed an instrumental habit. The authors speculate that sex differences in habit formation, as determined by the sex chromosome complement, could have implications for studying and understanding sex differences in drug addiction. Quinn, J.J., Hitchcott, P.K., Umeda, E.A., Arnold, A.P. and Taylor, J.R. Sex Chromosome Complement Regulates Habit Formation. Nature Neurosci. 10, pp. 1398-1400, 2007.

Behavioral and Brain Development Research

Predictors of Neonatal Abstinence Syndrome Severity in Methadone-Exposed Newborns

Investigators at Johns Hopkins University examined potential predictors of Neonatal Abstinence Syndrome (NAS), which is made up of symptoms reflecting dysfunction in autonomic and central nervous systems. Although infants born to mothers who experienced methadone-maintenance during pregnancy frequently show evidence of NAS, the signs and symptoms of NAS vary widely among infants. This study attempted to investigate some possible reasons behind such variation, with a focus on maternal vagal tone, a measure that reflects autonomic nervous system homeostasis, stress vulnerability, and self-regulation. Specifically, the investigators examined whether vagal tone responsivity to methadone administration in pregnant women provides insight into the pathophysiology and expression of NAS in the newborn. The expectation was that newborns born to mothers who show greater autonomic dysregulation, as reflected by increased levels of vagal suppression relative to methadone maintenance, would exhibit more severe NAS. At 36 weeks of gestation, electrocardiogram monitoring was carried out for 50 methadone-maintained pregnant women, at the times of trough and peak maternal methadone levels. NAS expression was related to maternal vagal activity; maternal vagal tone suppression and activation were associated with NAS symptomatology and treatment. NAS expression was not related to histories of maternal substance use or methadone maintenance, or to psychotropic medication exposure. The authors discuss potential mechanisms for interpretation of their findings. Jansson, L.M., DiPietro, J.A., Elko, A., and Velez, M. Maternal Vagal Tone Change in Response to Methadone is Associated with Neonatal Abstinence Syndrome Severity in Exposed Neonates. Journal of Maternal, Fetal and Neonatal Medicine, 20(9), pp. 677-685, 2007.

Prenatal and Adolescent Exposure to Tobacco Smoke Modulates the Development of White Matter Microstructure

Smoking during pregnancy is related to elevated risks of cognitive and auditory processing deficits. Preclinical studies have revealed that disruption in neurodevelopment by exposure to nicotine is likely linked to the disruption of the trophic actions of acetylcholine at nicotinic acetylcholine receptors. This study utilized diffusion tensor anisotropy and anatomical magnetic resonance images to examine white matter microstructure in 67 adolescent smokers and nonsmokers with and without prenatal exposure to maternal smoking. Auditory attention was assessed in all subjects. Adolescents with prenatal and/or adolescent exposure demonstrated increases in regional white matter fractional anisotropy (FA) primarily in anterior cortical and subcortical regions. Increased FA of regions of the internal capsule that contain auditory thalamocortical and corticofugal fibers was associated with adolescent smoking. Performance on the auditory performance task in smokers was positively correlated with FA of the posterior limb of the left internal capsule, but not in nonsmokers. The magnitude of tobacco exposure during adolescence was positively related to the FA of the genu of the corpus callosum further supporting the notion that the effects of nicotine on white matter maturation may be particularly significant during this developmental period. The results suggest that nicotine may disrupt the development of auditory corticofugal fibers which ultimately leads to reduced efficiency in the neurocircuitry that supports auditory processing. Jacobsen, L., Picciotto, M., Heath, C., Frost, S., Tsou, K., Dwan, R., Jackowski, M., Constable, R., and Menel, W. Prenatal and Adolescent Exposure to Tobacco Smoke Modulates the Development of White Matter Microstructure. The Journal of Neuroscience, 27(49) pp. 13491-13498, 2007.

Marijuana Use and HIV-Related Risk Factors

This study examined the role of early and current marijuana use as it relates to sexually transmitted infection (STI) risk in a sample of young women who had been pregnant teenagers. Pregnant adolescents (N= 279), ages 12-18, were recruited from an urban prenatal clinic as part of a study that was developed to evaluate the long-term effects of prenatal substance exposure. Six years later, they were asked about their substance use and sexual history. The association of early and late marijuana use to two HIV-related risk factors -- lifetime sexual partners and STIs --was examined, and then structural equation modeling (SEM) was used to illustrate the associations among marijuana use, number of sexual partners, and STIs. Bivariate analyses revealed a dose-response effect of early and current marijuana use on STIs in young adulthood. Early and current marijuana use also predicted a higher number of lifetime sexual partners. Using SEM, the effect of early marijuana use on STIs was mediated by lifetime number of sexual partners. African-American race, more externalizing problems, and a greater number of sexual partners were directly related to more STIs. Adolescent pregnancy, early marijuana use, mental health problems, and African-American race were significant risk factors for STIs in young adult women who had become mothers during adolescence. Pregnant teenage girls should be screened for early drug use and mental health problems, because they may benefit the most from the implementation of STI/HIV screening and skill-based STI and HIV prevention programs. DeGenna, N.M., Cornelius, M.D., and Cook, R.L. Marijuana Use and Sexually Transmitted Infections in Young Women Who Were Teenage Mothers. Women's Health Issues, 17(5), pp. 300-309, 2007.

Clinical Neuroscience Research

PET Study Reveals Minimal Gender Differences or Menstrual Cycle Effects on Nicotinic Acetylcholine Receptors

The effects of sex and hormones on brain chemistry and neurotransmission are not well-characterized, and are of increasing importance as evidence emerges of sex differences in behavioral symptoms and treatment response in neuropsychiatric disorders. The nicotinic acetylcholine receptor (nAChR) system has been implicated in a variety of psychiatric disorders, including tobacco smoking, for which there is strong evidence supporting sex differences in behaviors and response to smoking cessation treatments. Kelly Cosgrove, Julie Staley, and colleagues at Yale examined the availability of nAChR containing the ss2 subunit in healthy men and women nonsmokers, and the influence of menstrual phase among women. Regional brain activity was higher (39%-54%) in women than in men. When regional brain activity was normalized to total plasma parent to correct for individual differences in radiotracer metabolism (VT'), differences of 10%-16% were observed, with women greater than men. In contrast, when regional brain activity was normalized to free plasma parent (VT), there was less than a 4% difference by sex in regional brain ss2-nAChR availability. These sex differences in kBq/cm3 and VT' resulted from significantly higher levels of total plasma parent, free fraction (f1), and free plasma parent in women than in men nonsmokers. No differences in plasma measures or brain ss2-nAChR availability were observed across the menstrual cycle for any outcome measure. Overall, these findings demonstrate no significant difference in brain ss2-nAChR availability between men and women nonsmokers or across the menstrual cycle. Importantly, these findings demonstrate the need to control for sex differences in radiotracer metabolism and plasma protein binding. Cosgrove, K.P., Mitsis, E.M., Bois, F., Frohlich, E., Tamagnan, G.D., Krantzler, E., Perry, E., Maciejewski, P.K., Epperson, C.N., Allen, S., O'Malley S., Mazure, C,M,, Seibyl, J.P., van Dyck, C.H., and Staley, J.K. 123I-5-IA-85380 SPECT Imaging of Nicotinic Acetylcholine Receptor Availability in Nonsmokers: Effects of Sex and Menstrual Phase. J. Nucl. Med., 48(10), pp. 1633-1640, 2007.

Cocaine Impairs Attention by Disrupting Thalmo-Cortical Circuits

Functional magnetic resonance imaging (fMRI) and a sustained visuospatial attention task was used to assess the neuronal basis of visual attention network dysfunction in cocaine abusers (n = 14) compared to age-, gender-, and education-matched controls (n= 14). Compared with controls, cocaine abusers showed (1) hypoactivation of the thalamus, which may reflect noradrenergic and/or dopaminergic deficits; (2) hyperactivation in occipital and prefrontal cortices, which may reflect increased visual cortical processing to compensate for inefficient visual thalamic processing; and (3) larger deactivation of parietal and frontal regions possibly to support the larger hemodynamic supply to the hyperactivated brain regions. These findings provide evidence of abnormalities in thalamocortical responses in cocaine abusers that are likely to contribute to the impairments in sensory processing and in attention. The development of therapies that diminish these thalamo-cortical deficits could improve the treatment of cocaine addiction. Tomasi, D., Goldstein, R.Z., Telang, F., Maloney, T., Alia-Klein, N., Caparelli, E.C., and Vokow, N.D. Thalamo-Cortical Dysfunction in Cocaine Abusers: Implications In Attention And Perception. Psychiatry Research-Neuroimaging, 155(3), pp. 189-201, 2007.

Epidemiology and Etiology Research

A Twin Study of Delinquent Peer Affiliation

This study used genetic epidemiologic approaches to evaluate whether the association between delinquent peer affiliation and conduct problems may occur because of shared genetic liability. Data came from 553 monozygotic and 558 dizygotic (same sex and opposite sex) twin pairs, over half female, aged 11 to 18 years, recruited from community based samples in Colorado, assessed through self-report for delinquent peer affiliation and conduct problems. The authors investigated whether genes contribute to both delinquent peer affiliation and the correlation between delinquent peer affiliations and conduct problems. Modeling found that delinquent peer affiliation was influenced by genetic, shared environmental and non-shared environmental factors; genetic factors also contributed to the correlation between delinquent peer affiliations and conduct problems, providing evidence for genotype-environment correlation. The magnitude of the genetic variance of conduct problems was contextually dependent on levels of delinquent peer affiliation and was greater at higher levels of delinquent peer affiliation. Thus, this study adds to the growing literature showing that many putative environmental risks for drug abuse correlate with individuals "genotypes". Button, T., Corley, R., Rhee, S., Hewitt, J., Young, S., and Stallings, M. Delinquent Peer Affiliation and Conduct Problems: A Twin Study. J Abnorm. Psychol., 116(3), pp. 554-564, 2007.

Externalizing Symptoms among Children of Alcoholic Parents: Entry Points for an Antisocial Pathway to Alcoholism

The authors examined heterogeneity in risk for externalizing symptoms in children of alcoholic parents (COA), as it may inform the search for entry points into an antisocial pathway to alcoholism. That is, they tested whether the number of alcoholic parents in a family, the comorbid subtype of parental alcoholism, and the gender of the child predicted trajectories of externalizing symptoms over the early life course, as assessed in high-risk samples of children of alcoholic parents and matched controls. Data from the Michigan Longitudinal Study provided 596 children from 338 families, and Adolescent/Adult Family Development Project 454 adolescents and their parents, both with COA and matched controls assessed over multiple waves. Through integrative analyses of these independent, longitudinal studies, they showed that children with either an antisocial alcoholic parent or 2 alcoholic parents were at greatest risk for externalizing symptoms. Moreover, children with a depressed alcoholic parent did not differ from those with an antisocial alcoholic parent in reported symptoms. These findings were generally consistent across mother, father, and adolescent reports of symptoms; child gender and child age (ages 2-17); and the 2 independent studies examined. Multi-alcoholic and comorbid-alcoholic families may thus convey a genetic susceptibility to dysregulation along with environments that both exacerbate this susceptibility and provide few supports to offset it. Hussong, A., Wirth, R., Edwards, M., Curran, P., Chassin, L., and Zucker, R. Externalizing Symptoms among Children of Alcoholic Parents: Entry Points for an Antisocial Pathway to Alcoholism. J. Abnorm. Psychol., 116, pp. 529-542, 2007.

State Anti-Tobacco Advertising and Smoking Outcomes by Gender and Race/Ethnicity

Investigators examined overall and gender- and racial/ethnic-specific relationships between exposure to state-sponsored anti-tobacco televised advertising and smoking-related outcomes among US middle and high school students using five years of cross-sectional nationally representative data. Nationally representative 8th, 10th, and 12th grade student sample data for 1999-2003 were merged with commercial ratings data on mean potential audience exposure to network and cable television anti-tobacco advertising across the 74 largest US designated market areas, resulting in a final sample size for analysis of 122,340. Associations between state-sponsored anti-tobacco televised advertising exposure and youth smoking-related beliefs and behaviors' were modeled while controlling for relevant individual and environmental factors as well as other televised tobacco-related advertising. Authors found higher potential for exposure to state anti-tobacco advertising within the previous four months was generally associated with decreasing odds of current smoking across groups. In addition, such exposure was related, to varying degrees, with decreased perceptions that most/all friends smoked, stronger five-year intentions not to smoke, and increased perceived harm of smoking. These relationships appeared possibly to be weaker for Asian students. The results from these analyses indicate that state anti-tobacco advertising significantly relates to beneficial outcomes -- especially regarding current smoking behaviour -- among US youth as a whole. Terry-McElrath, Y., Wakefield, M., Emery, S., Saffer, H., Szczypka, G., O 'Malley, P., Johnston, L., Chaloupka, F., and Flay, B. State Anti-tobacco Advertising and Smoking Outcomes by Gender and Race/ethnicity. Ethn. Health, 12(4), pp. 339-362, 2007.

Gender Differences in Social Network Influence among Injection Drug Users: Perceived Norms and Needle Sharing

Whereas substantial research has linked perceived norms and HIV sexual risk behavior, less attention has been given to the relationship between perceived norms and injection drug practices. This study investigated the relationship between needle sharing and perceived norms in a sample of injection drug users. Data were collected through face-to-face interviews with 684 injectors from the STEP Into Action (STEP) project in Baltimore, Maryland. Logistic regression was used to assess the associations between perceived norms (descriptive and injunctive norms) and needle sharing. Results were stratified by gender. Descriptive norms were significantly related to needle sharing among males (AOR = 1.58, 95%CI = 1.20-2.40) and females (AOR = 1.78; 95%CI = 1.24-2.55). Whereas injunctive norms were significantly associated with needle sharing among men (AOR = 1.30 95%CI = 1.05-1.61), this association was not significant among women (AOR = 0.99; 95%CI = 0.74-1.31). These findings suggest the utility of peer education interventions that promote norms regarding risk reduction among injection drug users. The data also provide support for gender-specific HIV prevention interventions. Davey-Rothwell, M., and Latkin, C. Gender Differences in Social Network Influence among Injection Drug Users: Perceived Norms and Needle Sharing. J. Urban Health, 84(5), pp. 691-703, 2007.

HCV Synthesis Project: Preliminary Analyses of HCV Prevalence in Relation to Age and Duration of Injection

Early acquisition of hepatitis C virus (HCV) infection appears to affect a substantial proportion of IDUs--between 20 percent and 90 percent. Analyzing the range of HCV prevalence estimates in new injectors may help identify factors that can be modified to reduce HCV transmission. The HCV Synthesis Project is a meta-analysis of studies of HCV epidemiology and prevention in drug users worldwide. In this preliminary analysis, researchers examined data from 127 studies of IDUs that reported HCV prevalence in relation to age or year since onset of drug injection, analyzing heterogeneity and calculating summary statistics where appropriate. Six studies reported gender-specific HCV prevalence rates among young or new injectors; the group mean prevalence was 47 percent for men and 44 percent for women (NS). Group mean age for HCV-negatives was 24.7 years (range 24-28) and 26.1 years (range 21-31) for HCV-positives (n=8 studies). Data were examined from 13 studies that compared HCV prevalence among young injectors to older injectors using 5-year age categories; substantial variation was present within these categories such that measures of central tendency were not calculated. Similarly, among studies reporting HCV prevalence among IDUs in relation to 1-year intervals of duration of injection (<1 year, <2 years, and <3 years), considerable variability was observed. Notably, there were studies in each category that reported prevalence of 70 percent or higher among recent-onset drug injectors. These findings confirm previous studies reporting high risk of acquiring HCV shortly after onset of injection; thus, HCV prevention programmes must emphasize methods to reach new injectors. Future research should (1) report data on time to infection in depth, (2) provide detailed information on study methodology, and (3) characterize the research setting with respect to underlying factors that affect injection practices and networks. This will permit synthesis of a greater number of studies and may lead to the identification of factors that impede HCV transmission. Hagan, H., Des Jarlais, D., Stern, R., Lelutiu-Weinberger, C., Scheinmann, R., Strauss, S., and Flom, P. HCV Synthesis Project: Preliminary Analyses of HCV Prevalence in Relation to Age and Duration of Injection. Int. J. Drug Policy, 18(5), pp. 341-351, 2007.

Prevention Research

Effects of a Nurse Visiting Program with African American Mothers and Infants on Age 9 Outcomes

This study examined the effect of prenatal and infancy home visits by nurses on mothers' fertility and children's functioning 7 years after the program ended at child age 2. A randomized, controlled trial in a public system of obstetric and pediatric care was conducted. A total of 743 primarily black women <29 weeks gestation, with previous live births and at least 2 socio-demographic risk characteristics (unmarried, <12 years of education, unemployed), were randomly assigned to receive nurse home visits or comparison services. Primary outcomes consisted of intervals between births of first and second children and number of children born per year; mothers' stability of relationships with partners and relationships with the biological father of the child; mothers' use of welfare, food stamps, and Medicaid; mothers' use of substances; mothers' arrests and incarcerations; and children's academic achievement, school conduct, and mental disorders. Secondary outcomes were the sequealae of subsequent pregnancies, women's employment, experience of domestic violence, and children's mortality. Nurse-visited women had longer intervals between births of first and second children, fewer cumulative subsequent births/year, and longer relationships with current partners. From birth through child age 9, nurse-visited women used welfare and food stamps for fewer months. Nurse-visited children born to mothers with low psychological resources, compared with control-group counterparts, had better grade-point averages and achievement test scores in math and reading in grades 1-3. Nurse-visited children, as a trend, were less likely to die from birth through age 9, an effect accounted for by deaths that were attributable to potentially preventable causes. By child age 9, the program reduced women's rates of subsequent births, increased the intervals between the births of first and second children, increased the stability of their relationships with partners, facilitated children's academic adjustment to elementary school, and seems to have reduced childhood mortality from preventable causes. Olds, D., Kitzman, H., Hanks, C., Cole, R., Anson, E., Sidora-Arcoleo, K. et al. Effects of Nurse Home Visiting on Maternal and Child Functioning: Age-9 Follow-up of a Randomized Trial. Pediatrics, 120(4), pp. e832-e845, 2007.

An Acute Post-Sexual Assault Intervention to Prevent Drug Abuse

Sexual assault and rape routinely produce extreme distress and negative psychological reactions in victims. Further, past research suggests that victims are at increased risk of developing substance use or abuse post-rape. The post-rape forensic medical exam may itself exacerbate peritraumatic distress because it includes cues that may serve as reminders of the assault, thereby potentiating post-assault negative sequelae. To address these problems, a two-part video intervention was developed to take advantage of the existing sexual assault forensic exam infrastructure, and to specifically (a) minimize anxiety/discomfort during forensic examinations, thereby reducing risk of future emotional problems, and (b) prevent increased substance use and abuse following sexual assault. Updated findings with a sample of 268 sexual assault victims participating in the forensic medical exam and completing one or more follow-up assessments at: (1) less than 3 months post-assault; (2) 3 to 6 months post-assault; or (3) 6 months or longer post-assault indicated that the video was associated with significantly lower frequency of marijuana use at each time point, among women who reported use prior to the assault. Resnick, H.S., Acierno, R., Amstadter, A. B., Self-Brown, S., and Kilpatrick, D.G. An Acute Post-Sexual Assault Intervention to Prevent Drug Abuse: Updated Findings. Addictive Behaviors, 32, pp. 2032-2045, 2007.

Randomized Controlled Evaluation of an Early Intervention to Prevent Post-Rape Psychopathology

A randomized between-group design was used to evaluate the efficacy of a video intervention to reduce post-traumatic stress disorder (PTSD) and other mental health problems, implemented prior to the forensic medical examination conducted within 72 h post-sexual assault. Participants were 140 female victims of sexual assault (68 video/72 non video) aged 15 years or older. Assessments were targeted for 6 weeks (Time 1) and 6 months (Time 2) post-assault. At Time 1, the intervention was associated with lower scores on measures of PTSD and depression among women with a prior rape history relative to scores among women with a prior rape history in the standard care condition. At Time 2, depression scores were also lower among those with a prior rape history who were in the video relative to the standard care condition. Small effects indicating higher PTSD and Beck Anxiety Inventory (BAI) scores among women without a prior rape history in the video condition were observed at Time 1. Accelerated longitudinal growth curve analysis indicated a video X prior rape history interaction for PTSD, yielding four patterns of symptom trajectory over time. Women with a prior rape history in the video condition generally maintained the lowest level of symptoms. Resnick, H., Acierno, R., Waldrop, A., King, L., King, D., Danielson, C., Ruggiero, K., and Kilpatrick, D. Randomized Controlled Evaluation of an Early Intervention to Prevent Post-Rape Psychopathology. Behav. Res. Ther., 45(10), pp. 2432-2447, 2007.

Adolescent Friendship Interactions and Deviant vs. Normative Developmental Pathways

Interpersonal dynamics within friendships were observed in a sample of 120 (60 male, 60 female) ethnically diverse 16- and 17-year-old adolescents characterized as "persistently antisocial", "adolescent-onset", and normative. Group definitions were based on antisocial behavior scores from a survey of antisocial behavior and substance use developed by Dishion and Kavanagh and administered at four points in time to adolescents starting at age 11-12. Persistently antisocial adolescents were defined as those who had above average scores compared to those within their gender group and had greater than the median antisocial score at all assessment points. "Adolescent-onset" youth comprised participants whose antisocial behaviors increased from below the median in earlier waves of the survey to above the median in later waves. The normative group included participants with the lowest sum antisocial behavior scores of the group who also had below median antisocial behavior scores during all waves. Dyadic mutuality, i.e., talk that is mutually responsive, reciprocal, and harmonious, and deviant talk, i.e., inappropriate talk and talk about violating community or societal rules, were coded from videotaped friendship interactions. Persistently antisocial adolescents demonstrated lower levels of dyadic mutuality compared with adolescent-onset and normative adolescents. Persistently antisocial and adolescent-onset adolescents spent more time in deviant talk than did normative adolescents. Across groups, girls were rated as more mutual and coded less in deviant talk than boys. Furthermore, friendship dyads that engaged in high levels of deviant talk and were mutual in their interactions reported the highest rates of antisocial behavior, Piehler, T., and Dishion, T. Interpersonal Dynamics within Adolescent Friendships: Dyadic Mutuality, Deviant Talk, and Patterns of Antisocial Behavior. Child Dev., 78(5), pp. 1611-1624, 2007.

Research on Behavioral & Combined Treatments for Drug Abuse

Behavioral Incentives Improve Outpatient Treatment Participation/Retention for Pregnant Drug Abusers

Treating pregnant drug abusers poses unique challenges; compared with non-pregnant drug users they leave treatment more often and their attendance is often unreliable. This study examined the utility of providing 2 weeks of vouchers exchangeable for goods and services on an escalating schedule to motivate participation in a program comprised of seven days of residential and thirty days of outpatient treatment. Ninety-one pregnant women were assigned to either a standard treatment condition (ST) or a voucher reinforcement condition (VR) in which vouchers were earned for treatment program attendance. Voucher values began at $5.00 and increased by $5.00 for each day the participant attended up to a maximum value of $70.00 for 2 weeks. If a participant missed a single session they forfeited their voucher that day. Participant voucher value reset to $5.00 if more than one session was missed. VR assignment did not impact early treatment dropout; one third of participants in both groups left treatment against medical advice (AMA). Among those who did not leave AMA, those assigned to VR attended more treatment days than those in ST. Additionally, those assigned to VR were more likely to attend treatment consistently (12-14 full days) as opposed to the typical pattern of attendance for ST (only 4 or 6 full days). When all participants were categorized as either consistent or inconsistent attenders, consistent early attendance predicted better attendance in the 30 days following the intervention. Within five days of the voucher treatment ending, no consistent early attenders dropped out of treatment. However, 25% of inconsistent treatment attenders dropped out during the five days post-intervention. These findings are significant for several reasons. First, although inpatient treatment participation was not differentially impacted by vouchers, the voucher program begun during the inpatient treatment period appeared to have an important effect on pregnant women making the transition to outpatient treatment. Additionally, critics contend that voucher effects do not last after the treatment ends but in this case the voucher effect was sustained post-treatment. More research is needed to determine what if any effect vouchers can have on pregnant women entering treatment to reduce dropout AMA rates. Svikis, D., Silverman K, Haug, N., Stitzer, M., Keyser-Marcus, L. Behavioral Strategies to Improve Treatment Participation and Retention by Pregnant Drug-dependent Women. Substance Use Misuse, 42(10), pp. 1527-1535, 2007.

Bupropion and Cognitive-Behavioral Therapy for Smoking Cessation in Women

Dr. Schmitz and colleagues at the University of Texas Health Science Center at Houston conducted this study to examine the independent and interactive effects of medication (bupropion 300 mg/day vs. placebo) and psychotherapy (cognitive-behavioral therapy [CBT] vs. supportive therapy [ST]) in women in a two level factorial design. In addition to testing the hypothesis that bupropion with CBT would be the most effective of all the treatments, medication compliance and its role in the efficacy of bupropion was examined. Participants were 154 women who smoked more than 10 cigarettes/day. Compliance with study medication was assessed using Medication Event Monitoring Systems (MEMS) over 7 weeks of treatment. Psychological interventions were delivered in 60-min weekly group sessions. Longitudinal analysis of abstinence outcomes from end of treatment (EOT) through 12 months after treatment revealed a significant interaction of medication and therapy. Higher abstinence rates at EOT and 3, 6, 9, and 12-month follow-ups were observed when bupropion was delivered concurrently with CBT (44%, 24%, 30%, 23%, 17%) rather than with ST (18%, 1%, 8%, 5%, 2%). The bupropion-CBT combination, however, was not clearly superior to placebo, regardless of therapy assignment. Higher rates of medication compliance were positively predictive of abstinence, and this effect was most evident in the placebo condition. Findings provide only modest support for CBT as the preferred type of intensive therapy in conjunction with bupropion in women. Schmitz, J.M., Stotts, A.L., Mooney, M.E., DeLaune, K.A., and Moeller, F.G. Bupropion and Cognitive-Behavioral Therapy for Smoking Cessation in Women. Nicotine & Tobacco Research, 9, pp. 699-709, 2007.

Incremental Validity of Anxiety Sensitivity in Terms of Motivation to Quit, Reasons for Quitting, and Barriers to Quitting Among Community-Recruited Daily Smokers

Dr. Zvolensky and colleagues at the University of Vermont conducted the present investigation to examine the relationships between anxiety sensitivity and motivation to quit smoking, barriers to smoking cessation, and reasons for quitting smoking among 329 adult daily smokers. As expected, after covarying for the theoretically relevant variables of negative affectivity, gender, Axis I psychopathology, nonclinical panic attack history, number of cigarettes smoked per day, and current levels of alcohol consumption, it was found that anxiety sensitivity was significantly incrementally related to level of motivation to quit smoking as well as current barriers to quitting smoking. Partially consistent with the hypotheses, after accounting for the variance explained by other theoretically relevant variables, it was found that anxiety sensitivity was significantly associated with self-control reasons for quitting smoking (intrinsic factors) as well as immediate reinforcement and social influence reasons for quitting (extrinsic factors). These findings set the stage for additional research targeted at disentangling the specific mechanisms that underlie these documented associations between anxiety sensitivity and smoking, and should help guide the future development for specialized intervention programs for smokers with anxiety vulnerabilities. Zvolensky, M.J., Vujanovic, A.A., Bonn Miller, M.O., Bernstein, A., Yartz, A.R., Gregor, K.L., McLeish, A.C., Marshall, E.C., and Gibson, L.E. Incremental Validity of Anxiety Sensitivity in Terms of Motivation to Quit, Reasons for Quitting, and Barriers to Quitting Among Community-Recruited Daily Smokers. Nicotine & Tobacco Research, 9, Pp. 965-975, 2007.

Research on Pharmacotherapies for Drug Abuse

Bupropion for Methamphetamine Dependence, Clinical Trial

Bupropion was tested for efficacy in increasing weeks of abstinence in methamphetamine-dependent patients, compared to placebo. This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 30-day follow-up. Five outpatient substance abuse treatment clinics located west of the Mississippi participated in the study. One hundred and fifty-one treatment-seekers with DSM-IV diagnosis of methamphetamine dependence were consented and enrolled. Seventy-two participants were randomized to placebo and 79 to sustained-release bupropion 150 mg twice daily. Patients were asked to come to the clinic three times per week for assessments, urine drug screens, and 90-min group psychotherapy. The primary outcome was the change in proportion of participants having a methamphetamine-free week. Secondary outcomes included: urine for quantitative methamphetamine, self-report of methamphetamine use, subgroup analyses of balancing factors and comorbid conditions, addiction severity, craving, risk behaviors for HIV, and use of other substances. The generalized estimating equation regression analysis showed that, overall, the difference between bupropion and placebo groups in the probability of a non-use week over the 12-week treatment period was not statistically significant (p<0.09). Mixed model regression was used to allow adjustment for baseline factors in addition to those measured (site, gender, level of baseline use, and level of symptoms of depression). This subgroup analysis showed that bupropion had a significant effect compared to placebo, among male patients who had a lower level of methamphetamine use at baseline (p<0.0001). Comorbid depression and attention-deficit/ hyperactivity disorder did not change the outcome. These data suggest that bupropion, in combination with behavioral group therapy, was effective for increasing the number of weeks of abstinence in participants with low-to-moderate methamphetamine dependence, mainly male patients, regardless of their comorbid condition. Elkashef, A.M., Rawson, R.A., Anderson, A. L., Li, S.H., Holmes, T., Smith, E. V., Chiang, N., Kahn, R., Vocci, F., Ling, W., Pearce, V.J., McCann, M., Campbell, J., Gorodetzky, C., Haning, W., Carlton, B., Mawhinney, J., and Weis, D. Bupropion for the Treatment of Methamphetamine Dependence. Neuropsychopharmacology (advance online publication), 20 June 2007.

Buprenorphine and Norbuprenorphine in Hair of Pregnant Women and Their Infants after Controlled Buprenorphine Administration

Buprenorphine is under investigation as a pharmacotherapeutic agent for treating opioid dependence in pregnant women. The investigators hypothesized that there would be a relationship between the cumulative maternal dose of buprenorphine during pregnancy and the concentration of buprenorphine and norbuprenorphine in maternal and infant hair. This study examined buprenorphine and norbuprenorphine concentrations in hair obtained from 9 buprenorphine-maintained pregnant women and 4 of their infants. Specimens were analyzed by liquid chromatography-tandem mass spectrometry with limits of quantification of 3.0 pg/mg. All maternal hair specimens were washed with methylene chloride before analysis, and when sufficient amounts of maternal hair were available, specimens also were analyzed without washing. Infant hair specimens were not washed. Buprenorphine concentrations were significantly greater in unwashed hair than washed hair (P = 0.031). Norbuprenorphine concentrations were significantly greater than buprenorphine concentrations in both maternal (P = 0.0097) and infant hair (P = 0.0033). There were statistically significant associations between the cumulative maternal dose of buprenorphine administered and the concentrations of buprenorphine (washed, P <0.0001; unwashed, P = 0.0004), norbuprenorphine (washed, P <0.0001; unwashed, P = 0.0005), and buprenorphine plus norbuprenorphine (washed, P <0.0001; unwashed, P = 0.0005) for both washed and unwashed maternal hair specimens. There was a significant positive association between concentrations of buprenorphine and norbuprenorphine in maternal hair (washed, P <0.0001; unwashed, P = 0.0003), a trend for this association in infant hair (P = 0.08), and an association between buprenorphine concentrations in maternal unwashed hair and infant hair (P = 0.0002). The buprenorphine: norbuprenorphine ratio increased in distal segments. Buprenorphine treatment during gestation provides an opportunity for monitoring drug disposition in maternal and fetal tissues under controlled conditions. Goodwin, R.S., Wilkins, D.G., Averin, O., Choo, R.E., Schroeder, J.R., Jasinski, D.R. et al. Buprenorphine and Norbuprenorphine in Hair of Pregnant Women and Their Infants after Controlled Buprenorphine Administration. Clin. Chem. (e-pub ahead of print, 2007).

Opioid Antagonism of Cannabinoid Effects: Differences between Marijuana Smokers and Nonmarijuana Smokers

The objective of this study was to test a lower, more opioid-selective dose of naltrexone (12 mg) in combination with THC. The influence of marijuana-use history and sex was also investigated. Naltrexone (0, 12 mg) was administered 30 min before oral THC (0-40 mg) or methadone (0-10 mg) capsules, and subjective effects, task performance, pupillary diameter, and cardiovascular parameters were assessed in marijuana smoking (Study 1; n=22) and in nonmarijuana smoking (Study 2; n=21) men and women. The results show that in marijuana smokers, low-dose naltrexone blunted the intoxicating effects of a low THC dose (20 mg), while increasing ratings of anxiety at a higher THC dose (40 mg). In nonmarijuana smokers, low-dose naltrexone shifted THC's effects in the opposite direction, enhancing the intoxicating effects of a low THC dose (2.5 mg) and decreasing anxiety ratings following a high dose of THC (10 mg). There were no sex differences in these interactions, although among nonmarijuana smokers, men were more sensitive to the effects of THC alone than women. To conclude, a low, opioid-selective dose of naltrexone blunted THC intoxication in marijuana smokers, while in nonmarijuana smokers, naltrexone enhanced THC intoxication. These data demonstrate that the interaction between opioid antagonists and cannabinoid agonists varies as a function of marijuana use history. Haney, M. Opioid Antagonism of Cannabinoid Effects: Differences between Marijuana Smokers and Nonmarijuana Smokers. Neuropsychopharmacology, 32, pp. 1391-1403, 2007.

Gender Differences with High-dose Naltrexone in the Patients with Co-occurring Cocaine and Alcohol Dependence

This is a randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy of a higher-than-typical daily dose of naltrexone (150 mg/day), taken for 12 weeks, in 164 patients (n = 116 men and n = 48 women) with co-occurring cocaine and alcohol dependence. Patients were stratified by gender and then randomly assigned to either naltrexone or placebo, and to either cognitive-behavioral therapy or a type of medical management. The two primary outcomes were cocaine use and alcohol use. Significant Gender x Medication interactions were found for cocaine use via urine drug screens (three way, with time) and self-reports (two way) for drug severity (two way) and alcohol use (two way). The type of psychosocial treatment did not affect outcomes. Thus, 150 mg/day naltrexone added to a psychosocial treatment resulted in reductions in cocaine and alcohol use and drug severity in men, compared to higher rates of cocaine and alcohol use and drug severity in women. Pettinati, H., Kampman, K., Lynch, K., Suh, J., Dackis, C., Oslin, D. et al. Gender Differences with High-dose Naltrexone in the Patients with Co-occurring Cocaine and Alcohol Dependence. J. Subst. Abuse Treat. (e-pub ahead of print, 2007).

Nicotine Replacement and Behavioral Therapy for Smoking Cessation in Pregnancy

This study examines whether adding nicotine replacement therapy (NRT) to cognitive-behavioral therapy (CBT) for pregnant smokers increases rates of smoking cessation. An open-label randomized trial (Baby Steps, n=181) of CBT-only versus CBT+NRT (choice of patch, gum, or lozenge; 1:2 randomization) was used. Data were collected from 2003 through 2005; analyses were conducted in 2006 and 2007. Outcomes were biochemically validated self-reported smoking status at 7 weeks post-randomization, 38 weeks gestation, and 3 months postpartum. Women in the CBT+NRT arm were almost three times more likely than women in the CBT-only arm to have biochemically validated cessation at both pregnancy time points (after 7 weeks: 24% vs 8%, p=0.02; at 38 weeks gestation: 18% vs 7%, p=0.04), but not at 3 months postpartum (20% vs 14%, p=0.55). Recruitment was suspended early by an Independent Data and Safety Monitoring Board when an interim analysis found a higher rate of negative birth outcomes in the CBT+NRT arm than in the CBT-only arm. In the final analysis, the difference between the arms in rate of negative birth outcomes was 0.09 (p=0.26), when adjusted for previous history of preterm birth. The addition of NRT to CBT promoted smoking cessation in pregnant women. This effect did not persist postpartum. More data are needed to determine safety parameters and to confirm the efficacy of NRT use during pregnancy. Pollak, K.I., Oncken, C.A., Lipkus, I.M., Lyna, P., Swamy, G.K., Pletsch, P.K. et al. Nicotine Replacement and Behavioral Therapy for Smoking Cessation in Pregnancy. Am. J. Prev. Med., 33, pp. 297-305, 2007.

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

HIV/AIDS-Related

Factors Affecting Reproductive Hormones in HIV-infected, Substance-using Middle-aged Women

The objective of this study was to determine whether reproductive hormone levels are affected by human immunodeficiency virus (HIV) and drug use. HIV-infected and uninfected women (N=429), median age 45, were interviewed on menstrual frequency, demographic and psychosocial characteristics, and drug use behaviors. Serum was obtained on cycle days 1 to 5 in women reporting regular menses. Premenopausal-, early menopausal, and late menopausal transition and postmenopausal stages were assigned based on menstrual history. Serum was assayed for follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH), prolactin, thyroid-stimulating hormone, and inhibin B. Body mass index, HIV serostatus, and CD4+ counts were measured. Factors associated with hormone concentrations were assessed using uni- and multivariable analyses. Hormone concentrations were compared within menstrual status categories using nonparametric comparisons of means. In this cross-sectional analysis, LH and FSH increased, and E2 and inhibin B were significantly lower in women of older age and more advanced menopausal status. Increased body mass index was strongly associated with decreased LH. Opiate use was significantly associated with lower inhibin B and E2 and increased prolactin. Poorer self-rated health was statistically significantly associated with lower LH and FSH, but increased education was associated with higher LH and FSH. Among HIV-seropositive women, opiate users had detectably lower FSH and LH than nonusers, and use of highly active antiretroviral therapy was significantly related to higher LH, FSH, and E2, whereas cocaine use was associated with lower E2. Authors conclude that age and menopausal status are strongly related to reproductive hormones. Body mass index and use of opiates, cocaine, and highly active antiretroviral therapy as well as educational attainment and perceived health can significantly modify reproductive hormones during the menopausal transition and need to be considered when interpreting hormone levels in middle-aged women. Santoro, N., Lo, Y., Moskaleva, G., Arnsten, J.H., Floris-Moore, M., Howard, A.A., Adel, G., Zeitlian, G., Schoenbaum, E.E. Menopause, 14(5), pp. 859-865, 2007.

Hepatitis C or Dual Infections of HIV and HCV

Factors Affecting Serum Concentrations of Hepatitis C Virus (HCV) RNA in HCVgenotype 1-Infected Patients with Chronic Hepatitis

The serum concentration of hepatitis C virus (HCV) RNA is usually stable (4 to 8 log(10) IU/ml) in untreated patients with chronic hepatitis C. While this baseline HCV RNA concentration ([HCV RNA](BL)) is predictive of a sustained virologic response to treatment, its determinants are only partially identified. The authors therefore analyzed the baseline characteristics of 2,472 HCV genotype 1-infected patients to identify correlations with gender, age, race, weight, body mass index (BMI), HCV acquisition mode, HCV subtype, alanine aminotransferase concentration, or histopathologic changes in the liver. After separation of the data according to four [HCV RNA](BL) groups (< or =5.0, >5.0 to 5.6, >5.6 to 5.9, and >5.9 log(10) IU/ml), the authors determined that increasing [HCV RNA](BL) correlated (P < 0.05) with increasing proportions of patients who were male, >40 years of age, or heavier (a weight of >85 kg or a BMI of >27 kg/m(2)). Histologic activity index (HAI) data were available for 1,304 of these patients: increasing [HCV RNA](BL) correlated with higher fibrosis and necrosis-inflammation scores. As a continuous variable, [HCV RNA](BL) correlated with age, gender, weight (continuous or < or =85 versus >85 kg), BMI (continuous or < or =27 versus >27 kg/m(2)), subtype, fibrosis score, and necrosis-inflammation score; however, multiple-regression analysis yielded P values of <0.1 only for age, gender, BMI (< or =27 versus >27 kg/m(2)), and fibrosis score. While these findings are suggestive of a role for these factors in maintenance of the pretreatment state of HCV infection, the multiple-regression model accounted for only < or =4.6% of the [HCV RNA](BL) differences between individuals (R(2) = 0.046 for 1,304 patients with HAI scores; 0.043 for all 2,472 patients). Ticehurst, J., Hamzeh, F., Thomas, D. J. Clin. Microbiol. 45, pp. 2426-2433, 2007.

Co-morbid Medical and Psychiatric Illness and Substance Abuse in HCV-infected and Uninfected Veterans

Comorbidities may affect the decision to treat chronic hepatitis C virus (HCV) infection. The authors undertook this study to determine the prevalence of these conditions in HCV-infected persons compared with HCV-uninfected controls. Demographic and comorbidity data were retrieved for HCV-infected and -uninfected subjects from the VA National Patient Care Database using ICD-9 codes. Logistic regression was used to determine the odds of comorbid conditions in the HCV-infected subjects. HCV-uninfected controls were identified matched on age, race/ethnicity and sex. Authors identified 126,926 HCV-infected subjects and 126,926 controls. The HCV-infected subjects had a higher prevalence of diabetes, anemia, hypertension, chronic obstructive pulmonary disease (COPD)/asthma, cirrhosis, hepatitis B and cancer, but had a lower prevalence of coronary artery disease and stroke. The prevalence of all psychiatric comorbidities and substance abuse was higher in the HCV-infected subjects. In the HCV-infected persons, the odds of being diagnosed with congestive heart failure, diabetes, anemia, hypertension, OPD/asthma, cirrhosis, hepatitis B and cancer were higher, but lower for coronary artery disease and stroke. After adjusting for alcohol and drug abuse and dependence, the odds of psychiatric illness were not higher in the HCV-infected persons. The prevalence and patterns of comorbidities in HCV-infected veterans are different from those in HCV-uninfected controls. The association between HCV and psychiatric diagnoses is at least partly attributable to alcohol and drug abuse and dependence. These factors should be taken into account when evaluating patients for treatment and designing new intervention strategies. Butt, A., Khan, U., McGinnis, K. Et al. J. Viral Hepat.14, pp. 890-896, 2007.

Biochemical and Virologic Parameters in Patients Co-infected with Hepatitis C and HIV versus Patients with Hepatitis C Mono-infection

Previous studies of patients with hepatitis C virus (HCV) infection looking at the effect of human immunodeficiency virus (HIV) co-infection on biochemical parameters and HCV RNA level have shown conflicting results. Accurate characterization of the effect of HIV is important for evaluation and treatment of HCV in coinfected persons. Authors studied 315 HCV mono-infected and 75 HCV-HIV co-infected subjects to determine the effect of HIV on biochemical parameters and HCV RNA and to determine the predictors of elevated serum alanine aminotransferase (ALT) levels and HCV RNA levels. The co-infected subjects were more likely to be African-American (55% vs 26%, P<0.0005), have used injection drugs (68% vs 60%, P = 0.02), have detectable HCV RNA (84% vs 70.5%, P=0.018), have HCV RNA levels >6 log10 IU/mL (60% vs 38%, P=0.001), and have lower mean serum ALT levels (50.4 IU/mL vs 73.7 IU/mL, P=0.006). In multivariable analyses, the following factors predicted an ALT level >50 IU/mL: log10 HCV RNA (OR, 1.15; 95% CI, 1.00 to 1.32); HIV co-infection (OR, 0.48; 95% CI, 0.25-0.89); and having ever been treated for HCV (OR, 1.92; 95% CI, 1.16 to 3.18). The only significant predictor of HCV RNA level >6 log10 IU/mL was HIV co-infection (OR, 2.75; 95% CI, 1.46-5.15). Significant predictors of having a detectable HCV RNA level were female sex (OR, 3.81; 95% CI, 1.18-12.25); HIV co-infection (2.45; 95% CI, 1.14-5.26); and ever being treated for HCV (OR, 1.96; 95% CI, 1.10 to 3.48). HCV-HIV co-infected persons have higher HCV RNA levels but lower serum ALT levels than HCV mono-infected patients. Criteria for performing liver biopsy and treating HCV infection in co-infected patients may need to be revisited. Butt, A., Tsevat, J., Ahmad, J., et al., Am. J. Med. Sci. 333, pp. 271-275, 2007.

Services Research

Violence and HIV Risk among Incarcerated Women

The association between history of violence and risk for HIV infection among incarcerated women was examined. Specifically, physical violence and rape were considered as they relate to unprotected sex with male primary and non primary (male or female) sexual partners among a sample of HIV negative female inmates (n = 1,588) housed in Connecticut's sole correctional facility for women between November 1994 and October 1996. A supplement to the mandatory Connecticut Department of Correction Inmate Medical Screening/Health History was used to collect information on each woman's background, history of violence, and unprotected sex practices. Multivariate logistic regression was used to determine the associations between violence and unprotected sex by partner type. Experiencing any violence was found to be significantly associated with increased odds of unprotected sex with one's primary partner, even after controlling for race, history of sex work, drug use, employment status, and having other non primary partners. Of particular importance was having a history of physical violence. History of violence was not significantly associated with unprotected sex with non primary partners. These findings demonstrate the considerable vulnerability of incarcerated women to violence and suggest that this history is associated with increased unprotected sex practices, especially with male primary partners. HIV prevention interventions among women should take experiences of violence into account. Conversely, violence prevention and interventions aimed at coping with violence can be a part of the HIV prevention agenda for incarcerated women. Future longitudinal research can confirm the relationships of violence to HIV risk in women. Ravi, A., Blankenship, K., and Altice, F. The Association between History of Violence and HIV Risk: A Cross-Sectional Study of HIV-Negative Incarcerated Women in Connecticut. Womens Health Issues, 17(4), pp. 210-216, 2007.

Gender Differences in Housing Patterns and Homelessness

Homeless individuals experience high rates of morbidity and mortality, yet many homeless studies include small percentages of female participants. The authors therefore sought to determine correlates of homelessness separately for men and women in a sample of individuals visiting free food programs. Between August 2003 and April 2004, 324 individuals were recruited from San Francisco free food programs and interviewed regarding housing, sociodemographics, health, drug use, sex trade, and incarceration. Over one-half of women and almost three-fourths of men reported homelessness in the prior year. Among women, white race, younger age, not living with minor children, engaging in sex trade and recent incarceration were strongly associated with homelessness; however, only incarceration maintained the strong association in adjusted analysis (OR = 7.16, CI = 3.83-13.4). Among men, heavy alcohol use, drug use, years spent living in San Francisco and monthly income were strongly associated with homelessness; however, only years living in San Francisco (OR = 0.28, CI = 0.19-0.42) and monthly income maintained strong association in adjusted analysis (OR = 0.27, CI = 0.13-0.57). Housing patterns and the strongest correlates of homelessness among individuals visiting free food programs differ by sex. These results suggest the need to characterize homelessness and develop effective homeless interventions separately for men and women. Riley, E., Weiser, S., Sorensen, J., Dilworth, S., Cohen, J., and Neilands, T. Housing Patterns and Correlates of Homelessness Differ by Gender Among Individuals Using San Francisco Free Food Programs. J. Urban Health, 84(3), pp. 415-422, 2007.

Cultural Competence among Healthcare Providers

Mandates for culturally competent substance abuse and mental health services call for behavioral health providers to recognize and engage cultural issues. These efforts to incorporate culture typically focus on client culture, but provider views of culture can also influence the provision of services. Analysis of 42 semi-structured interviews with behavioral health providers suggests that culture is considered by many to be an obstacle to help seeking and treatment of substance-abusing youth. Although some providers do not highlight cultural issues, others conceptualize culture in terms of (a) generalized Hispanic cultural attributes, (b) male-dominant gender roles, and (c) the culture of poverty. Recommendations for provider training on cultural issues focus on ways they might critically consider their ideas about culture. Quintero, G., Lilliott, E., and Willging, C. Substance Abuse Treatment Provider Views of "Culture": Implications for Behavioral Health Care in Rural Settings. Qual. Health Res., 17(9), pp. 1256-1267, 2007.

Violence against Homeless Women

Research on violence against homeless women has focused mainly on individual rather than community-level risk factors. Using an ecological conceptual framework, the researchers estimated the independent association of community characteristics with sexual and physical assault in a probability sample of 974 homeless women. Participants were interviewed at 66 assistance programs in Los Angeles County, California in 1997. Individual responses were linked to community-level data from land use files and the U.S. Census by the facility ZIP codes. Multivariate logistic regression analysis showed that women using service providers in closer proximity to Skid Row had higher odds of physical assault (OR=1.48; 95% CI=1.03, 2.14). A number of individual characteristics were also associated with violent victimization. To reduce violence against homeless women, ensuring the safety of locations for shelters and other assistance programs should be a planning priority for local housing authorities. Heslin, K., Robinson, P., Baker, R., and Gelberg, L. Community Characteristics and Violence against Homeless Women in Los Angeles County. J. Health Care Poor Underserved, 18(1), pp. 203-218, 2007.

Gender-specific Substance Abuse Treatment for Women Promotes Continuity of Care

Research has stressed the value of providing specialized services to women and suggests the importance of treatment duration. This quasiexperimental retrospective study reports on the continuity of care for women with children who were admitted to long-term residential substance abuse treatment. Women were admitted to 7 agencies offering specialized, women's only treatment (SP, n = 747) or to 9 agencies that provided standard mixed-gender treatment (ST, n = 823). Client and treatment data were gathered from administrative sources. Women in SP programs (37%) were more likely than those in ST programs (14%) to continue care. Multivariate analyses revealed that SP clients who completed treatment with longer stays were most likely to continue care. The findings show that specialized treatment for women promotes continuing care and demonstrate the importance of treatment completion. Claus, R.E., Kissin, W., Krupski, A., Campbell, K., and Stark, K. Does Gender-Specific Substance Abuse Treatment for Woman Promote Continuity of Care. J. Subst. Abuse Treat., 32, pp. 29-39, 2007.

Children Are Important Sources of Social Support for Women in Addiction Treatment

The authors examined the status of children and the types of support available from children as reported by women in substance abuse treatment. Their findings indicate that children are viewed as sources of social support to women in addiction treatment. Children were viewed as providing as much sobriety support to respondents as that provided by adult network members. In addition, both children living with the respondent and children in the care of others were viewed as providers of specific types of social support. These study findings indicate that treatment providers need to be aware of the extent to which women clients may rely on support from children. Focusing only on adult relationships misses the fact that children may be a strong source of support for women in treatment, particularly for women in residential treatment, where the need for support may be greater. Tracy, E., and Martin, T. Children's Roles in The Social Networks of Women in Substance Abuse Treatment. J. Subst. Abuse Treat., 32(1), pp. 81-88, 2007.

Older Women Have Better Long-Term Addiction Treatment Outcomes than Older Men

This study examined participants at seven-year follow-up to assess long-term outcomes of older women (n = 25) and men (n = 59) ages 55 and over in an outpatient addiction program. It measured demographic characteristics, alcohol and drug use, psychiatric symptoms, Addiction Severity Index, treatment length, and outcomes. At seven years, 76.0% of women reported abstinence in the prior 30 days versus 54.2% of men (p = 0.05). Logistic regression analysis revealed that longer treatment stay predicted abstinence. Findings indicate that older women have better long-term addiction outcome than older men, but treatment length is more significant than gender in predicting outcome. Satre, D., Blow, F., Chi, F., and Weisner, C. Gender Differences in Seven-year Alcohol and Drug Treatment Outcomes Among Older Adults. Am. J. Addict., 16(3), pp. 216-221, 2007.

Measuring Offender Attributes and Engagement in Treatment Using the Client Evaluation of Self and Treatment

Monitoring drug abuse treatment delivery and progress requires the use of reliable and valid instruments to measure client motivation, psychosocial and cognitive functioning, and other treatment process dynamics. As part of the Criminal Justice Drug Abuse Treatment Studies (CJDATS) protocol to examine client performance indicators for corrections-based treatment populations, this study examined psychometric properties of the 108-item TCU Criminal Justice Client Evaluation of Self and Treatment (CJ CEST), which is composed of 15 scales across 3 major domains. Treatment Motivation includes scales on desire for help; treatment readiness; treatment needs; and pressures for treatment. Psychosocial Functioning includes scales on depression; anxiety; self-esteem; decision-making; hostility; and risk-taking. Treatment Engagement includes scales on treatment participation; treatment satisfaction; counseling rapport; peer support; and social support. The sample included 3,266 offenders from 26 corrections-based treatment programs located in 6 states. Overall, the client assessment demonstrated good reliabilities at individual and program levels, and in test-retest administrations. Additionally, evidence for construct validity was favorable, based on confirmatory factor analyses. All but 4 scales had conventionally acceptable fit indices; the remaining 4 scales (desire for help; treatment readiness; decision making; risk taking) had acceptable GFIs, but other indices indicated possible multidimensionality. Multilevel analyses were used to examine program level variation, after controlling for client-level attributes (e.g., age, race, time in treatment). Over 20% of treatment readiness and counseling rapport was at the program level, but only 5-7% of offender anxiety and hostility. Differences were also found between male-only and female-only programs (all but 3 programs). Women were more motivated and involved in their treatment, and had stronger social support systems. Finally, bivariate correlations were examined between CJ CEST scales and criminal thinking scales (using the CTU Criminal Thinking Scales), after removing program differences. Less criminal thinking was found with higher overall motivation, psycosocial functioning, and engagement. In conclusion, the CJ CEST is a brief yet comprehensive instrument that effectively and efficiently measures client needs and functioning at intake. It also is appropriate for use during treatment to monitor client progress over time. Garner, B.R., Garner, K.K., Flynn, M.P., Morey, J.T., and Simpson, D.D. Measuring Offender Attributes and Engagement in Treatment Using the Client Evaluation of Self and Treatment. Criminal Justice & Behavior, 34(9), pp. 1113-1130, 2007.

Self-rated Health and its Determinants among Adults in Syria: A Model from the Middle East

Self-rated health (SRH) has been widely used to research health inequalities in developed western societies, but few such studies are available in developing countries. Similar to many Arab societies, little research has been conducted in Syria on the health status of its citizens, particularly in regards to SRH. This Study aims to investigate and compare determinants of SRH in adult men and women in Aleppo, Syria. The authors performed a cross-sectional survey of adults 18 to 65 years old residing in Aleppo, Syria (2,500,000 inhabitants) in 2004. The study involved 2038 household representatives (45.2% men, age range 18-65 years, response rate 86%). SRH was categorized as excellent, normal, and poor. Odds ratios for poor and normal SRH, compared to excellent, were calculated separately for men and women using logistic regression. It was found that women were more likely than men to describe their health as poor. Men and women were more likely to report poor SRH if they were older, reported two or more chronic health problems, or had high self perceived functional disability. Important gender-specific determinants of poor SRH included being married, low socioeconomic status, and not having social support for women, and smoking with low physical activity for men. The authors conclude that women were more likely than men to describe their health as poor. The link with age and pre-existing chronic conditions seems universal and likely reflects natural aging process. Determinants of SRH differed between men and women, possibly highlighting underlying cultural norms and gender roles in the society. Understanding the local context of SRH and its determinants within the prevailing culture will be important to tailor intervention programs aimed at improving health of the Syrian and similar Arab societies. Asfar, T., Ahmad, B., Rastam, S., Mulloli, T., Ward, K., and Maziak, W. Self-Rated Health and its Determinants Among Adults in Syria: A Model From the Middle East. BMC Public Health, 7, pp. 177-186, 2007.

Measuring Offender Progress in Treatment Using the Client Assessment Inventory

The accurate and reliable assessment of client psychological and cognitive change during correctional substance abuse treatment has gained increasing importance during the past decade as criminal justice systems seek to evaluate and understand those treatment elements associated with long-term change. The 103-item Client Assessment Inventory (CAI) is a self-report instrument for measuring client change during treatment, using 14 subscales across four cognitive and behavioral domains. The Developmental dimension includes subscales on maturity; responsibility; and values. The Socialization dimension includes subscales on drug/criminal lifestyle; maintaining images; work attitude; and social skills. The Psychological dimension includes subscales on cognitive skills; emotional skills; and self-esteem/self-efficacy. The program participation dimension includes subscales on philosophy/understands program rules; engagement; attachment/investment; and role model. The reliability and internal consistency of the CAI, as adapted for use in criminal justice settings, were examined with data gathered from 1,170 offenders. The research addressed the utility of the CAI for different subpopulations of offenders (e.g., race/ethnicity, gender) across a variety of correctional treatment settings. Total CIA demonstrated high reliability (alpha = .96). Subscale alphas ranged from .42 to .90; with work attitudes and maintaining image demonstrating low unidimensionality (alphas = .42 and .53). Female clients were significantly higher on 9 of 14 subscales, after controlling for ethnicity, treatment program, and treatment retention. A sub-sample (n=165) were retested after 1 week. Total CAI test-retest reliability was Kappa = .68; subscale Kappa's ranged from .31 to .54.Validity of the instrument was evaluated using time in treatment at CAI administration, which ranged from 2 weeks to 15 mos. Longer time in treatment was associated with significantly higher scores on 13 of 14 scales. Overall, the data support the use of the CAI as a consistent, reliable, and easily administered instrument for measuring client performance and progress in treatment in both therapeutic community (TC) and non-TC correctional treatment settings. Sacks, J.Y., McKendrick, K., and Kressel, D. Measuring Offender Progress in Treatment Using The Client Assessment Inventory. Criminal Justice and Behavior, 64(9), pp. 1131-1142, 2007.

Gender Differences in Treatment Engagement among a Sample of Incarcerated Substance Abusers

This article examines gender differences in treatment engagement, psychosocial variables, and criminal thinking among a sample of male and female substance abusers (N = 2,774) enrolled in 20 prison-based treatment programs in five different states as part of the National Institute on Drug Abuse-funded Criminal Justice Drug Abuse Treatment Studies cooperative agreement. Results indicate that inmates in female treatment programs report more psychosocial dysfunction, less criminal thinking, and higher engagement than in male facilities, and there is a more negative relationship between psychosocial variables and treatment engagement (compared to male programs). Only one subscale of criminal thinking had a significant gender interaction, with males having a significantly stronger relationship between cold-heartedness and low treatment engagement. Implications for treatment interventions with a gender-specific focus are discussed. Staton-Tindall, M., Garner, B.R., Morey, J.S., Leukefeld, C., Krietemeyer, J., Saum, C.A., and Oser, C.B. Gender Differences in Treatment Engagement among a Sample of Incarcerated Substance Abusers. Criminal Justice and Behavior, 34(9), pp. 1143-1156, 2007.

An Assessment of Criminal Thinking among Incarcerated Youths in Three States

The Texas Christian University Criminal Thinking Scales (CTS) instrument has been shown to predict outcomes for institutionalized adult offenders. This article examines responses among male (n = 151) and female (n = 52) incarcerated adolescents, and they were compared to norms for incarcerated adult offenders. The results indicated that the adolescent sample had higher scores on four scales (Entitlement, Justification, Personal Irresponsibility, and Power of Orientation) but not on Criminal Rationalization. Scores did not differ by gender or ethnicity of respondents. The results provide convergent validity indicating that the scores for adolescents were correlated with prior history of criminal behavior, substance use, family dysfunction, and Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition diagnoses of conduct disorder and oppositional defiant disorder. Thus, the CTS may provide useful diagnostic information to help identify youth with a constellation of problem behaviors that predict poor outcomes following incarceration. It also may prove helpful in accounting for individual variations in response to treatment for incarcerated adolescents who receive treatment during reentry back into the community. Dembo, R., Turner, C. W., and Jainchill, N. An Assessment of Criminal Thinking Among Incarcerated Youths in Three States. Criminal Justice and Behavior, 34(9), pp. 1157-1167, 2007.

Application of Gelberg-Andersen Behavioral Model

The Gelberg-Andersen Behavioral Model for Vulnerable Populations was applied to predict health services utilization (HSU) in 875 homeless US women. Structural models assessed the impact of predisposing (demographics, psychological distress, alcohol/drug problems, and homelessness severity), enabling (health insurance, source of care, barriers) and need (illness) variables on HSU (preventive care, outpatient visits, and hospitalizations). Homelessness severity predicted illness, barriers and less insurance. Distress predicted more barriers, illness and less outpatient HSU. Drug problems predicted hospitalizations. Barriers predicted more illness and less outpatient HSU. Health and homelessness indicators were worse for White women. Better housing, access to care and insurance would encourage appropriate HSU. Stein, J., Andersen, R., and Gelberg, L. Applying the Gelberg-Andersen Behavioral Model for Vulnerable Populations to Health Services Utilization in Homeless Women. J. Health Psychol., 12(5), pp. 791-804, 2007.

Clinical Trials Network Research

Treatment Programs in the National Drug Abuse Treatment Clinical Trials Network

Drug abuse treatment programs and university-based research centers collaborate to test emerging therapies for alcohol and drug disorders in the National Drug Abuse Treatment Clinical Trials Network (CTN). Programs participating in the CTN completed Organizational Surveys (n=106 of 112; 95% response rate) and Treatment Unit Surveys (n=348 of 384; 91% response rate) to describe the levels of care, ancillary services, patient demographics, patient drug use and co-occurring conditions. Analyses describe the corporations participating in the CTN and provide an exploratory assessment of variation in treatment philosophies. A diversity of treatment centers participate in the CTN; not for profit organizations with a primary mission of treating alcohol and drug disorders dominate. Compared to National Survey of Substance Abuse Treatment Services (N-SSATS), programs located in medical settings are over-represented and centers that are mental health clinics are under-represented. Outpatient, methadone, long-term residential and inpatient treatment units differed on patients served and services provided. Larger programs with higher counselor caseloads in residential settings reported more social model characteristics. Programs with higher social model scores were more likely to offer self-help meetings, vocational services and specialized services for women. Conversely, programs with accreditation had less social model influence. The CTN is an ambitious effort to engage community-based treatment organizations into research and more fully integrate research and practice. McCarty, D., Fuller, B., Kaskutas, L.A., Wendt, W.W., Nunes, E.V., Miller, M., Forman, R., Magruder, K.M., Arfken, C., Copersino, M., Floyd, A., Sindelar, J., and Edmundson, E. Drug Alcohol Depend. 92(1-3), pp. 200-207, January 1, 2008. (e-pub September 17, 2007).

International Research

Publications by Former NIDA INVEST Drug Abuse Research Fellows

Gender Differences in the Relationship between Alcohol and Violent Injury: An Analysis of Cross-national Emergency Department Data

INVEST Fellow: Guilherme Borges, Mexico, 1997-1998
The objectives of the present study were twofold: (1) to determine whether gender differences exist in the roles of drinking in the event (i.e., self-reported drinking before the injury and estimated blood alcohol concentration [BAC] captured after injury) and drinking pattern (i.e., heavy episodic drinking) in explaining violent versus nonviolent injuries and (2) to assess whether these gender differences vary by country. Emergency department data were analyzed from 30 hospitals in 15 countries, as part of the Emergency Room Collaborative Alcohol Analysis Project and the World Health Organization Collaborative Study of Alcohol and Injuries. Interaction effects between gender and alcohol were tested in the prediction of violent versus nonviolent injury for each country. The bivariate analyses revealed significantly larger effects of drinking-in-the-event variables for men than for women in three countries (i.e., 6 hours before the injury in Argentina and having a positive BAC in Belarus and Spain). In the multivariate analyses, restricted to countries with sufficient sample sizes (i.e., Mexico, South Africa, and the United States), no significant gender differences were found between the drinking-in-the-event variables and violent injury. In the bivariate and multivariate analyses, a significant interaction effect between gender and heavy episodic drinking was found in the United States, indicating that heavy episodic drinking predicted violent injury for women but not for men. Although the results are preliminary, treatment and prevention programs may need to target both genders equally or perhaps even focus more on heavy-drinking women, particularly in the United States. Wells, S., Thompson, J.M., Cherpitel, C., Macdonald, S., Marais, S., and Borges, G. J. Stud. Alcohol Drugs, 68(6), pp. 824-833, 2007.

Age and Gender Effects on Olanzapine and Risperidone Plasma Concentrations in Children and Adolescents

INVEST Fellow: Gerald Zernig, Austria, 1993-1994
Risperidone and olanzapine are second-generation antipsychotics that are increasingly used in child and adolescent psychiatry. So far, little is known about plasma concentrations and concentration-to-dose (C/D) ratios of these agents in children and adolescents compared to adults. This study investigated whether age and gender influence risperidone and olanzapine plasma concentration by determining risperidone and olanzapine plasma levels by tandem mass spectrometry in 162 Caucasian patients (98 risperidone and 64 olanzapine). For risperidone and 9-hydroxyrisperidone, the C(total)/D ratio was almost identical in both age groups (10-18 and 19-45 years, respectively). In the younger age group, females exhibited significantly higher total plasma levels than males while receiving similar doses of risperidone. For olanzapine, in adolescents significantly higher C/D ratios were detected by an average of 43% (after adjustment for weight: 34%) compared to adults. This study demonstrates an age effect for olanzapine but not for risperidone resulting in higher olanzapine plasma levels in younger patients. For risperidone, the authors found a gender effect as female adolescent patients had significantly higher risperidone plasma concentrations than male adolescent patients. Future prospective studies are necessary to clarify whether the prescribed dosage should be different in young and older patients. Aichhorn, W., Marksteiner, J., Walch, T., Zernig, G., Hinterhuber, H., Stuppaeck, C., and Kemmler, G. J. Child Adolesc. Psychopharmacol. 17(5), pp. 665-674, 2007.

Study on the Association between Vaginal Douching and Sexually Transmitted Diseases among Female Sex Workers in a County of Yunnan Province

INVEST Fellow: Lan Zhang, China, 2004-2005
The objective of the present study was to explore the epidemic characteristics of vaginal douching, human immunodeficiency virus (HIV) and other sexually transmitted diseases(STD) among female sex workers (FSWs) in Yunnan province. FSWs were recruited to be investigated on their demographic data, drug abuse and sexual behavior, HIV/AIDS knowledge and procreation health status. Venous blood were collected to test for HIV, herpes simplex virus 2 (HSV-2) and syphilis while urine specimen was for morphine, cervical secretion for Gonorrhoea and Chlamydia trachomatis, and vaginal secretion for Trichomonas. A total number of 833 blood specimen were collected, in which 84 specimen were confirmed to be HIV positive with a prevalence rate of 10.1%. The prevalence rates of syphilis and HSV-2 were 8.2% and 68.4% respectively. 832 vaginal and cervical secretion specimens were collected with the prevalence rates of Gonorrhoea, Chlamydia trachomatis and Trichomonas were 11.5%, 28.2% and 11.9% respectively. In multivariate logistic analysis, the factors associated with vaginal douching were: being Han nationality, locations of sex work at middle/high level, ever heard of HIV/AIDS, emerged hypogastric pain last year, the number of sex work location > or =4. Vaginal douching was shown a risk factor for HIV and some STD. Wang, H.B., Wang, N., Ma, J.G., Wang, G.X., Chang, D.F., Ding, G.W., Xu, J.J., Zhang, G.L., Dong, R.L., Zhang, L., Wu, Z.L., and Zheng, X.W. Zhonghua Liu Xing Bing Xue Za Zhi. 28(6), pp. 558-561, 2007. [Article in Chinese]

Publications by Former NIDA Hubert H. Humphrey Fellows

Alcohol and Drug Use among University Students: Gender Differences

HHH Fellows: Arthur Guerra de Andrade, Brazil, 1991-1992, and Vladimir Stempliuk, Brazil, 2003-2004
This study compared the pattern of alcohol, legal and illegal drugs use among students of the Universidade de Sao Paulo (Brazil) in 1996 and 2001. Samples of 2.564 (1996) and 2.837 (2001) students answered a questionnaire proposed by the World Health Organization, which characterizes the consumption of alcohol, legal and illegal drugs in lifetime, in the last 12 months and in the last 30 days. Men showed a significant increase in lifetime use of tobacco (44.8% to 50.9%), marijuana (33.7% to 39.5%) and hallucinogens (6.6% to 14.1%) between 1996 and 2001. No significant change was observed among women between 1996 and 2001 in tranquilizer use. Concerning the consumption reported in the last 12 months, both genders displayed significant increases in the consumption of marijuana (22.3% to 27.1% for men and 12.9% to 16.9% for women), amphetamines (1.9% to 5.0% for men and 3.4% to 5.6% for women), and inhalants (9.8% to 15.7% for men and 5.4% to 10.6% for women). The greatest gender difference was observed in consumption reported in the last 30 days with significant increases in male use of tobacco (19.6% to 23.5%), marijuana (15.8% to 20.5%), amphetamines (1.1% to 3.2%), and inhalants (4.0% to 7.9%). Substance use reported in the last 30 days remained stable among women between the 2 surveys. Rates of substance use among university students increased. These gender differences in substance consumption should be taken into account in the development of preventive and treatment strategies for undergraduate university students. Wagner, G.A., Stempliuk, Vde A., Zilberman, M.L, Barroso, L.P., and de Andrade, A.G. Rev. Bras. Psiquiatr. 29(2), pp. 123-129, 2007.

Gender Differences in Sex Risk Behaviors among Ukraine Injection Drug Users

HHH Fellow: Sergiy Dvoryak, Ukraine, 1999-2000
The objective of this study was to assess gender differences in drug and sex risk behaviors and evaluate predictors of HIV-related sex risk behaviors among heterosexual injection drug users (IDUs) in Ukraine. Street-recruited IDUs from Kiev, Odessa, and Makeevka/ Donesk, Ukraine. From June 2004 through November 2006, outreach workers recruited 1557 IDUs, including 526 from Kiev, 494 from Odessa, and 537 from Makeevka/Donesk. Participants were administered a standardized computer-assisted interview assessing HIV-related drug and sex risk behaviors, self-efficacy for practicing safe sex, and HIV knowledge. Overall, 80% of the participants were sexually active in the 30-day period before their interview. They also engaged in high-risk sex behaviors during this brief 30-day window: 53% reported anal or vaginal sex without a condom, 27% had sex with more than 1 partner, 41% had an IDU sex partner, and 37% had an HIV-positive sex partner or a partner whose HIV status they did not know. Overall, women were at higher risk than men and were more likely to have been told they were HIV-positive. The extremely high HIV prevalence rate in Ukraine and in this cohort, combined with their recent high-risk sex behaviors, forecasts not only a continuance of the epidemic in the region but an escalation. Booth, R.E., Lehman, W.E., Brewster, J.T., Sinitsyna, L., and Dvoryak, S. J. Acquir. Immune Defic. Syndr. July 19, 2007 (e-pub ahead of print).

Intramural Research

Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch

Sex-dependent Metabolic, Neuroendocrine, and Cognitive Responses to Dietary Energy Restriction and Excess

Females and males typically play different roles in survival of the species and would be expected to respond differently to food scarcity or excess. To elucidate the physiological basis of sex differences in responses to energy intake, IRP scientists maintained groups of male and female rats for 6 months on diets with usual, reduced [20% and 40% caloric restriction (CR), and intermittent fasting (IF)], or elevated (high-fat/high-glucose) energy levels and measured multiple physiological variables related to reproduction, energy metabolism, and behavior. In response to 40% CR, females became emaciated, ceased cycling, underwent endocrine masculinization, exhibited a heightened stress response, increased their spontaneous activity, improved their learning and memory, and 44 maintained elevated levels of circulating brain-derived neurotrophic factor. In contrast, males on 40% CR maintained a higher body weight than the 40% CR females and did not change their activity levels as significantly as the 40% CR females. Additionally, there was no significant change in the cognitive ability of the males on the 40% CR diet. Males and females exhibited similar responses of circulating lipids (cholesterols/triglycerides) and energy-regulating hormones (insulin, leptin, adiponectin, ghrelin) to energy restriction, with the changes being quantitatively greater in males. The high-fat/high-glucose diet had no significant effects on most variables measured but adversely affected the reproductive cycle in females. Heightened cognition and motor activity, combined with reproductive shutdown, in females may maximize the probability of their survival during periods of energy scarcity and may be an evolutionary basis for the vulnerability of women to anorexia nervosa. Martin, B., Pearson, M., Kebejian Golden, E., Keselman, A., Bender, M., Carlson, O., Egan, J., Ladenheim, B., Cadet, J.L., Becker, K.G., Wood, W., Duffy, K., Vinayakumar, P., Muudsley, S. and Mattson, M.P. Endocrinology 148(9), pp. 4318-4333, 2007.