Director's Report to Council - Research Findings Excerpts

September, 2004

Behavioral Research

Alcohol Outcome Expectancies, Risk For Alcohol Use Problems, and Menstrual Cycle Effects in Women with and Without a Family History of Alcoholism

Drs. Allison Dorlen and Suzette Evans at the New York State Psychiatric Institute studied the role of alcohol outcome expectancies in the risk for alcoholism in women with either a family-history-positive (FHP) or family-history-negative (FHN) background for alcoholism. They prospectively tracked 85 women, ranging in age from 18-35, with regard to mood, alcohol use, and daily positive and negative consequences of alcohol used across one menstrual cycle. Results indicate that (a) at screening, expectancy scores on the Alcohol Expectancy Questionnaire (AEQ) were significantly higher in FHP than FHN women, regardless of drinking level, on four of the six AEQ subscales and on the composite score, (b) AEQ scores correlated with drinking behavior among FHN women, but among FHP women, AEQ scores were elevated independently of their level of drinking, (c) following prospective tracking of their drinking behavior and its consequences, AEQ scores decreased among FHP, but not FHN, women, and (d) independently of family history status, in moderate drinkers alcohol use was significantly greater during menses than during the follicular and luteal phases of the menstrual cycle, but this increased use during menses was not associated with significant increases in negative mood or physical discomfort. These data suggest that alcohol expectancies prospectively predict drinking behavior and may be associated with further risk for the development of alcohol use problems among high-risk women. Pastor, A.D. and Evans, S.M. Alcohol Outcome Expectancies and Risk for Alcohol Use Problems in Women With and Without a Family History of Alcoholism. Drug and Alcohol Dependence, 70, pp. 201-214, 2003.

Pharmacogenetic Analysis of Sex Differences in Opioid Antinociception in Rats

Animal research has shown that males are, in general, more sensitive to painkillers than females. This sex difference in the antinociceptive properties of opiates has been described in mice, rats and monkeys. There are some inconsistencies, however, in the outcomes of these experiments, inconsistencies that Dr. Jolan Terner from University of North Carolina at Chapel Hill hypothesized may be due in part to different genetic backgrounds of experimental animals and to the relative efficacy of the tested opioids. To assess this hypothesis, Dr. Terner and her colleagues used 12 rat strains and a warm-water tail-withdrawal procedure to test the antinociceptive properties of four different opioids (butorphanol, nalbuphine, morphine and buprenorphine). Males were more sensitive to the opiates than females in all 12 strains and for all four opiates. Among the opiates, the largest sex differences in the potency of the opioids were found with the low-efficacy opioids, butorphanol and nalbuphine, which were on average 14 times more potent in males than females, while the smallest differences were found with the high efficacy opiates, morphine and buprenorphine, which were on average 2.4 times more potent in males than females. Among the 12 strains, the largest sex differences were found in the F344 and F344-Sasco strains and the smallest differences were found in the Long Evans - Blue Spruce, Long Evans, Brown Norway, and Holtzman strains. This work suggests that studying strain variation response to low-efficacy opioids might be useful for understanding the mechanisms underlying sex differences in opioid antinociception. Terner, J.M., Lomas, L.M., Smith, E.S., Barrett, A.C., and Picker, M.J. Pharmacogenetic Analysis of Sex Differences in Opioid Antinociception in Rats. Pain, 106, pp. 381-391, 2003.

Sex Differences in the Conditioned Rewarding Effects of Cocaine

Studies have shown the importance of the hypothalamic-pituitary-adrenal axis in the acquisition of cocaine self-administration in rats. When corticosterone levels, for example, are decreased by either surgical or pharmacological adrenalectomy, cocaine self-administration is abolished. In the present study, Drs. Scott Russo and Vanya Quinones-Jenab and colleagues at Hunter College investigated the effects of surgical adrenalectomy on conditioned place preference (CPP) induced by cocaine in male and female rats. In the CPP design, rats receive cocaine or saline in separate, distinctive experimental chambers for 4 or 8 days followed by a test day in which preference for the cocaine-paired chamber is assessed. In the present experiment, intact female rats developed CPP for cocaine at lower doses and with fewer trials than intact males. Adrenal-ectomy, however, did not affect the acquisition of cocaine CPP in either males or females. The authors interpret these results as indicating that females are more sensitive to the rewarding effects of cocaine and that this higher sensitivity is not dependent on the HPA axis. Russo, S.J., Jenab, S., Fabian, S.J., Festa, E.D., Kemen, L.M. and Quinones-Jenab, V. Sex Differences in the Conditioned Rewarding Effects of Cocaine. Brain Research, 970, pp. 214-220, 2003.

Sex and Estrogen Influence Drug Abuse

In this review article, Dr. Marilyn Carroll and colleagues from the University of Minnesota describe animal and clinical research showing sex differences in all the phases of drug abuse: acquisition, maintenance, escalation, dependence, withdrawal, relapse and treatment. Animal models, for example, have shown that females are more sensitive than males to the rewarding effects of a variety of drugs, they often acquire self-administration faster and at lower doses than males, and they self-administer more drugs than males during the maintenance and escalation phases. Similar to the results obtained with animals, clinical studies, for example, show that women progress from drug use to abuse/dependence faster than men. Some of these sex differences are related to estrogen levels and to the role estrogen plays in reward. The research findings reviewed in this article serve to highlight the importance of sex and sex hormones in both animal models of drug abuse and in clinical research on drug abuse. Carroll, M.E., Lynch, W.J., Roth, M.E., Morgan, A.D. and Cosgrove, K.P. Sex and Estrogen Influence Drug Abuse. Trends in Pharmacological Sciences, 25, pp. 273-279, 2004.

Sex Differences in the Behavioral Effects of 24-h/day Access to Cocaine under a Discrete Trial Procedure

Clinical studies have shown a variety of sex differences in drug abuse. Women, for example, have an accelerated transition from casual use of cocaine to compulsive use when compared to men. Women also report higher levels of cocaine cravings than men suggesting greater motivation to use cocaine. These differences, which could be due to either sociocultural factors and/or to biological factors, were recently examined by Dr. Wendy Lynch and colleagues at Yale University using animal models of cocaine self-administration that permit study of the transition from use/abuse to addiction and that permit assessment of motivation for cocaine following that transition. The transition from use/abuse to addiction was studied by providing rats with a high-access to a cocaine regimen in which they could self-administer during four 10-min trials per hour, 24-hr per day, for seven days. This procedure has previously been shown to result in an escalation of cocaine self-administration and a binge-abstinence pattern of intake. Dr. Lynch and her colleagues found that under this procedure, compared to males, females self-administered more cocaine, self-administered for longer periods of time, showed greater disruption in the diurnal control over cocaine intake, and exhibited more cocaine toxicity as evidenced by rapid weight loss and death. In order to study the effect of the 7-day binge period on subsequent motivation to use cocaine, following a 10-day forced abstinence period, rats responded for cocaine under a progressive ratio (PR) schedule in which the number of responses required to receive a cocaine infusion was increased over successive infusions. Females exhibited an increase in PR responding compared to their own baseline of PR responding prior to the binge period. Males, however, did not exhibit an increase in PR responding following the binge period. The authors interpret their data as an indication that females have greater biological vulnerability to cocaine addiction than males and that following addiction females have greater motivation or compulsion for cocaine than males. Lynch, W.J. and Taylor, J.R. Sex Differences in the Behavioral Effects of 24-h/day Access to Cocaine Under a Discrete Trial Procedure. Neuropsychopharmacology, 29, pp. 943-951, 2004.

Sex Differences in the Acquisition of IV Methamphetamine Self-administration and Subsequent Maintenance under a Progressive Ratio Schedule in Rats

Studies have shown that female rats are more vulnerable than male rats to the acquisition of i.v. cocaine self-administration as evidenced by a faster rate of acquisition and by a greater percentage of females than males meeting the acquisition criterion. Additionally, female rats exhibit greater motivation for cocaine as evidenced by performance on a progressive ratio schedule wherein the number of responses required to obtain a cocaine infusion increases over successive infusion deliveries. Responding for cocaine under this schedule is greater by females than males. The present study by Drs. Megan Roth, Marilyn Carroll, and colleagues at the University of Minnesota extends those findings to another psychostimulant drug, methamphetamine (METH). In order to meet criterion for METH acquisition, rats had to self-administer a mean total of 500 infusions over a 5-day period. This criterion was met by over 50% (five out of nine) of the females, but only by 11 % of the males (one out of nine). Not only did more females than males meet the acquisition criterion, they did so faster. The female rats met criterion in an average of 9.4 days, whereas the single male that met criterion did so in 20 days. Sex differences were also observed during the maintenance phase of study in which under a progressive ratio schedule, females self-administered significantly more METH than males at each of four doses of cocaine (0.01, 0.02, 0.04 and 0.08 mg/kg) tested. The authors conclude that these data suggest that female rats are more vulnerable than males to the acquisition of METH self-administration and that they exhibit more motivation for METH. Roth, M.E. and Carroll, M.E. Sex Differences in the Acquisition of IV Methamphetamine Self-administration and Subsequent Maintenance Under a Progressive Ratio Schedule in Rats. Psychopharmacology, 172, pp. 443-449, 2004.

Emotion Regulation and Behavior During a Separation Procedure in 18-month-old cocaine-and-other-drug-exposed Children

Dr. Linda Mayes and colleagues at Yale University report that among toddlers prenatally exposed to cocaine, both maternal and child impairment was observed during a maternal-child separation procedure. The researchers observed 78 18-month old toddlers and their mothers before, during and after a play period during which a stranger entered the playroom and subsequently the mother left for approximately 3-minutes. Three groups of mother-child dyads from an ongoing longitudinal study were studied: those prenatally exposed to cocaine and other drugs (n= 26), those exposed to other drugs including alcohol, tobacco, and/or marijuana but not cocaine (n= 26), and those not exposed to any drugs prenatally (n= 26). All three groups are a very high-risk sample characterized by extreme poverty, adversity, and environmental instability. Upon separation from the mothers, the toddlers from the cocaine group did not show heightened reactivity, but rather showed the least level of reactivity. This effect was unrelated to various measures of maternal psychological functioning, other drug use, or by demographic or perinatal differences. During the mother-child reunion following the separation, the mothers in the cocaine group exhibited significantly less emotional engagement than the non-drug using mothers, an effect related to alcohol use among mothers in the cocaine group. The cocaine-exposed toddlers upon reunion exhibited less positive emotional engagement with their mothers compared to toddlers from the non-drug-using group. This effect was mediated by the mother's low level of emotional engagement and by a lower birth weight status in the cocaine group. Molitor, A., Mayes, L.C. and Ward, A. Emotion Regulation and Behavior During a Separation Procedure in 18-month-old cocaine-and-other-drug-exposed Children. Development and Psychopathology, 15, pp. 39-54, 2003.

Human Development and Clinical Neuroscience Research

Relationship of Ethnicity, Gender, and Ambulatory Blood Pressure to Pain Sensitivity: Effects of Individualized Pain Rating Scales

There have been many reports that the sensation of pain is modulated by blood pressure, but no systematic studies had been performed to determine whether this phenomenon is consistent across genders and ethnicities. Dr. Susan Girdler and her colleagues have investigated this issue in a study of 135 African American and white men and women. Their findings confirm the inverse relationship between blood pressure and the perception of pain. They also found that, when using a standardized scale for pain assessment, both African American men and women reported higher levels of pain intensity than white men and women. However, they also found that this difference was not present when using a scale in which each participant ranked the descriptors, rather than using a standardized scale. Beyond confirming previous findings relating blood pressure to the perception of pain, the results of this investigation emphasize that demographic differences may need to be taken into account in clinical pain assessment and management. Campbell, T.S., Hughes, J.W, Girdler S.S., Maixner, W., and Sherwood, A. The Journal of Pain. 5(3), pp. 183-191, 2004.

The Neural Correlates of Cue-Induced Craving in Cocaine-Dependent Women

Dr. Clinton Kilts and colleagues at Emory University School of Medicine used [O-15]H2O positron emission tomography (PET) imaging to determine if there are gender-related differences in the neural correlates of cocaine craving. Changes in regional cerebral blood flow to imagery depicting cocaine use and neutral imagery were examined in 8 cocaine-dependent women and a matched group of eight cocaine-dependent men. Compared with the results in cocaine-dependent men, conditioned cocaine craving in women was associated with less activation of the amygdala, insula, orbitofrontal cortex, and ventral cingulate cortex and greater activation of the central sulcus and widely distributed frontal cortical areas. These findings suggest the presence of sex differences in the functional anatomy of cue-induced cocaine craving associated with drug dependence and may underlie apparent sex differences in the effects of cocaine abstinence and the expectations of treatment outcome. Some support for the need for sex-specific strategies for treatment of cocaine dependence is also furnished by the findings of this study. Kilts, C.D., Gross R.E., Ely T.D. and Drexler, K.P.G. American Journal of Psychiatry, 161(2), pp. 233-241, 2004.

Prevalence of Drug Use and Duration of Problematic Use is Greater in Men Than Women, but Severity and Age of Onset Seems to be Equal

Among the many analyses conducted by Dr. Iacono and colleagues among families of the Minnesota Twin-Family Study, an assessment of twins' parents revealed that despite the greater prevalence of drug use among men, dependence symptoms and drug-associated difficulties were not different from those of women. Two exceptions were hallucinogens where there was no difference in duration of use but there was an earlier onset in women, and amphetamines where women had more frequent use of them. The latter may be related to eating disorders since more women with amphetamine abuse were anorexic. Also, the differences and similarities observed could not be attributed to age differences in the cohorts, assertive mating (marrying with individuals with like profiles), or ability to report symptoms. These data provide insight into characteristics of drug use between men and women. Holdcraft, L.C. and Iacono, W.G. Drug and Alcohol Dependence, 74, pp. 147-158, 2004.

Prenatal Marijuana Exposure and Academic Achievement at Age 10 Years

University of Pittsburgh researchers have reported their latest findings from a longitudinal cohort study of children exposed to marijuana in utero. In this study, women were interviewed about their substance use at the end of each trimester of pregnancy, and at multiple times during the child's development. The children were assessed on physical, emotional, and cognitive development at 8 and 18 months, and at 3, 6, 10, 14, and 16 years postpartum. This report provides findings on academic achievement at age 10 (606 children were assessed), using the Wide Range Achievement Test-Revised (WRAT-R), the reading comprehension subtext of the Peabody Individual Achievement Test-Revise (PIAT-R), and teacher reports of child performance in school. As a group, the women were of lower socioeconomic status, high-school-educated, light-to-moderate users of marijuana and alcohol, and equally distributed in terms of race/ethnicity (Caucasian and African-American). Exposure to one or more marijuana joints per day during the first trimester predicted deficits in WRAT-R reading and spelling scores, and a lower rating on the teachers' evaluations of the children's performance. These associations existed when home environment, race/ethnicity, socioeconomic status, and other prenatal substance exposure were controlled. However, these associations were mediated by effects of first-trimester marijuana exposure on the children's symptoms of depression and anxiety. Second-trimester marijuana use was associated with reading comprehension and underachievement. Exposure to alcohol during the first and second trimesters predicted poorer teacher ratings of overall school performance, whereas second-trimester binge drinking predicted lower reading scores. There was no interaction between prenatal marijuana and alcohol exposure. Each was an independent predictor of aspects of academic performance. The investigators compared their findings to those of the other cohort study of prenatal marijuana exposure reported in the literature, and they discussed possible reasons for differences in findings on school performance between the two studies. The investigators also discuss the limitations of the analyses and of the generalizability of the findings. Goldschmidt, L., Richardson, G.A., Cornelius, M.D., and Day, N.L. Prenatal Marijuana and Alcohol Exposure and Academic Achievement at Age 10. Neurotoxicology and Teratology, 26, pp. 521-532, 2004.

Maternal Substance Use Patterns During Pregnancy and Infant Growth Parameters at Birth

Maternal cocaine use during pregnancy has been associated with decreased growth parameters in multiple previous studies. Women who use cocaine often use other substances as well (e.g., alcohol and tobacco, both of which have been shown to have effects on birth weight). A recent publication from the Maternal Lifestyle Study (MLS) reported on how patterns of cocaine, alcohol, tobacco, and marijuana use during pregnancy were related to infant birth weight, length, and head circumference in a sample of 651 mothers and their infants. Because cocaine use has been associated with preterm delivery, only term pregnancies were evaluated for this report. The MLS is a multisite longitudinal study of in utero drug exposure that is jointly funded by NICHD and NIDA. It is the largest study of its type. Histories of substance use were obtained for the 3-month period before pregnancy and the three trimesters of pregnancy. Patterns of use were categorized for each substance as consistently high, moderate, or low/none, and increasing or decreasing. The effects on growth parameters were analyzed in multivariate linear regression analyses, with adjustment for clinical site, maternal age, prepregnancy weight, multidrug use, and socioeconomic status. Detailed results of use patterns and growth parameters are reported in the publication. Overall, with adjustments made for confounders, including multi-drug use, patterns of tobacco use during pregnancy were associated with deficits in birth weight, length, and head circumference, whereas cocaine use was linked to deficits in birth weight and head size. In addition, birth weight, length, and head circumference were significantly greater among infants born to women who used no drugs compared to women with any cocaine, opiate, alcohol, tobacco, or marijuana use during pregnancy. The investigators emphasize that a clinical implication of the study is the importance of curtailing use during pregnancy of illicit drugs as well as alcohol and tobacco. Shankaran, S., Das, A., Bauer, C.R., et al. Association between Patterns of Maternal Substance Use and Infant Birth Weight, Length, and Head Circumference. Pediatrics, 114(2), pp. e226-e234, 2004.

Immune System Parameters and Clinical Morbidity in Infants Exposed to Drugs and HIV in Utero

Recently published data from the Women and Infants Transmission Study (WITS) reported on associations between maternal drug use during pregnancy and lymphocyte subsets and clinical morbidity in uninfected infants born to HIV-infected mothers. WITS is a multi-site longitudinal study of the health of HIV-infected mothers and their children, as well as mother-to-child HIV transmission. It is jointly supported by NIAID, NICHD, and NIDA. The outcomes of HIV-exposed but uninfected infants is a major focus within WITS. The current report presents findings for infants through 2 years of age. The definition of drug use during pregnancy included use of cocaine, methadone, heroin, and other opiates. History of illness and clinical findings were recorded using standardized collection instruments for medical history and medical chart abstraction. Measurement of immune system parameters (CD4, CD8, CD19, NK cell lymphocyte percentage and absolute numbers) utilized standard laboratory procedures. A total of 401 of the 1436 uninfected infants were born to drug-using mothers. Infants born to drug-using mothers had lower gestational age and birth weight, and lower CD4 lymphocyte percentage over the first 4 months of life after adjusting for covariates and higher natural killer lymphocyte percentage. The clinical significance of the lower CD4 percentage and higher NK cell level remain unclear. The investigators suggest that future studies evaluating immunologic parameters in HIV-exposed but uninfected infants should control for the effect of drug exposure. They also indicate that additional research that includes functional assays of lymphocyte cell populations is needed in order to evaluate effects of drug exposure on immune function in addition to phenotype, whether such effects are transient or persist over time, and whether there is any clinical significance of such findings. Neu, N., Leighty, R., Adeniyi-Jones, S., et al. Immune Parameters and Morbidity in Hard Drug and Human Immunodeficiency Virus-Exposed but Uninfected Infants. Pediatrics, 113(5), pp. 1260-1266, 2004.

Retrospective Study: Influence of Menstrual Cycle on Cue-Induced Cigarette Craving

Dr. Theresa Franklin and colleagues at the University of Pennsylvania investigated whether menstrual cycle phase contributes to some of the sex differences observed in smokers. Since smoking in females is posited to be influenced more by cues whereas male smoking is influenced predominantly by the direct pharmacological actions of nicotine in the brain, this study tested the hypothesis that females may report more intense craving to smoking cue exposure than males and, further, that female craving scores may be influenced by menstrual cycle phase. The study sample consisted of 69 male and 41 female treatment-seeking subjects who smoked more than 15 cigarettes per day for more than 10 years. Self-report measures were collected from subjects prior to and immediately following exposure to visual smoking stimuli. Females were grouped according to cycle phase. Of the female subjects, 17 were classified as follicular phase females (FFemales) and 24 were classified as luteal phase females (LFemales). Contrary to our hypothesis, overall, males and all females did not differ in their level of cue-induced craving. However, when females were separated into groups by cycle phase, FFemales reported significantly less craving than either males or LFemales (p <.05). The suppressed craving response in FFemales suggests an influence of cycle phase on cue-induced craving. These results suggest that menstrual cycle phase needs to be incorporated in the development of treatments for nicotine addiction. Franklin, T.R., Napier, K., Ehrman, R., Gariti, P., O'Brien, C.P. and Childress, A.R. Nicotine & Tobacco Research, 6(1), pp. 171-175, 2004.

Cognitive Outcomes of Preschool Children with Prenatal Cocaine Exposure

Researchers at Case Western Reserve University report that 4-year-old children who were exposed to cocaine in utero scored significantly lower on some specific measures of intelligence than did children who were not exposed to the drug in utero. The two groups did not differ on overall, verbal, and performance IQ scores, although exposed children were less likely to have above-average overall IQ. The study results also suggest that mentally stimulating home environments may positively affect brain development and lessen prenatal effects of cocaine. At 4 years of age, 190 cocaine-exposed and 186 nonexposed children were assessed using the Wechsler Preschool and Primary Scales of Intelligence-Revised. This test revealed that exposed children had lower scores than nonexposed children in the specific areas of information, arithmetic, and object assembly (reflecting visual-spatial skills). In arithmetic skills, cocaine-exposed boys had lower scores than girls and nonexposed boys. The researchers also compared two groups within the cocaine-exposed children, i.e., 148 cocaine-exposed children living with their biological mothers or other relatives, and 42 cocaine-exposed children living in adoptive or foster care. They found that 25 percent of cocaine-exposed children living with their mothers or relatives had overall IQ scores lower than 70, compared with only 10 percent of cocaine-exposed children in adoptive or foster care. The researchers report that caregivers in the adoptive and foster homes were better educated, and had better vocabulary and intelligence test scores than the caregivers who were family members. Additional findings indicated that adoptive or foster care was associated with a lower rate of mental retardation in the cocaine-exposed children, despite the fact that these children had been exposed to twice as much cocaine while in utero, and that the cocaine-exposed children in the more stimulating environments had IQ scores that were similar to those of nonexposed children. The findings of this study are consistent with and expand on other preschool cocaine-exposure studies that show specific (but not global) IQ deficits. The results also emphasize how important it is to examine childrearing environments when assessing developmental progress of drug-exposed children, and they also provide optimism that interventions may be effective for children who are affected by prenatal cocaine exposure. Singer, L.T., Minnes, S., Short, E., et al. Cognitive Outcomes of Preschool Children with Prenatal Cocaine Exposure. JAMA, 291(20), pp. 2248-2456, 2004.

Cerebral Reserve Capacity: Implications for Alcohol and Drug Abuse

This review article discusses cerebral reserve capacity (or functional reserve), which refers to the brain's ability to maintain function when confronted by degenerative processes. There is accumulating evidence that the magnitude of reserve capacity is important in determining the onset and progression of the clinical manifestations of neurodegenerative brain diseases. The concept of cerebral functional reserve has important implications for alcohol and drug abuse morbidity. First, given the high genetic contribution to substance abuse, there is an increased likelihood that the parents of substance abusers were substance abusers themselves. Substance abuse during pregnancy can inhibit brain growth, resulting in reduced brain size and reduced reserve capacity (and therefore less ability to compensate for loss of function later in life). Second, substance abuse is often coupled with poverty, and both substance abuse and poverty are associated with some of the same conditions that reduce brain growth. The authors comment on the most important public health implications of the cerebral reserve capacity model for drug and alcohol addiction. Fein, G. and Di Sclafani, V. Alcohol, 32(1), pp. 63-67, 2004. 204-212, 2004.

Epidemiology and Etiology Research

Prevalence of Marijuana Use Disorders in the United States: 1991-1992 and 2001-2002

Among illicit substance use disorders, marijuana use disorders are the most prevalent in the population. Yet, information about the prevalence of current DSM-IV marijuana use disorders and how prevalence has changed is lacking. To examine changes in the prevalence of marijuana use, abuse and dependence in the United States between 1991-1992 and 2001-2002, face-to-face interviews were conducted in two large national surveys conducted ten years apart: the 1991-1992 National Longitudinal Alcohol Epidemiologic Survey (NLAES: n=42,862), and the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC: n = 43,093). Among the adult U.S. population, the prevalence of marijuana use remained stable at about 4.0% over the past decade. In contrast, the prevalence of DSM-IV marijuana abuse or dependence significantly (p < 0.05) increased between 1991-1992 (1.2%) and 2001-2002 (1.5%), with the greatest increases observed among young Black men and women and young Hispanic men (p < 0.01). Further, marijuana use disorders among marijuana users significantly increased (p < 0.01) in the absence of increased frequency and quantity of marijuana use, suggesting that the concomitant increase in potency of _9-THC may have contributed to the rising rates. Despite the stability in the overall prevalence of marijuana use, more adults in the U.S. had a marijuana use disorder in 2001-2002 than in 1991-1992. Increases in the prevalence of marijuana use disorders were most notable among young Black men and women and young Hispanic men. Although rates of marijuana abuse and dependence did not increase among young white men and women, their rates have remained high. The results of this study underscore the need to develop and implement new prevention and intervention programs targeted at youth, particularly minority youth. Compton, W.M., Grant, B.F., Colliver, J.D., Glantz, M.D. and Stinson, F.S. Prevalence of Marijuana Use Disorders in the United States: 1991-1992 and 2001-2002. Journal of the American Medical Association, 291(17), pp. 2114-2121, 2004.

Factors Associated with Cessation of Smoking in Young Adults

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

Transitions to Drug Use

This study examines whether patterns in the transition from alcohol and tobacco in the Mexican State of Morelos, Mexico are similar to those observed in other countries. The data were from a representative sample of youth age 11-21 (n=13,105), who participated in a paper-and-pencil survey in middle schools, high schools, and colleges in the State of Morelos, Mexico. Drug use was assessed via the standardized instrument most used in Mexican student surveys. Cox's models for discrete-time survival analyses, stratified by school and age group were used to estimate the risk of drug use in relation to early or non early alcohol and tobacco use initiation by gender, while accommodating the complex survey design. The study findings suggest that about five percent of the students were estimated to have used drugs in their life. Male early users of alcohol or tobacco were more likely to use other drugs, compared to students who did not have an early alcohol or tobacco onset. Recommendations for future studies includes an exploration of the role of social mechanisms and their relationship to patterns of drug involvement, even in the context of important differences in rates of drug use. Wagner, F.A., Velasco-Mondrag—n, H.E., Herrera-Vazquez, M., Borges, G. and Lazcano, E. Early Alcohol and Tobacco Use and Transition to Other Drug Use Among Students in the State of Morelos, Mexico. Drug and Alcohol Dependence. Corrected proof available online 24 August 2004.

Unequal Opportunity: Neighborhood Disadvantage and the Chance to Buy Illegal Drugs

This study investigates whether subgroups of people living in disadvantaged neighborhoods may be more likely to come into contact with drug dealers as compared with persons living in more advantaged areas, with due attention to male-female and race-ethnicity differences. Standardized survey data were collected using stratified, multistage area probability sampling of household residents age 12 or older (N=25,500) living in the United States of America in 1998. Results suggest that women are less likely to be approached by someone selling illegal drugs. The study also found no more than modest and generally null racial and ethnicity differences, even for residents living within socially disadvantaged neighborhoods, where chances to buy illegal drugs are found to be more common. These findings lend support to the inference that physical and social characteristics of a neighborhood can set the stage for opportunities to become involved with drugs. Storr, C.L., Chen, C.Y. and Anthony, J.C. Journal of Epidemiology and Community Health, 58(3), pp. 231-237, 2004.

Early Adolescent Through Young Adult Alcohol and Marijuana Use Trajectories

This study takes a developmental approach to subgrouping and examines the trajectories of substance use from early adolescence through young adulthood among a community sample of 481 individuals. The patterns of use were examined, subgroups were identified separately for men and women and for alcohol and marijuana, and psychosocial predictors and psychopathology outcomes that differentiated the groups were identified. The results revealed three substantially overlapping subgroups for both alcohol and marijuana: early onset, late onset, and nonuser. Although the general patterns of which dependent variables were related to group were similar for alcohol and marijuana, a closer examination revealed important subgroup differences. For alcohol use, the early-onset group was more dysfunctional in terms of predictors and outcomes whereas the late-onset and nonuser groups were better adjusted. In contrast, for marijuana, the early- and late-onset groups were both more dysfunctional than the nonuser group. In a final analysis, the researchers examined the predictive utility of our developmental approach to subgrouping compared to a traditional, static approach. Flory, K., Lynam, D., Milich, R., Leukefeld, C., and Clayton, R. Early Adolescent through Young Adult Alcohol and Marijuana Use Trajectories: Early Predictors, Young Adult Outcomes, and Predictive Utility. Development and Psychopathology, 16(1), pp. 193-213, 2004.

Relationship of Tobacco Smoking with Depressive Symptomatology

This study aims to estimate the association of depressive symptomatology with tobacco smoking, nicotine dependence, cigarettes smoked daily, and smoking cessation in a representative sample of the Mexican population. A probability sample of 1,935 adults answered a version of the Third National Mexican Addictions Survey that included the CES-D depression scale and specific questions on tobacco use. Analyses addressed the survey's complex design. Active smokers had higher odds of depression than ex-smokers, who had higher odds than non-smokers. Higher levels of tobacco use were more strongly associated with depression as was nicotine dependence in women. Those who ceased smoking recently had lower odds of depression than active smokers. Study findings suggest that smoking cessation interventions should be coupled with attention to depressive symptomatology. Benjet, C., Wagner, F.A., Borges, G., and Medina-Mora M.E. The Relationship of Tobacco Smoking with Depressive Symptomatology in the Third Mexican National Addictions Survey. Psychological Medicine. Published online 18 March 2004.

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

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

Personality and Drug Use, Abuse and Dependence

This study used data from a population-based twin registry to assess the genetic and environmental factors contributing to the associations between personality factors and illicit drug use, abuse, and dependence. Based on data from a large sample of same-sex adult twin pairs, the authors found that genetic factors explained much of the relationship between personality and drug abuse. Novelty-seeking related most strongly, particularly for males and particularly for cannabis use. Neuroticism showed the greatest genetic overlap with sedative use. The authors conclude that the findings on novelty-seeking and cannabis use in males may be useful for candidate gene studies. Agrawal, A., Jacobson, K.C., Prescott, C.A., and Kendler K.S. A Twin Study of Personality and Illicit Drug Use and Abuse/Dependence. Twin Research, 7, pp. 72-81, 2004.

Correlates of Aggression in African American and Puerto Rican Children

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

Cannabis and Other Drugs: Modeling Comorbidity

The authors sought to use a genetically informed approach to explain the comorbidity between cannabis and other drug use. Data from over 2000 same-sex twin pairs were used to test 13 models of comorbidity including versions of the gateway and common risk factor models. For drug use, the correlated liability (common risk factor) model was the best fit, although there may be a subgroup of high-risk cannabis users at increased risk for other drug use (the extreme multiformity of cannabis model). For abuse/dependence, the correlated liability model fit the data best for males; it was difficult to distinguish models for females, probably due to low prevalence of drug abuse. The authors discuss the implications of these findings for prevention: if indeed the use, abuse, and dependence on various drugs is related to common risk factors, then programs that seek to control a specific drug such as cannabis as a ÒgatewayÓ will not be effective; rather, interventions that focus on common risk factors may be appropriate. Agrawal, A., Neale, M.C., Prescott, C.A., and Kendler, K.S. Cannabis and Other Illicit Drugs: Comorbid Use and Abuse/Dependence in Males and Females. Behavior Genetics, 34, pp. 217-228, 2004.

Prevention Research

Social Assertiveness, Internalizing, and Gender Moderation Effects Of A Preventive Intervention

The current study investigated gender moderation of the longitudinal pathways from internalizing to both social competency and the initiation of substance use as well as the effects of a preventive intervention on that process. Rural Midwestern adolescents who were participating in a school-based preventive intervention study were an average of 12.3 years old at the pretest assessment. A latent growth curve comparison analysis found that internalizing was inversely related to initial levels of social assertiveness skill among girls. Internalizing was positively related to substance use initiation growth trajectories among girls. Girls who participated in the preventive intervention demonstrated a slower increase over time in substance use initiation and a faster increase in social assertiveness. Lillehoj, C.J., Trudeau, L., Spoth, R.and Wickrama, K.A.S. Internalizing, Social Competence, and Substance Initiation: Influence of Gender Moderation and a Preventive Intervention. Substance Use and Misuse, 39(6), pp. 963-991, 2004.

Gender Identity, Ethnicity, Acculturation and Drug Use

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

D.A.R.E Plus Is More Effective in Preventing Violence Among Boys Than Girls

Twenty-four middle schools were randomly assigned to: 1) DARE curriculum; 2) DARE Plus multi-component curriculum; or 3) control condition. Outcomes of the three conditions on violence-related behaviors were compared, and mediational analyses were conducted to examine how interventions reduced physical and verbal violence. Generally, boys demonstrated higher rates of violence and victimization than girls. Boys in the DARE Plus condition had a marginally significant lower number of verbally violent acts than boys in the control condition. Boys in the DARE Plus condition had a marginally lower number of physically violent acts than boys in the DARE condition. There were no significant differences between the DARE only and control groups. There were no significant differences between the three groups in victimization. The small behavioral effect that DARE Plus demonstrated on physical and verbal violence among boys was mediated by a decrease of norms that support violence, an increase in outcome expectancies about being violence-free, and an increase in parental consequences for fighting. DARE Plus was not as effective in preventing violence among girls, however, girls in the DARE Plus condition had significantly lower scores on the Victimization Scale than girls in the DARE only condition. Komro, K.A., Perry, C.L., Veblen-Mortenson, S., Stigler, M.H., Bosma, L.M., Munson, K.A. and Farbakhsh, K. Violence-related Outcomes of the DARE Plus Project. Health Education & Behavior, 31(3), pp. 335-354, 2004.

Psychosocial Factors Related to Drinking Among Rural Adolescents

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

Perceptions of Rural Parents Regarding Family-Focused Programs

Data collected in the Promoting School-Community-University Partnership to Enhance Resilience (PROSPER) project during telephone interviews with 1,156 parents of sixth graders from 36 rural schools were used in multilevel structural equation modeling. Results of analyses show that: 1) parents considered their children to be at low risk for substance use; 2) parents perceived themselves to be effective in helping their children avoid maladaptive behaviors; 3) mothers perceived themselves to be more efficacious than did fathers; 4) parental efficacy perceptions inversely affected perceptions of child susceptibility; 5) parents' perceptions of child susceptibility positively affected perceived program benefits; and 6) higher perceived program benefits and higher perceived child susceptibility were associated with mothers, male children, single parents, lower household income, and lower parent education. Redmond, C., Spoth, R, Shin, C. and Hill, G. Engaging Rural Parents in Family-Focused Programs to Prevent Youth Substance Abuse. Journal of Primary Prevention, 24(3), Spring, 2004.

Research on Behavioral & Combined Treatments for Drug Abuse

Do Changes in Mood and Concerns About Weight Relate to Smoking Relapse in the Postpartum Period?

The majority of women who quit smoking during pregnancy will resume smoking during the postpartum period. Little is known about the predictors of postpartum relapses to smoking. Changes in mood and increases in concerns about weight are common during the postpartum period, and these factors may affect women's postpartum smoking behavior. Investigators at the University of Pittsburgh reviewed the literature on postpartum relapse prevention trials and present evidence of a connection between changes in mood and weight concerns to postpartum relapse. Directions for future research on the prevention of smoking relapses during the postpartum period, and the roles of mood and weight concerns in smoking relapse are presented. Levine, M.D. and Marcus, M.D. Archives of Women's Mental Health, 7(3), pp. 155-166, 2004.

Research on Pharmacotherapies for Drug Abuse

Nicotine Withdrawal and Depressive Symptomatology During Short-term Smoking Abstinence: A Comparison of Postmenopausal Women Using and Not Using Hormone Replacement Therapy

This study investigated whether taking medications for transdermal hormone replacement therapy (HRT) influenced smoking-cessation variables in postmenopausal women undergoing short-term abstinence from cigarettes. Women were recruited into two groups according to their pre-enrollment medication status--those currently on HRT (n = 17) or those not on HRT (n = 13). The HRT group had their previous medication replaced with a standard 0.1 mg estradiol transdermal system and 2.5 mg of Cycrin daily. After 2 weeks of medication adjustment, participants continued smoking as usual for 1 week, at which time baseline measurements were taken. Participants were then instructed to quit smoking for the remaining 2 weeks. They were provided with smoking-cessation counseling and monitored for abstinence. Data were collected during five clinic visits on all dependent measures: Minnesota Nicotine Withdrawal Scale, Beck Depression Inventory (BDI) scale, Profile of Mood States, Motor Speed Tasks, and Reaction Time Test. Contrary to our hypothesis, the exogenous hormone use did not have a differential effect on most of the dependent variables during the first 2 weeks of smoking abstinence. One exception was depressive symptomatology: the BDI change scores (week 2 - baseline) differed significantly for the HRT and non-HRT groups (p = .045), with women in the HRT group experiencing an increase in depressive symptomatology. This finding, though preliminary, may have clinical implications for postmenopausal women who attempt to quit smoking while on HRT, particularly since depressed mood following abstinence is associated with a relapse to smoking. Allen, S.S., Hatsukami, D.K. and Christianson, D. Nicotine Withdrawal and Depressive Symptomatology During Short-term Smoking Abstinence: A Comparison of Postmenopausal Women Using and Not Using Hormone Replacement Therapy. Nicotine. Tob. Res., 5, pp. 49-59, 2003.

Response to Alcohol in Females with a Paternal History of Alcoholism

Several studies have demonstrated that males with a family history of alcoholism (FHP) show less of a response to alcohol (e.g. lower ratings of intoxication) than males without a family history of alcoholism (FHN). The purpose of this pilot study was to determine if FHP females also showed a reduced sensitivity to alcohol compared to FHN females. The effects of placebo and alcohol (0.25, 0.50, 0.75 g/kg, based on total body water) were evaluated using a double-blind, placebo-controlled outpatient design. Drug effects were assessed using performance tasks, observer ratings of drug effect and subjective ratings of drug effect. There were no differences in breath alcohol levels between FHN and FHP women. FHP women were less impaired by alcohol than FHN women, as shown by DSST scores and observer-ratings. However, FHP women were more impaired on the Digit Recall task after alcohol than FHN women and they tended to have higher ratings of "Good Drug Effect," "Drug Liking" and "Willingness to Take Again." Of note, FHP women reported more dysphoric mood than FHN women in the absence of alcohol administration. The results of the study suggest that FHP women may have a reduced response to alcohol on some measures, but FHP women report greater positive effects on other measures. Overall, the differences between FHP and FHN women are subtle compared to the previous studies demonstrating a reduced response to alcohol in FHP men. Evans, S.M. and Levin, F.R. Response to Alcohol in Females with a Paternal History of Alcoholism. Psychopharmacology (Berl), 169, pp. 10-20, 2003.

Differential Response to Alcohol in Light and Moderate Female Social Drinkers

Individuals who are moderate drinkers are at increased risk to abuse alcohol. Moreover, women are more vulnerable than men to the adverse consequences of alcohol consumption and recent data indicate that the drinking pattern in women is becoming more similar to that of men. However, few studies have determined whether female moderate drinkers (MD) show a differential response to the subjective and performance effects of alcohol, compared to female light drinkers (LD). Fifteen female MD who consumed an average of 34.7 drinks/month were compared to 15 female LD who consumed an average of 6.7 drinks/month. None of the participants had a first-degree family history of alcoholism or substance abuse. The acute effects of alcohol (0, 0.25, 0.50, 0.75 mg/kg) were evaluated using a double-blind, placebo-controlled outpatient design. Drug effects were assessed using a full range of performance measures, subjective-effects questionnaires and observer ratings. Alcohol impaired performance in a dose-related manner on all performance tasks for both groups of females. However, MD was less impaired than LD on balance and Digit Symbol Substitution Test (DSST). This reduced response was also evident from the observer ratings, with MD being viewed as less impaired by alcohol than LD. While ratings of Drug Liking increased in both groups of women on the ascending limb of the breath alcohol curve, alcohol was disliked by LD on the descending limb and LD reported increased ratings of Bad Drug Effects following the high dose of alcohol. The reduced performance impairment, coupled with the positive subjective effects and relative absence of adverse subjective effects, suggestive of behavioral tolerance, could result in a progression towards increased alcohol consumption among moderate female social drinkers. Evans, S.M. and Levin, F.R. Differential Response to Alcohol in Light and Moderate Female Social Drinkers. Behav. Pharmacol., 15, pp. 167-181, 2004.

Gender Differences in Pathological Gambling

Sixty-nine consecutive individuals with DSM-IV pathological gambling (47 men and 22 women) applying to a specialized outpatient treatment program were evaluated with structured interviews, self-report questionnaires, and psychological scales. Sixty-seven percent of men (N = 26) versus 25% of women (N = 5) had been exposed to gambling in adolescence. Women had a later age at first bet and a faster evolution of the disorder. Female pathological gamblers were more likely to play bingo, whereas men tended to prefer slot machines. Male and female pathological gamblers had similar gambling severity and overall rates of psychiatric comorbidity. However, male pathological gamblers had higher rates of alcohol abuse/dependence and antisocial personality disorder, whereas women had higher rates of affective disorders and history of physical abuse. There are substantial gender differences in the clinical presentation and comorbidity of pathological gambling. These gender differences should be incorporated in the selection and planning of treatment for pathological gamblers. Ibanez, A., Blanco, C., Moreryra, P. and Saiz-Ruiz, J. Gender Differences in Pathological Gambling. J. Clin. Psychiatry, 64, pp. 295-301, 2003.

Gender and Smoking Status-based Analysis of Views Regarding Water Pipe and Cigarette Smoking in Aleppo, Syria

Narghile (water pipe) smoking is increasing across the Eastern Mediterranean region (EMR), though little is known about the social attitudes and perceptions related to this method of tobacco use, and how those attitudes and perceptions are influenced by gender. Data from two cross-sectional surveys conducted in 2003 in Aleppo, Syria, were used to examine these issues. Overall, 855 participants were included (439 men, 416 women; mean age, 24.4+/-7.1 years; response rate, 97%). The current analysis focuses on responses to four similar nine-item questions tapping perceptions related to narghile smoking by women or men, and cigarette smoking by women or men. Scores on the nine items were summed to yield a total score to gauge participants' perceptions about narghile and cigarette. Generally, participants were less positive about women smoking relative to men smoking, and cigarette smoking relative to narghile smoking. Cigarette smoking by women was the behavior least associated with positive perceptions. Individuals who resided in the city, were economically better off, and were Christian, had higher perception scores (i.e., more positive attitudes) toward all forms of smoking, whereas older and married participants had higher perception scores for narghile only. Smoking status of participants, especially narghile smoking, was also associated with more positive perceptions toward smoking in general. We conclude that preliminary analysis shows that views on different forms of smoking in Syria differ by gender and smoking status. Maziak, W., Rastam, S., Eissenberg, T., Asfar, T., Hammal, F., Bachir, M.E. et al. Gender and Smoking Status-based Analysis of Views Regarding Water Pipe and Cigarette Smoking in Aleppo, Syria. Prev. Med., 38, pp. 479-484, 2004.

Cocaine-Abusing Buprenorphine-Maintained Patients Treated with Desipramine and Contingency Management

Depression is common among patients who abuse both opiates and cocaine, and its treatment has had mixed success. This study compares buprenorphine-maintained patients with lifetime major depressive disorder (MDD, N = 53) with those never depressed (ND, N = 96) on cocaine and opiate-free urines during a 12-week outpatient double-blind, placebo-controlled, randomized clinical trial. The 149 subjects were assigned to four groups: 1) desipramine (DMI) + contingency management (CM); 2) DMI + noncontingency management (NCM); 3) placebo + CM; and 4) placebo + NCM. Depression assessments included Hamilton Depression Rating Scale, Center for Epidemiological Studies Depression Inventory, and Structured Clinical Interview for DSM-IV interview for diagnosis of lifetime MDD. Urine toxicologies were performed thrice weekly and the CES-D was performed monthly. The MDD group had a larger proportion of females (45% vs. 21%, P = 0.02) and was more likely to be married (13.2% vs. 7.3%, P = 0.02) than the ND group. Treatment retention did not vary by depression status. Hierarchical Linear Modeling found that depressive symptoms decreased comparably across the four treatment groups. Although participation in CM improved drug-free urines more for patients with MDD than for the ND group (Z = 2.44, P = 0.01), treatment with DMI was significantly more efficacious for the ND group than for the MDD group (Z = -2.89, P = 0.003). These results suggest that patients with MDD may respond better to behavioral treatments such as CM than to desipramine plus buprenorphine. The ND cocaine-abusing, opiate-dependent patients may be more responsive to the anti-craving effects of DMI. Gonzalez, G., Feingold, A., Oliveto, A., Gonsai, K. and Kosten, T.R. Comorbid Major Depressive Disorder as a Prognostic Factor in Cocaine-abusing Buprenorphine-maintained Patients Treated with Desipramine and Contingency Management. Am. J. Drug Alcohol Abuse, 29, pp. 497-514, 2003.

Genetics of Pathological Gambling

Pathological gambling (PG) is an impulse control disorder and a model 'behavioral' addiction. Familial factors have been observed in clinical studies of pathological gamblers, and twin studies have demonstrated a genetic influence contributing to the development of PG. Serotonergic, noradrenergic, and dopaminergic dysfunction have been reported as biological factors contributing to the pathophysiology of PG. Molecular genetic techniques have been used to investigate the role of genetic factors in PG. Molecular genetic research has identified specific allele variants of candidate genes corresponding to these neurotransmitter systems to be associated with PG. Associations have been reported between pathological gamblers and allele variants of polymorphisms at dopamine receptor genes, the serotonin transporter gene, and the monoamine-oxidase A gene. Although preliminary data suggest that some of these differences are gender-specific, more research needs to be performed to substantiate gender-specific genetic contributions to the development of pathological gambling. The review of the current findings on genetics of PG suggests that liability to PG is in part mediated by genetic factors. Additional studies are needed to replicate and extend these findings, as well as to better understand the influence of specific allelic variants to differences in biological and behavioral functioning. Ibanez, A., Blanco, C., de Castro, I.P., Fernandez-Piqueras, J. and Saiz-Ruiz, J. Genetics of Pathological Gambling. J. Gambl. Stud., 19, pp. 11-22, 2003.

Research on Medical Consequences of Drug Abuse

HIV Risk, Seropositivity, and Predictors of Infection Among Homeless and Non-Homeless Women Sex Workers in Miami

Although homelessness has frequently been associated with substance abuse, and has been established as a predictor of HIV risk among substance abusers, little is known about the impact of homelessness on HIV risk among female sex workers. This analysis investigated the contribution of homelessness to sexual risk taking among a sample of 485 female sex workers recruited into an HIV prevention program in Miami, Florida, 41.6% of whom considered themselves to be currently homeless. In comparison to non-homeless sex workers, significantly more homeless sex workers were daily users of alcohol and crack, and their past month sex work reflected more frequent vaginal and oral sex acts, higher levels of unprotected vaginal sex and more numerous sexual activities while Ôhigh' on drugs. At the same time, a significantly greater proportion of homeless sex workers encountered customers that refused to use condoms than did the non-homeless sex workers. There were no significant differences in HIV seropositivity between the homeless and non-homeless women (22.5 and 24.9%, respectively), primarily because the majority of the women in the study cycled in and out of homelessness. These findings show how urgent it is to break the continuing cycle of homelessness in the lives of these women. Such cost-effective approaches as specialized HIV/AIDS interventions, intensive outreach to the homeless sex worker community to increase willingness to participate and retention in intervention programs, improved referral linkages to substance abuse treatment facilities, and readier access to treatment and other community services, would have tremendous public health benefit both to the women and to society as a whole. Surratt, H. and Inciardi, J. HIV Risk, Seropositivity, and Predictors of Infection Among Homeless and Non-Homeless Women Sex Workers in Miami. AIDS Care, 16(5), pp. 594-604, 2004.

Efficacy of a Woman-Focused Intervention to Reduce HIV Risk and Increase Self-Sufficiency Among African American Crack Abusers

Researchers compared 3- and 6-month outcomes of a woman-focused HIV intervention for crack abusers, a revised NIDA standard intervention, and a control group. Outreach workers in the community were trained to refer out-of-drug-treatment African American women (n=620) who used crack to field sites for participation in a randomized field experiment. The results showed that all 3 groups significantly reduced crack use and high-risk sex at each follow-up, but only woman-focused intervention participants consistently improved on measures of employment and housing status. Compared with control subjects at 6 months, woman-focused intervention participants were least likely to engage in unprotected sex; revised standard intervention women reported greatest reductions in crack use. The results of this study are consistent with previous research that out-of-treatment African American women who use crack and are at high risk of HIV successfully reduce drug use and sex risk behaviors when they receive tailored educational and skill-building interventions. Moreover, the women who received the women-focused intervention also improved in measures of employment and housing status. These changes can provide greater stability to the daily lives of these women and thereby help to reduce the frequency of drug use and unprotected sex in the longer term. Wechsberg, W., Lam, W., Zule, W. and Bobashev, G. Efficacy of a Woman-Focused Intervention to Reduce HIV Risk and Increase Self-Sufficiency Among African American Crack Abusers. Am J Public Health, 94, pp. 1165Ð1173, 2004.

Medication Compliance and Satisfaction with Treatment for HIV Disease in a Sample of African-American Crack Cocaine Smokers

The development of treatment regimes for African-American HIV-infected crack cocaine users has often been based on assumptions about compliance with medication regimes rather than evidence. This study sought to obtain baseline information on the adherence to antiretroviral medications among 137 members of this important risk population in Houston, Texas. The median age of respondents was 40 years, with half (51%) aged 40 years and older; one-fourth (27%) were women. All participants in the sample were smoking crack or injecting drugs at the time they were interviewed. Most who reported smoking crack (82%) reported smoking daily. About one-fifth (18%) of injectors were injecting daily. Of those who were injecting, 18% had shared needles and 82% had shared paraphernalia used for preparing drug solution. Length of time since HIV diagnosis ranged among the respondents from less than 1 year to 18 years. It was found that for only 5 of a range of 16 antiviral medications was there a significant correlation between levels of compliance and beliefs as to how effective these medications are. Medication compliance was also found not to be associated with frequency of crack cocaine use in the month prior to interview. Irrespective of gender and reported extent of medication compliance, the respondents tended to report positive relationships with their treating physicians, with higher levels of satisfaction reported by women. These results suggest that the majority of African-American crack cocaine users are able to comply with HIV treatment regimes, with more than half (53%) claiming full compliance for one or more medications, and a further one third (31%) claiming compliance more than half the time. Medication compliance, which presumably reflects responsibility and desire to maximize both the quality and the length of one's life, seems to be at odds with reports of HIV-infected cocaine users engaging in irresponsible and high-risk behaviors, yet these findings suggest that they will continue to take antiretroviral medications even if they have doubts about the effectiveness of these medications. Crisp, B., Williams, M., Timpson, S. and Ross, M. Medication Compliance and Satisfaction with Treatment for HIV Disease in a Sample of African-American Crack Cocaine Smokers. AIDS and Behavior, 8(2), pp. 199-206, 2004.

Mortality in a Long-term Open Cohort of Prostitue Women

In this study, the authors estimated overall and cause-specific mortality among prostitute women. They recorded information on prostitute women identified by police and health department surveillance in Colorado Springs, Colorado, from 1967 to 1999. The authors assessed cause-specific mortality in this open cohort of 1,969 women using the Social Security Death Index and the National Death Index, augmented by individual investigations. They identified 117 definite or probable deaths and had sufficient information on 100 to calculate a crude mortality rate (CMR) of 391 per 100,000 (95% confidence interval (CI): 314, 471). In comparison with the general population, the standardized mortality ratio (SMR), adjusted for age and race, was 1.9 (95% CI: 1.5, 2.3). For the period of presumed active prostitution only, the CMR was 459 per 100,000 (95% CI: 246, 695) and the SMR was 5.9 (95% CI: 3.2, 9.0). Violence and drug use were the predominant causes of death, both during periods of prostitution and during the whole observation period. The CMR for death by homicide among active prostitutes was 229 per 100,000 (95% CI: 79, 378), and the SMR was 17.7 (95% CI: 6.2, 29.3). Deaths from AIDS occurred exclusively among prostitutes who admitted to injecting drug use or were inferred to have a history of it. Potterat, J., Brewer, D., Muth, S., Rothenberg, R., Woodhouse, D., Muth, J., Stites, H. and Brody, S. Mortality in a Long-Term Open Cohort of Prostitute Women. Am J Epidemiol, 159(8), pp. 778-785, 2004.

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.

HIV Risk Behaviors Among Male-to-Female Transgender Persons of Color in San Francisco

Researchers examined HIV risk behaviors among drug-using African American, Asian/Pacific Islander (API), and Latina male-to-female (MTF) transgender persons to identify factors that can be addressed in behavioral prevention interventions aimed at reducing HIV and other infections and transmissions. They conducted individual survey interviews with MTF transgender persons of color (n=332; 112 African Americans, 110 Latinas, and 110 APIs), and found that the prevalence and correlates of receptive anal sex and unprotected receptive anal sex (URAS) varied by type of partner (primary, casual, or commercial sex partners). In addition, URAS with primary partners was associated with drug use before sex; URAS with casual partners was associated with HIV-positive status and drug use before sex; and URAS with commercial sex partners was associated with African American ethnicity and low income. Of major public health concern was the finding that HIV-positive participants were 3.8 times more likely to have recently engaged in URAS with casual partners than HIV-negative participants. Findings on ethnic differences in HIV-related sexual risk behaviors under the influence of drugs and with commercial partners were consistent with previous findings. The extremely high-risk behaviors found among MTF transgender persons in this study demonstrate the important need for community outreach, drug treatment, and social service programs to target and reach MTF transgender persons to participate in HIV prevention interventions. Nemoto, T., Operario, D., Keatley, J., Han, L. and Soma, T. HIV Risk Behaviors Among Male-to-Female Transgender Persons of Color in San Francisco. Am J Public Health, 94, pp. 1193Ð1199, 2004.

Services Research

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

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

Medical Provider Referrals of Adolescents to Substance Abuse and Mental Health Treatment

This study examines the factors related to referrals of adolescents with substance use disorders to substance abuse or mental health treatment by their medical providers. Administrative and chart review data from the membership of a large private health maintenance organization (HMO) were collected from a probability sample of 400 adolescents, ages 13-18, who were diagnosed with a substance use disorder in 1999. Logistic regression analyses examined referral to substance abuse treatment and referral to mental health treatment in the aggregate and stratified by gender. Documented use of both alcohol and another illicit drug, and legal problems increased likelihood of referral to substance abuse and mental health treatment, whereas diagnoses of alcohol and marijuana use disorders decreased likelihood of referral to substance abuse treatment. Mental health diagnoses played a limited role in both types of referrals, although specific psychosocial problems were associated with increased likelihood of referrals. Treatment history and location of first mention of problem were significant predictors of referral. There were no gender differences in referral rates to either substance abuse or mental health treatment; however predictors of referral differed by gender. These findings extend our knowledge about factors that influence clinicians' treatment referrals of adolescents with substance abuse diagnoses and have implications for influencing clinician referral behavior within health plans. Scott, M., Parthasarathy, S., Kohn, C., Hinman, A., Sterling, S. and Weisner, C. Medical Provider Referrals of Adolescents to Substance Abuse and Mental Health Treatment. Ment Health Serv Res, 6(1), pp. 47-60, March 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. The aim is to assess the burden of medical illness, identify patient and substance dependence characteristics associated with worse physical health, and compare measures of illness burden in this population. This was accomplished through a cross-sectional study among alcohol-, heroin- or cocaine-dependent persons without primary medical care who were admitted to an urban inpatient detoxification unit. The mean age of these patients was 35.7 (SD 7.8) years: 76% were male and 46% were 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 lower than the general U.S. population norm (44.1 vs 50.1; p<0.001). In multivariable analysis, female gender (adjusted mean change in PCS score: _3.71 points, p=.002), problem use of hallucinogens (_3.51, p=0.013), heroin (_2.94, p=0.008), other opiates (_3.20, p=.045), living alone (_3.15, p=.023), having medical insurance (_2.26, p=0.014) and older age (_.22 points per year, p=0.001) were associated with worse health. From these data, it seems that 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 Care. Am J Addict, 13, pp. 33-45, 2004.

Woman-Focused HIV Intervention with African American Crack Abusers

Out-of-drug-treatment African American women (n = 620) who use crack participated in a comparison randomized trial comparing a women-focused HIV intervention, a revised National Institute on Drug Abuse standard intervention, and a control group. Risk behavior, employment, and housing status were assessed with linear and logistic regression. All groups significantly reduced crack use and high-risk sex at each 3 and 6 month follow-up, but only woman-focused intervention participants consistently improved employment and housing status. Compared with control subjects at 6 months, woman-focused intervention participants were least likely to engage in unprotected sex; revised standard intervention women reported greatest reductions in crack use. A woman-focused intervention can successfully reduce risk and facilitate employment and housing and may effectively reduce the frequency of unprotected sex in the longer term. Wechsberg, W.M., Lam, W.K., Zule, W.A. and Bobashev, G. Efficacy of a Woman-Focused Intervention to Reduce HIV Risk and Increase Self-Sufficiency Among African American Crack Abusers. Am J Public Health, 94(7), pp. 1165-1173, 2004.

Are Rates of Psychiatric Disorders in the Homeless Population Changing?

The objective is to examine the prevalence of psychiatric illness among 3 homeless populations in St. Louis, MO, in approximately 1980, 1990, and 2000. Selected demographics and lifetime substance abuse and dependence and other mental illness among the 3 populations are compared. Among the homeless populations, the prevalence of mood and substance use disorders dramatically increased, and the number of minorities within these populations has increased. The prevalence of drug use disorder increased dramatically among both men and women over the past 2 decades, and among women, the increase was higher than the prevalence of alcohol use disorder. In 2000, 84% of men and 58% of women had an alcohol or other drug use disorder. Also in 2000, substance use disorders accounted for the vast majority of psychopathology (prevalence of any psychiatric disorder was 88% among men and 69% among women). In 1980, the abused drug of choice was cannabis, but it was surpassed over the next 2 decades by cocaine, which had not been found among homeless men or women in 1980. The popularity of amphetamine and sedative-hypnotic abuse decreased after 1980. Opioid abuse remained relatively unchanged over the 2 decades and was the third most prevalent abused drug of choice in 2000. The prevalence of psychiatric illness, including substance abuse and dependence, is not static in the homeless population. Service systems need to be aware of potential prevalence changes and the impact of these changes on service needs. North, C.S., Eyrich, K.M., Pollio, D.E., and Spitznagel, E.L Are Rates of Psychiatric Disorders in the Homeless Population Changing? Am J Public Health, 94, pp. 103-108, 2004.

Prevalence of Psychiatric and Substance Use Disorders in Opioid Abusers in a Community Syringe Exchange Program

The present study evaluates the prevalence of psychiatric and substance use disorders in male and female intravenous opioid abusers participating at a community needle exchange program (NEP). All participants (n = 422) were administered the Structured clinical Interview for the DSM-IV (SCID) for Axis I disorders and antisocial personality disorder (APD). Psychiatric and substance abuse comorbidity were highly prevalent. Major depression was the most common current and lifetime Axis I non-substance use disorder (6 and 21% of the sample, respectively); 37% were diagnosed with APD. Over 50% of the sample was diagnosed with at least one non-substance use Axis I disorder or APD. In addition to opioid dependence, cocaine dependence was the most prevalent current and lifetime substance use disorder (68 and 78% of the sample, respectively), followed by alcohol and cannabis dependence. Overall, participants reported a mean of over one current and over three lifetime substance use disorders in addition to opioid dependence. Women reported higher rates of post-traumatic stress disorder (PTSD), while men were more likely diagnosed with APD. Presence of a psychiatric disorder was associated with increased prevalence of substance use disorder for all drug classes. The high rates of comorbidity observed in this sample suggest that the harm reduction efforts of NEPs can be significantly enhanced through referral of participants to programs that treat substance use and/or other psychiatric disorders. Kidorf, M., Disney, E.R., King, V.L., Neufeld, K., Beilenson, P.L. and Brooner, R.K. Prevalence of Psychiatric and Substance Use Disorders in Opioid Abusers in a Community Syringe Exchange Program. Drug and Alcohol Dependence, 74, pp. 115Ð122, 2004.

Many Adults Do Not Link with Primary Medical Care after Alcohol or Drug Detoxification

This prospective cohort studyÑconducted in the context of a randomized trial of a linkage intervention and an expansion of Medicaid benefitsÑidentified patient characteristics and health care experiences associated with primary care linkage after alcohol or drug detoxification. Researchers collected primary interview data over two years from 400 adults without primary medical care, in an urban residential detoxification program. Linkage was defined as self-report of at least one visit with a primary care clinician during follow-up. Of 400 subjects, 63% linked with primary medical care. In a multivariable model adjusting for randomization assignment, predisposing, enabling and illness variables, women, those with no recent incarceration, those with support for abstinence by family or friends, and those who had visited a medical clinic or physician recently were significantly more likely to link with primary care. Those with health insurance during follow-up were also more likely to link. Recent mental health or addictions treatment utilization and health status were not associated with linkage. Researchers conclude that a substantial proportion of adults with addictions do not link with primary medical care. These data suggest that efforts could be focused on those least likely to link, that contacts with mental health and addictions treatment providers are underutilized opportunities for these efforts, and that health policy changes such as expanding health insurance benefits may improve entry of substance dependent patients into primary medical care. Saitz, R., Larson, M.J., Horton, N.J., Winter, M., and Samet, J.H. Linkage with Primary Medical Care in a Prospective Cohort of Adults with Addictions in Inpatient Detoxification: Room for Improvement. Health Services Research, 39(3), pp. 587-606, 2004.

Are Health Plans Adequately Identifying Adolescents With Substance Use Problems?

Three measures developed by the Washington Circle, a group focused on the development of substance abuse performance measures, have been adapted for the 2004 Health Plan Employer Data and Information Set. One measureÑthe identification rateÑcan be used to examine the extent to which private health plans are able to identify adolescent enrollees with substance use problems. The researchers calculated this rate for adolescents using MarketScan, a database of private health plan claims for selected employers maintained by the MEDSTAT Group. About a quarter million adolescents were covered in 1997. The number of adolescents with any primary or secondary substance abuse claims during the year was divided by the member-years for adolescents aged 12 to 18. For enrolled adolescents, the overall identification rate was .5 percent and .7 percent for males and .4 percent for females. The researchers compared these results to the 6.8 percent rate of alcohol dependence or drug dependenceÑor bothÑobtained from a special analysis of a subset of adolescents covered by commercial insurance who were included in the 1998 National Household Survey on Drug Abuse. No meaningful variation was observed across health plan type. The low rate points to the urgent need to close the gap between the number of adolescents who need treatment and those who receive it. Lee, T.M., Garnick, D.W., Miller, K., and Horgan, C.M. Are Health Plans Adequately Identifying Adolescents With Substance Use Problems? Psychiatric Services, 55(2), pp. 116, 2004.

Predicting Adolescent Drug Abuse Treatment Outcome with the Personal Experience Inventory

This study examined the clinical utility of the Personal Experience Inventory (PEI) Psychosocial scales to predict adolescent drug abuse treatment outcome. The role of psychosocial risk factors in predicting treatment outcome also has theoretical interest given that such factors have been associated with the development of drug abuse. The sample consisted of 138 male and 105 female adolescents recruited at a hospital-based adolescent drug abuse treatment program. Clients were assessed at intake, discharge, and 6 and 12 months after discharge. Intake PEI Psychosocial scales were modestly predictive of outcome; the magnitude of the predictions was higher for boys than girls. Three PEI Psychosocial domains of deviance, family dysfunction, and peer drug use were predictive of boys' outcome; sibling and peer drug use were predictive of girls' outcome. The strength of these predictive relationships was similar to those found in other treatment outcome prediction research. There was limited support for the predictive validity of the PEI. These PEI Psychosocial scales that show predictive associations with outcome may be helpful in treatment planning. Stinchfield, R.D. and Winters, K.C. Predicting Adolescent Drug Abuse Treatment Outcome with the Personal Experience Inventory (PEI). Journal of Child and Adolescent Substance Abuse, 13, pp. 103-120, 2003.

An HIV Prevalence-based Model for Estimating Urban Risk Populations of Injection Drug Users and Men Who Have Sex with Men

Issues of cost and complexity have limited the study of the population sizes of men who have sex with men (MSM) and injection drug users (IDUs), two groups at clearly increased risk for human immunodeficiency virus (HIV) and other acute and chronic diseases. The researchers developed a prototypical, easily applied estimation model for these populations and applied it to Miami, Florida. This model combined HIV prevalence estimates, HIV seroprevalence rates, and census data to make plausible estimates of the number and proportion of MSM and IDUs under a number of assumptions. Sensitivity analyses were conducted to test the robustness of the model. The model suggests that approximately 9.5% (plausible range 7.7%Ð11.3%) of Miami males aged 18 years or older are MSM (point estimate, N =_76,500), and 1.4% (plausible range 0.9%Ð1.9%) of the total population aged 18 years or older are IDUs (point estimate, N=_23,700). Males may be about 2.5 times more likely than females to be IDUs. The estimates were reasonably robust to biases. The model was used to develop MSM and IDU population estimates in selected urban areas across Florida and should be replicable in other medium-to-large urban areas. Such estimates could be useful for behavioral surveillance and resource allocation, including enhanced targeting of community-based interventions for primary and secondary HIV prevention. Lieb, S., Friedman, S.R., Zeni, M.B., Chitwood, D., Liberti, T.M., Gates, G.J., Metsch, L.R., Maddox, L.M. and Kuper, T. Journal of Urban Health: Bulletin of the New York Academy of Medicine, 81(3), pp. 401-415, 2004.

Intramural Research

Molecular Neuropsychiatry Section, Molecular Neuropsychiatry Research Branch

Sex-related Differences in a Gambling Task and Its Neurological Correlates

IRP scientists investigated sex-related differences in task performance and brain activity in the orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) during performance of a decision-making task (the Iowa Gambling Task). When men and women were examined separately, men activated extensive regions of the right lateral OFC and right DLPFC, as well as the left lateral OFC. In contrast, women activated the left medial OFC. Examining sex differences directly, men showed better task performance and greater lateralized brain activity to the right hemisphere than women. This was exemplified by greater activation in a large area of the right lateral OFC of men during their performance of the Iowa Gambling Task. In contrast, women had greater activation in the left DLPFC, left medial frontal gyrus and temporal lobe during this task. Thus, brain mechanisms engaged by men and women when solving the same decision-making task are different. These observations indicate that sex-related differences contribute to the heterogeneity observed in both normal and abnormal brain functioning. These results also provide further evidence of sexual dimorphism in neurocognitive performance and brain function. Bolla, K.I., Eldreth, D.A., Matochik, J.A. and Cadet, J.L. Cerebral Cortex, VOLUME, PAGES, 2004.