Director's Report to Council - Research Findings Excerpts

February, 2007

Basic Neurosciences Research

Paternal Cocaine Exposure & Its Consequences

In a recent study, NIDA supported researchers, Dr. Michael Lidow and his associates report that paternal cocaine abuse may have a significant negative impact on offspring development and that such paternal impact could be brought about by long-term cocaine exposure of males prior to coitus. This study conducted using a novel drug inhalation model revealed that male mice were capable of learning self-administration of cocaine via inhalation route as well as achieving and maintaining blood levels of this drug during daily inhalation sessions comparable to that reported for females. Authors also noted a reduction in biparietal head diameter in newborn pups sired by cocaine-inhaling males suggesting a decreased cerebral volume. Most importantly, they observed a greater negative impact in female offspring compared to males with respect to working memory and light stimulus duration. This study also showed that chronic cocaine exposure in male mice did not result in substantial breakage of spermatozoal DNA, but significantly altered expression of DNA methyltransferase 1 and 3a in the germ cell-rich seminiferous tubules of the testis. Since these enzymes are essential for generating and maintaining parental gene imprinting in germ cells, the authors' observations point to an intriguing possibility that cocaine may cause paternally induced neuroteratological effects by interfering with gene-imprinting patterns in male gametes. He, F., Lidow, I.A., and Lidow, M.S. Consequences of Paternal Cocaine Exposure in Mice, Neurotoxicology and Teratology, 28, pp. 198-209, 2006.

Basic Behavioral Research

Gestational Nicotine Exposure Changes Basal Neuronal Activity in Areas Associated with Motivated Behavior

Dr. Frances Leslie and colleagues investigated whether nicotine, infused into a pregnant dam during gestation, would affect the neuronal response to acute nicotine during adolescence. One of three challenge doses of nicotine, or saline, was administered during postnatal days 38-40 (i.e., adolescence in the rat), and c-fos mRNA was used as a measure of neuronal activity. Gestational exposure to nicotine did not alter response to acute nicotine challenge during adolescence. The highest dose of acute nicotine challenge, however, did result in a significant increase in c-fos mRNA in the nucleus accumbens, the superior colliculus and the dorsolateral geniculate nucleus. Stress-sensitive areas of the lateral bed nucleus of the stria terminalis and the paraventricular nucleus also showed increased neuronal activity in response to acute nicotine. Two brain areas showed significant increases in c-fos mRNA as a result of gestational treatment, independently of nicotine challenge during adolescence: the infralimbic cortex and the nucleus accumbens core. These regions are important mediators of executive function and inhibitory control. These data suggest that gestational nicotine exposure results in long-term changes in neuronal activity, that it does not interact with acute adolescent exposure, but that the neuronal activity of adolescent rats can be significantly altered by a single, acute dose of nicotine. Park, M.K., Loughlin, S.E. and Leslie, F.M. Gestational Nicotine-Induced Changes in Adolescent Neuronal Activity. Brain Research, 1094, pp. 119-126, 2006.

Salvinorin-A, a -Opioid Hallucinogen, Produces Time- and Dose-Dependent Neuroendo-crine Effects

Salvinorin A is a potent kappa-opioid agonist in vitro and salvinorin A-containing products have been emerging as drugs of abuse for their hallucinogenic effects. NIDA researcher Dr. Eduardo Butelman recently tested the drug for kappa effects in vivo using serum prolactin levels as biomarkers of efficacy, and also cloned the Macaca mulatto (M. mulatto) OPRK1 gene, which codes for the kappa opioid receptor. He treated M. mulattos with salvinorin A, U69,593 (a kappa-agonist) or vehicle, followed by blood sampling at 5-120 minutes post-injection. Both kappa agonists produced robust, dose-and time-dependent increases in prolactin levels in males. U69,593 produced a longer-lasting effect; however the maximum effect and potency were the same as produced by salvinorin A. In females in the follicular phase, salvinorin A produced robust prolactin release. This was longer lasting, and had a faster onset than in males. In antagonist challenge studies the opioid antagonist nalmefene and/or the serotonin antagonist ketanserin was administered prior to a dose of salvinorin A. In both males and females, antagonist pretreatment with nalmefene produced robust antagonism of salvinorin A-stimulated prolactin release at the high, but not low, dose. Ketanserin produced no antagonism and did not affect prolactin levels, indicating that serotonin receptors were not involved. In these studies, salvinorin A was shown to be a potent kappa agonist, and was effective in both males and females. Butelman, E.R., Mandau, M., Prisinzano, T.E., Yuferov, V. and Kreek, M.J. Effects of Salvinorin A, a -Opioid Hallucinogen, on a Neuroendocrine Biomarker Assay in Non-human Primates with High k-Receptor Homology to Humans. Journal of Pharmacology and Experimental Therapeutics, 320(1), pp. 300-306, 2006.

Environmentally Enriched Conditions Reduce Impulsivity in an Animal Model

Rats reared in an enriched environment (EE) show enhanced cortical plasticity and improved learning. EE also protects against the development of drug abuse behavior in animal models of vulnerability such as i.v. self-administration. As socially isolated (SI) rats react more intensely to light and sound stimuli, they may more easily acquire self-administration because they are more emotionally responsive. A recent study by Dr. George Rebec suggests that either greater arousal, or impaired cognitive function, on the part of SI reared animals interferes with learning a complex appetitive task. In this study all rats were initially cross-fostered to a single mother to control for effects of rearing. At post-natal day 45, they were food deprived to 85% body weight and subjected to three sequential phases of an experiment as follows: Phase I. Associate licking sucrose from a spout with the feeder cue (tone + light). Phase II. Train contingent nose poke responses to elicit this feeder cue; when the light was illuminated animals could nose poke into either of two holes where sucrose was delivered and the tone was provided. Phase III. Only one nose poke hole was lit and nose pokes into that hole activated the feeder cue, followed by sucrose delivery. EE and SI animals showed no differences in learning during Phases I and II, but during phase III SI animals made significantly more "bad nose pokes" (in the incorrect hole) so their mean number of sessions to learn the task was significantly greater. As this group was not hyperactive in the task it appears that the difference is due to an inability to withhold anticipatory responses. In support of this interpretation, SI rats also performed more nose pokes during inter-trial intervals when sucrose was not available. SI and EE groups did not differ in consummatory behavior, as lick measures were no different during any part of the session. The investigators infer that for animals reared in SI conditions, salience of rewarding stimuli is increased and these animals are less able to inhibit approach responding. This interpretation is compatible with the previous finding of greater drug self-administration by SI animals. Wood, D.A., Siegel, A.K. and Rebec, G.V. Environmental Enrichment Reduces Impulsivity During Appetitive Conditioning, Physiology & Behavior, 88, pp. 132-137, 2006.

Sex Differences in Decision Making on the Iowa Gambling Task

On the Iowa Gambling Task subjects choose cards from four decks that provide monetary gains or monetary losses. Selections from two of the decks result in an overall net gain, but choices from the other two produce an overall net loss. Optimal performance requires the subject to identify and select from a low pay/low loss deck, and men typically select significantly more cards from these advantageous decks whereas women consistently choose more cards from disadvantageous decks with high penalties. Successful performance depends on integrity of the prefrontal cortex (PFC) and measurement of PFC activation during the task reveals that men activate bilateral areas of the dorsolateral PFC, right lateral orbital PFC, and right parietal lobe. By contrast, women activate a smaller region of the left medial orbital PFC. Recently, Dr. William Overman conducted a study to determine if a task known to activate dorsolateral PFC areas might improve IGT performance in women. One task that activates this region is deliberation of moral personal dilemmas. In the present study, 200 participants were divided into three groups and asked to contemplate a scenario every 10 trials - either a moral personal dilemma, a moral impersonal dilemma, or a nonmoral dilemma. Results show that sex differences on the Iowa Gambling Task were eliminated in groups contemplating PM whereas men in the other two conditions selected a significantly greater proportion of cards from advantageous decks than did the women. Finally, in order to test whether improvement might be due to generalized emotional arousal, another 229 students were tested after moral personal dilemma deliberation on a Wisconsin Card Sort Task that relies upon dorsolateral and dorsomedial PFC substrates. Wisconsin Card Sort Task scores were unaffected by moral personal dilemma deliberation suggesting that improvement by females on the Iowa Gambling Task is due to a shift in activation of PFC regions and enhanced cognitive control over an emotional response to rewards in the disadvantageous decks. Overman, W., Graham, L., Redmond, A. Eubank, R., Boettcher, L., Samplawski, O. and Walsh, K. Contemplation of Moral Dilemmas Eliminates Sex Differences on the Iowa Gambling Task. Behavioral Neuroscience, 120, pp. 817-825, 2006.

Conditioned Psychostimulant Effects Are Moderated by Age and Sex

Individual differences in locomotor response to novelty predict the behavioral activating effects and self-administration of psychomotor stimulants. Rats that are more reactive in a novel environment (high responders, HR) show greater drug-induced stimulation and more readily acquire self-administration of amphetamine, cocaine, and nicotine, than their low-responding (LR) counterparts. Dr. Michael Bardo and colleagues recently completed a study to determine if individual differences in novelty response predict: 1) Locomotor sensitization to the psychostimulant, methylphenidate or 2) methylphenidate-conditioned locomotion in the drug-paired environment. Moreover, they sought to determine if novelty response would predict behavioral change differentially for male versus female rats and for adolescent (25 days old) versus adult (60 days old). A median split between HR and LR rats was based on locomotor counts and time spent in a novel compartment. Rats were then treated with saline, 3.0 or 10.0 mg/kg methylphenidate, for 10 days. After 14 days of withdrawal animals were assessed for conditioned locomotor activity with saline and for sensitization with a single 10.0mg/kg methylphenidate injection in the test cage. The investigators found: 1) Adolescent rats selected novelty in a free choice situation significantly more than adults; however, choice did not predict methylphenidate sensitization or conditioning; 2) HR showed greater methylphenidate behavioral activation and adult females had greater dose-dependent activity than adult males; 3) Adolescent Rats developed sensitization at 3.0 mg/kg METH, whereas adults only sensitized to 10 mg/kg; 4) Only HR adult females had increased sensitization to 5) All animals showed a methylphenidate conditioned to the test environment except the adult males; 6) HR rats showed an greater methylphenidate conditioned locomotor activity but a HR>LR difference was only significant for adolescent males and adult females; 7) Only HR adult feamlaes showed greater sensitization on the methylphenidate challenge. These findings suggest that: 1) Gender differences in sensitization emerge during development; 2) Adolescent rats in general are more sensitive to psychomotor stimulant sensitization; 3) Initial response to novelty predicts methylphenidate -induced conditioned locomotion to the test chamber and sensitized behavioral response to methylphenidate; and 4) This individual difference is moderated by both age and gender. Wooters, T.E., Dwoskin, L.P. and Bardo, M.T. Age and Sex Differences in the Locomotor Effect of Repeated Methylphenidate in Rats Classified as High or Low Novelty Responders. Psychopharmacology, 188, pp. 18-27, 2006.

Menstrual Cycle Phase Effects on Nicotine Withdrawal and Cigarette Craving: A Review

Research over the past several years has uncovered numerous male-female differences in cigarette smoking. In studies of quitting, for example, women are less successful than men, and there is clinical and laboratory evidence that nicotine versus non-nicotine factors play a differential role in smoking for men versus women. The menstrual cycle has been shown to be a factor in smoking for women with several studies finding more smoking in the luteal phase (post-ovulation/premenstrual) of the cycle than in the follicular phase (menses/pre-ovulation). Researchers at the Medical University of South Carolina conducted a literature review to examine whether this higher level of smoking in the luteal phase reflects greater nicotine withdrawal and craving. Using MEDLINE and PsychInfo databases, a total of 13 studies were identified, of which 3 examined the naturalistic time course of withdrawal and craving under ad libitum smoking, 6 examined these measures under laboratory conditions of abstinence, and 4 conducted comparisons of the two conditions. The review yielded mixed results although there was evidence for greater withdrawal and craving in the luteal phase. The authors conclude that "the most striking implication from this review is the need for further research," noting that inconsistencies in outcomes among studies could be due to heterogeneity of methods including differences in statistical power to detect cycle effects, inconsistency in identification and corroboration of menstrual cycle phase, definition of cycle phase (two phases versus four-phases), and inclusion versus exclusion of women with a history of premenstrual dysphoric disorder. The authors recommend that future research in this area uses hormonal verification of menstrual phase status and follows a four-phase conceptualization: early follicular, late follicular, early luteal, and late luteal. This area of research has important clinical implications for choice of quit date for nicotine cessation and thus warrants future study. Carpenter, M.J., Upadhyaya, H.P., LaRowe, S.D., Saladin, M.E., and Brady, K.T. Menstrual Cycle Phase Effects on Nicotine Withdrawal and Cigarette Craving. A Review. Nicotine & Tobacco Research, 8, pp. 627-638, 2006.

Behavioral and Brain Development Research

Effects of Prenatal Methamphetamine Exposure, Polydrug Exposure, and Poverty on Intrauterine Growth

Methamphetamine use among pregnant women is an increasing problem in the United States. Effects of methamphetamine use during pregnancy on fetal growth have not been reported in large, prospective studies. Dr. Barry Lester and his colleagues at four clinical centers in California, Oklahoma, Hawaii and Iowa examined the neonatal growth effects of prenatal methamphetamine exposure. Of 13,808 subjects screened, 1,618 were eligible and consented, among which 84 were methamphetamine exposed, and 1,534 were unexposed. Both groups included prenatal alcohol, tobacco, or marijuana use, but excluded use of opiates, LSD, PCP or cocaine only. The methamphetamine exposed group was 3.5 times more likely to be small for gestational age than the unexposed group. Mothers who used tobacco during pregnancy were nearly two times more likely to have small-for-gestational-age infants. In addition, less maternal weight gain during pregnancy was more likely to result in a small-for-gestational-age infant. Birth weight in the methamphetamine exposed group was lower than the unexposed group. These findings suggest that prenatal methamphetamine use is associated with fetal growth restriction after adjusting for covariates. Continued follow-up will determine if these infants are at increased risk for growth and/or neurodevelopmental deficits in the future. Smith, L.M., LaGasse, L.L., Derauf, C., Grant, P., Shah, R., Arria, A., Huestis, M., Haning, W., Strauss, A., Della Grotta, S., Liu, J., and Lester, B.M. The Infant Development, Environment, and Lifestyle Study: Effects of Prenatal Methamphetamine Exposure, Polydrug Exposure, and Poverty on Interuterine Growth, Pediatrics, 118(3), pp. 1149-1156, 2006.

Neuroimaging of Frontal White Matter and Executive Functioning in Cocaine-Exposed Children

Researchers at the University of Florida have reported on the use of Diffusion Tensor Imaging (DTI) to assess frontal white matter development in prenatally cocaine-exposed and non-exposed children, and also have reported on associations between frontal white matter development and executive functioning in these children. DTI uses magnetic resonance imaging (MRI) to investigate white matter microstructure by measuring the movement, or diffusion, of water molecules in tissues. Using different DTI quantification indices, researchers study maturation of white matter tracts. Executive functioning is a concept that describes a diverse set of skills involved in goal-directed behavior such as problem solving, and includes skills such as attention control, inhibition abilities, and management of cognitive, emotional, and behavioral functions. Executive functioning was assessed using two frequently used instruments (the Stroop color and word test and the Trail Making Test). The sample for these analyses (tested and scanned in the age range 9.6 to 12.2 years) was drawn from an ongoing longitudinal study of development following prenatal cocaine exposure, and involved 28 cocaine-exposed children and 25 non-exposed children with similar sociodemographic characteristics. The investigators conclude that prenatal cocaine exposure, alone and in combination with exposure to other drugs, is associated with slightly poorer executive functioning and with subtle microstrucural characteristics that may suggest less mature development of frontal white matter pathways. They also state that the relative contribution of postnatal environmental factors (e.g., caregiving environment) on brain development and behavioral functioning in polydrug-exposed children awaits further research. Warner, T.D., Behnke, M., Eyler, F.D., et al. Diffusion Tensor Imaging of Frontal White Matter and Executive Functioning in Cocaine-Exposed Children. Pediatrics, 118, pp. 2014-2024, 2006.

Discrete Opioid Gene Expression Impairment in the Human Fetal Brain Associated with Maternal Marijuana Use

The most commonly used illicit drug by pregnant women is marijuana. In light of the strong interactions between the cannabinoid and Opioid systems, Dr. Yasmin Hurd and her colleagues investigated the effects of in utero marijuana exposure on expression levels of Opioid-related genes in the human fetal forebrain. The Opioid peptide precursors (preprodynorphin and preproenkephalin (PENK)) and receptor (mu, kappa and delta) mRNA expression were assessed in distinct brain regions in 42 midgestation fetuses from saline-induced voluntary abortions and the effects of prenatal cannabis exposure was analyzed while controlling for confounding variables such as maternal alcohol and cigarette use, fetal age, sex, growth measure and post-mortem interval. Prenatal cannabis exposure was found to be significantly correlated with increased mu receptor expression in the amygdala, reduced kappa receptor mRNA in mediodorsal thalamic nucleus and reduced preproenkephalin expression in the caudal putamen. Prenatal alcohol exposure was found to primarily influence kappa receptor mRNA, with reduced levels in the amygdala, claustrum, putamen and insula cortex. No significant effect of prenatal nicotine exposure was seen in the analyses performed. These results indicate that maternal cannabis and alcohol exposure during pregnancy differentially affect opioid-related genes in distinct brain circuits; alterations that may have long-term effects on cognitive and emotional behaviors. Wang, X., Dow-Edwards, D., Anderson, V., Minkoff, H., and Hurd, Y.L. Discrete Opioid Gene Expression Impairment in the Human Fetal Brain Associated with Maternal Marijuana Use. Pharmacogenomics Journal, 6(4), pp. 255-264, 2006.

Prenatal Cocaine Exposure and Risk for Developing Learning Disabilities

Dr. Emmalee Bandstra and her colleagues at the University of Miami examined prenatal cocaine exposure and risk for developing a learning disability (LD) or impaired intellectual functioning by age seven in a sample of 409 children (212 cocaine-exposed, 197 non-cocaine-exposed) born full term and enrolled prospectively at birth. LDs were categorized based on ability-achievement discrepancy scores. The cocaine-exposed children had 2.8 times greater risk of developing a LD by age seven than non-cocaine-exposed children. No differences were found in the estimate of relative risk for impaired intellectual functioning (IQ below 70) between children with and without prenatal cocaine exposure. Results remained stable with adjustment for multiple child and caregiver covariates including but not limited to maternal education, caregiver substance use, the home environment, and attendance in Head Start/prekindergarten suggesting that children with prenatal cocaine exposure are at increased risk for developing a learning disability by age seven when compared to their non-cocaine-exposed peers. Morrow, C.E., Culbertson, J.L., Accornero, V.H., Xue, L., Anthony, J.C., and Bandstra, E.S. Learning Disabilities and Intellectual Functioning in School-Aged Children with Prenatal Cocaine Exposure. Developmental Neuropsychology, 30(3), pp. 905-931, 2006.

Prenatal Smoking Exposure and Developmental Patterns of Conduct Problems in Boys

There are reports in the research literature of associations between prenatal smoking exposure and increased risk of conduct problems among offspring. This report examines associations of prenatal smoking exposure with oppositional defiant disorder (ODD) and attention-deficit/hyperactivity disorder (ADHD) in young boys (during first grade), and with developmental patterns of delinquent behavior during adolescence. Researchers from the University of Illinois at Chicago and from the University of Pittsburgh examined data from the Pittsburgh Youth Study, a prospective, population-based study of conduct problems in boys. In the analyses for this report, prenatal smoking exposure was examined relative to the presence of ODD and ADHD, singly and as comorbid conditions at age 7 years. Also investigated was the association of prenatal exposure with the timing of onset of both mild and more serious conduct problems, using in-depth measures of delinquency administered prospectively from early school age through age 19 years. Multiple potentially confounding factors were controlled in multivariate analyses. The investigators report that exposed boys were more likely to show evidence of ODD and comorbid ODD-ADHD, but not ADHD alone. They also report that exposed boys were more likely to have an earlier onset of significant delinquent behavior. The authors note that whether prenatal smoking plays an etiological role in, or is a marker for risk of antisocial behavior, it is clear that the offspring of prenatal smokers as a group are at increased risk for an early-starter pathway to antisocial behavior that is evident as early as first grade. Wakschlag, L.S., Pickett, K.E., Kasza, K.E., and Loeber, R. Is Prenatal Smoking Associated with a Developmental Pattern of Conduct Problems in Young Boys? Journal of the American Academy of Child and Adolescent Psychiatry, 45, pp. 461-467, 2006.

Prenatal Cannabis Exposure Increases Heroin Seeking with Allostatic Changes in Limbic Enkephalin Systems in Adulthood

Very little is known about the long-term consequences of prenatal cannabis exposure on behavior and neural systems. Dr. Yasmin Hurd and her colleagues used an animal model to study the effects of prenatal exposure to 9-tetrahydrocannabinol (THC) on heroin self-administration behavior and opioid neural systems in adult male rats (postnatal day 62) that were exposed to THC from gestational day five to postnatal day two. They found that THC-exposed rats exhibited shorter latency to pressing a lever for heroin, responded more for low heroin doses, and had more readily sought heroin when stressed and during drug extinction. Neurobiologically, they found that THC exposure reduced preproenkephalin (PENK) mRNA expression in the nucleus accumbens during early development, but this was elevated in adulthood. PENK mRNA was also increased in the central and medial amygdala in adult THC-exposed animals. Finally, THC animals had reduced heroin-induced locomotor activity and nucleus accumbens opioid receptor coupling. This study demonstrates that the effects of prenatal THC exposure endure into adulthood and that these effects are evident on heroin-seeking behavior and in changes in mesocorticolimbic PENK systems relevant to drug motivation/reward and stress responses. Spano, M.S., Ellgren, M., Wang, X., and Hurd, Y.L. Prenatal Cannabis Exposure Increases Heroin Seeking with Allostatic Changes in Limbic Enkephalin Systems in Adulthood. Biological Psychiatry, July 27, 2006.

Intrauterine Growth Restriction and Prenatal Substance Exposure in Term Infants and Risk for Hypertension at Age Six

Researchers from the Maternal Lifestyle Study, a prospective longitudinal multi-site study of prenatal cocaine and opiate exposure, investigated the association between intrauterine growth restriction (IUGR) status at birth among full-term infants, exposure to substance use during pregnancy, and risk of hypertension at six years of age. Of the 1,388 infants (600 cocaine exposed, 781 non-exposed, and seven indeterminate, matched by gestational age, race, and sex), enrolled in this study, 950 children (415 exposed, 535 non-exposed) completed the age six assessment, 891 had blood pressure data and of these, 516 were born at full term. One hundred and forty-four (28%) of the 516 children had a diagnosis of IUGR at birth. At six years of age, 93 (19%) of 516 children had hypertension, defined as either systolic or diastolic blood pressure higher than the 95th percentile for sex, age, and height. Of 144 children with IUGR, 35 (24%) had hypertension as compared with 58 (16%) of 372 children without IUGR. The study did not find any association with cocaine, opiate, marijuana, tobacco, or alcohol use during pregnancy and hypertension at 6 years of age. Twenty percent of cocaine-exposed children had hypertension as compared with 16% of nonexposed children. Intrauterine growth restriction status at birth was significantly associated with hypertension adjusting for site; maternal race, education, and tobacco, marijuana, alcohol, and cocaine use during pregnancy; and child's current body mass index. In term infants, IUGR is linked to risk of hypertension in early childhood, which may be a marker for adult cardiovascular disease. Shankaran, S., Das, A., Bauer, C.R., Bada, H., Lester, B., Wright, L., Higgins, R., and Poole, K. Fetal Origin of Childhood Disease: Intrauterine Growth Restriction in Term Infants and Risk for Hypertension at Age Six. Archives of Pediatrics and Adolescent Medicine, 160(9), pp. 977-981, 2006.

Perinatal HIV Infection, In Utero Substance Exposure and Cognitive Development in Young Children

Researchers from the Women and Infants transmission study examined the effect of HIV in combination with other health and social factors including in utero exposure to drugs on the development of cognitive abilities of children perinatally exposed to HIV and substances of abuse. Serial cognitive assessments were performed for 117 children who were infected vertically and 422 children (50% African American, 32% Hispanic, and 12% Caucasian) who were exposed to but not infected with HIV. Forty-one percent of the children were exposed to cocaine, heroin, or methadone in utero as measured by self-report and/or urine screen and 63% were exposed to alcohol, tobacco, or marijuana as measured by self-report. Repeated-measures analyses were used to evaluate the neurocognitive development of these children between the ages of three and seven years. Children with HIV/no Class C conditions were more likely to experience exposure to hard drugs during pregnancy than were children without HIV. (Class C refers to the CDC categorization of clinical conditions or symptoms of HIV infection considered severe including recurrent serious bacterial infections and encephalopathy). Children with HIV infection and class C status scored significantly lower in all domains of cognitive development, across all time points, than did those who were HIV infected without an AIDS-defining illness and those who were HIV exposed but not infected adjusting for presence of hard and soft substance exposure and other maternal factors during pregnancy and delivery, social demographic variables, test administration variables, and maternal and child disease stages. There were no significant differences between the two latter groups in General Cognitive Index or specific domain scores. Rates of change in cognitive development were parallel among all three groups over a period of four years. Factors that were associated consistently and significantly with lower mean scores were HIV status, number of times an examination had been completed previously, primary language, maternal education, and gender. No factors were related to rate of change of any mean domain score. An early AIDS-defining illness increased the risk of chronic static encephalopathy during the preschool and early school age years. Children with HIV infection but no class C event performed as well as non-infected children in measures of general cognitive ability. No significantly different profiles of strengths and weaknesses for verbal, perceptual-performance, quantitative, or memory functioning were observed among children with or without HIV infection. The authors recommend that future research include various environmental stressors in these children's lives including current parental drug use. Smith, R., Malee, K., Leighty, R., Brouwers, P., Mellins, C., Hittelman, J., Chase, C., Blasini, I., and the Women and Infants Transmission Study Group. Effects of Perinatal HIV Infection and Associated Risk Factors on Cognitive Development among Young Children. Pediatrics, 117(3), pp. 851-862, 2006.

Prenatal Exposure to Cocaine and Childhood Exposure to Violence: Association with Friends' and Own Substance Use

Children exposed to substances of abuse in utero may also be at risk for environmental stressors during childhood that can influence their neurodevelopmental trajectories and risk for substance use. This study examined the association between exposure to violence during childhood and own and friends' substance use in a sample of children from a prospective longitudinal study of in-utero cocaine exposure (IUCE). One hundred and four children were assessed at age 8.5, 9.5, and 11 years with the Violence Exposure Scale for Children-Revised (VEX-R) and the Substance Exposure Assessment, a child-report measure of their own and their friends' ATOD use. The sample consisted of 90% African-American/ Caribbean children (mean age 8.5 years, SD 3 years), 53% males, and 49% with IUCE. Twenty-eight percent of the sample reported own use of any ATOD by age 11. The percentage of children who reported having substance-using friends was 12% at 8.5 years, 25% by 9.5 years, and 45% by 11 years. In multivariate survival analyses controlling for caregiver type, in-utero cocaine exposure category (heavy, light, and none), and child gender, children in the upper quartile of violence exposure at age 8.5 years were at significantly greater risk of having reported friends' use of ATOD by age 11 compared to those in the first through third quartiles. Quartiles of the violence exposure score, however, were not significantly associated with children's acknowledgment of their own use. Findings suggest an association between exposure to violence in childhood and report of peer ATOD use at school age. Campaigns to prevent ATOD use should address the impact of childhood exposure to violence. Joseph, N.P., Augstyn, M., Cabral, H., and Frank, D.A. Preadolescents' Report of Exposure to Violence: Association with Friends' and Own Substance Use. Journal of Adolescent Health, 38(6), pp. 669-674, 2006.

Maternal Cocaine Use and Caregiving Status: Group Differences in Caregiver and Infant Risk Variables

This study examined differences between cocaine and non-cocaine-using mothers, and between parental and non-parental caregivers of cocaine-exposed infants on caregiver childhood trauma, psychiatric symptoms, demographic, and perinatal risks. Participants included 115 cocaine and 105 non-cocaine mother-infant dyads recruited at delivery. Approximately 19% of cocaine mothers lost custody of their infants by one month of infant age compared to 0.02% of non-cocaine mothers. Mothers who used cocaine during pregnancy had higher demographic and obstetric risks and their infants had higher perinatal risks. Birth mothers who retained custody of their infants had higher demographic risks and perinatal risks, higher childhood trauma, and higher psychiatric symptoms compared to birth mothers who did not use cocaine and non-parental caregivers of cocaine-exposed infants. Results highlight the importance of addressing childhood trauma issues and current psychiatric symptoms in substance abuse treatment with women who engaged in substance use during pregnancy. Eiden, R.D., Foote, A., and Schuetze, P. Maternal Cocaine Use and Caregiving Status: Group Differences in Caregiver and Infant Risk Variables. Addictive Behaviors, 32(3), pp. 465-476, 2007.

Gender, Substance Exposure, Lymphocyte Populations, Plasma HIV RNA Levels, and Disease Progression in a Cohort of HIV Exposed Children

Researchers from the Women and Infants Transmission study analyzed blood samples from antiretroviral therapy-treated, HIV-infected children (n = 158) and HIV-uninfected children (n = 1801) to examine gender and substance exposure differences in lymphocyte subsets and plasma RNA levels. In terms of immunologic parameters, for anti-retroviral therapy (ART) treated, HIV-infected children, maternal hard drug use during pregnancy showed a trend toward children having lower CD4+ cell counts (p= .06). Children whose mothers did not use hard drugs during pregnancy also had, on average, greater CD16+ CD56+ natural killer cell counts. In contrast, children exposed to hard drugs during pregnancy but not HIV infected had a higher CD4+ percentage. In terms of virologic parameters and mortality rates, ART-treated, HIV-infected children whose mothers used hard drugs during pregnancy had a higher mean log RNA level. Maternal alcohol use during pregnancy had no effect on CD4+ cell counts or percentages, however, ART-treated, HIV-infected children whose mothers did not use alcohol during pregnancy had on average higher absolute CD19+ cell counts and higher mean log RNA level. ART-treated, HIV-infected female children had lower plasma RNA levels than did their male counterparts, but lymphocyte differences were not noted. Despite their higher plasma RNA level, a greater proportion of male children survived through 8 years of age. There were no gender differences with respect to the age of diagnosis of HIV, time to antiretroviral therapy after diagnosis of HIV, or type of antiretroviral therapy. Lymphocyte differences were noted for uninfected children. Plasma RNA levels differed among antiretroviral therapy-treated, HIV-infected children according to gender, in a manner similar to that noted in previous pediatric and adult studies. Lymphocyte subsets varied according to gender in a cohort of HIV-exposed but uninfected children. Most importantly, overall mortality rates for this cohort differed according to gender. Foca, M., Moye, J., Chu, C., Matthews, Y., Rich, K., Handelsman, E., Luzuriaga, K., Paul, M., Diaz, C., and the Women and Infants Transmission Study. Gender Differences in Lympocyte Populations, Plasma HIV RNA Levels, and Disease Progression in a Cohort of Children Born to Women Infected with HIV. Pediatrics, 118(1) pp. 146-155, 2006.

A Framework to Monitor Environment-induced Major Genes for Developmental Trajectories: Implications for a Prenatal Cocaine Exposure Study

Whether there are specific genes involved in response to different environmental agents and how such genes regulate developmental trajectories during lifetime are of fundamental importance in health, clinical and pharmaceutical research. Drs. Fonda Eyler, Marylou Behnke and colleagues at the University of Florida developed a novel statistical model for monitoring environment-induced genes of major effects on longitudinal outcomes of a trait. This model is derived within the maximum likelihood framework, incorporated by mathematical aspects of growth and developmental processes. A typical structural model is implemented to approximate time-dependent covariance matrices for the longitudinal trait. This model allows for a number of biologically meaningful hypothesis tests regarding the effects of major genes on overall growth trajectories or particular stages of development. It can be used to test whether and how major genetic effects are expressed differently under altered environmental agents. In a well-designed case-control study, the model has been employed to detect cocaine-dependent genes that affect growth trajectories for head circumference during childhood. The detected gene triggers significant effects on growth curves in both cocaine-exposed (case) and unexposed groups (control), but with different extents. Significant genotype-environment interactions due to this so-called environment-sensitive gene are promising for further studies toward its genomic mapping using polymorphic molecular markers. Hou, W., Garvan, C.W., Littell, R.C., Behnke, M., Eyler, F.D., and Wu, R. A Framework to Monitor Environment-Induced Major Genes for Developmental Trajectories: Implication for a Prenatal Cocaine Exposure Study. Statistics in Medicine, 25, pp. 4020-4035, 2006.

Prevalence of Primary HIV-1 Drug Resistance among Recently Infected Adolescents

Dr. Craig Wilson and his colleagues in the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) examined the prevalence of primary human immunodeficiency type 1 (HIV-1) drug resistance among recently infected youth in the United States. Previous studies on HIV drug resistance have been conducted primarily with adult, male, Caucasian samples. Fifty-five HIV+ youth were recruited from 15 clinical sites across the U.S. and Puerto Rico. Participants included male (65%) and female (35%), African American (47%), Hispanic (24%), Caucasian (22%) youth with an average age of 19.3 years (SD 1.9 yrs). Risk factors for HIV acquisition reported among the youth included having sex under the influence of drugs or alcohol (36% male, 21% female) and exchanging sex for money or drugs (14% male and 5% female). Major mutations conferring HIV drug resistance were present in 10 participants (18%). Eight (15%) had nonnucleoside reverse-transcriptase inhibitor (NNRTI) mutations, with the majority (6) having the K103N mutation; 2 (4%) had nucleoside reverse-transcriptase inhibitor (NRTI) mutations; and 2 (4%) had protease inhibitor (PI) mutations. Phenotypic drug resistance was present in 12 (22%) subjects: 10 (18%) for NNRTIs, 2 (4%) for NRTIs, and 3 (5.5%) for PIs. There was a high prevalence of primary HIV-1 drug resistance, particularly to NNRTIs, in this group of recently infected youth. Vivani, R.M., Peralta, L., Aldrovandi, G., Kapogiannis, B.G., Mitchell, R., Spector, S.A. Wilson, C.M. and the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Prevalence of Primary HIV-1 Drug Resistance among Recently Infected Adolescents: A Multicenter Adolescent Medicine Trials Network for HIV/AIDS Interventions Study. Journal of Infectious Diseases, 194(11), pp. 1505-1509, 2006.

Clinical Neuroscience Research

Sex Differences in Amphetamine-Induced Displacement of [F-18] Fallypride in Striatal and Extrastriatal Regions: A PET Study

Dr. David Zald and colleagues at Vanderbilt University used PET to examine gender differences in d- amphetamine-induced dopamine release striatal and extrastriatal brain regions. Dopamine release was indexed by displacements of [F-18]. In addition, these displacements were correlated with cognition and sensation seeking. Method: Six women and seven men underwent positron emission tomography (PET) with [F-18] fallypride before and after an oral dose of d-amphetamine. Percent displacements were calculated using regions of interest and parametric images of dopamine 2 (D-2) receptor binding potential. The results demonstrated that female subjects had greater dopamine release than the male subjects in the right globus pallidus and right inferior frontal gyrus. Gender differences were observed in correlations of changes in cognition and sensation seeking with regional dopamine release. The finding that women exhibit greater dopamine release in response to amphetamine as well as gender differences in the relationship between regional dopamine release and sensation seeking and cognition may underlie gender differences in vulnerability for the abuse of psychostimulants. Schmidt, D., Baldwin, R., and Kessler, R. American Journal of Psychiatry, 163(9), pp. 1639-1641, 2006.

Sex Differences in Orbitofrontal Cortex (OFC) As Assessed by SPECT in Cocaine Dependent Subjects

Dr. Brian Adinoff and associates studied regional cerebral blood (rCBF) flow in treatment-seeking cocaine abusers after at least 11 days abstinence. This study reported relative rCBF between patients and healthy controls following saline infusion. The key finding was a decreased rCBF in the right and left lateral OFC in males but not female cocaine-dependent subjects in contrast with a decreased rCBF in the medial OFC in the female but not males. Additionally, it was found that increases in rCBF were found in diffuse regions in males with no significant increases in females. In other words, cerebral blood flow was disturbed to a greater extent in males and in different areas than in females. Post-hoc inferences based on other reported findings suggested sex differences in responsiveness or brain function during decision-making tasks or, possibly, assessment or suppression of reward saliency. In any case, it is concluded that these findings amplify the relevance of sex-specific differences in drug effects to the orbitofrontal cortex and the implications for clinical course and treatment. Adinoff, B., Williams, M.J., Best, S.E., Harris, T.S., Chandler, P., Devous, M.D. Gender Med, 3(3), pp. 206-222, 2006.

Individual Differences in the Functional Neuroanatomy of Inhibitory Control

Dr. Hugh Garavan of Trinity University performed combined the data of five event-related fMRI studies of response inhibition. Functional differences were observed between the sexes with greater activity in females in many of these cortical regions. Despite the relatively narrow age range (18-46), cortical activity, on the whole, tended to increase with age, echoing a pattern of functional recruitment often observed in the elderly. More absentminded subjects showed greater activity in fronto-parietal areas, while speed of Go trial responses produced a varied pattern of activation differences in more posterior and subcortical areas. Although response inhibition produces robust activation in a discrete network of brain regions, these results reveal that individual differences impact on the relative contribution made by the nodes of this network. These results provide a framework to interpret changes in brain activity during inhibitory control in substance abusers. Garavan, H., Hester, R., Murphy, K., Fassbender, C., and Kelly, C. Brain Research, 1105, pp. 130-142, 2006.

Epidemiology and Etiology Research

Modeling Initation and Progression of Substance Use and Abuse

The authors note that twin data can provide valuable insight into the relationship between the stages of phenomena such as substance abuse, but existing models for the relationship between initiation and progression have been difficult to extend because they are usually expressed in terms of explicit integrals. In this paper, the problem is overcome by regarding the analysis of twin data on initiation and progression as a special case of missing data, in which individuals who do not initiate are regarded as having missing data on progression measures. Using the general framework for the analysis of ordinal data with missing values available in Mx makes extensions that include other variables much easier. The effects of continuous covariates such as age on initiation and progression becomes simple. Also facilitated are the examination of initiation and progression in two or more substances, and transition models with two or more steps. This paper describes and then applies these methods to twin data from 1942 adult female twins in the Virginia Twin Registry; models studied the effects of cohort on liability to cannabis use and abuse, bivariate analysis of tobacco use and dependence and cannabis use and abuse, and the relationships between initiation of smoking, regular smoking and nicotine dependence. In addition to the methodologic advances, this article offers substantive findings including a strong relationship between initiation of cannabis and smoking, and a stronger relationship between smoking initiation and regular smoking than either with nicotine dependence. These new methods hold much promise for making use of existing data and advancing our understanding of drug use progression and phenotypes. Neale, M., Harvey, E., Maes, H., Sullivan, P., and Kendler, K. Extensions To The Modeling of Initiation And Progression: Applications To Substance Use and Abuse. Behav Genet, 36(4), pp. 507-524, 2006.

Childhood Trauma Among Incarcerated Women in Substance Abuse Treatment

Authors sought to describe the prevalence of childhood traumatic events among incarcerated women in substance abuse treatment and to assess the relation between cumulative childhood traumatic events and adult physical and mental health problems. The study was modeled after the Adverse Childhood Events study's findings. In-depth baseline interview data for 500 women participating in the Female Offender Treatment and Employment Program evaluation were analyzed. Hypotheses were supported, and regression results showed that the impact of childhood traumatic events on health outcomes is strong and cumulative (greater exposure to childhood traumatic events increased the likelihood of 12 of 18 health-related outcomes, ranging from a 15% increase in the odds of reporting fair/poor health to a 40% increase in the odds of mental health treatment in adulthood). These findings suggest a need for early prevention and intervention, and appropriate trauma treatment, within correctional treatment settings. Messina, N., and Grella, C. Childhood Trauma and Women's Health Outcomes in a California Prison Population. Am J Public Health, 96(10), pp. 1842-1848, 2006.

DAST Drug Abuse Screening of College Students

The present study assesses the prevalence of items from a modified version of the Drug Abuse Screening Test, Short Form (DAST-10) for substances other than alcohol among undergraduate students. More than 4,500 undergraduate students at a large Midwestern research university completed a web-based survey in 2005. Nearly 1 in every 10 undergraduate students experienced three or more DAST-10 items in the past 12 months. Although the prevalence of illicit drug use did not differ by gender, undergraduate men were significantly more likely than women to report DAST-10 items. Less than 6% of individuals who reported three or more drug DAST-10 items had ever used treatment services for substance use. As a brief screening instrument, the DAST-10 offers promise for detecting possible drug abuse among college students. Based on the prevalence of drug use, colleges and universities are encouraged to provide screening opportunities to identify and to provide services for students at high risk for drug abuse. McCabe, S., Boyd, C., Cranford, J., Morales, M., and Slayden, J. A Modified Version of The Drug Abuse Screening Test Among Undergraduate Students. J Subst Abuse Treat, 31(3), pp. 297-303, 2006.

Substance Abusing Mothers and Disruptions in Child Custody

Using an attachment framework, authors examined (1) whether substance-abusing mothers' perceptions of how they were parented were related to the severity of their substance abuse and psychological maladjustment and (2) whether these two factors mediated the association between mothers' perceptions of how they were parented and their childrens' placement out of home. There were 108 mothers of 248 children who completed interviews upon admission to a methadone maintenance program for women. A multilevel modeling approach was used to model effects of the hierarchically organized data (e.g., children nested within families). Findings are consistent with an attachment perspective on parenting suggesting that the internal psychological processes of a parent play a critical role in the continuity of parenting. When multiple risk domains associated with children's out-of-home placement were examined together within the same statistical model, maternal substance abuse severity and psychological maladjustment were the strongest predictors of children's out of home placement. Furthermore, mothers who perceived their own mothers as uncaring and intrusive were more likely to have lost custody of a minor child. There was also evidence that this effect was partially mediated by maternal substance abuse severity and psychological maladjustment. Suchman, N., McMahon, T., Zhang, H., Mayes, L., and Luthar, S. Substance-Abusing Mothers and Disruptions in Child Custody: An Attachment Perspective. J Subst Abuse Treat, 30(3), pp. 197-204, 2006.

Parent-Child Attachment, Parenting, Family Ecology and Persistent Conduct Problems

A small proportion of children exhibit extreme and persistent conduct problems through childhood. The present study employed the multiple-domain model of Greenberg and colleagues as the framework for person-oriented analyses examining whether parent-child attachment combines with parenting, family ecology, and child characteristics in particular configurations of risk that are linked to this problematic developmental pathway. Using prospective data from a community sample of adolescent mothers and their children (n=255), latent variable growth mixture modeling identified a normative trajectory with declining problem behaviors during the preschool period. Consistent with research on early-starter pathways, a distinct group of children featured a higher intercept and a positive slope, indicating an escalation in disruptive behaviors. Attachment security played a role in defining specific risk profiles associated with the probability of exhibiting this problem trajectory. Given particular patterns of risk exposure, secure attachment served a protective function. Avoidant, but not disorganized, attachment was associated with significantly higher likelihood of the disruptive problem trajectory. The results also indicated the general accumulation of risk was detrimental, but the particular configuration of risk made a difference. Overall, the findings suggest that early attachment operates in conjunction with personal and contextual risk to distinguish the development of later problem behaviors. Keller, T., Spieker, S., and Gilchrist, L. Patterns of Risk and Trajectories of Preschool Problem Behaviors: A Person-oriented Analysis of Attachment in Context. Dev Psychopathol, 17(2), pp. 349-384, 2005.

Early Risk Factors Predict Success in Transition to Adulthood Among Adolescent Mothers

This prospective longitudinal study is based on a diverse sample of adolescent mothers in the Northwest. Data have been collected from pregnancy through adulthood. Five risk factors were used (individually and in a cumulative risk index) to predict young mothers' life course pathways from age 17 through 23 years. A multinomial logistic regression indicated that, relative to the normative group, the problem-prone group had significantly greater odds of having a history of school problems, delinquency, and hard substance use. The psychologically vulnerable group had significantly greater odds of mental health problems, hard substance use, and marginally more delinquency. Importantly, the cumulative risk index (the sum of the five risk factors) predicted the patterns of transition into adulthood and demonstrated significant sensitivity and specificity in distinguishing those in the normative pathway from those in either the problem-prone or psychologically vulnerable pathway. Results suggest that specific risk factors assessed at pregnancy can differentiate among adolescent mothers who experience varying levels of success in their transition into early adulthood. The cumulative risk index demonstrates applied utility as a risk assessment tool capable of distinguishing among life-course pathways. Oxford, M., Gilchrist, L., Gillmore, M., and Lohr, M. Predicting Variation in the Life Course of Adolescent Mothers as they Enter Adulthood. J Adolesc Health, 39(1), pp. 20-26, 2006.

Heritability of DSM-IV Nicotine Withdrawal

The authors determined the heritability of the eight symptoms of DSM-IV symptoms of nicotine withdrawal in adult twins in the Australian Twin Registry. They examined both the genetic influences on nicotine withdrawal as well as the genetic factors specific to nicotine withdrawal, after controlling for factors responsible for risk of progression beyond experimentation with cigarettes and for quantity smoked (average number of cigarettes per day at peak lifetime use). Epidemiologic and genetic analyses were conducted using telephone diagnostic interview data from young adult Australian twins reporting any cigarette use (3026 women, 2553 men; mean age 30 years). Genetic analysis of the eight symptoms of DSM-IV nicotine withdrawal suggests heritability is intermediate for most symptoms (26-43%), and similar in men and women. The exceptions were depressed mood upon withdrawal, which had stronger additive genetic influences in men (53%) compared to women (29%), and decreased heart rate, which had low heritability (9%). Although prevalence rates were substantially lower for DSM-IV nicotine withdrawal syndrome (15.9%), which requires impairment, than for the DSM-IV nicotine dependence withdrawal criterion (43.6%), heritability was similar for both measures: as high as 47%. Genetic modeling of smoking more than 1 or 2 cigarettes lifetime ( ''progression ''), quantity smoked and nicotine withdrawal found significant genetic overlap across all three components of nicotine use/dependence (genetic correlations = 0.53-0.76). Controlling for factors associated with risk of cigarette smoking beyond experimentation and quantity smoked, evidence for genetic influences specific to nicotine withdrawal (up to 23% of total variance) remained. Their results suggest that at least some individuals become ''hooked '' or progress in the smoking habit, in part, because of a vulnerability to nicotine withdrawal. Pergadia, M., Heath, A., Martin, N., and Madden, P. Genetic Analyses of DSM-IV Nicotine Withdrawal in Adult Twins. Psychol Med, 36(7), pp. 963-972, 2006.

Examination of Transitions from Initiation through Dependence in Adolescent Substance Involvement

The present study examined Lengths of Times for important transitions in substance involvement from Initiation to Regular use (LOTIR), first Problem from drug use (LOTIP), and first experience of Dependence (LOTID) for alcohol, tobacco, cannabis, cocaine, and opiates. Data were from a longitudinal study of 590 children (22.2% female) at different levels of risk for substance use disorders based on their fathers' substance use-related diagnoses. Participants' substance involvement was assessed at four ages: 10-12, and follow-ups at two, five, and eight years later. Results suggested that faster transitions were more due to drug-related constructs (including possible social milieus of different drug classes and interactions between drug class and neurophysiology) than intrapersonal constructs. The shortest transition times (and greatest addictive liabilities) were for opiates followed respectively by cocaine, cannabis, tobacco, and alcohol. Females had shorter transition times, though gender differences were small. Some evidence was found for a familial influence on transition times above what was accounted for by differences between substances. Ridenour, T., Lanza, S., Donny, E., and Clark, D. Different Lengths of Times for Progressions in Adolescent Substance Involvement. Addict Behav, 31(6), pp. 962-983, 2006.

HTLV-2 Infection in Injection Drug Users in King County, Washington

Human T-cell lymphotropic virus type 2 (HTLV-2) is endemic in injection drug users (IDU), and Native American populations in the Americas. Transmission is associated with high-risk injection and sexual practices. A cohort of 2561 IDU in King County, Washington completed 2 study visits over 1 year. HTLV-2 infection was detected in 190 (7.4%) of 2,561 IDU, and 13 (7.8 cases per 1000 person-years) incident infections occurred during the study. Prevalent infection was associated with female gender, non-white race, longer duration as IDU, having a tattoo, combined injection of heroin and cocaine, and with serologic evidence of hepatitis B and C infection. Seroconversion was more common in women, and was associated with African American race, heterosexual identity and longer duration as IDU. Increased risk of HTLV-2 infection was associated with non-white race, and injection drug of choice, suggesting injection networks may play an important role in transmission of HTLV-2. The high correlation of HTLV-2 infection with HCV infection suggests the major route of transmission in IDU is via injection practices. This study points to the need for studies on the clinical manifestations of HTLV-2 infection, as well as the clinical and virological manifestations of HTLV-2/HCV coinfection. Zunt, J., Tapia, K., Thiede, H., Lee, R., and Hagan, H. HTLV-2 Infection in Injection Drug Users in King County, Washington. Scand J Infect Dis, 38(8), pp. 654-663, 2006.

Gender Differences in Sexual Behaviors, Sexual Partnerships, and HIV among Drug Users in New York City

Researchers sought to compare sexual behaviors/partnerships and sexual risk correlates associated with HIV by gender among sexually active, street-recruited drug users in New York City. The study sample included 818 men and women (average age 28 vs 30 years, p<.01). Men were more likely to be Latino (63% vs 41%, p<.01), recently homeless (61% vs 50%, p<.01) or previously incarcerated (90% vs 79%, p<.01) compared to women. More men than women reported being an IDU (29% vs 20%, p<.01). Among non-IDUs, men were less likely to report crack use, more likely to report marijuana use, and use of hallucinogens. Men reported higher risk sexual behaviors, yet fewer high-risk sexual partners than women. After adjustment, HIV seropositive men were more likely than seronegatives to be older, MSM, use condoms, and have an HIV-infected partner. HIV seropositive women were more likely to be older, have an HIV-infected partner, and not use non-injected heroin. IDU was not associated with HIV. These findings highlight the need to determine how gender-specific sexual behaviors/partnerships among drug users affect HIV acquisition. Absalon, J., Fuller, C.M., Ompad, D.C., Blaney, S., Koblin, B., Galea, S., and Vlahov, D. Gender Differences in Sexual Behaviors, Sexual Partnerships, and HIV Among Drug Users in New York City. AIDS Behav, 10(6), pp. 707-715, 2006.

Neglect and Later Externalizing Problems in Children of Adolescent Mothers

The present study examines the role of neglect potential in adolescent mother-child dyads, both in terms of antecedents and its consequences for children's development. Participants were 100 adolescent mother-child dyads who were part of a larger, longitudinal study. Data were collected from the third trimester of pregnancy until the children's 10th year. Histories of maternal neglect and the quality of mother-child interactions during early childhood were found to predict neglect potential during middle childhood. Mothers with high neglect potential had children who exhibited more externalizing problems and fewer adaptive behaviors, with neglect potential mediating the effects of both early abuse potential and the quality of parenting on children's later externalizing behaviors. Results suggest that neglect potential may be a mechanism through which early potential for child abuse and insensitive maternal interactions affect later externalizing problems in children of adolescent mothers. Lounds, J., Borkowski, J., and Whitman, T. The Potential for Child Neglect: The Case of Adolescent Mothers and their Children. Child Maltreat, 11(3), pp. 281-294, 2006.

Prevention Research

Recommendations for the Prevention of HIV Transmission in Hispanic Adolescents

This article reviews the state of the science in HIV prevention for Hispanic adolescents. Literature is reviewed in three broad areas: (1) the prevalence rates of drug and alcohol misuse, sexual practices, and HIV infection; (2) risk and protective factors for drug and alcohol misuse and unprotected sex (in general and specifically for Hispanics); and (3) the state of HIV prevention intervention development and evaluation targeting Hispanic youth. Little basic and intervention research has been conducted on HIV prevention in Hispanic adolescents, with even less attention given to Hispanic young men who have sex with men (YMSM). There are a number of areas in which further knowledge development and scientific advancement are needed. The seven areas identified in this review were (a) the need for analyses of nationwide epidemiological data examining risk and protective factors for substance use and unsafe sexual behavior for heterosexual and homosexual youth; (b) explaining variations in drug/alcohol use, unsafe sexual behavior, and HIV infection among Hispanic subgroups; (c) need for adaptive preventive interventions for Hispanic subgroups with varying risk and protection profiles; (d) incorporation of ethnic, cultural, and sexual identity into prevention programs for Hispanic adolescents; (e) examination of the role of gender in preventive interventions for Hispanic adolescents; (f) research on the effects of psychiatric comorbidity on drug/alcohol use and unsafe sex and on the efficacy of prevention programs; and (g) increased focus on intravenous drug use as a mode of HIV infection among Hispanics, particularly Puerto Ricans. Research addressing these research needs has the potential to facilitate progress toward achieving the two primary objectives of Healthy People 2010--improving the quality of life for all Americans and reducing health disparities between and among segments of the U.S. population. Prado, G., Schwartz, S.J., Pattatucci-Aragon, A., Clatts, M., Pantin, H., Fernandez, M., Lopez, B., Briones, E., Amarof, H., and Szapocznik, J. The Prevention of HIV Transmission in Hispanic Adolescents. Drug Alcohol Depend, 84S pp. S43-S53, 2006.

Predictors of HIV-Related Stigma among Young People Living with HIV

Enacted and perceived HIV stigma was examined among 147 substance-using young people living with HIV (YPLH) in Los Angeles, San Francisco, and New York City. Almost all YPLH (89%) reported perceived stigma, 31% reported enacted experiences in the past 3 months; and 64% reported experiences during their lifetime. The HIV stigma questions were characterized by factors of avoidance, social rejection, abuse, and shame. In multivariate models, enacted stigma was associated with gay or bisexual identity, symptomatic HIV or AIDS, and bartering sex. Perceived stigma was associated with female gender, symptomatic HIV or AIDS, bartering sex, lower injection drug use, and fewer friends and family knowing serostatus. Gay or bisexual YPLH who were also HIV symptomatic or AIDS diagnosed experienced more HIV stigma than their heterosexual peers. Swendeman, D., Rotheram-Borus, M., Comulada, S., Weiss, R., and Ramos, M. Predictors of HIV-Related Stigma Among Young People Living with HIV. Health Psychol, 25(4), pp. 501-509, 2006.

Gender Differences in Associations Between Depressive Symptoms and Patterns of Substance Use and Risky Sexual Behavior Among a Nationally Representative Sample of U.S. Adolescents

This study uses a cluster analysis of adolescents, based on their substance use and sexual risk behaviors, to 1) examine associations between risk behavior patterns and depressive symptoms, stratified by gender, and 2) examine gender differences in risk for depression. Data are from a nationally representative survey of over 20,000 U.S. adolescents. Logistic regression was used to examine the associations between 16 risk behavior patterns and current depressive symptoms by gender. Compared to abstention, involvement in common adolescent risk behaviors (drinking, smoking, and sexual intercourse) was associated with increased odds of depressive symptoms in both sexes. However, sex differences in depressive symptoms vary by risk behavior pattern. There were no differences in odds for depressive symptoms between abstaining male and female adolescents (OR = 1.07, 95% CI 0.70-1.62). There were also few sex differences in odds of depressive symptoms within the highest-risk behavior profiles. Among adolescents showing light and moderate risk behavior patterns, females experienced significantly more depressive symptoms than males. It was concluded that adolescents who engage in risk behaviors are at increased risk for depressive symptoms. Girls engaging in low and moderate substance use and sexual activity experience more depressive symptoms than boys with similar behavior. Screening for depression is indicated for female adolescents engaging in even experimental risk behaviors. Waller, M., Hallfors, D., Halpern, C., Iritani, B., Ford, C., and Guo, G. Gender Differences in Associations Between Depressive Symptoms and Patterns of Substance use and Risky Sexual Behavior Among A Nationally Representative Sample of U.S. Adolescents. Arch Womens Ment Health, 9(3), pp. 139-150, 2006.

Genetic Contribution to Suicidal Behaviors and Associated Risk Factors Among Adolescents in the U.S.

This paper examines genetic contribution to suicidal behaviors and other risk factors associated with suicidal behavior among adolescents in the U.S. Using adolescent twin data in the National Longitudinal Study of Adolescent Health (N=1448), authors compared concordance in suicidal ideation and attempt among monozygotic (MZ) and dizygotic (DZ) twins. Heritability of risk factors for suicidal behaviors also was examined using Pearson correlation and mixed-model analyses. A trend of higher concordance in suicidal ideation and attempt was found among MZ than DZ twins but the difference was not statistically significant by the stringent test of bootstrapping analysis. Evidence of heritability was found for several suicide risk factors. The percentage of variance explained by heritability was larger among female twins for depression, aggression, and quantity of cigarettes smoked in comparison to heritability estimates for male twins. However, estimated heritability was larger among male than female twins for alcohol use and binge drinking. Heritability influence was negligible among both sexes for other drug use. Risk factors for suicidal behaviors among adolescents may be heritable. Gender differences found in the heritability of some suicide risk factors suggest these genetic contributions are gender specific. Future research examining potential interactions between expression of genetic influence and particular environmental contexts may enhance prevention and intervention efforts. Cho, H., Guo, G., Iritani, B.J., and Hallfors, D.D. Genetic Contribution to Suicidal Behaviors and Associated Risk Factors Among Adolescents in the U.S. Prev Sci, 7(3), pp. 303-311, 2006.

In School Alcohol and Marijuana Use Among High School Students

The problem of adolescent substance use has been examined extensively. Beyond simple prevalence estimates, however, little research has been conducted on substance use in the school context. The present investigation was an in-depth study of students' attitudes and behaviors regarding alcohol and marijuana use during the school day. Based on a representative sample of 1123 high school students, 48% male, in grades 9-12 in western New York state, this study assessed the frequency of alcohol and marijuana use at school among demographic subgroups, the accessibility of drugs in school, and students' perceived consequences of being caught using drugs in school. Twelve percent of the sample reported using alcohol during school hours in the past 6 months while 16% reported using marijuana at school. Among students who used alcohol outside of school, 18% also used alcohol at school. For marijuana users, 47% used marijuana at school. There was evidence of some demographic differences in school drug use. Specifically, male and Hispanic students had slightly higher levels of drug use at school compared to female and white students, respectively, and in school drug use was more prevalent among older students. In terms of accessibility, students reported that alcohol and marijuana were easily obtained and used on school grounds. Many students (40%) were not aware of the specific actions taken in their schools to punish drug use. The need for additional research on school-related drug use is emphasized. Finn, K. V. Patterns of Alcohol and Marijuana Use at School. Journal of Research on Adolescence, 16(1), pp. 69-77, 2006.

Time Varying Family and Peer Influences on Adolescent Daily Mood

The time-varying influences of peer and family support on adolescent daily mood were explored among 268 youth transitioning from middle school to high school (8th to 9th grade) as compared to 240 youth transitioning from 10th to 11th grade. The participants were part of a larger study examining the natural history of smoking. Real-time ecological momentary assessments measures of daily positive and negative affect were collected via palmtop computers at baseline, 6 months, and 12 months. Participants rated 12 mood adjectives in response to 5 to 7 random prompts per day for 7 consecutive days. Perceived peer and family support were assessed via self-report. Mixed-effects regression analyses revealed significant grade by time by peer support interactions for positive and negative mood, with the younger cohort showing greater increases in the relation between peer support and affect over time than the older cohort. Family support did not interact with cohort or time. The authors summarize that peer influences may increase as adolescents develop, thus developmental influences should be included in examinations of dynamic relations between peers and adolescent mood. Also, these results may help elucidate transitions that may be optimal times for preventive interventions targeting emotional well-being of adolescents, specifically transition to high school. This transition point also coincides with a growth in mood disorders in adolescents, in particular girls. Girls were found to exhibit higher levels of negative moods at lower levels of peer support, relative to boys. The authors call for future research that captures the bidirectional nature of support--mood relations across adolescence. Weinstein, S., Mermelstein, R., Hedeker, D., Hankin, B., and Flay, B. The Time-varying Influences of Peer and Family Support on Adolescent Daily Positive and Negative Affect. J Clin Child Adolesc Psychol, 35(3), pp. 420-430, 2006.

Trajectories of Depression in Male and Female Children of Depressed Mothers

This study reports on relationships among gender, maternal depressed mood, and children's trajectories of depressive phenomena across middle childhood and early adolescence. It tested the hypothesis that, compared to boys, girls become increasingly vulnerable to maternal depression as they enter adolescence. The study sample consisted of 834 families from 10 Pacific Northwest schools that participated in the Raising Healthy Children project, a longitudinal study of the etiology of problem behaviors and test of a multicomponent, multiyear intervention targeting risk and protective factors within key child socializing domains of family, school, peer, group, and individual. Maternal depressed mood and children's depressive phenomena were assessed annually during an 8-year period that spanned Grade 3 through Grade 10 for the children. Mean scores for girls' depressive phenomena increased relative to those for boys as children matured. Maternal depressed mood was significantly and positively associated with children's level of depressive phenomena. An interaction effect of gender and maternal depressed mood on acceleration in children's depressive phenomena indicated that girls' trajectories of depressive phenomena were sustained in the presence of maternal depression while those of boys declined in the presence of maternal depression. Implications for the prevention and treatment of adolescent depression are discussed. Cortes, R.C., Fleming, C.B., Catalano, R.F., and Brown, E.C. Gender Differences in the Association Between Maternal Depressed Mood and Child Depressive Phenomena from Grade 3 Through Grade 10. J Youth Adolescence, 35, pp. 815-826, 2006.

Research on Behavioral & Combined Treatments For Drug Abuse

Smoking Status in the Initial Weeks of Quitting as a Predictor of Smoking-Cessation Outcomes in Pregnant Women

In the general population of smokers, seminal findings of Kenford et al. (1994) suggest a robust relationship between early smoking during a quit attempt and later smoking. The findings indicate that any smoking during the initial 2 weeks of a quit attempt predicts poor longer-term outcomes. However, it is not known whether this same predictor rule applies under conditions where patients are quitting related to a medical condition for which smoking is contraindicated, like pregnancy. Investigators at the University of Vermont conducted this study to examine the association between smoking status during the initial 2 weeks of attempting to quit and smoking status at an end-of-pregnancy assessment among women enrolled in smoking cessation studies. Data were obtained from 129 women participating in clinical trials on smoking-cessation examining the efficacy of voucher-based incentives delivered contingent on biochemically-verified abstinence or a control conditions wherein incentives were given independent of smoking status. Smoking status was assessed in weeks 1 and 2 of the cessation effort and again at an end-of-pregnancy. The findings show that women who smoked in the first 2 weeks of quitting had a greater than 80% chance of being classified as smokers at an end-of-pregnancy assessment and that relationship held across the two treatment conditions. These finding indicate that the predictor rule for the general population of smokers applies to pregnant women who are smokers. Thus, it is recommended that clinicians monitor smoking status during the initial weeks of a quit attempt and provide a change in treatment when smoking is detected. Higgins, S.T., Heil, S.H., Dumeer, A.M., Thomas, C.S., Solomon, L.J., and Bernstein, I.M. Drug and Alcohol Dependence, 85, pp. 138-141, 2006.

Weight Concerns Affect Motivation to Remain Abstinent From Smoking Postpartum

This study assessed motivation for postpartum abstinence among pregnant women who had quit smoking and examined the relationship of weight concerns and mood to abstinence motivation. Participants (N=119) completed assessments of smoking, weight concerns, depressive symptoms, and perceived stress. Sixty-five percent were highly motivated to remain abstinent postpartum. Women who were and were not motivated were similar in age, race, and nicotine dependence. Motivated women reported more stress, greater self-efficacy for weight management, less hunger and less smoking for weight control than less motivated women. After controlling for intention to breast-feed, nicotine dependence, years of smoking, partner smoking, and race, self-efficacy for weight control was related to motivation to maintain postpartum abstinence. This study suggests that weight concerns are linked with motivation for postpartum smoking abstinence, and interventions designed to prevent postpartum smoking may need to target eating, weight and shape concerns. Levine, M.D., Marcus, M.D., Kalarchian, M.A., Weissfeld, L., and Qin, L. Annals of Behavioral Medicine, 32, pp. 147-153, 2006.

Relationship of DSM-IV-Based Depressive Disorders to Smoking Cessation and Smoking Reduction in Pregnant Smokers

Investigators at the University of Texas M.D. Anderson Cancer Center in Houston conducted this study to examine psychiatric disorders as predictors of smoking outcomes among pregnant smokers. Eighty-one pregnant women participating in a low-intensity smoking cessation trial were investigated. Thirty-two percent of the sample met criteria for current dysthymia, major depressive disorder in partial remission, or minor depression. The findings showed that no significant reduction in smoking among women with or without current depressive disorders was shown. Unexpectedly, compared to women without depressive disorders, women with dysthymia significantly increased the mean number of cigarettes smoked (from 8 to 23 cigarettes per day during the 2 to 30 days post-targeted quit date period) and were smoking significantly more at 30 days. A main effect approaching significance suggested that women with current depressive disorders were less likely to be abstinent than women without current depressive disorders. The current results add to previous findings indicating a correlation between depressive symptoms and continued smoking in pregnant women. These findings indicate that additional research is needed in evaluating the impact of depression on smoking outcomes in pregnant women and that investigation of mood-focused smoking cessation interventions may be warranted. Blalock, J.A., Robinson, J.D., Wetter, D.W., and Cinciripini, P.M. The American Journal on Addictions, 15, pp. 268-277, 2006.

Research On Pharmacotherapies For Drug Abuse

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

In non-human animals, opioid antagonists block the reinforcing and discriminative-stimulus effects of Delta(9)-tetrahydrocannabinol (THC), while in human marijuana smokers, naltrexone (50 mg) enhances the reinforcing and subjective effects of THC. The objective of this study was to test a lower, more opioid-selective dose of naltrexone (12 mg) in combination with THC. The influence of marijuana-use history and sex was also investigated. Naltrexone (0, 12 mg) was administered 30 min before oral THC (0-40 mg) or methadone (0-10 mg) capsules, and subjective effects, task performance, pupillary diameter, and cardiovascular parameters were assessed in marijuana smoking (Study 1; n=22) and in nonmarijuana smoking (Study 2; n=21) men and women. The results show that in marijuana smokers, low-dose naltrexone blunted the intoxicating effects of a low THC dose (20 mg), while increasing ratings of anxiety at a higher THC dose (40 mg). In nonmarijuana smokers, low-dose naltrexone shifted THC's effects in the opposite direction, enhancing the intoxicating effects of a low THC dose (2.5 mg) and decreasing anxiety ratings following a high dose of THC (10 mg). There were no sex differences in these interactions, although among nonmarijuana smokers, men were more sensitive to the effects of THC alone than women. To conclude, a low, opioid-selective dose of naltrexone blunted THC intoxication in marijuana smokers, while in nonmarijuana smokers, naltrexone enhanced THC intoxication. These data demonstrate that the interaction between opioid antagonists and cannabinoid agonists varies as a function of marijuana use history. Haney, M. Neuropsychopharmacology, advance online publication, 8 November 2006.

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

Micronutrient Levels and HIV Disease Status in HIV-Infected Patients on Highly Active Antiretroviral Therapy in the Nutrition for Healthy Living Cohort

Low serum micronutrient levels were common before widespread use of highly active antiretroviral therapy (HAART) and were associated with adverse outcomes. Few data are available on micronutrient levels in subjects taking HAART. This cross-sectional study was conducted to determine the prevalence of low serum retinol, alpha-tocopherol, zinc, and selenium in HIV-infected subjects taking HAART and to assess the association of micronutrient levels with HIV disease status. Participants were HIV-infected subjects on HAART in an ongoing Nutrition for Healthy Living (NFHL) study at Tufts. Retinol, alpha-tocopherol, zinc, and selenium were determined in frozen serum samples from 171 men and 117 women. Low serum levels were defined as retinol <30 mug/dL, selenium <85 mug/L, alpha-tocopherol <500 mug/dL, and zinc <670 mug/L. Association of micronutrient quartiles with CD4 cell count, CD4 count <200 cells/mm, HIV viral load (VL), and undetectable VL was assessed using adjusted multivariate regression. Results indicated that 5% of men and 14% of women had low retinol, 8% of men and 3% of women had low selenium, and 7% of men and no women had low alpha-tocopherol. Forty percent of men and 36% of women had low zinc, however. Subjects in the upper quartiles of zinc had lower log VL levels than those in the lowest quartile (significant for women). Subjects in the upper quartiles of selenium also tended to have lower VL levels compared with those in the lowest quartile. Surprisingly, women in the upper quartiles of retinol had higher log VLs than those in the lowest quartile. There was no significant association of any micronutrient with CD4 cell count or likelihood of CD4 count <200 cells/mm. The level of CD4 cell count influenced the association of retinol with log VL in men, however. In men with CD4 counts >350 cells/mm, those with higher retinol had higher log VLs compared with the lowest quartile, whereas in men with CD4 counts <350, those with higher retinol levels had lower log VLs compared with the lowest quartile. The authors concluded that low retinol, alpha-tocopherol, and selenium are uncommon in HIV-infected subjects on HAART. Zinc deficiency remains common, however. Jones, C.Y., Tang, A.M., Forrester, J.E., Huang, J., Hendricks, K.M., Knox, T.A., Spiegelman, D., Semba, R.D., and Woods, M.N. J Acquir Immune Defic Syndr. 43(4), pp. 475-482, December 1, 2006.

Increased Serum Lipids are Associated with Higher CD4 Lymphocyte Count in HIV-Infected Women

Highly active antiretroviral therapy (HAART) has been associated with dyslipidaemia; however, the roles of immune status and non-HIV-disease risk factors remain unclear. A cross-sectional analysis of fasting lipids was carried out for 231 women, of whom 132 were HIV-infected and 99 were uninfected. The concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoprotein B (apo B) were measured. CD4 lymphocyte count, hepatitis C status, demographics, diet, and anthropometrics were also assessed. A total of 132 women were HIV-infected [30 were antiretroviral-naive, 68 were on protease inhibitors (PIs), and 34 were on non-PI HAART]. HIV infection was associated with higher triglycerides, lower HDL-C, and, among obese women, higher total cholesterol and LDL-C. Non-PI and PI HAART were each independently associated with higher total cholesterol, LDL-C, and apo B, compared with being ART-naive. Among HIV-infected women, after adjustment for HAART use, women with a CD4 lymphocyte count > or =500 cells/microL had total cholesterol 41.8 mg/dL (P = 0.002) and LDL-C 28.8 mg/dL (P = 0.01) higher, on average, than women with a CD4 count <200 cells/microL. Women with a CD4 count of 200-499 cells/microL had total cholesterol 26.31 mg/dL higher, on average, than those with a CD4 count <200 cells/microL (P = 0.04), although differences in LDL-C did not reach significance (15.51 mg/dL; P = 0.12). A higher CD4 count was also associated with higher apo B (P < 0.001). Active hepatitis C infection was associated with lower total cholesterol, LDL-C, triglycerides, and apo B. The authors concluded that higher CD4 ymphocyte counts were associated with higher lipid levels, suggesting that immune competence may independently affect the dyslipidaemia seen in the HAART era. In addition, it is important that hepatitis C status be assessed in studies of dyslipidaemia in the HIV-infected population. Floris-Moore, M., Howard, A.A., Lo, Y., Arnsten, J.H., Santoro, N., and Schoenbaum, E.E. Increased Serum Lipids are Associated with Higher CD4 Lymphocyte Count in HIV-infected Women. HIV Med. 7(7), pp. 421-430, 2006.

Services Research

Welfare Reform, Employment, and Alcohol and Drug Use among Low-Income Women

In 1996 welfare reform legislation transformed income assistance for needy families by imposing work requirements, time-limited benefits, and explicit provisions allowing states to sanction recipients who fail to meet program requirements. Though they represent a minority of the welfare population, women with substance use disorders (SUDs) experience multiple, and more severe, employment barriers than other Temporary Assistance to Needy Families (TANF) recipients. This review of welfare reform, substance abuse, and employment documents the evidence to date regarding the employment patterns of women with SUDs before and after welfare reform, and proposes several topics for further research. Based on higher rates of unemployment, less work experience, and lower earnings when working, women with SUDs have worse employment records than other TANF recipients. Despite elevated employment barriers, women with SUDs left TANF after 1996 as fast as, or faster than, other women. Since the 1996 welfare reform, women with SUDs have increased their employment and earnings, but by less than similar women without SUDs. Future research should describe how specific state welfare policies relate to employment of low-income women with SUDs, how the well-being of these women and their children changes with employment, and how welfare and employment interact to affect access to health insurance among this population. Meara, E. Welfare Reform, Employment, and Drug and Alcohol Use Among Low-Income Women. Harv Rev Psychiatry, 14(4), pp. 223-232, 2006.

Mental Health Problems and Criminal Justice Involvement Among Female Street-Based Sex Workers

This paper examines the connections of mental health, victimization, and criminal justice involvement among a sample of 343 street-based female sex workers in Miami, Florida. Using targeted sampling strategies, drug-using sex workers were recruited into an HIV prevention intervention and research program. Data were collected by trained interviewers using standardized questionnaires that focused on drug use, childhood abuse, recent victimization, mental health, and criminal justice involvement. More than half of the participants reported histories of physical (54.5%) or sexual (54.2%) abuse as children, and more than one-third reported violent victimization in the past year. Nearly 32% were classified with moderate or severe anxiety symptoms, 46.2% had symptoms of moderate or severe depression, and 64.6% had symptoms of acute traumatic stress. In addition, 81.9% had prior arrest histories. The intersection of these factors suggests that police and law enforcement agencies must play a substantial role in managing an offender population with impaired mental health functioning. The policy implications of these findings are discussed. Surratt, H. Mental Health Problems and Criminal Justice Involvement Among Female Street-Based Sex Workers. Law Enforcement Executive Forum, 6, pp. 121-134, 2006.

Blood Pressure Levels May Vary in Population because of Genetic, Ethnic and Body Size Factors

Blood pressure data of 2278 Indian boys and 2930 Indian girls in the age group of 3-18 years were analyzed to study the distribution pattern of systolic blood pressure and diastolic blood pressure and to develop reference values to define hypertension. Blood pressure was measured using standardized techniques in all. The first and fifth phases of Korotkoff sounds were taken as indicative of systolic blood pressure and diastolic blood pressure respectively. Height percentiles were computed for each one-year age group. According to percentiles of height 50th, 90th, 95th and 99th percentiles of systolic blood pressure and diastolic blood pressure were estimated for every one-year age. Results indicated that the blood pressure (both systolic and diastolic) tends to increase with age. The stepwise regression analysis revealed that the age and height but not gender, are important determinants of blood pressure. Age and height specific, 50th, 90th and 95th and 99th percentiles of systolic and diastolic blood pressure were derived and are presented in tabular form. Authors concluded that the blood pressure of children and adolescents can be evaluated using the reference table according to body size. The table provided helps to classify blood pressure as 'normal' or 'pre hypertension' and to define different stages of 'hypertension'. Pushpa, K., KumanPrasanna, K.M., Nagaraj, D., and Thennarasu, K. Blood Pressure Reference Tables for Children and Adolescents of Karnataka. Indian Pediatrics, 43 (June), pp. 491-501, 2006.

International Research

NIDA-Supported Researchers Identify New Injection Practice Among Tanzanian Women

Dr. Mark Williams, University of Texas at Houston and colleagues (Dr. Sheryl McCurdy, University of Texas at Houston; Dr. Gad P. Kilonzo and Dr. M. T. Lesheaberi, University of Muhumbili, Dar Es Salaam, Tanzania) presented their recent epidemiological findings on Tanzanian IDUs and HIV at a conference December 1, 2006 - World AIDS Day - at the University of Muhumbili. The research was supported by a NIDA International Program collaborative research supplement (NOT-02-003) and a subsequent R21 (DA19394). The binational research team reports that heroin injection and risky injection practices are continuing to increase in Dar Es Salaam and spreading outward to neighboring communities. Using modified snowball sampling and outreach, the team recruited 537 heroin IDUs in Dar Es Salaam (318 male, 219 female); 42% of whom tested HIV positive (27% among males, 64% among females). The team observed a new and unusual practice among women IDUs - termed "flashblood" - where IDUs share blood-filled syringes after one has injected heroin. The research has been published in AIDS Care, June 2005; 17(Supplement 1): S65-S76; BMJ 2005; 331: 778-781; Drug and Alcohol Dependence 82 Supplement 1(2006): S23-S27; and AIDS Behavior DOI 10.1007/s10461-006-9102-x. Participants at the conference included representatives from the University of Muhumbili medical faculty; the Tanzanian Ministry of Labor, Employment, and Youth; the Tanzanian Ministry of Health; other Tanzanian officials; and invited media. The binational research team also met with Tanzanian Deputy Minister of Labor, Employment, and Youth Dr. Emmanuel Nchimbi on October 18, 2006.