Director's Report to Council - Research Findings Excerpts

May, 2005

Basic Neurosciences Research

Morphine and Stress Response in Adult Female Offspring

It has been shown that adult female rats react to stressors more intensely than adult male rats and that opioids have an inhibitory effect on the stress response. Furthermore, the response of the hypothalamic pituitary adrenal (HPA) axis to stress is known to be gender specific. In a recent paper, Dr. Ilona Vathy and her associates report that prenatal morphine exposure alters the HPA axis-regulated stress response and the sensitivity of negative feedback that are affected by the fluctuation of ovarian hormones. This study examined the effects of prenatal morphine exposure on ACTH and CORT plasma concentrations before and after restraint stress in proestrus (high estrogen level) and diestrus (low estrogen level) female rats. Prenatal morphine exposure differentially altered the ACTH and CORT responses to stress and the sensitivity of negative feedback of glucocorticoid (GR) probably by affecting the characteristics of GR receptors, and thereby altering the HP axis-controlled stress response. Slamberova, R., Rimanoczy, A., Riley, M.A., and Vathy, I. Hypothalamo-Pituitary-Adrenal Axis-Regulated Stress Response and Negative Feedback Sensitivity is Altered by Prenatal Morphine Exposure in Adult Female Rats. Neuroendocrinology, 80, pp. 192-200, 2004.

Basic Behavioral Research

Analogous Changes in Striatal Gene Expression Follow Sexual Experience or Exposure to Drugs of Abuse

It has been suggested that drugs of abuse "hijack" neural systems that evolved to support natural motivated behaviors. Thus, an understanding of the neural control of natural behaviors can help us understand the specific pathology of drug abuse. Motivated behaviors that exhibit properties such as sensitization - an increase in behavioral response with repeated exposures to motivating stimuli - are of particular interest in this regard. Repeated sexual experiences, like repeated drug use, produce long-term changes including sensitization of dopamine release in the nucleus accumbens and dorsal striatum. Previously, Drs. Katherine Bradley and Robert Meisel showed that amphetamine-stimulated locomotor activity was sensitized by previous sexual experience in female Syrian hamsters. They are now collaborating with Dr. Paul Mermelstein to investigate the molecular mechanisms underlying neuroadaptations produced by sexual experience. In this study, they used DNA microarray techniques to identify genes differentially expressed within the nucleus accumbens and dorsal striatum between sexually experienced and sexually naive female hamsters. For these experiments, female hamsters were ovariectomized and hormonally primed. Half of them were then exposed to a stimulus male once a week for six weeks, while the other half remained naive. On week seven, the two groups were subdivided, with one half of each exposed to a stimulus male. In comparison with sexually naive animals, sexually experienced hamsters that received a stimulus male on week seven exhibited an increase in a large number of genes. Conversely, sexually experienced females that did not receive a stimulus male on week seven exhibited a reduction in the expression of many genes compared to naive animals. The data for the nucleus accumbens and dorsal striatum were similar in terms of directional changes and the categories of genes regulated by the experimental conditions. However, the specific genes exhibiting changes in expression differed between these two brain areas. The investigators also observed that many of the gene classes and specific genes regulated by sexual experience overlapped with those previously reported to be regulated by chronic administration of drugs of abuse, and that many of these genes are involved in forms of neuronal plasticity such as changes in excitability or dendritic growth. These experiments are among the first to profile genes regulated by sexual behaviors in brain areas (the mesolimbic and nigrostriatal dopamine pathways) involved in long term neuroadaptive changes underlying addiction. And, importantly, studies like this may help us understand why, unlike drug use, natural motivated behaviors do not, in general, progress to an uncontrolled, compulsive state. Bradley, K.C., Boulware, M.B., Jiang, H., Doerge, R.W., Meisel, R.L. and Mermelstein, P.M. Sexual Experience Generates Distinct Patterns of Gene Expression Within the Nucleus Accumbens and Dorsal Striatum of Female Syrian Hamsters. Genes, Brain and Behavior, 4, pp. 31-44, 2005.

Early Life Stress Enhances Relapse in an Animal Model

Observations from clinical studies on cocaine abusers show that both psychological and physical stress elicit drug craving. Moreover, risk for drug use has been associated with adverse life events and chronic stress. Thus, stress may contribute to the vulnerability for drug abuse behavior and to the propensity to maintain this behavior or to relapse. A vast preclinical literature has modeled deleterious effects of physical and social stressors on acquisition, maintenance and reinstatement of drug seeking. Animal models of early life stress employ neonatal isolation procedures that involve prolonged separation from the mother for one hour per day over post-natal days 2 through 12. Neonatal stress has previously been shown to enhance vulnerability for acquisition of cocaine self-administration, but subsequent effects on relapse after self-administration has been extinguished are unknown. In the present study, the investigators compared male and female rats that were subjected to neonatal isolation with controls that were only handled and returned to the litter. All animals were trained for cocaine i.v. self-administration at 90 days of age, under a fixed ratio 1 schedule of reinforcement. They were then subjected to seven consecutive sessions of a 24-hr discrete trial procedure that provides extended access to drug and has been used to develop excessive, uncontrollable intake. This was followed by 10 days of extinction during which time animals did not receive drug infusion for operant responses in the chamber. After the tenth session, rats were tested in a single one-hour reinstatement session in the presence of cues previously paired with i.v. drug delivery. Group comparisons revealed that during acquisition, female rats took more cocaine than males, replicating findings of many prior preclinical studies on gender differences in cocaine intake. During extinction responding, females also tended to respond at higher levels during initial extinction sessions than males, and isolated rats responded at much higher levels than handled controls. Similarly, neonatally isolated rats responded at much higher levels during cue-induced reinstatement testing - making approximately 48% more responses in the presence of drug-associated cues. The findings of this study indicate that early stress may enhance the vulnerability for relapse to cocaine-seeking behavior in adulthood, when cues previously associated with drug reinforcement are encountered. Lynch,W.J., Mangini, L.D., and Taylor, J.R. Neonatal Isolation Stress Potentiates Cocaine-Seeking Behavior in Adult Male and Female Rats. Neuropsychopharmacology, 30, pp. 322-329, 2005.

Sucrose Intake Enhances Behavioral Sensitization Produced by Cocaine

Prior research has revealed interactions between an animal's history with sweet solutions and psychostimulant drug self-administration. For example, access to a sweet solution can prevent acquisition, and decrease the continued maintenance of cocaine self-administration. Dr. Blake Gosnell from the Neuropsychiatric Research Institute has now shown that experience with sucrose can sensitize animals to the locomotor-activating effects of cocaine. For 38 days, three groups of rats had daily 1-hr access either to sucrose, ground rat chow, or alternating daily access to either chow or sucrose. On the following two days, respectively, rats were given an i.p cocaine injection and an i.p saline injection. In response to the cocaine injection, rats pre-exposed to sucrose exhibited an elevated, although non-significant, locomotor response compared to the other two groups. Next, for five days, rats were given an injection of cocaine and immediately returned to their home cage. Then one and 15 days after the final cocaine injection they were tested for their locomotor response to cocaine. On the first day, all rats exhibited a sensitized locomotor response to cocaine with the sucrose group exhibiting the greatest sensitization. When tested 15 days after the last cocaine injection, sensitization was still present and was greater in the previously exposed sucrose group than the other two. These outcomes indicate that repeated, intermittent intake of a palatable food can potentiate the effect of cocaine on locomotor behavior, and are consistent with other studies showing that food reward and drug reward are subserved by overlapping neural circuits. This area of investigation may contribute to understanding high rates of comorbidity between eating disorders and substance abuse, especially in females. Gosnell, B.A. Sucrose Intake Enhances Behavioral Sensitization Produced by Cocaine. Brain Research, 1031, pp. 194-201, 2005.

Pharmacokinetics of Intravenous Cocaine Across the Menstrual Cycle in Rhesus Monkeys

Numerous rodent studies have demonstrated that cocaine sensitivity is greater in females than in males and that this sensitivity varies with the estrus cycle. Laboratory-based studies in humans have also documented sex differences and menstrual cycle differences in the subjective effects of cocaine thus raising questions about possible fluctuations in cocaine pharmacokinetics during the menstrual cycle. Drs. Suzette Evans and Richard Foltin addressed this issue by studying the rhesus monkey, which has a menstrual cycle similar in length and hormonal fluctuations to that in humans. They examined cocaine pharmacokinetics in five female rhesus monkeys given acute i.v. doses of 0, 0.25, 0.50 and 1.0 mg/kg cocaine during four phases of the menstrual cycle: menses, midfollicular, periovulatory and midluteal. Plasma levels of cocaine and cocaine metabolites benzoylecgonine (BZE) and ecgonine methyl ester (EME) were measured at multiple time points during 90 min following each cocaine injection. The researchers found that peak plasma levels of cocaine increased as a function of dose, but did not vary with the menstrual cycle. There were also no menstrual cycle differences in either the time to achieve peak plasma levels of cocaine or the half-life of cocaine. On the other hand, levels of cocaine metabolites did vary with the menstrual cycle. Plasma levels of BZE and EME were greatest during the luteal phase particularly following the highest cocaine dose. In an analysis of their data from a prior study in which plasma cocaine metabolite levels were collected in women who received repeated doses of 12 mg smoked cocaine during the follicular and luteal phases (Evans et al., 2002), Drs. Evans and Foltin also found that BZE plasma levels were higher in the luteal phase than in the follicular. The present findings, along with the similarity of the menstrual cycle in rhesus monkey and in humans, point to the feasibility of the rhesus monkey model to further our understanding of the role of the menstrual cycle in acute and chronic effects of cocaine. Evans, S.M., and Foltin, R.W. Pharmacokinetics of Intravenous Cocaine Across the Menstrual Cycle in Rhesus Monkeys. Neuropsychopharmacology, 29, pp. 1889-1900, 2004.

Impulsivity (Delay Discounting) as a Predictor of Acquisition of IV Cocaine Self-Administration

Studies in humans have shown a relationship between drug abuse and impulsivity as measured by delayed discounting. Cigarette smokers, crack/cocaine abusers, and opioid dependent individuals, for example, discount delayed rewards more than non-drug users, although it is not clear whether the impulsivity precedes the development of drug abuse or is a consequence. This question was addressed by researchers at the University of Minnesota and University of Wisconsin-Eau Claire using an animal model in which they compared acquisition of cocaine self-administration in female rats that differed in baseline level of impulsivity, as measured by choice for an immediate small reinforcer (one 45 mg food pellet) over a delayed larger reinforcer (three 45 mg food pellets). The researchers found that acquisition of cocaine self-administration occurred in a greater percentage of the rats that exhibited high levels of baseline impulsivity compared to those that exhibited low levels of baseline impulsivity. These data are consistent with and extend prior research showing that rats that exhibited high impulsive choices consumed more ethanol than those that exhibited medium or low impulsive choices (Poulos et al., 1995) and therefore point to impulsivity as a factor that may predispose one to drug abuse. The authors caution, however, that the relationship between impulsivity and drug use may not be unidirectional, citing findings from an earlier study (Richards et al., 1999) in which rats receiving chronic methamphetamine showed increased delay discounting. Perry, J.L., Larson, E.B., German, J.P., Madden, G.J., and Carroll, M.E. Impulsivity (Delay Discounting) as a Predictor of Acquisition of IV Cocaine Self-Administration in Female Rats. Psychopharmacology, 178, pp. 193-201, 2005.

Repeated Maternal Separation in Mice: Sex Differences in Cocaine-Induced Behavioral Sensitization in Adulthood

Experimental protocols in rats have documented that repeated maternal separation (MS) of the neonate can produce changes in the dopamine system and in the hypothalamic-pituitary-adrenal axis (HPA axis), including enhancement of cocaine-induced increases in ventral striatal dopamine levels and elevated basal levels of circulating glucocorticoids and glucocorticoid response to mild stress. Dr. Klaus Miczek and colleagues now report the effects of MS on cocaine-induced sensitization, on glucocorticoid receptors in the hippocampus, and on the dopamine transporter in the nucleus accumbens in male and female neonatal mice. MS occurred for 1 hour per day on postnatal days (PD)1-13. Induction of sensitization occurred during PD 50-59 with mice receiving daily i.p. injections of 10-mg/kg cocaine. The development of locomotor sensitization was assessed on PD 50, 54, and 59. Expression of sensitization was assessed on PD 69 or 71 and on PD 99 by measuring the locomotor response to 7.5 mg/kg i.p. cocaine injections. On PD 50, the locomotor response to cocaine was greater in MS females than in non-MS females, MS males, and non-MS males. On PD 54 and 59, all MS mice exhibited enhancement of cocaine-induced locomotion. Assessment of the expression of cocaine locomotor sensitization on PD 69 or 71 and on PD 99 indicated an enhancement of sensitization in MS males, but not in females. This study is the first to report a relationship between MS and cocaine reactivity in mice. Whereas prior studies of MS rats have shown down-regulation of hippocampal glucocorticoid receptor expression and increased accumbal dopamine transporter binding, in the present study neither of these measures were affected by MS; however, but both measures were greater in females than males. Possible explanations for these discrepancies between MS rats and MS mice include differences in maternal care in rats and mice and differences in the daily length of MS used in this study and prior studies with rats. Kikusui, T., Faccidomo, S., and Miczek, K.A. Repeated Maternal Separation: Differences in Cocaine-Induced Behavioral Sensitization in Adult Male and Female Mice. Psychopharmacology, 178, pp. 202-210, 2005.

Behavioral and Brain Development Research

Motor Development During the First 18 Months of Life in Children with Prenatal Cocaine Exposure In a recent report from the multi-site Maternal Lifestyle Study, Miller-Loncar and colleagues examined patterns of motor development during the first 18 months of life in children with in utero exposure to cocaine. Motor development was examined at 1, 4, 12, and 18 months of age. The children were divided into two groups: 392 cocaine-exposed and 776 comparison. Exposure status was determined by meconium assay and maternal self-report. Relationships between level of exposure and motor development were also analyzed. Motor skills were assessed at 1 month using the NICU Network Neurobehavioral Scale (NNNS), at 4 months using the posture and fine motor assessment of infants (PFMAI), at 12 months using the Bayley Scales of Infant Development-Second Edition (BSID-II), and at 18 months using the Peabody Developmental Motor Scales (PDMS). Hierarchical linear modeling (HLM) was used to analyze change in motor skills from 1 to 18 months of age. Children with prenatal cocaine exposure showed low motor skills at their initial status of 1 month but displayed significant increases over time. Both higher and lower levels of tobacco use related to poorer motor performance on average. Heavy cocaine use related to poorer motor performance as compared to no use, but there were no effects of level of cocaine use on change in motor skills. Miller-Loncar, C., Lester, B.M., Seifer, R., et al. Predictors of Motor Development in Children Prenatally Exposed to Cocaine. Neurotoxicology and Teratology, 27(2), pp. 213-220, 2005.

Gender and Alcohol Exposure Influence Prenatal Cocaine Effects on Child Behavior at 7 Years of Age

A Wayne State University study research team has reported findings from analyses intended to provide new information on how gender and prenatal exposure to alcohol affect relationships between prenatal cocaine exposure and behavior problems at school age. This report is based on assessments conducted when the children were 7 years of age (a total of 499 children, 214 of which were exposed prenatally to cocaine). Analyses of teacher-reported child externalizing behavior problems data were stratified by gender and prenatal alcohol exposure status, and controlled for significant pre- and postnatal confounders. Results indicated that among boys with prenatal alcohol exposure, those with persistent cocaine exposure throughout pregnancy had significantly higher levels of delinquent behavior compared to boys with no cocaine exposure. Boys with any prenatal cocaine exposure were twice as likely as unexposed boys to have clinically significant externalizing behavior scores. However, no association was found between prenatal cocaine exposure and scores on externalizing behavior and specific syndromes for boys with no prenatal alcohol exposure. Among girls with no prenatal alcohol exposure, those with persistent cocaine exposure had significantly higher levels of externalizing behaviors and aggressive behaviors compared to girls with no prenatal cocaine exposure, and were almost five times as likely to have clinically significant externalizing behavior scores. However, for girls with prenatal alcohol exposure, no association between prenatal cocaine exposure and scores on externalizing behavior and specific syndromes was found after control for confounding. The investigators state that the current findings support gender- and alcohol-moderated effects of prenatal cocaine exposure on school-age teacher-reported child behavior problems. They also note that these findings are similar to what they have reported for independent parent-reported behaviors. Nordstrom Bailey, B., Sood, B.G., Sokol, R.J., et al. Gender and Alcohol Moderate Prenatal Cocaine Effects on Teacher-report of Child Behavior. Neurotoxicology and Teratology, 27(2), pp. 181-189, 2005.

Attentional Functioning and Impulse Control in 10-Year-Old Children Exposed to Cocaine in Utero

University of Pennsylvania investigators examined the question of whether children with gestational cocaine exposure may be at risk for difficulties in attentional functioning and impulse control. They administered the Gordon Diagnostic System (GDS) and subtests of the Halstead-Reitan Battery to inner-city children with and without gestational cocaine exposure at age 10 years. The GDS involves a visual computerized task battery that measures impulsivity and sustained attention through three tasks of increasing stress arousal. The subtests of the Halstead-Reitan Battery used were the Trail Making Test (a measure of visual attention) and the Seashore Rhythm Test (a measure of auditory attention). These assessments involved 40 exposed and 40 non-exposed children, a subset of the original study cohort. Subtle differences were found between the prenatally cocaine-exposed children and those not exposed to cocaine during gestation (on the GDS Delay and Distractibility Tasks). With these two exceptions, children had similar performance, with both groups performing poorly. Attentional functioning and impulse control were also assessed in school. Teachers did not distinguish between exposed and non-exposed children, although both groups presented behavioral problems. The researchers concluded that gestational cocaine exposure may be associated with subtle problems in attention and impulse control, putting exposed children at higher risk of developing significant behavioral problems as cognitive demands increase. They also noted that these analyses involved a small sample, and that there is need for continued investigation of the interplay between school performance and attentional regulation and impulse control in order to more fully develop knowledge of long-term effects of gestational cocaine exposure. Savage, J., Brodsky, N.L., Malmud, E., et al. Attentional Functioning and Impulse Control in Cocaine-Exposed and Control Children at Age Ten Years. Developmental and Behavioral Pediatrics, 26(1), pp. 42-47, 2005.

Youth Tobacco and Marijuana Use Relative to Prenatal Cigarette and Marijuana Exposure

As part of their long-term follow-up of prenatal marijuana and tobacco exposure, researchers at Carleton University have examined whether maternal cigarette smoking and marijuana use during pregnancy were associated with an increased risk of initiation and daily/regular use of tobacco and marijuana among one hundred fifty-two 16- to 21-year-old adolescent offspring. The participants were from a low risk, predominately middle-class sample participating in an ongoing, longitudinal study. Findings indicated that offspring whose mothers reported smoking cigarettes during their pregnancy were more than twice as likely to have initiated cigarette smoking during adolescence than offspring of mothers who reported no smoking while pregnant. Offspring of mothers who reported using marijuana during pregnancy were at increased risk for both subsequent initiation of cigarette smoking (OR=2.58) and marijuana use (OR=2.76), as well as daily cigarette smoking (OR=2.36), as compared to offspring of whose mothers did not report using marijuana while pregnant. There was also evidence indicating that dose-response relationships existed between prenatal exposure to marijuana and offspring use of cigarettes and marijuana. These associations were found to be more pronounced for males than females, and remained after consideration of potential confounding variables. The authors note that these results suggest that maternal cigarette smoking and marijuana use during pregnancy are risk factors for later smoking and marijuana use among adolescent offspring, and add to the weight of evidence supporting the importance of programs aimed at drug use prevention and cessation among women during pregnancy. Porath, A.J. and Fried, P.A. Effects of Prenatal Cigarette and Marijuana Exposure on Drug Use Among Offspring. Neurotoxicology and Teratology, 27(2), pp. 267-277, 2005.

Suicidal Behavior, Drug Use and Depressive Symptoms After Detoxification: a 2-Year Prospective Study

Individuals with substance-related disorders are at increased risk for suicidal behavior. This study examined factors associated with drug-related suicidal behavior using multivariable regression analyses in a 2-year prospective study of 470 inpatients enrolled from an unlocked, detoxification unit. Suicidal behavior included suicidal ideation (SI) and suicide attempt (SA). Lifetime prevalence for SI was 28.5%, and for SA, 21.9%. During the 2-year follow-up, 19.9% of the sample endorsed suicidal ideation and 6.9% reported a suicide attempt. Correlates of lifetime suicidal behavior included younger age, female, Hispanic, greater depressive symptoms, past sexual abuse, and problem sedative or alcohol use. Factors associated with suicidal behavior at follow-up included past suicidal behavior, more depressive symptoms, and more frequent benzodiazepine and alcohol use. Cocaine and heroin use did not reach statistical significance. Differences in "suicide potential" may exist between drug categories with CNS depressants increasing the risk. These findings highlight the importance of addressing the recurrent 'suicide risk' of patients with substance-related disorders and regular monitoring for changes in depressive symptoms and drug use. Based on the prevalence and severity of this problem, the role of universal suicide screening of individuals with substance-related disorders merits greater attention. Wines, J.D. Jr., Saitz, R., Horton, N.J., Lloyd-Travaglini, C., and Samet, J.H. Drug and Alcohol Dependence, 76, Supplement 1, pp. S21-S29, 2004.

Predictors of Infection with Chlamydia or Gonorrhea in Incarcerated Adolescents

This cross-sectional study examined the prevalence, multiple correlates, and gender differences in chlamydia and gonorrhea infections among adolescents, aged 13 to 18, incarcerated in a youth detention center in the southern region of the United States. Rates of undiagnosed chlamydia were 24.7% for incarcerated girls and 8.1% for boys. Gonorrhea was detected in 7.3% of the girls and 1.5% of the boys. Predictors of STD positivity differed for boys and girls. Demographic characteristics (gender, race, and age) account for 52% of the total variance in STD infections; youths' behavior accounts for approximately one third of the total variance, and psychological and family variables account for 8.6% and 7.2% of the total variance, respectively. Sexual activity while under the influence of alcohol was associated with a greater likelihood of testing positive for an STD. Beliefs about alcohol and other drugs regarding loss of control and enhancement of sex were not associated with testing positive. This study demonstrates that an approach that considers psychological and social influences on adolescent sexual behavior is useful for identifying potential risk and protective factors of adolescent STD/HIV risk that are amenable to intervention. Robertson, A.A., Thomas, C.B., St Lawrence, J.S., and Pack, R. Sexually Transmitted Diseases, 32(2), pp. 115-122, 2005.

Effects of Smoking and Smoking Abstinence on Cognition in Adolescent Tobacco Smokers

There is considerable evidence that exposure to nicotine during early development can have neurotoxic effects. In this study, Dr. Leslie Jacobsen and her colleagues sought to determine whether exposure to nicotine during adolescence had demonstrable cognitive effects. Behavioral data from 41 adolescent smokers and 32 non-users were obtained on a number of cognitive tasks. Abstinence from smoking, for both male and female adolescent nicotine users, significantly decreased their performance on a test of verbal learning. In a memory task, smokers performed less accurately than non-smokers; this difference was greater when the smokers were abstinent. Whether abstinent or not, the magnitude of the performance difference between smokers and non-smokers was positively correlated with smoking history (number of pack-years). In tests of visual and auditory attention, smokers were found to perform as accurately as non-smokers, but their reaction times were slower. Finally, in terms of gender effects, male smokers were found to perform less accurately than female smokers. Male smokers, however, tended to have smoked longer than female smokers and to have started smoking earlier, which may account for at least part of the difference. These findings strongly suggest that nicotine exposure during adolescence has deleterious effects. Jacobsen, L.K., Krystal, J.H., Mencl, W.E., Westerveld, M., Frost, S.J., and Pugh, K.R. Biol. Psychiatry pp. 56-66, 2005.

Clinical Neuroscience Research

Neurotoxic Effects of Prenatal Methamphetamine (METH) Exposure on the Developing Brain and on Cognition

Dr. Linda Chang and associates at the University of Hawaii examined Meth-exposed children (n=13) and unexposed controls (n=15) with MRI in a pilot study to examine neurotoxic effects of prenatal METH exposure. Global brain volumes and regional brain structures were quantified. Ten METH-exposed and nine unexposed children also completed neurocognitive assessments. METH-exposed children scored lower on measures of visual motor integration, attention, verbal memory and long-term spatial memory. There were no differences among the groups in motor skills, short delay spatial memory or measures of non-verbal intelligence. Despite comparable whole brain volumes in each group, the METH-exposed children had smaller putamen bilaterally (-17.7%), smaller globus pallidus (left: -27%, right: 30%), smaller hippocampus volumes (left: -19%, right: -20%) and a trend for a smaller caudate bilaterally (-13%). The reduction in these brain structures correlated with poorer performance on sustained attention and delayed verbal memory. No group differences in volumes were noted in the thalamus, midbrain or the cerebellum. In summary, compared with the control group, children prenatally exposed to METH exhibit smaller subcortical volumes and associated neurocognitive deficits. These preliminary findings suggest that prenatal METH exposure may be neurotoxic to the developing brain. Chang, L., Smith, L.M., LoPresti, C., Yonekura, M.L., Kuo J., Walot, I. and Ernst, T. Psychiatry Research, 132, pp. 95-106, 2004.

New Measures of Corpus Callosum Size Are Related To Drug Abuse and To Childhood Neglect and Abuse

While many neuroimaging studies focus on deficits in cortical gray matter in patients with drug abuse or with cognitive deficits, Dr. Moeller and associates at the University of Texas Health Science Center, Houston, have used recent technology in Diffusion Tensor Imaging (DTI) and found reduced white matter integrity in areas of the corpus callosum in cocaine-dependent subjects. In addition, tests of impulsivity showed significant (negative) correlations with callosal integrity. It should be noted, however, that not the entire callosum showed a difference between cocaine-dependent subjects and controls; differences were found only in the genu and rostral body and are likely related to cross-connecting areas in the prefrontal cortex. Moeller, F.G., Hasan, K.M., Steinberg, J.L., Kramer L.A., Dougherty, D.M., Santos, R.M., Valdes, I., Swann, A.C., Barratt, E.S. and Narayan, P.A. Neuropsychopharmacology, 30, pp. 610-617, 2005.

Childhood Neglect Is Associated With Reduced Corpus Callosum Area

Dr. Teicher and colleagues at McLean Hospital reported reduced corpus callosum area in children who were neglected or abused. This is important because early physical or sexual abuse is likely associated with later drug abuse. However, the affected areas were posterior to those found by Moeller and associates. Nevertheless, these data may help understand the effect of early events in brain development and their impact on drug abuse liability. Teicher, M.H., Dumont, N.L., Ito, Y., Vaituzis, C., Giedd, J.N and Anderson, S.L. Biological Psychiatry, 56, pp. 80-85, 2004.

Specific Brain Regions Are Activated Following Script-Induced Emotions In Cocaine Users and in Non-Using Individuals

Dr. Sinha at Yale University has found limbic and other brain structures to be activated as measured by fMRI in cocaine users and in non-using subjects as they listen personalized scripts designed to induce heightened emotions. In non-using subjects, increases were observed in limbic and midbrain regions such as the striatum, and thalamic regions, caudate, putamen, hippocampus, parahippocampus and posterior cingulate. In some of these areas, left activation was greater. In cocaine users, stress tended to activate temporal areas in addition to medial and superior frontal gyri and anterior cingulate. Of most interest, women seemed to have the greater activation. Sinha, R., Lacadie, C., Skudlarksi, P. and Wexler, B.E., Annals of the New York Academy of Science, 1032, pp. 254-257, 2004; Li, C-S.R., Koston, T.R. and Sinha, R. Biological Psychiatry, 57, pp. 487-494, 2005.

Epidemiology ad Etiology Research

Caregiver Factors Buffer Effects of Violence Exposure on Adjustment Problems

This short-term, longitudinal interview study used an ecological framework to explore protective factors within the child, the caregiver, the caregiver-child relationship, and the community that might moderate relations between community violence exposure and subsequent internalizing and externalizing adjustment problems and the different patterns of protection they might confer. Participants included 101 pairs of African American female caregivers and one of their children (56% male, M = 11.15 yrs, SD = 1.28) living in high-violence areas of a mid-sized southeastern city. Child emotion regulation skill, felt acceptance from caregiver, observed quality of caregiver-child interaction, and caregiver regulation of emotion each were protective, but the pattern of protection differed across level of the child's ecology and form of adjustment. Kliewer, W., Cunningham, J.N., Diehl, R., Parrish, K.A., Walker, J.M, Atiyeh, C., Neace, B., Duncan, L., Taylor, K. and Mejia, R. Violence Exposure and Adjustment in Inner-city Youth: Child and Caregiver Emotion Regulation Skill, Caregiver-child Relationship Quality, and Neighborhood Cohesion as Protective Factor. J Clin Child Adolesc Psychol. 33(3), pp. 477-487, 2004.

Effects of Parent and Peer Support on Adolescent Substance Use

This research tested comparative effects of parent and peer support on adolescent substance use (tobacco, alcohol, and marijuana) with data from 2 assessments of a multiethnic sample of 1,826 adolescents, mean age 12.3 years. Multiple regression analyses indicated that parental support was inversely related to substance use and that peer support was positively related to substance use, as a suppression effect. Structural modeling analyses indicated that effects of support were mediated through pathways involving good self-control, poor self-control, and risk-taking tendency, parent and peer support had different patterns of relations to these mediators. The mediators had pathways to substance use through positive and negative recent events and through peer affiliations. Effects for gender and ethnicity were also noted. Mechanisms of operation for parent and peer support are discussed. Wills, T.A., Resko, J.A., Ainette, M.G. and Mendoza, D. Role of Parent Support and Peer Support in Adolescent Substance Use, A Test of Mediated Effects. Psychology of Addictive Behaviors, 18, pp.122-134, 2004.

Reliability of Proxy Reports of Parental Smoking

To investigate the accuracy of offspring assessments of parental smoking status, this study assessed 116 parents and 151 adult children (276 parent-child dyads) who provided data on both their own and their parents' smoking status. All currently smoking and all ex-smoking parents were correctly classified as ever-smokers by their offspring (n=79 and 100, respectively). Of the 97 offspring who reported on never-smoking parents, 88 correctly classified their parents as never-smokers. Thus, sensitivity for detecting ever-smoking in parents was 100%, and specificity, 91%. Because all incorrect classifications involved never-smoking parents, further analyses focused on this group. Too few parents were misclassified to permit testing of parental characteristics. Offspring who misclassified their parents were significantly older than those who did not; neither sex nor smoking status of the offspring was associated with the increased likelihood of misclassification. No significant differences were discovered for dyadic factors (concordance/discordance for sex; parent-offspring age difference). Overall, these results support the utility of proxy reports of parental smoking phenotype by adult informants when self-report is unavailable. Pomerleau, C.S., Snedecor, S., Ninowski, R., Gaulrapp, S., Pomerleau, O.F. and Kardia, S.L. Differences in Accuracy of Offspring Assessment Based on Parental Smoking Status. Addictive Behaviors 30, pp. 437-441, 2005.

Identifying Venues for Purposive Sampling of Hard-to-reach Latino Youth

This study of recruitment venues in a Latino neighborhood was designed with the following objectives: (1) to identify venues where Latino youth at risk for unintended pregnancies and sexually transmitted infections (STIs) could be reached; (2) to describe different youth crowds, and (3) to investigate how and where youth meet their sex partners. Based on neighborhood venues mapped using Map-Info, and ethnographic interviews conducted with 62 youth recruited primarily from street sites, 3 types of "crowds" were identified, including gang related "regulars," individuals affiliated with street economy, and females. Findings suggest that gang members dominate venues in The Mission and that street sites are important venues to meet sexual partners. This qualitative assessment produced insights into research planning, outreach, and interventions with Latino youth who are at disproportionate risk for unintended pregnancies and STIs. Auerswald, C.L., Greene, K., Minnis, A., Doherty, I., Ellen, J. and Padian, N. Qualitative Assessment of Venues for Purposive Sampling of Hard-to-reach Youth. Sexually Transmitted Diseases, 31, pp. 133-138, 2004.

School-level Clustering of Youthful Drug Involvement in Seven Latin American Countries

This study estimated the occurrence and school-level clustering of drug involvement among school-attending adolescent youths in each of seven countries in Latin America. During 1999-2000, anonymous self-administered questionnaires on drug involvement and related behaviors were administered to a cross-sectional, nationally representative sample that included a total of 12,797 students in the following seven countries, Costa Rica (n = 1,702), the Dominican Republic (n = 2,023), El Salvador (n = 1,628), Guatemala (n = 2,530), Honduras (n = 1,752), Nicaragua (n = 1,419), and Panama (n = 1,743). (The PACARDO name concatenates PA for Panama, CA for Centroamerica, and RDO for Republica Dominicana). Estimates for exposure opportunity and actual use of alcohol, tobacco, inhalants, marijuana, cocaine (crack/coca paste), amphetamines and methamphetamines, tranquilizers, ecstasy, and heroin were assessed via responses about questions on age of first chance to try each drug, and first use. Cumulative occurrence estimates for alcohol, tobacco, inhalants, marijuana, and illegal drug use for the overall sample were, respectively, 52%, 29%, 5%, 4%, and 5%. In comparison to females, males were more likely to use alcohol, tobacco, inhalants, marijuana, and illegal drugs, the odds ratio estimates were 1.3, 2.1, 1.6, 4.1, and 3.2, respectively. School-level clustering was noted in all countries for alcohol and tobacco use. It was also noted in Costa Rica, El Salvador, Guatemala, and Panama for illegal drug use. This report sheds new light on adolescent drug experiences in Panama, the five Spanish-heritage countries of Central America, and the Dominican Republic, and presents the first estimates of school-level clustering of youthful drug involvement in these seven countries. Placed in relation to school survey findings from North America and Europe, these estimates indicate lower levels of drug involvement in these seven countries of the Americas. For example, in the United States of America 70% of surveyed youths had tried alcohol and 59% had smoked tobacco. By comparison, in these seven countries, only 51% have tried alcohol and only 29% have smoked tobacco. Future research will help to clarify explanations for the observed variations across different countries of the world. In the meantime, strengthening of school-based and other prevention efforts in the seven-country PACARDO area may help these countries slow the spread of youthful drug involvement, reduce school-level clustering, and avoid the periodic epidemics of illegal drug use that have been experienced in North America. Dormitzer, C.M., Gonzalez, G.B., Penna, M., Bejarano, J., Obando, P., Sanchez, M., Vittetoe, K., Gutierrez, U., Alfaro, J., Meneses, G., Diaz, J.B., Herrera, M., Hasbun, J., Chisman, A., Caris, L., Chen, C.Y. and Anthony, J.C. The PACARDO Research Project, Youthful Drug Involvement in Central America and the Dominican Republic. Pan American Journal of Public Health, 15, pp. 400-416, 2004.

Difference between Ever- and Never-Smokers

This study examined whether 52 same-sex sibling pairs discordant for ever-smoking differed on psychiatric cofactors, alcohol and caffeine use, and responses to initial exposure to smoking. Ever-smokers scored significantly higher on measures of novelty seeking, depression, and childhood ADHD, and on alcohol dependence, alcohol intake, and caffeine intake. They reported significantly more pleasurable experiences, dizziness, "buzz," and relaxation upon initial exposure to smoking and significantly fewer displeasurable sensations, nausea, and cough than did nicotine-exposed, never-smoking siblings. Ever-smokers had significantly fewer years of education than their never-smoking siblings, suggesting that the concentration of smokers in lower socioeconomic strata may be partly due to downward mobility among smokers, possibly because of the observed elevation in psychiatric cofactors, which may interfere with academic performance. These findings are consistent with differences previously identified in unrelated ever- and never-smokers. Because same-sex siblings typically share a large set of common environments during childhood, the findings could be due either to genetic differences among siblings and/or (excepting educational level and responses to early exposure) to differences in adult environments. Pomerleau, C.S., Pomerleau, O.F., Snedecor, S.M., Gaulrapp, S. and Kardia, S.L.R. Heterogeneity in Phenotypes Based on Smoking Status in the Great Lakes Smoker Sibling Registry. Addictive Behaviors 29, pp. 1851-1855, 2004.

HPA-axis Dysregulation among Female Smokers with and without Depression

To determine whether smokers with a history of depression are differentially susceptible to smoking withdrawal, depressed mood induction and/or hypothalamic-pituitary-adrenal (HPA) axis dysregulation during smoking abstinence, 24 women smokers with and without such a history were studied. During one 5-day interval, participants smoked ad libitum, during a second they abstained. On day 4, the participants were exposed to the Velten mood induction procedure (VMIP). Participants were then instructed to take 1 mg dexamethasone at 11 pm. At 4 pm on day 5, blood samples were withdrawn to determine the cortisol and ACTH response. Despite lower baseline cotinine levels, history-positive participants displayed more pronounced overall withdrawal distress than did history-negative participants, regardless of condition. The VMIP increased depression as well as negative responses on other profile of mood states subscales. Despite many overall group differences, no significant main effects for smoking condition nor interaction effects emerged. All participants evinced cortisol suppression in response to dexamethasone during both conditions, but the degree of suppression did not differ as a function of either abstinence or depression history. In history-positive smokers, however, ACTH levels trended toward overall elevation and showed almost no suppression during abstinence, thus exacerbation of HPA dysregulation in history-positive smokers during smoking abstinence cannot be ruled out. Pomerleau, O.F., Pomerleau, C.S., Snedecor, S.M., Gaulrapp, S., Brouwer, R.N. and Cameron, O.G., Depression, Smoking Abstinence and HPA Function in Women Smokers. Human Psychopharmacology-Clinical and Experimental, 19, pp. 467-476, 2004.

Impact of September 11 Attacks on Young Adult Drug Abuse

The authors took advantage of their ongoing longitudinal study to assess the impact of the September 11 attacks on psychopathology in young adults who lived far from New York City. During that year, 730 rural 19-21 year olds were re-assessed, one third after the attacks. Findings differed by gender and by level of prior stress. Although men showed slightly more tendency to have one or more symptoms of posttraumatic stress disorder, their rates of substance use disorder after September 11 were lower, regardless of prior use history. Women showed increased rates of substance use and abuse after the attacks. The attacks also proved a greater stressor for those under low to moderate levels of stress than for those already under significant stress. No other psychiatric disorders showed an increase after September 11 in this sample. This "natural experiment" suggests that, if confirmed in other studies, even those who are geographically removed from a traumatic event may be vulnerable, and that interventions for those at greater risk may be indicated to prevent further costs in event of such an attack. Costello, E.J, Erkanli, A., Keeler, G., and Angold, A. Distant Trauma: A Prospective Study of the Effects of September 11th on Young Adults in North Carolina. Applied Developmental Science, 8, pp. 211-220, 2004.

Prevention Research

Predicting Early Adolescent Gang Involvement from Middle School Adaptation

This study examined the role of adaptation in the first year of middle school (Grade 6, age 11) to affiliation with gangs by the last year of middle school (Grade 8, age 13). The sample consisted of 714 European American (EA) and African American (AA) boys and girls. Specifically, academic grades, reports of antisocial behavior and peer relations in 6th grade were used to predict gang involvement by 8th grade, measured through self-, peer, teacher, and counselor reports. Unexpectedly, self-report measures of gang involvement did not correlate highly with peer and school staff reports. The results, however, were similar for other and self-report measures of gang involvement. Analysis of means revealed statistically reliable differences in 8th-grade gang involvement as a function of the youth gender and ethnicity. Structural equation prediction models revealed that peer nominations of rejection, acceptance, academic failure, and antisocial behavior were predictive of gang involvement for most youth. These findings suggest that the youth level of problem behavior and the school ecology (e.g., peer rejection, school failure) require attention in the design of interventions to prevent the formation of gangs among high-risk young adolescents. Dishion, T.J., Nelson, S.E. and Yasui, M. Journal of Clinical Child and Adolescent Psychology 34(1), pp. 62-73, 2005.

Maternal Stress and Distress Increase Disruptive Behavior Problems in Boys

This study examined how self-reported maternal stress and distress are associated with child disruptive behaviors, based on mother and teacher ratings of child disruptive behavior problems (attention problems, aggression, and delinquency) collected for 215 boys between 9 and 12 years of age. Participating mothers also provided self-report data on socioeconomic status (SES), parenting stress, and distress (depression and anxiety/somatization). Low SES was significantly associated with both mother- and teacher-reported child disruptive behavior problems. In addition, the relation between parenting stress and mother-reported child disruptive behavior problems was found when SES was controlled. A significant relation between maternal distress and mother-reported child disruptive behavior problems (particularly attention problems), also was observed when both SES and parenting stress were controlled. Maternal stress and distress were not significantly related to teacher-reported child disruptive behavior problems. Although the lack of an association between teacher-reported behavior problems and maternal stress and distress might be interpreted as a rater bias by these mothers, it may be that the mothers' symptoms are associated with a stressful home environment, thus exacerbating child disruptive behavior problems and eventually leading to a reciprocal relation between symptomatology in mothers and children. Barry, T.D., Dunlap, S.T., Cotton, S.J., Lochman, J.E. and Wells, K.C. The Influence of Maternal Stress and Distress on Disruptive Behavior Problems in Boys. Journal of the American Academy of Child and Adolescent Psychiatry, 44(3), pp. 265-273, 2005.

Tobacco and Alcohol Use as an Explanation for the Association between Externalizing Behavior and Illicit Drug Use among Delinquent Adolescents

Substance use among adolescents is frequently comorbid with other psychiatric disorders. Most studies of these comorbidities use samples of middle or high school students or draw from inpatient settings. Less is known about substance use and psychiatric comorbidity among delinquent adolescents. The present study examined data from two cohorts of juvenile offenders collected over a 2-year period (n=245, n=299). Participants reported frequency of cigarette, alcohol, marijuana, and other substance use. Participants' parents completed a measure of behavior problems. Path analyses suggested that parental reports of externalizing problems were significantly related to self-reported substance use while parental reports of internalizing problems were not. These findings suggest that smoking and alcohol use act as mediators between externalizing problems and marijuana and other drug use. Although there were some mean differences by gender, the pattern of relationships among the variables did not differ by gender. Helstrom, A., Bryan, A., Hutchison, K.E., Riggs, P.D. and Blechman, E.A. Tobacco and Alcohol Use as an Explanation for the Association between Externalizing Behavior and Illicit Drug Use among Delinquent Adolescents. Prevention Science, 5(4), pp. 267-277, 2004.

Vulnerability of Children of Incarcerated Addict Mothers: Implications for Preventive Intervention

This preliminary report examined the characteristics, experiences, and behavior of 88 primarily African-American adolescents with incarcerated addict mothers. The age, gender, and risk factor profiles with the children's adjustment status, based on self-reported questionnaire information and selected personality/behavioral assessment inventories, indicated that in spite of the incarceration of their substance-abusing mothers, the majority of these children were neither especially deviant nor maladjusted. All but a small percentage had successfully avoided substance abuse and the adoption of a deviant lifestyle at this point in their development. In most cases, mother surrogates (usually a grandmother or other family member) had functioned as primary caregivers of the children for many years prior to the incarceration of their birth mothers, possibly attenuating the negative impact ordinarily associated with a mother's absence from the home. However, there was a general indication of problematic school behavior and vulnerability to deviant peer influences that should be addressed in efforts aimed at preventing the escalation of deviant activity in such children. In almost all cases the child's caregiver needed caseworker support services. Hanlon, T.E., Blatchley, R.J., Bennett-Sears, T., O'Grady, K.E., Rose, M. and Callaman, J.M. Vulnerability of Children of Incarcerated Addict Mothers: Implications for Preventive Intervention. Children and Youth Services Review, 27(1), pp. 67-84, 2005.

Characteristics and Vulnerability of Incarcerated Drug-Abusing Mothers

Although the number of drug-addicted incarcerated mothers has grown substantially in recent years, there is little information on their unique characteristics and vulnerabilities. This study examined data on 167 incarcerated drug-abusing mothers from Baltimore City who had volunteered for a parenting program offered at a Maryland correctional facility. Prior to entering this program, these mothers completed a battery of assessment measures including an extensive interview covering their early developmental and current experiences and standardized tests of psychological adjustment and parenting satisfaction. Analyses of these data focused on the link between risk/protective factors drawn from the early development experiences of these and their current adjustment status. There were significant relationships between higher risk levels and less favorable current adjustment suggesting the need to develop both prevention and clinical intervention efforts targeting both mothers and their children. Hanlon, T.E., O'Grady, K.E., Bennett-Sears, T. and Callaman, J.M. Incarcerated Drug-Abusing Mothers: Their Characteristics and Vulnerability. American Journal Of Drug And Alcohol Abuse, 31(1), pp. 59-77, 2005.

Racial and Gender Differences in Patterns of Adolescent Sexual Risk Behaviors

Sexual and substance use behaviors co-vary in adolescence. There also are racial and gender differences in the prevalence of HIV and other sexually transmitted diseases (STDs). These differences in subgroup risk behavior differences have not been systematically investigated with nationally representative data. Using cluster analysis 13,998 non-Hispanic black and white participants in the National Longitudinal Study of Adolescent Health, Wave 1, were grouped according to self-reported substance use and sexual behavior. Multinomial logit analyses examined racial and gender differences by cluster. Among 16 clusters, the two defined by the lowest risk behaviors (sexual abstinence and little or no substance use) comprised 47% of adolescents; fewer than 1% in these groups reported ever having received an STD diagnosis. The next largest cluster--characterized by sexual activity (on average, with one lifetime partner) and infrequent substance use--contained 15% of participants but nearly one-third of adolescent with STDs. Blacks were more likely than whites to be in this group. Black males also were more likely than white males to be in three small clusters characterized by high-risk sexual behaviors (i.e., having had sex with a male or with at least 14 partners, or for drugs or money). Although Black females generally were the least likely to be in high-risk behavior clusters, they were most likely to report STDs. Thus, adolescents' risk behavior patterns vary by race and gender, and do not necessarily correlate with their STD prevalence. Halpern, C.T., Hallfors, D., Bauer, D.J., Iritani, B., Waller, M.W. and Cho, H. Implications of Racial and Gender Differences in Patterns of Adolescent Risk Behavior for HIV and Other Sexually Transmitted Diseases. Perspectives on Sexual and Reproductive Health, 36(6), pp. 239-247, 2004.

Development and Validation of a Gender-Balanced Measure of Aggression-Relevant Social Cognition

This study examined the psychometric properties of the Social-Cognitive Assessment Profile (SCAP), a gender-balanced measure of social information processing (SIP) in a sample of 371 (139 girls, 232 boys) 2nd- to 4th-grade children. The SCAP assesses 4 dimensions of SIP (Inferring Hostile Intent, Constructing Hostile Goals, Generating Aggressive Solutions, and Anticipating Positive Outcomes for Aggression) in the context of peer conflict involving relational and overt provocation. Confirmatory factor analyses indicated that the 4 latent factors provided a good fit to the data for girls and boys and for African American and non-African American children. Regression analyses in which teacher and peer evaluations of aggression and peer evaluations of social competencies were regressed on each of the 4 SCAP scales supported the test's convergent and discriminant validity. These results suggest that the SCAP is an easily administered and brief measure of SIP that is appropriate for racially diverse populations of elementary boys and girls. Hughes, J.N., Meehan, B.T., and Cavell, T.A. Journal of Clinical Child and Adolescent Psychology, 33(2), pp. 292-302, 2004.

Infusion-LST Compared to LST as Usual

Findings from the first two years of a study to compare a standard Life Skills Training (LST) program with an infused (I-LST) approach was conducted in 9 small, rural school districts that were randomly assigned to LST, I-LST, or control conditions. Male and female subjects were in grade seven. The LST program significantly reduced alcohol use, binge drinking, marijuana use, and inhalant use after one year for females, and the I-LST program significantly reduced smoking, binge drinking, and marijuana use for females. At the end of the second year the I-LST program continued to impact female smoking, but all other results were non-significant. There were no effects on males at either time point. Smith, E.A. Evaluation of Life Skills Training and Infused-Life Skills Training in a Rural Setting: Outcomes at Two Years. Journal of Alcohol & Drug Education, 48(1), pp. 51-70, 2004.

Cost Comparison of LST and Infusion-LST

A cost-effectiveness comparison of the Life Skills Training (LST) to a LST curriculum infusion approach (I-LST) was conducted. Male and female seventh graders from nine rural schools (2 intervention conditions and control) were followed for two years. After one year, significant effects were observed only for females on alcohol, marijuana, and inhalant use in LST condition and for tobacco, alcohol, and marijuana use for I-LST females. After year two, only the I-LST program affected female smoking. Costs for the two programs included actual expenditures for training and materials as well as estimates of teachers' salaries for their project time were calculated. Both programs were almost equally effective after one year, but LST was more cost-effective. I-LST cost more to implement, but sustained effects into year two and was therefore more cost-effective overall. Swisher, J. D. A Cost-Effectiveness Comparison of Two Approaches to Life Skills Training. Journal of Alcohol & Drug Education, 48(1) pp. 71-78, 2004.

Perceived Life Chances and Alcohol Use

The relationship between low perceived chances for success in life and binge drinking was examined in a sample of economically disadvantaged, predominantly black and Hispanic students, urban adolescents (N = 774) from 13 inner-city schools. Subjects completed confidential questionnaires in the 7th, 8th, and 9th grades. Eight items measured students' estimation of achieving certain adaptive life goals. Students who reported that they typically drink five or more drinks per drinking occasion were identified as binge drinkers. Results indicated that rates of binge drinking increased and perceived life chances decreased for both boys and girls from the 7th to 9th grade. Moreover, higher perceived life chances in the 7th grade predicted less binge drinking in the 8th grade, whereas binge drinking in the 8th grade predicted lower perceived life chances in the 9th grade, controlling for change over time in both variables. Griffin, K.W., Botvin, G.J., Nichols, T.R. and Scheier, L.M. Low Perceived Chances for Success in Life and Binge Drinking among Inner-city Minority Youth. Journal of Adolescent Health, 34, pp. 501-507, 2004.

Self-esteem and Alcohol Use

Prior studies have found inconsistent relationships between measures of self-concept and adolescent alcohol use. This study explored whether the link between various measures of self-concept and alcohol use depends on gender and whether negative rather than positive self-esteem (i.e., self-derogation) might be more useful in predicting alcohol use. Students (N = 1459) attending 22 middle and junior high schools in New York City completed surveys that included measures of efficacy, self-derogation, and alcohol use. Participants completed surveys at baseline, 1-year follow-up, and 2-year follow-up. Findings indicate that lower efficacy was related to greater self-derogation a year later across gender. Increased self-derogation predicted higher alcohol use for girls but not boys. These findings are congruent with a literature highlighting the importance of negative thoughts about the self in drinking behavior for women but not men. Epstein, J.A., Griffin, K.W. and Botvin, G.J. Efficacy, Self-derogation, and Alcohol Use among Inner-city Adolescents: Gender Matters. Journal of Youth & Adolescence 33, pp. 159-166, 2004.

Influence of Parents on Child Anti-social Behavior

This study examined the unique influence of mothers and fathers on their children's antisocial behavior using a sample of 325 families with sixth grade children. Multiple-group comparisons were conducted to identify differences in the relationships for mothers and fathers with daughters versus sons. Results suggested that, while the relationships were often similar for both parents and for both daughters and sons, mothers and fathers uniquely influenced their child's antisocial behavior depending on the child's gender. Overall, cross-gender influence appeared to be particularly important for fathers' control of their daughters' antisocial behavior. Kosterman, R., Haggerty, K.P., Spoth, R. and Redmond, C. Unique Influence of Mothers and Fathers on their Children's Antisocial Behavior: A Social Development Perspective. Journal of Marriage and Family 66(3), pp. 762-778, 2004.

Does Perception of Behavior Affect Behavior?

This research examined whether parents' and children's perceptions have reciprocal self-fulfilling prophecy effects on each others' behavior. Mothers, fathers, and their adolescent children completed self-report surveys and engaged in videotaped dyadic interaction tasks. The surveys assessed parents' and children's perceptions of their own and the other's typical hostility and warmth. Observers coded the videotaped interactions to assess the actual hostility and warmth exhibited by mothers, fathers, and children. Data from 658 mother-child dyads were consistent with the conclusion that children had a self-fulfilling effect on their mothers' hostile behavior, but that mothers did not have a reciprocal self-fulfilling effect on their children's hostility. The data did not support the existence of self-fulfilling prophecies among the mother-child dyads with respect to warmth, or among the 576 father-child dyads for either the hostility- or warmth-relevant data.. Madon, S., Guyll, M. and Spoth, R. The Self-fulfilling Prophecy as an Intra-family Dynamic, Journal of Family Psychology 18(3), pp. 459-469, 2004.

Research on Behavioral & Combined Treatments For Drug Abuse

A Pilot Study on Voucher-based Incentives to Promote Abstinence from Cigarette Smoking during Pregnancy and Postpartum

Dr. Higgins and colleagues from the University of Vermont report results from a pilot study examining the use of vouchers redeemable for retail items as incentives for smoking cessation during pregnancy and postpartum. Fifty-eight women who were still smoking upon entering prenatal care were assigned to either contingent or noncontingent voucher conditions. Vouchers were available throughout pregnancy and for 12 weeks postpartum. In the contingent condition, vouchers were earned for biochemically verified smoking abstinence; in the noncontingent condition, vouchers were earned independent of smoking status. Contingent vouchers significantly increased abstinence at the end-of-pregnancy (37% vs. 9%), and 12-week postpartum (33% vs. 0%) assessments. That effect remained significant at the 24-week postpartum assessment (27% vs. 0%), which was 12 weeks after discontinuation of the voucher program. The magnitude of these treatment effects exceeds levels typically observed with pregnant and recently postpartum smokers, and the maintenance of effects through 24 weeks postpartum extends the duration beyond those reported previously. Higgins, S.T., Heil, S.H., Solomon, L.J., Lussier, J.P. and Lynch, M.E. Nicotine and Tobacco Research, 6(6), pp. 1015-1020, 2004.

Perceived Risks and Benefits of Smoking Cessation: Gender-specific Predictors of Motivation and Treatment Outcome

The primary aim of this study was to examine gender differences in perceived risks and benefits of smoking cessation and their relationship to pretreatment motivation and treatment outcome. A self-report instrument was developed for this purpose. Findings are reported from a subsample of 93 participants out of 573 treatment seeking smokers entering a smoking cessation study. Females indicated greater likelihood ratings of perceived risks and benefits than males. For women and men, perceived benefits were positively associated with motivation, and perceived risks were negatively associated with motivation and treatment outcome. Women evidenced stronger associations between perceived risks and pretreatment motivation, and treatment outcome. Knowledge of perceived risks and benefits associated with smoking cessation is critical for public education campaigns and could inform intervention strategies designed to modify sex-specific beliefs associated with lowered behavioral intentions to quit smoking. McKee, S.A., O'Malley, S.S., Salovey, P., Krishnan-Sarin, S. and Mazure, C.M. Addictive Behaviors, 30, pp. 423-435, 2005.

Dual and Multiple Diagnosis among Runaway and Homeless Youth

Dr. Natasha Slesnick and Jillian Prestopnik report on the clinical presentations of 226 youth at two homeless shelters participating in a study of family treatment for substance abuse. Regarding substance use disorders, 81% met criteria for marijuana abuse or dependence, 64% met criteria for alcohol abuse or dependence, and about half (44%) met criteria for two substance use disorders. About 60% of youth met criteria for at least one substance use disorder and at least one psychiatric diagnosis. Of these youth, 60% met criteria for Oppositional Defiant Disorder or Conduct Disorder (ODD/CD); 34% met criteria for an Affective Disorder; and 54% met criteria for an Anxiety Disorder. Youth with ODD/CD were significantly more likely to use marijuana than other youth. Young men were significantly more likely than young women to meet criteria for ODD/CD, while young women were significantly more likely to meet criteria for Affective Disorders and Anxiety Disorders, and to have multiple diagnoses. These results highlight the large overlap between substance use disorders and psychiatric disorders found, and the need for appropriate treatment, among runaway youth. Slesnick, N. and Prestopnik, J.L. American Journal of Drug and Alcohol Abuse, 31, pp. 179-201, 2005.

Research on Pharmacotherapies For Drug Abuse

Transdermal Nicotine Use in Postmenopausal Women and Hormone Replacement Therapy

Ninety-four postmenopausal female smokers were recruited according to HRT and non-HRT use (self-selecting) then randomized within strata to active nicotine or placebo nicotine patch. After 1 baseline week of smoking, participants quit smoking for 2 weeks. Women received cessation counseling and were monitored for abstinence. Dependent measures were collected during five clinic visits. Two-way analysis of covariance (ANCOVA) were run on change scores for dependent variables, with nicotine patch group (active/placebo) and HRT group (HRT/non-HRT) as independent variables and age as a covariate. No interactions were found between HRT and patch condition, but both showed specific effects. During the first abstinent week, women on active nicotine patch (compared with placebo) experienced less severe withdrawal, greater reductions in cigarette cravings, and lower (more favorable) Factor 1 scores on the Questionnaire of Smoking Urges. During the second abstinent week, women using HRT (compared with the non-HRT group) exhibited better mood (Profile of Mood States scores) and less depression (Beck Depression Inventory scores). These results suggest the following: First, the efficacy of transdermal nicotine replacement is not adversely modified by women's HRT use; second, ovarian hormones might influence women's responses to smoking cessation, and thus should be considered in developing effective strategies for women to quit smoking. Allen, S.S., Hatsukami, D.K., Bade, T. and Center, B. Transdermal Nicotine Use in Postmenopausal Women: Does the Treatment Efficacy Differ in Women Using and Not Using Hormone Replacement Therapy? Nicotine Tob. Res., 6(5), pp. 777-788, October 2004.

Re-emergence of Tobacco Smoking Using a Waterpipe

Waterpipes are increasing in popularity, and more must be learned about them so that we can understand their effects on public health, curtail their spread, and help their users quit. Research regarding waterpipe epidemiology and health effects is limited; no published studies address treatment efforts. Waterpipe use is increasing globally, particularly in the Eastern Mediterranean Region, where perceptions regarding health effects and traditional values may facilitate use among women and children. Waterpipe smoke contains harmful constituents and there is preliminary evidence linking waterpipe smoking to a variety of life threatening conditions, including pulmonary disease, coronary heart disease, and pregnancy related complications. More scientific documentation and careful analysis is required before the spread of waterpipe use and its health effects can be understood, and empirically guided treatment and public policy strategies can be implemented. Maziak, W., Ward, K. D., Afifi Soweid, R. A. and Eissenberg, T. Tobacco Smoking Using a Waterpipe: A Re-emerging Strain in a Global Epidemic. Tob. Control, 13(4), pp. 327-333, 2004.

Gender Effects of Reported in Utero Tobacco Exposure on Smoking Initiation, Progression and Nicotine Dependence in Adult Offspring

The investigators studied the relationship between self-reported in utero tobacco exposure and gender on smoking initiation, progression of cigarette use (i.e., telescoping), and current levels of nicotine dependence in adult treatment-seeking smokers. Subjects (N = 298) who reported "yes" (28% of the original sample) or "no" (50% of the original sample) to in utero tobacco exposure were included in the analyses. Telescoping was calculated as the difference between the age respondents smoked their "first full cigarette" and the age when they started smoking daily. Females who reported being exposed in utero transitioned from initial to daily cigarette use more rapidly than females not exposed. The opposite effect was found for males, which may be related to our finding that in utero exposure lowered the age of cigarette experimentation in exposed compared with unexposed males. Measures of current cigarette use and dependence (i.e., Fagerstrom Test for Nicotine Dependence, prior withdrawal, number of past year quit attempts) were significantly associated with reported in utero exposure, gender, or interactions of exposure and gender. In utero tobacco exposure may accelerate the progression from experimentation to daily use in girls, result in early tobacco experimentation among boys, and produce higher levels of nicotine dependence among adult smokers. Oncken, C., McKee, S., Krishnan-Sarin, S., O'Malley, S. and Mazure, C. Gender Effects of Reported In Utero Tobacco Exposure on Smoking Initiation, Progression and Nicotine Dependence in Adult Offspring. Nicotine Tob. Res., 6(5), pp. 829-833, October 2004.

Progesterone Treatment and Cocaine Responses

The investigators examined the interaction between progesterone and cocaine in both male and female cocaine users using subjective, physiological and behavioral outcomes. A total of 10 subjects, 6 male and 4 female cocaine users, had two experimental sessions. Before each session, participants received either two oral doses of 200 mg of progesterone or placebo. Two hours after the second dose of medication treatment, the participants received a 0.3 mg/kg dose of cocaine intravenously and started the self-administration period, in which five optional doses of cocaine were available. Progesterone treatment attenuated the cocaine-induced diastolic blood pressure increases without affecting the systolic blood pressure and heart rate increases. Progesterone treatment also attenuated the subjective ratings of high and feel the effect of last dose in response to cocaine but did not affect cocaine self-administration behavior. These results suggest that progesterone attenuates some of the physiological and subjective effects of cocaine in both male and female participants. Sofuoglu, M., Mitchell, E. and Kosten, T.R. Effects of Progesterone Treatment on Cocaine Responses in Male and Female Cocaine Users. Pharmacol Biochem Behav., 78(4), pp. 699-705, August 2004.

Research on Medical Consequences of Drug Abuse

Sexual Risk Among Injection Drug Users Recruited from Syringe Exchange Programs in California

The objective of this study was to examine correlates of sexual risk among injection drug users (IDUs). A total of 1445 IDUs were recruited from California syringe exchange programs. Consistent condom use was independently related to being HIV-positive, having multiple sex partners, not having a steady partner, not sharing syringes, and not injecting amphetamines for men; and engaging in sex work, not sharing syringes, and not having a steady partner for women. Having multiple recent sexual partnerships that included a steady partner was related to engaging in sex work, speedball injection, and amphetamine use among men; and younger age, having had a sexually transmitted disease (STD), engaging in sex work, and using alcohol among women. Having heterosexual anal sex was related to having had an STD, having multiple sexual partners, using amphetamines, and syringe-sharing for men; and younger age and amphetamine use for women. Authors conclude that comprehensive prevention interventions addressing multiple sexual and injection risk behaviors are needed for IDUs. Bogart, L.M., Kral, A.H., Scott, A., Anderson, R., Flynn, N., Gilbert, M.L. and Bluthenthal, R.N. Sexual Risk Among Injection Drug Users Recruited from Syringe Exchange Programs in California. Sex Transm Dis., 32(1), pp. 27-34, January 2005.

Early Puberty in Girls: The Case of Premature Adrenarche

In this article authors examine the issue of early puberty in girls. First, a brief overview of normal pubertal development is provided, including the two endocrine components of puberty: gonadarche and adrenarche. Second, authors critically discuss the controversy regarding whether puberty truly is occurring earlier in girls. Third, they emphasize one type of early puberty, the case of premature adrenarche (PA). PA is used to illustrate the importance of identifying types of early puberty, evaluating the types to determine causality, determining whether follow-up of early puberty is necessary, and showing the potential ramifications of ignoring this variation in pubertal development. Findings from a pilot study comparing PA and on-time puberty children are used to show the importance of determining whether early puberty is normal in all cases. Dorn, L.D. and Rotenstein, D. Early Puberty in Girls: The Case of Premature Adrenarche. Womens Health Issues, 14(6), pp. 177-183, November-December 2004.

Vitamin D Deficiency and Seasonal Variation in an Adult South Florida Population

Hypovitaminosis D is associated with impaired neuromuscular function, bone loss, and fractures. If a person is not taking a vitamin supplement, sun exposure is often the greatest source of vitamin D. Thus, vitamin D deficiency is not uncommon in the winter, particularly in northern latitudes. The goal of this study was to establish the prevalence of vitamin D deficiency in south Florida (U.S.), a region of year-round sunny weather. At the end of the winter, 212 men and women attending an internal medicine clinic at a local county hospital were enrolled for measurements of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, and PTH; 99 participants returned at the end of summer. The mean (sd) winter 25(OH)D concentration was 24.9 8.7 ng/ml (62.3 21.8 nmol/liter) in men and 22.4 8.2 ng/ml (56.0 20.5 nmol/liter) in women. In winter, the prevalence of hypovitaminosis D, defined as 25(OH)D less than 20 ng/ml (50 nmol/liter), was 38% and 40% in men and women, respectively. In the 99 subjects who returned for the end of summer visit, the mean 25(OH)D concentration was 31.0 11.0 ng/ml (77.5 27.5 nmol/liter) in men and 25.0 9.4 ng/ml (62.5 23.5 nmol/liter) in women. Seasonal variation represented a 14% summer increase in 25(OH)D concentrations in men and a 13% increase in women, both of which were statistically significant. The prevalence of hypovitaminosis D is considerable even in southern latitudes and should be taken into account in the evaluation of postmenopausal and male osteoporosis. Levis, S., Gomez, A., Jimenez, C., Veras, L., Ma, F., Lai, S., Hollis, B. and Roos, B.A. Vitamin D Deficiency and Seasonal Variation in an Adult South Florida Population. J Clin Endocrinol Metab., 90(3), pp. 1557-1562, March 2005.

Services Research

Treatment Outcomes Among Women and Men Methamphetamine Abusers In California

A prospective longitudinal study examined treatment outcomes among 1073 methamphetamine-abusing patients (567 women, 506 men) from 32 community-based outpatient and residential programs in 13 California counties. Data were collected at intake and at 3 months and 9 months after admission. With one exception, improvements from baseline to follow-up were observed in all areas measured by the Addiction Severity Index (ASI) for both women and men in either modality. However, compared to men, women demonstrated greater improvement in family relationships and resolution of medical problems, while maintaining the same level of improvement as men in all other areas. These results showed gains for women despite higher unemployment, greater childcare responsibilities, co-habitation with someone who also used alcohol or drugs, relatively more reports of physical or sexual abuse and more psychiatric symptoms. Hser, Y., Evans, E., and Huang, Y. Treatment Outcomes Among Women and Men Methamphetamine Abusers In California. Journal of Substance Abuse Treatment, 28(1), pp. 77-85, 2005.

Housing Offers Protective Function For Substance Abuse and Violence in Indigent Women

A study examining retrospective self-reports of stratified random samples of women residing in shelters (N = 460) and low-income housing (N = 438) in Los Angeles County, California found that sheltered women were more likely than housed women to report physical and sexual violence, substance use and disorder, HIV risk behavior, and the co-occurrence of these problems in the past year. Differences remained when propensity weights were used to equate the groups on demographic and background characteristics. Wenzel, S.L., Tucker, J.S., Elliott, M.V., Hambarsoomians, K., Perlman, J., Becker, K., Kollross, C. and Golinelli, D. Prevalence and Co-occurrence of Violence, Substance Use and Disorder, and HIV Risk Behavior: A Comparison of Sheltered and Low-income Housed Women in Los Angeles County. Preventive Medicine 39, pp. 617-624, 2004.

Men and Women Similar In Recovery Rates But Different In Psychosocial Functioning

Gender differences were examined at 36 months following residential or outpatient drug-free treatment among 951 participants in the Chicago Target Cities Project, the majority of whom were female (62%) and African American (93%). There were no differences in the proportion of men and women who reported any alcohol or drug use at the 36-month follow-up, with an overall reduction of 41% from intake. Greater proportions of men were incarcerated or employed, whereas greater proportions of women had returned to treatment, lived with their children, lived with a substance user, or had interpersonal problems. Women, as a group, had greater increases over time in self-help participation, free time spent with family, non-using family/friends, and employment. Although both men and women showed significant improvements following treatment, gender differences persisted in several areas of psychosocial functioning related to recovery. Grella, C.E., Scott, C.K, and Foss, M.A. Gender Differences in Long-term Drug Treatment Outcomes in Chicago PETS. Journal of Substance Abuse Treatment, 28, pp. 3-12, 2005.

Using Client Characteristics to Understand Treatment Process in the Therapeutic Community

Therapeutic communities (TCs) improve post-treatment outcomes for substance abusers, but little is known about the in-treatment experience for clients with different backgrounds, experiences, and needs. This study examined the in-treatment experience of TC participants and examined the relationships between treatment process and client characteristics. Research participants included 447 adults and 148 adolescents receiving treatment in community-based TC programs in New York, California, and Texas. Data related to treatment process were collected using the Therapeutic Community Treatment Process: Dimensions of Change Instrument. Data on demographic characteristics, substance use and treatment history, and client risk factors were extracted from intake interviews and analyzed separately for adolescent and adult residents. Multivariate general linear models were used to examine the effect of client variables on treatment process, after controlling for treatment duration and program effects. Adult clients in the study were on average 36 years old, over half were male, and 57% were African American. The average age of adolescent clients was 17, with 73% being male, and 43 % Hispanic. Adult program participants who were 25 years or older, female, and had prior drug treatment were more positive about their experiences in the TC as indicated in their higher Community Environment scores. Adolescents with one or more arrests within the past 2 years were more negative about both their experiences in the TC and their self-concept as indicated in lower scores on process dimensions of the Community Environment and Personal Development and Change scales. Results from this study indicate how differences in client characteristics affect important treatment process variables including readiness for change and motivation for treatment. Chan, K.S., Wenzel, S., Orlando, M., Montagnet, C., Mandell, W., Becker, K. and Ebener, P. How Important are Client Characteristics to Understanding Treatment Process in the Therapeutic Community? The American Journal of Drug and Alcohol Abuse, 30(4), pp. 871-891, 2004.

Women's Perception of Therapeutic Communities

A comprehensive measure of treatment was administered to 447 adults and 148 adolescents receiving treatment at community-based TC programs in New York, California, and Texas. Data on demographic characteristics, substance use and treatment history, and client risk factors were extracted from intake interviews and analyzed separately for adult and adolescent residents. Controlling for treatment duration and program effects, female clients over 25 who had prior drug treatment experience reported more positive perceptions of the therapeutic community environment and expressed more willingness to change in contrast to younger males with no prior treatment experience or with one or more arrests within the past 2 years. Chan, K.S., Wenzel, S., Orlando, M., Montagnet, C., Mandell, W., Becker, K., and Ebener, P. How Important Are Client Characteristics to Understanding Treatment Process in the Therapeutic Community? The American Journal of Drug and Alcohol Abuse 30(4), pp. 871-891, 2004.

Physical Violence Against Impoverished Women: Risk and Protective Factors

Violence represents a significant threat to the health of impoverished women. Few studies have attempted to identify risk and protective factors associated with violence directed at these women, although this information might be useful for violence prevention. In a representative probability sample of impoverished women, this study prospectively examined multiple risk and protective factors to understand their relative importance to physical victimization. Study participants included 810 women in Los Angeles County, 402 living in shelters and 408 living in Section 8 low-income housing, who completed structured interviews at baseline and 6-month follow-up. Significant (p < .05) multivariate predictors of physical violence experienced during the 6 months prior to the follow-up interview included physical or sexual violence experienced as a child, physical violence experienced during the 6 months prior to baseline interview, having multiple sexual partners, psychological distress, and poor social support. Results highlight the persistence of physical violence in the lives of impoverished women and prospective risk factors for this violence. Findings also highlight opportunities to reduce women's risk of experiencing violence through enhancing social support and mental health. Wenzel, S.L., Tucker, J.S., Elliott, M.N., Marshall, G.N. and Williamson, S.L. Physical Violence Against Impoverished Women: A Longitudinal Analysis of Risk and Protective Factors. Women's Health Issues, 14(5), pp. 144-154, 2004.

Gender Differences Found in Comprehensive Services in Substance Abuse Treatment

Utilizing data from the National Treatment Improvement Evaluation Study (NTIES), collected from 1992 to 1997, researchers report noteworthy gender differences. The analytic sample consisted of 3,142 clients (1,123 women and 2,019 men) from 59 treatment facilities. Findings show that greater proportions of women receive services; and when individual, service, and treatment organizational characteristics are controlled for, women show greater reductions in post-treatment substance use. Further, women and men differ in their responsiveness to organizational characteristics. The availability of on-site services and the frequency of counseling significantly predict reduced post-treatment substance use for men, but not for women. Marsh, J.C., Cao, D. and D'Aunno, T.D. Gender Differences in the Impact of Comprehensive Services in Substance Abuse Treatment. Journal of Substance Abuse Treatment, 27, pp. 289-300, 2004.