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Director's Report to the National Advisory Council on Drug Abuse - September, 2007

Research Findings - Behavioral and Brain Development Research

Demographic and Psychosocial Characteristics of Mothers Using Methamphetamine During Pregnancy: Preliminary Results from the Infant Development, Environment, and Lifestyle Study (IDEAL)

The psychological characteristics and caretaking environments of 131 women enrolled in the first longitudinal study of prenatal methamphetamine (MA) exposure and child development were examined. Preliminary results from this study found that prenatal MA use was associated with lower maternal perceptions on quality of life, greater likelihood of substance use among family and friends, increased risk for ongoing legal difficulties, and a markedly increased likelihood of developing a substance abuse disorder. Preliminary findings also suggest that MA using women are more likely to have multiple, intertwined psychosocial risks that may result in maladaptive parenting and caregiving. These factors may impact the developmental outcomes of affected children. Derauf, C., LaGasse, L.L., Smith, L.M., Grant, P., Shah, R., Arria, A., Huestis, M., Haning, W., Strauss, A., Della Grotta, S., Liu, J., and Lester, B.M. Demographic and Psychosocial Characteristics of Mothers Using Methamphetamine During Pregnancy: Preliminary Results of the Infant Development, Environment, and Lifestyle study (IDEAL). The American Journal of Drug and Alcohol Abuse, 33(2), pp. 281-289, 2007.

Impact of Prenatal Cocaine Exposure on Attention and Response Inhibition

This study examined the influence of prenatal cocaine exposure on attention and response inhibition measured by continuous performance tests (CPTs) at ages 5 and 7 years. Participants included 219 cocaine-exposed and 196 non-cocaine-exposed children enrolled prospectively at birth and assessed comprehensively through age 7 years in the longitudinal Miami Prenatal Cocaine Study. Deficits in attention and response inhibition were estimated in relation to prenatal cocaine exposure using generalized estimating equations within the general linear model. Results indicate cocaine-associated increases in omission errors at ages 5 and 7 as well as increases in response times for target tasks (i.e., slower reaction times) and decreased consistency in performance at age 7. There were no demonstrable cocaine-associated deficits in commission errors. Estimates did not change markedly with statistical adjustment for selected prenatal and postnatal covariates. Evidence supports cocaine-associated deficits in attention processing through age 7 years. Accornero, V.H., Amado, A.J., Morrow, C.E., Xue, L., Anthony, J.C., Bandstra, E.S. Impact of Prenatal Cocaine Exposure on Attention and Response Inhibition as Assessed by Continuous Performance Tests. Journal of Developmental and Behavioral Pediatrics, 28(3), pp. 195-205, 2007.

Children's Language Trajectories Relative to Prenatal Cocaine Exposure

In this ongoing longitudinal study at Case Western Reserve University, language development was assessed at 1, 2, 4, and 6 years of age, and performance was analyzed for two groups of children based on cocaine exposure in utero (209 exposed, 189 not exposed). The groups were compared on receptive, expressive, and total language scores across time. Multiple potentially confounding and moderating factors were included in the analyses. A relationship between prenatal cocaine exposure and language development was seen over time for receptive, expressive, and total language scores, with cocaine exposure related to poorer performance. Analyses also indicated that prenatal tobacco exposure was related to lower receptive language scores, and that environmental factors were associated with language scores. The authors note that their findings are consistent with and extend the findings of other longitudinal studies of prenatal cocaine exposure and language development. In addition, it was noted that both the cocaine-exposed and nonexposed children declined in language performance over time, a result believed to be related to factors common to both groups (such as low SES, education, and poverty), and also consistent with findings from another prenatal cocaine exposure cohort study. Lewis, B.A., Kirchner, H.L., Short, E.J., Minnes, S., Weishampel, P., Satayathum, S., and Singer, L.T. Prenatal Cocaine and Tobacco Effects on Children's Language Trajectories. Pediatrics, 120(1), pp. e78-e85, 2007.

Prenatal Cocaine Exposure and Physical Growth Patterns to Age 8 Years

This report focuses on longitudinal growth patterns in a cohort of children observed from birth until 8 years of age following prenatal exposure to cocaine. Birth weight, length, and head circumference were recorded. Weight, length or height, and head circumference were assessed at 6, 12, 24, 48, 72, and 96 months of age. Analyses were reported for 202 primarily African American/ Caribbean children. Ninety of these children were classified as prenatally unexposed to cocaine, 38 as having heavier cocaine exposure (top quartile of meconium concentration for cocaine metabolites, and/or top quartile days of self-reported use during the entire pregnancy), and 74 as having lighter exposure. Prenatal cocaine and prenatal alcohol exposure were independently associated with lower weight, length, and head circumference at birth. The relationships between prenatal cocaine exposure and longitudinal growth patterns to 8 years of age were analyzed using multiple linear regression models, including covariates of gestational age, gender, ethnicity, age at assessment, current caregiver, birth mother's use of alcohol, marijuana, and tobacco during the pregnancy, and maternal pre-pregnancy weight and height indicators. The association of prenatal cocaine exposure and growth did not persist beyond the neonatal period. The authors report that although the rate of change in growth parameters for cocaine-exposed children (heavier exposure compared to unexposed, and lighter exposure compared to unexposed) exceeded those of unexposed children in the first two years and then lagged up to age 4, the negative association with cocaine ultimately largely dissipated by school age. The authors also note that their findings agree with school-age results from another cohort of children prenatally exposed to cocaine, and differ in some ways from the findings for two other study cohorts, adding that ongoing examination of growth patterns in their cohort as well as in cohorts from other studies will continue to clarify the potential impact of in utero cocaine exposure on growth patterns to school age and beyond. Lumeng, J.C., Cabral, H.J., Gannon, K., Heeren, T., and Frank, D.A. Pre-natal Exposures to Cocaine and Alcohol and Physical Growth Patterns to Age 8 Years. Neurotoxicology and Teratology, 29(4), pp. 446-457, 2007.

Visuospatial Working Memory in School-Aged Children Exposed in Utero to Cocaine

Among the neurocognitive impairments reported as associated with prenatal cocaine exposure, slower response time, and less efficient learning in school-aged children are common to findings from several laboratories. This study by Dr. Linda Mayes and her colleagues presents performance data on a spatial working memory task in 75 prenatally cocaine exposed (CE) and 55 nondrug-exposed (NDE) 8- to 10-year-old children. Children were administered a novel neuropsychological measure of immediate- and short-term memory for visuospatial information, the Groton Maze Learning Test (GMLT), a computer-based hidden maze learning test that consists of a "timed chase test" (a simple measure of visuomotor speed), eight learning trials followed by a delayed recall trial after an 8-minute delay and a reverse learning trial. Performance is expressed as correct moves per second and number of errors per trial. Across all trials, the cocaine-exposed group showed significantly slower correct moves per second and made significantly more errors. There were no significant main effects for amounts of alcohol, tobacco, or marijuana exposure. After an 8-minute delay and compared to the eighth trial, cocaine-exposed children showed less consolidation in learning compared to nonexposed children. When asked to complete the maze in reverse, cocaine-exposed children showed a greater decrement in performance (decreased correct moves per second and increased errors) compared to the eighth learning trial. Children exposed in utero to cocaine exhibit a possible impairment in procedural learning and diminished efficiency in creating and accessing an internal spatial map to master the hidden maze. Mayes, L., Snyder, P.J., Langlois, E., and Hunter, N. Visuospatial Working Memory in School-aged Children Exposed in utero to Cocaine. Child Neuropsychology, 13(3), pp. 205-218, 2007.

Multivariate Examination of Brain Abnormality Using Structural and Functional MRI with Adolescents Prenatally-Exposed to Cocaine

This article presents a methodological framework for extracting regional brain features simultaneously from both structural and functional images as a means for detecting brain abnormalities, and reports on the application of this method with a sample of 25 adolescents who had been exposed to cocaine in utero and a socioeconomically-matched comparison group of 24 non-exposed adolescents. High-resolution 3D structural MRI and arterial spin labeling perfusion MRI were the imaging modalities used. The procedure involved a regional statistical feature extraction approach to capture discriminative features from voxel-wise morphometric and functional representations of brain images. This feature extraction method was used in conjunction with a hybrid feature selection method and a nonlinear support vector machine for the classification of brain abnormalities. The investigators conclude that the method is capable of accurately detecting spatially distributed and complex patterns of brain alterations associated with prenatal cocaine exposure in an adolescent sample. Fan, Y., Rao, H., Hurt., H., Giannetta, J., Korczykowski, M., Shera, D., Avants, B.B., Gee, J.C., Wang J., and Shen, D. Multivariate Examination of Brain Abnormality Using Both Structural and Functional MRI. Neuroimage, 36(4), pp. 1189-1199, 2007.

Abnormal Cortical Thickness and Brain-Behavior Correlation Patterns in Individuals with Heavy Prenatal Alcohol Exposure

Quantitative magnetic resonance imaging (MRI) studies in children with fetal alcohol spectrum disorders (FASDs) have shown regional patterns of dysmorphology, most prominent in parietal and posterior temporal cortices. Various methods of image analysis have been employed in these studies, but abnormalities in cortical thickness have not yet been mapped over the entire cortical surface in individuals with FASD. Further, relationships between cognitive dysfunction and cortical thickness measures have not yet been explored. In this study Dr. Elizabeth Sowell and her colleagues applied cortical pattern matching algorithms and techniques for measuring cortical thickness in millimeters to the structural brain MRI images of 21 subjects with heavy prenatal alcohol exposure (8-22 years, mean age 12.6 years), and 21 normally developing control subjects (8-25 years, mean age 13.5 years). Dissociable cognitive measures, of verbal recall and visuospatial functioning, were correlated with cortical thickness, and group by test score interactions were evaluated for predicting cortical thickness. Significant cortical thickness excesses of up to 1.2 mm were observed in the FASD subjects in large areas of bilateral temporal, bilateral inferior parietal, and right frontal regions. Significant group by test score interactions were found in right dorsal frontal regions for the verbal recall measure and in left occipital regions for the visuospatial measure. These results are consistent with earlier analyses from this and other research groups and, for the first time, show that cortical thickness is also increased in right lateral frontal regions in children with prenatal alcohol exposure. Further, the significant interactions show for the first time that brain-behavior relationships are altered as a function of heavy prenatal alcohol exposure. Sowell, E.R., Mattson, S.N., Kan, E., Thompson, P.M., Riley, E.P., and Toga, A.W. Abnormal Cortical Thickness and Brain-Behavior Correlation Patterns in Individuals with Heavy Prenatal Alcohol Exposure. Cerebral Cortex, April 18, 2007 (e-published ahead of print).

fMRI of Verbal Learning in Children with Heavy Prenatal Alcohol Exposure

Dr. Elizabeth Sowell and her colleagues examined functional MRI activation patterns corresponding to verbal paired associate learning in a group of 11 children (between 8 and 13 years of age) with heavy prenatal alcohol exposure compared with 16 typically-developing children (between 7 and 15 years old). Among the typically developing children, prominent activation was observed in the left medial temporal lobe, left dorsal frontal lobe and bilateral posterior temporal cortices during learning and recall. Analyses revealed significantly less activation in left medial and posterior temporal regions and significantly more activation in right dorsal frontal cortex in the alcohol-exposed children relative to controls, even when group differences in memory test performance were statistically controlled. These results may indicate an increased reliance on frontal memory systems in the children with heavy prenatal alcohol exposure, perhaps compensating for dysfunctional medial temporal memory systems. These findings are consistent with neuropsychological and structural imaging studies, and provide the first evidence for brain activation abnormalities, independent of group performance differences, during verbal learning and recall in children with heavy prenatal alcohol exposure. Sowell, E.R., Lu, L.H., O'Hare, E.D., McCourt, S.T., Mattson, S.N., O'Connor, M.J., and Bookheimer, S.Y. Functional Magnetic Resonance Imaging of Verbal Learning in Children with Heavy Prenatal Alcohol Exposure. NeuroReport, 18(7), pp. 635-639, 2007.

Magnetic Resonance and Spectroscopic Imaging in Prenatal Alcohol-Exposed Children: Preliminary Findings in the Caudate Nucleus

This study was designed to identify and compare the neuroanatomical and neurochemical abnormalities that are associated with prenatal exposure to alcohol in both fetal alcohol syndrome (FAS)-diagnosed children and those diagnosed with fetal alcohol effects (FAE). MR data of three age-, gender- and race-balanced small groups of children (age range 9.6 to 12.7 years), FAS-diagnosed, FAE-diagnosed, and non-exposed controls, were compared. Effects of prenatal alcohol exposure, regardless of diagnosis, were found in the caudate nucleus. Specifically, a significantly smaller caudate nucleus was found for the FAS and FAE participants compared to the controls. In addition, the metabolite ratio of N-acetyl-aspartate to creatine (NAA/Cr), an indicator of neuronal function, in left caudate nucleus of both the FAS and FAE participants was elevated compared to the control group. Analysis of absolute concentrations revealed that the increase in the ratio of NAA/Cr was due to an increase in NAA alone. Although its exact function in the CNS is unknown, NAA is believed to be a neuronal marker due to its exclusive localization to neurons. Some also speculate a role for NAA in myelination. Elevated NAA in the prenatal alcohol-exposed participants could indicate a lack of normal programmed cell death, dendritic pruning and/or myelination during development. The present study demonstrates that prenatal alcohol-exposed children, with or without facial dysmorphology, have abnormal brain anatomy and chemistry. Corteses, B.M., Moore, G.J., Bailey, B.A., Jacobson, S.W., Delaney-Black, V., and Hannigan, J.H. Magnetic Resonance and Spectroscopic Imaging in Prenatal Alcohol-exposed Children: Preliminary Findings in the Caudate Nucleus. Neurotoxicology and Teratology, 28(5), pp. 597-606, 2006.

Smoking During Teenage Pregnancies and Behavioral Problems in Offspring

In this paper, Cornelius and colleagues at the University of Pittsburgh report on relationships between prenatal tobacco exposure (PTE) and school-age child behavior in a cohort of 357 offspring of teenage mothers. PTE was defined as any exposure across pregnancy for some of the analyses, and exposure within each trimester in other analyses. Interviews were conducted with the mothers at the fourth or fifth prenatal month visit and within 24-36 hours after delivery. Child exposure to environmental tobacco smoke (ETS) was assessed by urinary cotinine. Average age of the offspring in the analyses was 6.4 years. PTE (any exposure across pregnancy) was a significant predictor (p < .01) of increased activity (Routh Activity Scale) when controlling for other prenatal substance exposure, demographics, maternal psychological characteristics, home environment, and ETS. When controlling for the same factors, PTE (in each of the three trimesters) significantly (p < .01) predicted increased activity, and PTE (in the second trimester) significantly (p < .05) predicted attention problems (SNAP). ETS was not a significant predictor of behavioral outcomes when PTE was taken into account. The researchers indicate that their finding of an association of PTE with higher activity levels in exposed offspring agrees with results from animal and other human studies, and adds new evidence of the strength of this association given the extent of control for covariates in this study. Cornelius, M.D., Goldschmidt, L., DeGenna, N., and Day, N.L. Smoking During Teenage Pregnancies: Effects on Behavioral Problems in Offspring. Nicotine and Tobacco Research, 9(7), pp. 739-750, 2007.

Gender-Specific Effects of Prenatal and Adolescent Exposure to Tobacco Smoke on Auditory and Visual Attention

Smoking during pregnancy results in elevated risks of cognitive and auditory processing deficits and of smoking in the offspring. Preclinical studies have revealed that nicotine exposure in the prenatal and/or adolescent period results in a sex-specific pattern of reduction in cortical cholinergic markers. This study was designed to examine gender-specific effects of exposure to smoking in adolescents on auditory and visual attention. The sample consisted of 181 adolescent smokers and nonsmokers who had previously been exposed to maternal smoking or had not. The results demonstrated that both auditory and visual attention performance accuracy was decreased in females who were exposed to tobacco smoke during prenatal or adolescent development; however, the greatest deficits on these tasks were seen in female smokers who had also been exposed to tobacco smoke in the prenatal period (combined exposure). The pattern was somewhat different in males in that combined exposure resulted in greater deficits during the auditory attention conditions versus the visual processing tasks. Functional neuroimaging was conducted in a subset of 63 subjects while they were engaged in auditory and visual attentional tasks. In those adolescents with prenatal or adolescent exposure, activation of brain regions that support auditory attention was greater relative to controls with no exposure to tobacco smoke. The results of the functional imaging data suggest that reduced cortical cholinergic neurotransmission resulting from prenatal exposure or adolescent exposure to tobacco smoke results in a loss of efficiency in cortical regions that support auditory attention. This study supports the need for effective smoking prevention programs for women of childbearing age and for adolescents. Jacobsen, L., Slotkin, T., Mencl, W., Frost, S., and Pugh, K. Gender-Specific Effects of Prenatal and Adolescent Exposure to Tobacco Smoke on Auditory and Visual Attention. Neuropsychopharmacology, 2007 March 21; (Epub ahead of print).

The Adolescent Trials Network for HIV/AIDS Interventions: A Case Study of Developing Adolescent Health Community-Researcher Partnerships in Fifteen U.S. Communities

This article describes the partner selection process in 15 U.S. communities developing community-researcher partnerships for the Connect to Protect (C2P): Partnerships for Youth Prevention Interventions, an initiative of the Adolescent Trials Network for (HIV/AIDS) Interventions. Each site generated an epidemiological profile of urban youth in their community, selected a focus population and geographic area of youth at risk for HIV, conducted a series of successive structured interviews, and engaged in a process of relationship-building efforts culminating in a collaborative network of community agencies. Sites chose as their primary target population young women who have sex with men (n = 8 sites), young men who have sex with men (n = 6), and intravenous drug users (n = 1). Of 1162 agencies initially interviewed, 281 of 335 approached (84%) agreed to join the partnership (average 19/site). A diverse array of community agencies were represented in the final collaborative network; specific characteristics included: 93% served the sites' target population, 54% were predominantly youth oriented, 59% were located in the geographical area of focus, and 39% reported provision of HIV/STI (sexually transmitted infection) prevention services. Relationship-building activities, development of collaborative relationships, and lessons learned, including barriers and facilitators to partnership, are also described. Study findings address a major gap in the community partner research literature. Health researchers and policymakers need an effective partner selection framework whereby community-researcher partnerships can develop a solid foundation to address public health concerns. Straub, D.M., Deeds, B.G., Willard, N., Castor, J., Peralta, L., Francisco, V.T., Ellen, J., and the Adolescent Trials Network for HIV/AIDS Interventions. Partnership Selection and Formation: A Case Study of Developing Adolescent Health Community-Researcher Partnerships in Fifteen U.S. Communities. Journal of Adolescent Health, 40(6), 489-498, 2007.

Prototypical Images in Condom Scripts among AIDS-Bereaved Adolescents

Twenty-five HIV-negative late adolescents (13 women and 12 men) who had lost a parent to AIDS generated vignettes in which the characters were deciding whether to use a condom (condom scripts). Two clinically trained judges rated the interpersonal tone of the condom scripts on 17 semantic differential scales. Three other clinically trained raters described script characters' attributes by selecting from a list of 36 terms. Multidimensional scaling (MDS) and individual differences hierarchical classes analyses (INDCLAS) were used to inductively derive a typology of condom scripts. Two dimensions emerged from MDS analysis: incompatibility and inequality. Condom scripts culminating in unprotected sex depicted situations in which partners held unequal influence. INDCLAS results suggested a prototype for equal-influence condom scripts - excited male and assertive, powerful female, and for unequal-influence (unprotected sex) condom scripts - powerful, disengaged male and permissive female. These results inform the development of theoretical models and HIV prevention program materials. Reich, W.A. and Rubin, R.M. Prototypical Images in Condom Scripts among AIDS-bereaved Adolescents, AIDS Education and Prevention, 19(1), pp. 82-94, 2007.

Predictors of Repeat Pregnancy among HIV-1 Infected Women

In the Women and Infants Transmission Study (WITS), a prospective cohort study of HIV-infected pregnant women at six US mainland and Puerto Rican sites, changes in the HIV-1 epidemic have included higher income, better education, and better-controlled HIV disease among more recently enrolled women. Because these changes may alter the reproductive patterns of these women, an awareness of these women's current reproductive behaviors is essential. Predictors of repeat pregnancy among HIV-1-infected women enrolled in the Women and Infants Transmission Study (WITS) were investigated. Women enrolled in WITS without a history of sterilization were included. Using bivariate and multivariate analyses, predictors of a repeat pregnancy were modeled. Changes in risk factors for repeat pregnancy over time were examined and important predictors of repeat pregnancy were determined. Of 2246 eligible women, 22% had more than one WITS-enrolled pregnancy. In bivariate analyses, risk of repeat pregnancy was associated with younger age, lower educational status, higher CD4%, and lower viral loads. There was little change in risk factors for repeat pregnancy over time. HIV-1-infected women who are younger and healthier are more likely to have more than one pregnancy. Factors associated with repeat pregnancy among HIV-1-infected women have remained stable over time. Awareness of these factors will better equip healthcare providers to address the reproductive needs of HIV-1-infected women. Bryant, A.S., Leighty, R.M., Shen, X., Read, J.S., Brouwers, P., Turpin, D.B., LaRussa, P.S., Pacheco-Acosta, E., Paul, M.E., Vajaranant, M., Tuomala, R.E. and the Women and Infants Transmission Study. Predictors of Repeat Pregnancy among HIV-1 Infected Women. Journal of Acquired Immune Deficiency Syndrome, 44(1), pp. 87-92, 2007.

Heritability of Illicit Drug Use and Transition to Dependence in Southwest California Indians

The rates of drug use and dependence are high in Native Americans, but information is lacking regarding the etiology or clinical course in this high risk population. Dr. Cindy Ehlers conducted analyses from data obtained through a larger study conducted to determine risk factors for substance dependence in Southwest California (SWC) Indians. The analyses conducted in this project were designed to answer questions regarding the age of onset, prevalence and heritability of substance use in the following classes of illicit drugs: marijuana, cocaine, stimulants, sedatives, opiates, hallucinogens, phencyclidine (PCP), and solvents. Progression of substance use to dependence was also determined for each drug class in this community sample. Each participant in the sample which included 460 subjects (190 men and 270 women) was administered the Semi-Structured Assessment for the Genetics of Alcoholism. The participants in this sample reported the first used drugs were solvents and marijuana, which typically occurred at age 14-15. Ninety-one percent of the sample reported using at least one of the illicit drug classes with marijuana (88%) and stimulants (60%) being the most commonly tried substances. Using variance component methods from SOLAR, substantial heritability was found for marijuana, opiates, PCP, sedatives and stimulants, but the results were only modest for initiation to cocaine, hallucinogens, and solvents. The results from this study suggest that heritability of the initiation of substance use, in SWC Indians, may be similar to other population samples; however, once initiation of the substance has occurred, higher rates of dependence are seen in this population for marijuana, opiates and stimulants. Ehlers, C., Wall, T., Corey, L., Lau, P., Glider, D., and Wilhelmsen, K. Heritability of Illicit Drug Use and Transition to Dependence in Southwest California Indians. Psychiatric Genetics, 17(3), pp. 171-176, 2007.

Depressive Symptoms in Adolescents: Associations with White Matter Volume and Marijuana Use

Decreased white matter and reduced hippocampal volumes have been associated with depressed mood. Chronic marijuana use appears moderately associated with an increased risk of depressive symptoms in both adolescents and adults. The purpose of this study was to examine whether marijuana use moderates the relationship between brain structure and depressive symptoms in an adolescent sample aged 16 - 18. Substance use, mood, and anatomical measures were collected after 28 days of monitored abstinence from marijuana users (n = 16) and demographically similar controls (n = 16). Consistent with prior studies, marijuana users demonstrated higher depressive scores compared to controls. A significant negative relationship was found between increased depressive scores on the Beck Depression Inventory and smaller white matter volume in the marijuana users group, but not the control group. The findings suggest that connections between areas involved in mood regulation may be disrupted by subtle neurodevelopmental white matter abnormalities. Longitudinal studies are needed to address the temporal and directional relationship of white matter volume, marijuana use, and depressive symptoms. Medina, K., Nagel, B., Park, A., McQueeny, T., and Tapert, S. Depressive Symptoms in Adolescents: Associations with White Matter Volume and Marijuana Use. Psychology and Psychiatry, 48(6), pp. 592-600, 2007.

Functional MRI of Inhibitory Processing in Abstinent Adolescent Marijuana Users

The results of studies examining marijuana use in adults have revealed abnormal neural inhibitory processing, compensatory hyperactivity, and altered neural processing differences even in the absence of this drug. Marijuana is the most commonly used illicit substance in the adolescent population. Existing data from the relatively few studies examining the effects of marijuana use in adolescent marijuana users on neurocognition indicate that there are deficits in executive functioning and evidence of neural dysfunction. This study utilized blood oxygen level dependent (BOLD) fMRI during a go/no-go task to examine response inhibition in marijuana using adolescents after being abstinent from the drug for at least 28 days. Although the marijuana users did not differ from the non-users on task performance, an increased BOLD response in dorsolateral prefrontal and parietal areas was seen in the marijuana users compared to control adolescents with limited substance use histories. These results may suggest a greater cognitive load associated with attending to the stimuli in marijuana users. However, it is uncertain whether this pattern of increased brain processing predates the onset of regular use or results from it. Additional studies are warranted to determine if altered inhibitory processing is a risk factor for substance use initiation and escalation. Tapert, S., Schweinsburg, A., Drummond, S., Paulus, M., Brown, S., Yang, T., and Frank, L. Functional MRI of Inhibitory Processing in Abstinent Adolescent Marijuana Users. Psychopharmacology (Berl), 2007 June 9; (Epub ahead of print).

Behavioral Impulsivity in Adolescents With Conduct Disorder Who Use Marijuana

Conduct disorder (CD), which is characterized by a variety of disruptive and antisocial behaviors, is frequently comorbid with substance abuse. A common component underlying both CD and substance abuse is impulsivity. Marijuana is the most frequently used illicit substance among adolescents in the United States, but little is known about the effects of marijuana on impulsivity. This study was designed to examine impulsive behavior in adolescents who have a psychiatric diagnosis of CD and who have used marijuana. Three groups of adolescents who were between 13 to 17 years of age were compared on the Immediate Memory Task (a measure of response initiation). The groups consisted of 1) adolescents with a current diagnosis of CD and a positive urine test for marijuana; 2) adolescents with CD, but with a negative urine-drug screen and 3) healthy adolescents without psychiatric diagnosis or previous drug use. The results showed a significant increase in laboratory impulsive responses across the three groups with the highest proportion of impulsive responses being emitted by the individuals who had CD and a positive urine test for marijuana. Although the results are preliminary, in adolescents with CD, marijuana use may further enhance impulsive behavior. Further studies are needed to determine the specific causal mechanisms for these differences. Dougherty, D., Mathias, C., Liguori, A., Marsh, D., Dawes, M., and Moeller, F.G. Behavioral Impulsivity in Adolescents With Conduct Disorder Who Use Marijuana. Addictive Disorders & Their Treatment. 6(1), pp. 43-50, 2007.

Neurocognitive Functioning in Adolescent and Young Adult Smokers

This study examines cognitive performance at 17-21 years of age in relation to current smoking and past regular smoking, while taking into account cognitive functioning prior to initiation of smoking. All participants were part of a longitudinal study in which they were followed from birth, and for whom data were available on multiple aspects of development, including cognitive functioning prior to initiation of smoking (i.e., in the 9-12 year-old age period). When they were 17-21 years old, 112 participants were divided into four groups, determined by urinalysis and self-report: current heavy smokers (> 9 cigarettes per day), current light smokers (< 9 cigarettes per day), former smokers (had smoked regularly in the past, but had not smoked for at least 6 months), and a comparison group who had never smoked regularly. Regular use was defined as smoking at least once daily. After accounting for potential confounders, including educational attainment, family income, marijuana use, and pre-smoking-initiation cognitive performance, current regular smokers performed worse than non-smokers in a variety of cognitive areas, including receptive and expressive vocabulary, oral arithmetic, and auditory memory. Former smokers differed from the non-smokers only in the arithmetic task. The authors note that the impact of current smoking appears to behave in a dose-response and duration-related fashion. They also indicate that the findings suggest that cognitive deficits associated with regular smoking during early adulthood may be reversed upon cessation. Fried., P.A., Watkinson, B., and Gray, R. Neurocognitive Consequences of Cigarette Smoking in Young Adults - A Comparison with Pre-Drug Performance. Neurotoxicology and Teratology, 28(4), pp. 517-525, 2006.

Impact of Smoking Abstinence on Working Memory Neurocircuitry in Adolescent Daily Tobacco Smokers

Recent surveys indicate that 50% of adolescents in the 12th grade report smoking tobacco at some point in their life and 13.5% report daily use of cigarettes. Nicotine exposure has been shown to induce withdrawal-emergent alterations in dopaminergic transmission in rodents during the adolescent period. Dr. Leslie Jacobsen and her colleagues examined whether acute smoking abstinence in adolescent daily tobacco smokers affects the efficiency of neurocircuitry supporting working memory. Using functional magnetic resonance imaging, fifty-five daily tobacco adolescent smokers were compared with 38 nonsmokers while performing a task with high verbal working memory load. The smokers were tested during smoking and after 24 hours of abstinence from tobacco use. Less accuracy in performance and greater activation of the left ventrolateral prefrontal cortex and left inferior parietal lobe was seen among the smokers relative to nonsmokers. While nonsmoking adolescents exhibited increases in functional connectivity between components of the working memory neurocircuit with increasing memory load, the adolescent smokers during abstinence did not. The reduced efficiency and alterations in the functional coordination between components of the working memory neurocircuit may be due to the effects of nicotine exposure on catecholaminergic systems during adolescent development. These results underscore the need to eliminate smoking in adolescents and of the role that withdrawal-emergent deficits in brain function may play in treatment. Jacobsen, L., Mencl, W., Constable, R., Westerveld, M., and Pugh, K. Impact of Smoking Abstinence on Working Memory Neurocircuitry in Adolescent Daily Tobacco Smokers. Psychopharmacology, 193(4) pp. 557-566, 2007.


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