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Director's Report to the National Advisory Council on Drug Abuse - May, 2005

Research Findings - 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.

Evaluation of Behavioral Measures of Risk Taking Propensity with Inner City Adolescents

This study examined the utility of behavioral measures of risk-taking propensity in the assessment of self-reported real-world risk-taking behaviors using a sample of 51 high-school-aged inner-city adolescents. Results indicated that performance on one behavioral measure, the balloon analogue risk task (BART), accounted for unique variance in self-reported delinquency/safety risk behaviors as well as substance use risk behaviors, above and beyond that provided with demographics and self-report measures of risk-related constructs (i.e., impulsivity and sensation seeking). These results suggest the potential utilization of BART as part of a multimethod assessment to measure risk-taking propensity in adolescents. Aklin, W.M., Lejuez, C.W., Zvolensky, M.J., Kahler, C.W., and Gwadz, M., Behaviour Research and Therapy, 43(2), pp. 215-228, 2005.

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.

Contributions of Amygdala and Striatal Activity in Emotion Regulation

Understanding how emotion influences cognitive processes is critical for understanding both normal and atypical behavior. Dr. B.J. Casey and her colleagues have used functional magnetic resonance imaging to probe the role of the amygdala and the striatum in processing emotional information in a paradigm in which individuals were instructed to respond to the presentation of a happy or fearful face. They found that reaction time when presented with fearful faces was longer than when presented with happy faces and that the increased reaction time was correlated with increased activation in the right amygdala. Activation in the right caudate nucleus was increased when a subject was successful in not responding to a happy face when instructed to do so, implicating this structure in behavioral inhibition or impulse control. These findings, in normal subjects, can be used to probe the possible alterations in brain responses that may accompany drug use or abuse. Hare, T.A., Tottenheim, N, Davidson, M.C., Glover, G.H. and Casey, B.J., Biol. Psychiatry 57, pp. 624-632, 2005.

T-maze Performance after Developmental Exposure to F-19 Tagged 5-HTP in Chicks

Many neurotransmitter systems that are known to be affected by drug use and drug exposure are present in the central nervous system in quantities that are undetectable by conventional neuroimaging techniques. Dr. Sherry Dingman and her colleagues have synthesized a 5-hydroxytryptophan molecule (5-HTP) tagged with multiple fluorine atoms that should allow for the visualization of the serotonin neurotransmitter pathway using magnetic resonance spectroscopy. To determine whether the introduction of this molecule during development would affect serotonin function, it was injected into the airsac of chick eggs prior to hatching. Three days after hatching, the chicks that had been injected with the tagged 5-HTP were compared with chicks that had been injected with a control solution on a t-maze task selected for its sensitivity to serotonin function. No differences were found between the groups, indicating that performance on this task was unimpaired by the presence of the fluorine tagged molecule. Dingman, S., Nash, L., Hogan, J. and Branch, C., Perceptual and Motor Skills 99(3), pp. 793-798, 2004.

Alcoholism Risk, Tobacco Smoking, and P300 Event-related Potential

The amplitude of the P300 event-related potential has been reported to be smaller in children of alcoholic parents, i.e., in children at high risk for developing alcoholism, in some studies while other studies have not reported a difference. In this study, the amplitude of the P300 in response to a visual discrimination task was compared among young adults at low and high risk for the development of alcoholism that also differed on whether they smoked cigarettes. The results indicated that more of the variance in P300 amplitude was linked with smoking status than the risk for development of alcoholism. Since it has been suggested that alterations in P300 amplitude may be related to genetic risk for other disorders, the results of this study emphasize the need for taking smoking status into account in interpreting the results of studies using event-related potentials. Polich, J. and Ochoa, C.J., Clinical Neurophysiol. 115, pp. 1374-1383, 2004.

Small Tip Angle Three-Dimensional Tailored Radiofrequency Slab-Select Pulse for Reduced B1 Inhomogeneity at 3T

High field strength imaging systems have the advantages of increased signal-to-noise and signal-to-contrast ratios. Along with these advantages, however, is an increase in image artifacts due to inhomogeneities in the field. Dr. Stenger and his colleagues have developed a protocol that uses tailored radio frequency pulses and, in this report, provide evidence that the use of this protocol greatly reduces artifacts in high field strength images due to inhomogeneity while maintaining a reasonably short acquisition time. Saekho, S., Boada, F.E., Noll, D.C., and Stenger, V.A., Magnetic Resonance in Medicine 53, pp. 479-484, 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.

Early Development of Subcortical Regions Involved in Non-Cued Attention Switching

Being able to change one's focus between tasks, or among salient cues, is an important element in our cognitive repertoire that becomes more refined with age. In the series of experiments reported on here, Dr. B.J. Casey and her colleagues monitored brain activation patterns using fMRI as subjects of different ages switched from discriminating among stimuli based on shape or color. The results showed that both children and adults activated the caudate nuclei bilaterally when switching tasks (i.e., from a color-based discrimination to a shape-based discrimination or vice-versa). Adults, however, had quicker reaction times and were more accurate in performing the task. The quicker reaction time was correlated with decreased activation of the caudate nuclei and increased activation in prefrontal and parietal cortical regions. These results suggest that subcortical regions are important in attention-switching and that the task increasingly involves cortical regions as the individual becomes older. Casey, B.J., Davidson, M.C., Hara, Y., Thomas, K.M., Martinez, A., Galvan, A., Halperin, J.M., and Tottenham, N. Developmental Science 7(5), pp. 534-542, 2004.

Imaging the Developing Brain: What Have We Learned About Cognitive Development

Dr. B.J. Casey and her colleagues authored an article in a special issue of Trends on Cognitive Sciences entitled "Cognitive Development: At the Crossroads" in which they reviewed the neuroimaging literature on the neurobiology of cognitive development. A general principle in cognitive development is the ability to filter and suppress irrelevant information and attend to relevant information. As this capacity increases with age activation of areas of association cortex becomes less diffuse and more focal and anatomical evidence suggests a concurrent refinement in the connections of these areas. In general, imaging studies of the developing human nervous system indicate that basic functions, such as motor and sensory processing, mature first followed by areas involved in control of actions and that this maturation process is accompanied by a more refined and specific pattern of brain activation. Casey, B.J., Tottenham, N., Liston, C., and Durston, S. Trends in Cognitive Sciences 8(3), pp. 104-110, 2005.


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