Research Findings - Behavioral and Brain Development Research

Prenatal Cocaine Exposure, Gender, and Preadolescent Substance Use and Other Health Risk Behaviors

Dr. Michael Lewis and his colleagues examined prenatal cocaine exposure, gender, and environmental risk as predictors of self-reported substance use, aggression, and a disregard for safety precautions on the Youth Risk Behavior Survey in a sample of 10.5 year olds (n = 154, including 60 who were prenatally exposed to cocaine). Gender tended to moderate the effects of prenatal cocaine exposure because exposure effects were found for boys but not girls. Boys who were prenatally exposed to cocaine reported engaging in more high-risk behavior. In examining individual outcomes, cocaine exposed boys had the highest scores for aggression, substance use, and a disregard for safety precautions, although these differences were significant only for the composite health risk behavior measure. The findings extend earlier work showing that prenatal cocaine exposure places boys at risk for problems of inhibitory control, emotional regulation, and antisocial behavior. Research is needed to examine whether the effects of prenatal cocaine on health risk behaviors persist into adolescence, when such behaviors tend to increase. Bennett, D., Bendersky, M., and Lewis, M. Preadolescent Health Risk Behavior as a Function of Prenatal Cocaine Exposure and Gender. Journal of Behavioral Pediatrics, 28(6), pp. 467- 472, 2007.

Longitudinal Analysis of the Effects of Prenatal Cocaine Exposure on Growth

Dr. Gale Richardson and her colleagues at the University of Pittsburgh investigated the effects of prenatal cocaine exposure on offspring growth from 1 through 10 years of age using a repeated-measures growth-curve model. Cross-sectional analyses showed that children exposed to cocaine during the first trimester (n = 99) were smaller on all growth parameters at 7 and 10 years, but not at 1 or 3 years, than the children who were not exposed to cocaine during the first trimester (n = 125). The longitudinal analyses indicated that the growth curves for the 2 groups diverged over time: children who were prenatally exposed to cocaine grew at a slower rate than children who were not exposed. These analyses controlled for other factors associated with child growth. This is the first study of the long-term effects of prenatal cocaine exposure to conduct longitudinal growth-curve analyses using four time points in childhood. Children who were exposed to cocaine during the first trimester grew at a slower rate than those who were not exposed. These findings indicate that prenatal cocaine exposure has a lasting effect on child development. Richardson, G.A., Goldschmidt, L., and Larkby, C. Effects of Prenatal Cocaine Exposure on Growth: A Longitudinal Analysis. Pediatrics, 120(4), pp. e1017-1027, 2007.

fMRI and Working Memory in Adolescents with Prenatal Cocaine Exposure

This fMRI study examined prefrontal cortex activation during task performance on an n-back task with 34 adolescents, 17 who were exposed to cocaine and 17 who were not exposed. Five functionally derived regions of interest (ROI) were defined; in addition, 2 a priori anatomical ROIs were generated for Brodmann regions 10 and 46. Groups had similar performance on the n-back task (P >/= .4), with both showing a fewer number of correct responses on the 2-back than the 1-back (P < .001), indicating increased demands on working memory with greater task difficulty. In functionally derived ROIs, imaging results showed increased activation for both groups in the 2-back versus the 1-back condition. In anatomical ROIs, both groups showed greater activation in the 2-back versus the 1-back condition, with activation in the non-exposed group proportionally greater for the left prefrontal region (P = .05). In this sample of adolescents, participants who were exposed to cocaine and participants who were not exposed were similar in performance on an executive function task and in fMRI activation patterns during task performance. Hurt, H., Giannetta, J.M., Korczykowski, M., Hoang, A., Tang, K.Z., Betancourt, L., Brodsky, N.L., Shera, D.M., Farah, M.J., and Detre, J.A. Functional Magnetic Resonance Imaging and Working Memory in Adolescents with Gestational Cocaine Exposure. Journal of Pediatrics, 152(3), pp. 371-377, 2008.

Smoking During Teenage Pregnancies and Offspring Behavioral Problems

Dr. Nancy Day and her colleagues at the University of Pittsburgh prospectively examined the relationship between prenatal tobacco exposure (PTE) and child behavior in a birth cohort of 357 offspring of teenage mothers. PTE was defined as any exposure across pregnancy and, in separate analyses, exposure within each trimester. Outcomes included measures of behavior problems, activity, and attention. On average, the children were 6.4 years of age, 48% were females, and 69% were Black. Data on maternal tobacco and other substance use were collected prenatally and postnatally: 46% of the mothers smoked in the first trimester and 58% smoked 6 years later. Child urinary cotinine measured exposure to environmental tobacco smoke (ETS). PTE predicted significantly increased offspring activity; impulsivity; and aggression, externalizing, and total behavior problems in step 1. PTE remained a significant predictor of increased activity when maternal psychological characteristics, home environment, and ETS were added. The results were similar when PTE was examined by trimesters, although later pregnancy tobacco exposure predicted the most behavioral outcomes. In the final model, PTE (all three trimesters) and PTE (second trimester) were significant predictors of increased activity and attention problems, respectively. Other predictors of child behavior included maternal anxiety, depression, hostility, and home environment. ETS was not a significant predictor of child behavior when PTE was considered. Smoking during pregnancy among adolescents is a significant predictor of increased activity and attention problems in their offspring after controlling for covariates in the prenatal and current environments. Smoking cessation interventions are recommended for this population to avoid the effects of PTE on the offspring of pregnant adolescents. This is particularly important because these mothers will likely become pregnant again and many will increase their level of tobacco use as they mature. 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.

Volumetric MRI Study of Brain in Children with Intrauterine Exposure to Cocaine, Alcohol, Tobacco, and Marijuana

This study used volumetric MRI to study brain volumes of thirty-five 10- to 14-year-old children with (n=14) and without (n=21) intrauterine exposure to cocaine, alcohol, cigarettes, or marijuana. Volumetric MRI was performed to determine the effect of prenatal drug exposure on volumes of cortical gray matter; white matter; subcortical gray matter; cerebrospinal fluid; and total parenchymal volume. Head circumference was also obtained. Analyses of each individual substance were adjusted for demographic characteristics and the remaining 3 prenatal substance exposures. Regression analyses adjusted for demographic characteristics showed that children with intrauterine exposure to cocaine had lower mean cortical gray matter and total parenchymal volumes and smaller mean head circumference than comparison children. After adjustment for other prenatal exposures, these volumes remained smaller but lost statistical significance. Similar analyses conducted for prenatal ethanol exposure adjusted for demographics showed significant reduction in mean cortical gray matter; total parenchymal volumes; and head circumference, which remained smaller but lost statistical significance after adjustment for the remaining 3 exposures. Notably, prenatal cigarette exposure was associated with significant reductions in cortical gray matter and total parenchymal volumes and head circumference after adjustment for demographics that retained marginal significance after adjustment for the other 3 exposures. Finally, as the number of exposures to prenatal substances grew, cortical gray matter and total parenchymal volumes and head circumference declined significantly with smallest measures found among children exposed to all 4. These data suggest that intrauterine exposures to cocaine, alcohol, and cigarettes are individually related to reduced head circumference; cortical gray matter; and total parenchymal volumes as measured by MRI at school age. Adjustment for other substance exposures precludes determination of statistically significant individual substance effect on brain volume in this small sample; however these substances may act cumulatively during gestation to exert lasting effects on brain size and volume. Rivkin, M.J., Davis, P.E., Lemaster, J.L., Cabral, H.J., Warfield, S.K., Mulkern, R.V., Robson, C.D., Rose-Jacobs, R., and Frank, D.A. Volumetric MRI Study of Brain in Children with Intrauterine Exposure to Cocaine, Alcohol, Tobacco, and Marijuana. Pediatrics, 121(4), pp. 741-750, 2008.

Methadone Maintenance and Breastfeeding in the Neonatal Period

In a sample of methadone-maintained breastfeeding women and a matched group of formula-feeding women, this study evaluated concentrations of methadone in breast milk among breastfeeding women and concentrations of methadone in maternal and infant plasma in both groups. Eight methadone-maintained (dose: 50-105 mg/day), lactating women provided blood and breast milk specimens on days 1, 2, 3, 4, 14, and 30 after delivery, at the times of trough and peak maternal methadone levels. Eight matched formula-feeding subjects provided blood samples on the same days. Infant blood samples for both groups were obtained on day 14. Urine toxicological screening between 36 weeks of gestation and 30 days after the birth confirmed that subjects were not using illicit substances in the perinatal period. Concentrations of methadone in breast milk were low (range: 21.0-462.0 ng/mL) and not related to maternal dose. There was a significant increase in methadone concentrations in breast milk over time for all 4 sampling times. Concentrations of methadone in maternal plasma were not different between groups and were unrelated to maternal dose. Concentrations of methadone in infant plasma were low (range: 2.2-8.1 ng/mL) in all samples. Infants in both groups underwent neurobehavioral assessments on days 3, 14, and 30; there were no significant effects of breastfeeding on neurobehavioral outcomes. Fewer infants in the breastfed group required pharmacotherapy for neonatal abstinence syndrome, but this was not a statistically significant finding. Results contribute to the recommendation of breastfeeding for methadone-maintained women. Jansson, L.M., Choo, R., Velez, M.L., Harrow, C., Schroeder, J.R., Skakleya, D.M., and Huestis, M.A., Methadone Maintenance and Breastfeeding in the Neonatal Period. Pediatrics, 121(1), pp. 106-114, 2008.

Impact of Prenatal Cocaine Exposure on Attention and Response Inhibition as Assessed by Continuous Performance Tests

This longitudinal 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. The sample included 415 children from the Miami Prenatal Cocaine Study (219 cocaine-exposed, 196 non-cocaine-exposed as determined by maternal self-report and infant bioassays). Children were enrolled prospectively at birth and assessed comprehensively through age 7 years. 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., and Bandstra, E.S. Impact of Prenatal Cocaine Exposure on Attention and Response Inhibition as Assessed by Continuous Performance Tests. Journal of Developmental Behavioral Pediatrics, 28(3), pp. 195-205, 2007.

Sensation Seeking and Risk-Taking Propensity as Mediators in the Relationship Between Childhood Abuse and HIV-related Risk Behavior

Although a wealth of literature suggests that childhood physical, emotional, and sexual abuse are related to later-life HIV-related risk behaviors, few studies have explored disinhibition (e.g., impulsivity, risk-taking propensity, and sensation-seeking) as a risk factor in this relationship. In this cross-sectional study Dr. Carl Lejuez and his colleagues at the University of Maryland examined impulsivity, risk-taking propensity, and sensation seeking as mediators in the relationship between abuse history and engagement in HIV-related risk behaviors among a sample of 96 inner-city African American adolescents. Findings indicated that abuse history was positively related to self-reported engagement in HIV-related risk behaviors, as well as risk-taking propensity and sensation seeking. Abuse history was not related to impulsivity. Further, while sensation-seeking and risk-taking propensity (to a lesser extent) mediated this relationship, impulsivity did not. These findings provide an initial step in the examination of the mechanisms underlying the relationship between childhood abuse and engagement in HIV-related risk behaviors. Bornovalova, M.A., Gwadz, M.A., Kahler, C., Aklin, W.M., and Lejuez, C.W. Sensation Seeking and Risk-Taking Propensity as Mediators in the Relationship between Childhood Abuse and HIV-Related Risk Behavior. Child Abuse and Neglect, 32(1), pp. 99-109, 2008.

P3 Components of the Event-Related Potential and Marijuana Dependence in Southwest California Indians

Marijuana use and abuse is very high in Native Americans; however, little is known about neurobiological measures that are associated with marijuana addiction in this population. This study utilized event-related potentials to examine the responses to a facial recognition task in an adult sample of 317 Southwest California (SWC) Indians with (1) no drug dependence diagnosis; (2) marijuana use, but not other drug dependence diagnosis; and (3) marijuana dependence, as well as other drug dependence diagnosis. After taking age, gender, and the presence of a lifetime diagnosis of alcohol dependence into consideration; an increased latency in the P350 and P450 component peaks was found in those individuals with a diagnosis of marijuana dependence and also marijuana dependence co-morbid with other drug dependence. The amplitudes of these late component peaks were not associated with a diagnosis of marijuana dependence. Women appeared to be more impacted by a marijuana dependence diagnosis in that the P450 latencies were longer in females than in males which may be indicative of greater toxicity. The findings suggest that marijuana dependence may be associated with delays in the evaluation and identification of emotional stimuli in SWC Indians. Further longitudinal studies will be necessary to determine whether pre-disposing or co-morbid factors are a possible cause of the P300 latency effects in this high risk and understudied ethnic group. Ehlers, C., Gilder, D., and Phillips, E. P3 Components of the Event-Related Potential and Marijuana Dependence in Southwest California Indians. Addiction Biology, 13(11), pp. 130-142, 2008.