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NIDA Home > Publications > Director's Reports > May, 2009 Index    

Director's Report to the National Advisory Council on Drug Abuse - May, 2009

Research Findings - Behavioral and Brain Development Research

Prenatal Exposure to Cigarettes, MAOA Genotype, Gender and Antisocial Behavior in Youth

Genetic susceptibility to antisocial behavior may increase fetal sensitivity to prenatal exposure to cigarette smoke. Dr. Laurie Wakschlag and her colleagues tested whether a functional polymorphism in the gene encoding the enzyme monoamine oxidase A (MAOA) interacts with prenatal exposure to predict pathways to adolescent antisocial behavior. One hundred seventy-six adolescents and their mothers participated in a follow-up of a pregnancy cohort with well-characterized exposure. A sex-specific pattern of gene x exposure interaction was detected. Exposed boys with the low-activity MAOA 5' uVNTR genotype were at increased risk for conduct disorder (CD) symptoms. In contrast, exposed girls with the high-activity MAOA uVNTR genotype were at increased risk for both CD symptoms and hostile attribution bias on a face-processing task. There was no evidence of a gene-environment correlation (rGE). Findings suggest that the MAOA uVNTR genotype, prenatal exposure to cigarettes and sex interact to predict antisocial behavior and related information-processing patterns. Future research to replicate and extend these findings should focus on elucidating how gene x exposure interactions may shape behavior through associated changes in brain function. Wakschlag LS, Kistner EO, Pine DS, Biesecker G, Pickett KE, Skol AD, Dukic V, Blair RJ, Leventhal BL, Cox NJ, Burns JL, Kasza KE, Wright RJ, Cook EH Jr. Interaction of prenatal exposure to cigarettes and MAOA genotype in pathways to youth antisocial behavior. Molecular Psychiatry. 2009; March; (Epub ahead of print).

Maternal Methadone Dosing Schedule and Fetal Neurobehavior

Daily methadone maintenance is the standard of care for opiate dependency during pregnancy. Previous research has indicated that single-dose maternal methadone administration significantly suppresses fetal neurobehaviors. The purpose of this study by Dr. Lauren Jansson was to determine if split-dosing would have less impact on fetal neurobehaviour than single-dose administration. Forty methadone-maintained women were evaluated at peak and trough maternal methadone levels on single- and split-dosing schedules. Monitoring sessions occurred at 36- and 37-weeks gestation in a counterbalanced study design. Fetal measures included heart rate, variability, accelerations, motor activity and fetal movement-heart rate coupling (FM-FHR). Maternal measures included heart period, variability, skin conductance, respiration and vagal tone. Repeated measure analysis of variance was used to evaluate within-subject changes between split- and single-dosing regimens. All fetal neurobehavioural parameters were suppressed by maternal methadone administration, regardless of dosing regimen. Fetal parameters at peak were significantly lower during single versus split methadone administration. FM-FHR coupling was less suppressed from trough to peak during split-dosing versus single-dosing. Maternal physiologic parameters were generally unaffected by dosing condition. Split-dosed fetuses displayed less neurobehavioral suppression from trough to peak maternal methadone levels as compared with single-dosed fetuses. Split-dosing may be beneficial for methadone-maintained pregnant women. Jansson LM, Dipietro JA, Velez M, Elko A, Knauer H, Kivlinghan KT. Maternal Methadone Dosing Schedule and Fetal Neurobehavior. J Matern Fetal Neonatal Med. 2009;22(1):29-35.

Maternal Smoking during Pregnancy and Newborn Neurobehavior

Dr. Laura Stroud and her colleagues examined effects of maternal smoking during pregnancy on newborn neurobehavior at 10 to 27 days. Participants were 56 healthy infants (28 smoking-exposed, 28 unexposed) matched on maternal social class, age, and alcohol use. Maternal smoking during pregnancy was determined by maternal interview and maternal saliva cotinine and postnatal smoke exposure was quantified by infant saliva cotinine. Infant neurobehavior was assessed through the NICU Network Neurobehavioral Scale. Smoking-exposed infants showed greater need for handling and worse self-regulation and trended toward greater excitability and arousal relative to matched, unexposed infants (all moderate effect sizes). In contrast to prior studies of days 0 to 5, no effects of smoking-exposure on signs of stress/abstinence or muscle tone emerged. In stratified, adjusted analyses, only effects on need for handling remained significant (large effect size). Effects of maternal smoking during pregnancy at 10 to 27 days are subtle and consistent with increased need for external intervention and poorer self-regulation. Along with parenting deficits, these effects may represent early precursors for long-term adverse outcomes from maternal smoking during pregnancy. That signs of abstinence shown in prior studies of 0- to 5-day-old newborns did not emerge in older newborns provides further evidence for the possibility of a withdrawal process in exposed infants. Stroud LR, Paster RL, Papandonatos GD, Niaura R, Salisbury AL, Battle C, Lagasse LL Lester, B. Maternal smoking during pregnancy and newborn neurobehavior: effects at 10 to 27 days. J Pediatr. 2009;154(1):10-6.

Stability of Early Living Arrangements, Behavior Outcomes, and Prenatal Drug Exposure

Dr. Henrietta Bada and her colleagues from the Maternal Lifestyle Study, the largest longitudinal prospective study of prenatal cocaine exposure, evaluated whether living arrangements of children with or without prenatal drug exposure would be associated with their behavior outcomes and adaptive functioning. At age three, 1092 children were evaluated with the Child Behavior Checklist and Vineland Adaptive Behavior Scales. Total and externalizing behavior problems T scores of children in relative care were lower (better) than those in parental care; externalizing behavior scores were lower than those in non-relative care (p < .05). Total behavior problem scores increased 2.3 and 1.3 points, respectively, with each move per year and each year of Child Protective Services involvement. Compared to children in non-relative care, those in parental or relative care had higher (better) scores in the Vineland Adaptive Behavior Scales total composite (p < .023), communication (p < .045), and daily living (p < .001). Each caretaker change was associated with a decrease of 2.65 and 2.19 points, respectively, in communication and daily living scores. Children's living arrangements were significantly associated with childhood behavior problems and adaptive functioning. The instability of living situation was also a significant predictor of these outcomes. While family preservation continues to be the goal of the child welfare system, expediting decision toward permanency remains paramount once children are placed in foster care. Bada HS, Langer J, Twomey J, Bursi C, Lagasse L, Bauer CR, Shankaran S, Lester BM, Higgins R, Maza PL. Importance of stability of early living arrangements on behavior outcomes of children with and without prenatal drug exposure. J Dev Behav Pediatr. 2008;29(3):173-82.

Parenting Stress and Child Behavior Problems in High-Risk Children with and without Prenatal Drug Exposure

This study examined the relationship between early parenting stress and later child behavior in a high risk sample of children exposed and unexposed to cocaine in utero. The study also examined the role of drug exposure on the relationship between parenting stress and child behavior. A subset of child-caregiver dyads (n=607, 221 prenatal cocaine exposure, 386 unexposed) were selected from the Maternal Lifestyle Study (MLS), the largest longitudinal prospective study of prenatal cocaine exposure. Selection was based on the presence of a stable caregiver at 4 and 36 months with no evidence of change in caregiver between those time points. Parenting stress at 4 months significantly predicted child externalizing behavior at 36 months. These relations were unaffected by cocaine exposure suggesting the relationship between parenting stress and behavioral outcome exists for high-risk children regardless of drug exposure history. These results extend the findings of the relationship between parenting stress and child behavior to a sample of high-risk children with prenatal drug exposure and have implications for child outcomes and treatment interventions for high risk children. Bagner DM, Sheinkopf SJ, Miller-Loncar C, LaGasse LL, Lester BM, Liu J, Bauer CR, Shankaran S, Bada H, Das A. The effect of parenting stress on child behavior problems in high-risk children with prenatal drug exposure. Child Psychiatry Hum Dev. 2009;40(1):73-84.

Prenatal Drug Exposure, Caregiving Context and Sustained Visual Attention

Dr. Maureen Black and her colleagues at the University of Maryland, Baltimore, examined three groups of children from low-income, urban environments to determine the effects of prenatal drug exposure (PDE) and caregiving environment on sustained visual attention (SVA) at 7 years of age. Drug-exposed children remaining in maternal care (n = 43), drug-exposed children placed in non-maternal care (n = 45), and community comparison (CC) children (n = 56) were administered a battery of neurocognitive tests, including the Conners' Continuous Performance Test (CPT). PDE children remaining in maternal care displayed more omission errors than CC children. PDE children in non-maternal care had intermediate scores that did not differ significantly from PDE children in maternal care or CC children. There were no group differences with respect to commission errors or reaction time. CPT errors of omission and commission were significantly correlated with parent-reported attention problems and academic achievement scores. PDE in the context of care provided by a maternal caregiver with persistent drug use patterns may contribute to problems in children's SVA at school-age. As parental drug abuse can interfere with the provision of early care, children raised in a drug-using context may be highly vulnerable to problems with self-regulation, including sustained attention. SVA problems may contribute to subsequent academic and behavioral problems as demands for concentration and sustained effort increase throughout childhood. Children who have been prenatally exposed to drugs or raised in a drug-using household may benefit from early intervention services to avoid problems in SVA that may interfere with subsequent neurocognitive functioning and academic performance. Ackerman JP, Llorente AM, Black MM, Ackerman CS, Mayes LA, Nair P. The effect of prenatal drug exposure and caregiving context on children's performance on a task of sustained visual attention. J Dev Behav Pediatr. 2008;29(6):467-74.

Modeling Prenatal Exposure to Cigarettes

While there is a burgeoning body of research linking smoking during pregnancy to problem behavior in offspring, a major criticism of this work has been the measurement of exposure in these studies (e.g. retrospective, self-reported only) that could lead to biased estimates. To address this issue, this study examined a pregnancy cohort with repeated prospective measures of exposure as well as biological assays to generate estimates of exposure patterns using a range of modeling techniques. In this sample the more complex assessments of exposure, including biological measures, generally did not perform better than simple indicators of exposure based on repeated self-report measures, with one exception: a combined self-report cotinine 'best estimate' of third trimester exposure was uniquely associated with lower brain : body ratio. Further study is needed using more sophisticated cotinine assays and testing prediction of a range of outcomes to ascertain whether these findings represent true differences or are specific to the sample, methods and outcomes used. Such research will inform the development of guidelines for adequate exposure characterization in developmental studies. Pickett KE, Rathouz PJ, Dukic V, Kasza K, Niessner M, Wright RJ, Wakschlag LS. The complex enterprise of modeling prenatal exposure to cigarettes: what is 'enough'? Paediatr Perinat Epidemiol. 2009;23(2):160-70.

Pregnancy and Sexual Health among Homeless Young IDUs

Research on pregnancy and sexual health among homeless youth is limited. In this study, qualitative interviews were conducted with 41 homeless young injection drug users (IDUs) in Los Angeles with a history of pregnancy. The relationship between recent pregnancy outcomes, contraception practices, housing status, substance use, utilization of prenatal care, and histories of sexual victimization are described. A total of 81 lifetime pregnancies and 26 children were reported. Infrequent and ineffective use of contraception was common. While pregnancy motivated some homeless youth to establish housing, miscarriages and terminations were more frequent among youth who reported being housed. Widespread access to prenatal and medical services was reported during pregnancy, but utilization varied. Many women continued to use substances throughout pregnancy. Several youth reported childhood sexual abuse and sexual victimization while homeless. Pregnancy presents a unique opportunity to encourage positive health behaviors in a high-risk population seldom seen in a clinical setting. Hathazi D, Lankenau SE, Sanders B, Jackson Bloom J. Pregnancy and sexual health among homeless young injection drug users. J Adolesc. 2009;32(2):339-55.

Distress Tolerance and Early Adolescent Externalizing and Internalizing Symptoms: The Moderating Role of Gender and Ethnicity

A large body of research has examined the development of internalizing and externalizing symptoms in childhood and early adolescence. Notably, there is significant concomitant impairment associated with early adolescent symptomatology, as well as association of these symptoms with future development of psychopathology, poor physical health, self-destructive thoughts and behaviors, criminal behavior, and HIV risk behaviors. Drawing on negative reinforcement theory, the current study sought to examine the potential role of distress tolerance, defined as the ability to persist in goal-directed activity while experiencing emotional distress, as a potential mechanism that may underlie both internalizing and externalizing symptoms among 231 Caucasian and African American youth (M age=10.9 years; 45.5% female; 54.5% Caucasian ethnicity). A series of regressions resulted in significant moderated relationships, such that low distress tolerance conferred increased risk for alcohol use among Caucasians, delinquent behavior among African Americans, and internalizing symptoms among females. Clinical implications, including the potential role of negative reinforcement models in early intervention with young adolescents, are discussed. Daughters SB, Reynolds EK, MacPherson L, Kahler CW, Danielson CK, Zvolensky M, Lejuez CW. Distress tolerance and early adolescent externalizing and internalizing symptoms: The moderating role of gender and ethnicity. Behav Res Ther. 2009;47(3):198-205.

Gene-Environment Interactions across Development: Exploring DRD2 Genotype and Prenatal Smoking Effects on Self-Regulation

Genetic factors dynamically interact with both pre- and postnatal environmental influences to shape development. Considerable attention has been devoted to gene-environment interactions (G x E) on important outcomes. It is also important to consider the possibility that these G x E effects may vary across development, particularly for constructs like self-regulation that emerge slowly, depend on brain regions that change qualitatively in different developmental periods, and thus may be manifested differently. To illustrate one approach to exploring such developmental patterns, the relation between variation in the TaqIA polymorphism, related to D2 dopamine receptor expression and availability, and prenatal exposure to tobacco was examined in two exploratory studies. First, in 4-week-old neonates, genotype-exposure interactions were observed for attention and irritable reactivity, but not for stress dysregulation. Second, in preschool children, genotype was related to Preschool Trail Making Test task performance on conditions requiring executive control; children with both the A1+ genotype and a history of prenatal tobacco exposure displayed disproportionately poor performance. Despite study limitations, these results illustrate the importance of examining the interplay between genetic and prenatal environmental factors across development. Wiebe SA, Espy KA, Stopp C, Respass J, Stewart P, Jameson TR, Gilbert DG, Huggenvik JI. Gene-environment interactions across development: Exploring DRD2 genotype and prenatal smoking effects on self-regulation. Dev Psychol. 2009;45(1):31-44.

Substance Use and HIV-Risk Behaviors among Young Men Involved in the Criminal Justice System

Dr. Nicholas Freudenberg and his colleagues examined the relationship between substance use and sexual HIV-risk behaviors among young men who have been incarcerated, in order to understand how HIV risks develop for this vulnerable population. A sample of 552 young men in a New York City jail was interviewed at the time of incarceration. Logistic regression was used to examine associations between alcohol and marijuana use and sexual HIV-risk behaviors in the 90 days prior to incarceration. Respondents were predominantly Black (57%) or Latino (37%), with a mean age of 17.4 years. The most common substances used were marijuana (82%) and alcohol (65%). Alcohol use prior to incarceration was significantly associated with having three or more sexual partners in the same time period (OR = 2.40, p < .001), as well as with having unprotected sex with a long-term partner (OR = 1.72, p < .01). Marijuana use was significantly associated with having multiple sex partners (OR = 1.55, p < .01). Heavy alcohol and marijuana use did not result in an increased likelihood of sexual HIV-risk behaviors. High rates of substance use and unprotected sex may have unintended health consequences for incarcerated young men. Severity of substance use is not a significant predictor of risk behaviors, suggesting the importance of contextual and social factors. Results highlight the need for HIV prevention efforts for this population that take into account contextual and social factors. Valera P, Epperson M, Daniels J, Ramaswamy M, Freudenberg N. Substance use and HIV-risk behaviors among young men involved in the criminal justice system. Am J Drug Alcohol Abuse. 2009;35(1):43-7.

Maternal Brain Response to Own Baby-Cry Affected by Cesarean Section

A range of early circumstances surrounding the birth of a child affects peripartum hormones, parental behavior and infant wellbeing. One of these factors, which may lead to postpartum depression, is the mode of delivery: vaginal delivery (VD) or cesarean section delivery (CSD). To test the hypothesis that CSD mothers would be less responsive to own baby-cry stimuli than VD mothers in the immediate postpartum period, Dr. Linda Mayes and her colleagues conducted functional magnetic resonance imaging, 2-4 weeks after delivery, of the brains of six mothers who delivered vaginally and six who had an elective CSD. VD mothers' brains were significantly more responsive than CSD mothers' brains to their own baby-cry in the superior and middle temporal gyri, superior frontal gyrus, medial fusiform gyrus, superior parietal lobe, as well as regions of the caudate, thalamus, hypothalamus, amygdala and pons. Also, within preferentially active regions of VD brains, there were correlations across all 12 mothers with out-of-magnet variables. These include correlations between own baby-cry responses in the left and right lenticular nuclei and parental preoccupations (r = .64, p < .05 and .67, p < .05 respectively), as well as in the superior frontal cortex and Beck Depression Inventory (r = .78, p < .01). First this suggests that VD mothers are more sensitive to own baby-cry than CSD mothers in the early postpartum in sensory processing, empathy, arousal, motivation, reward and habit-regulation circuits. Second, independent of mode of delivery, parental worries and mood are related to specific brain activations in response to own baby-cry. Swain JE, Tasgin E, Mayes LC, Feldman R, Constable RT, Leckman JF. Maternal brain response to own baby-cry is affected by cesarean section delivery. J Child Psychol Psychiatry. 2008;49(10):1042-52.


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