Research Findings - Behavioral and Brain Development Research

Prenatal Smoking and Disruptive Behavior in Early Development

An association between prenatal smoking and disruptive behaviors in children has been documented in the research literature, but little is known about the possible emergence of these behaviors in early development. Dr. Lauren Wakschlag and colleagues investigated very early precursors to disruptive behavior problems, examining behaviors of prenatally-exposed children and non-exposed children at 12, 18, and 24 months of age. Maternal reports were recorded at 12, 18, and 24 months, and behavioral observations were carried out at 24 months. Analyses took into account multiple covariates (e.g., other substances used during pregnancy, parenting practices, and cumulative family risk, which included demographic, psychiatric, and psychosocial factors). The investigators report that exposed toddlers exhibited higher levels of behavior problems from 12 to 24 months, and that virtually all of the toddlers with clinically significant problems at age 2 years had been exposed. They also report that exposure was associated with social, rather than emotional aspects of early problem behaviors. Those exposed were more likely to exhibit stubbornly defiant and aggressive behavior, and lower social engagement. The two groups did not differ on difficulty regulating negative emotion. While pointing out that the data do not prove a causal relationship, the researchers do note that the findings allow generating ideas concerning which areas of the brain may be affected by exposure, and highlight a potential window of opportunity for early interventions aimed at altering disruptive behavior pathways before they become serious clinical patterns. Wakschlag, L.S., Leventhal, B.L., Pine, D.S., Pickett, K.E., and Carter, A.S. Elucidating Early Mechanisms of Developmental Psychopathology: The Case of Prenatal Smoking and Disruptive Behavior. Child Development, 77, pp. 893-906, 2006.

Postnatal Cocaine Use and Parental Behavior During Mother-Infant Interactions

Within a broader conceptual model for maternal behavior among polydrug cocaine-using mothers, this study investigated the relationship between maternal cocaine use (prenatal and postnatal) and maternal behavior during mother-infant interactions. Specifically, behaviors were observed in a feeding context between 4 and 8 weeks of infant age. The categories of maternal behaviors analyzed were maternal insensitivity (e.g., position without support, misses infant cues) and maternal warmth (e.g., talks to infant, pleasure toward infant). The conceptual model used by Dr. Eiden and her colleagues included prenatal and postnatal polydrug use, maternal psychopathology, maternal childhood history, and infant birth weight. There were no group differences in maternal warmth or between maternal psychological functioning and maternal warmth. Results of conceptual model testing indicated that only postnatal cocaine use was a significant and unique predictor of maternal insensitivity during feeding. Maternal depression/anxiety was marginally associated with maternal insensitivity. The investigators point out that the results add to a growing body of evidence that indicates the importance of examining postnatal caregiving as a predictor of child outcome among children exposed to substances in the prenatal period. Eiden, R.D., Stevens, A., Schuetze, P., and Dombkowski, L.E. A Conceptual Model for Maternal Behavior Among Polydrug Cocaine-Using Mothers: The Role of Postnatal Cocaine Use and Maternal Depression. Psychology of Addictive Behaviors, 20, pp. 1-10, 2006.

Prediction of Parenting Stress and Perception of Infant Temperament

This investigation was conducted from the perspective that prenatal cocaine exposure is a marker of developmental risk, and the risk may involve a range of social, environmental, and biological factors. The researchers note that two factors likely to mark heightened risk are the degree to which mothers perceive their parental role as highly stressful and the degree to which they perceive their infant as temperamentally difficult. Therefore, the goal of this study was to understand processes that may heighten or attenuate levels of parenting stress and perceptions of infant temperament for infants prenatally-exposed to cocaine. Neonatal behavior, infant temperament, parenting stress, and maternal psychopathology were assessed in a large sample of mother-infant dyads (394 prenatally-exposed infants and 590 comparison infants). The sample was drawn from the multi-site longitudinal Maternal Lifestyle Study, and infants were selected for inclusion if they were in the care of their biological mother. Neonatal behavior was observed at 1 month corrected age, and other assessments were carried out at 4 months corrected age. Results indicated that neonatal behavioral characteristics and certain maternal psychological characteristics interacted to predict maternal ratings of infant temperament, and maternal self-reports of parenting stress. Results were not related to drug exposure history. The researchers conclude that for mothers of at risk infants, with or without prenatal cocaine exposure, psychological distress affects the degree to which infant behavioral characteristics are experienced as stressful or difficult. The researchers also discuss implications of the findings for interventions. Sheinkopf, S.J., Lester, B.M., LaGasse. L.L., et al. Interactions Between Maternal Characteristics and Neonatal Behavior in the Prediction of Parenting Stress and Perception of Infant Temperament. Journal of Pediatric Psychology, 31, pp. 27-40, 2006.

Predicting Caregiver-Reported Behavior Problems in Cocaine-Exposed Children

The purpose of this study was to investigate predictors of caregiver-reported behavior problems in a sample of 3-year-old children. The children were either in a group exposed to cocaine prenatally, or in a comparison group. Two measures of behavior problems were used: the Conners' Parent Report Scale, and the Eyberg Child Behavior Inventory. The Conners' Scale has scales assessing conduct problems and impulsive/hyperactive behaviors. The Eyberg Inventory was designed to assess disruptive behaviors, especially those associated with oppositional-defiant and conduct disorders. Concurrent maternal/caregiver depression as measured by the Center for Epidemiologic Studies-Depression (CES-D) Scale was the only significant predictor of reported child behavior problems in a model that included prenatal drug exposure, child sex, and the quality of the child's environment. Comparisons involving maternal and non-maternal caregivers relative to depression scores and child behavior ratings are also provided in the report. The researchers discuss implications of the findings for clinical care and for future research on behavioral functioning of prenatally exposed children. Warner, T.D., Behnke, M., Hou, W., et al. Predicting Caregiver-Reported Behavior Problems in Cocaine-Exposed Children at 3 Years. Journal of Developmental and Behavioral Pediatrics, 27, pp. 83-92, 2006.

Behavioral Reactivity and Regulation in Preschoolers Prenatally-Exposed to Cocaine

Based on concerns in the literature that prenatal exposure to cocaine may increase risk for problems related to reactivity and regulation in infancy and childhood, this study examined whether cocaine-exposed children show such difficulties during the preschool period, a time of increased social and cognitive demands, and a time of rapid changes in reactivity and regulation. The procedure involved observing reactivity and regulation during a frustrating problem-solving task at 4.5 years of age. Frustration reactivity was measured by latency to show frustration and number of disruptive behaviors. Regulation was measured by latency to approach and attempt the problem-solving task and by the number of problem-solving behaviors. Results indicated that cocaine-exposed children took longer to engage in the problem-solving task, and that cocaine-exposed boys showed the most difficulties. The cocaine-exposed boys expressed frustration more rapidly and had a larger number of disruptive behaviors compared to non-exposed children and cocaine-exposed girls. The researchers make note that the effect sizes were relatively small, and feel that the results indicate both resilience and vulnerabilities. They also comment on implications for intervention and prevention. Dennis, T., Bendersky, M., Ramsay, D., and Lewis, M. Reactivity and Regulation in Children Prenatally Exposed to Cocaine. Developmental Psychology, 42, pp. 688-697, 2006.

Prenatal Cocaine Exposure and Childhood Externalizing and Internalizing Behavior Problems at Age 7 Years

In this longitudinal study on the neurodevelopmental consequences of in utero exposure to cocaine Dr. Emalee Bandstra and her colleagues at the University of Miami examined the relationship between prenatal cocaine exposure and parent-reported child behavior problems at age 7 years in a birth cohort of 407 African-American children (210 cocaine-exposed, 197 non-cocaine-exposed). The Achenbach Child Behavior Checklist (CBCL), a measure of childhood externalizing and internalizing behavior problems, was completed by the child's current primary caregiver during an assessment visit scheduled when the child was seven years old. Structural equation and GLM/GEE models disclosed no association linking prenatal cocaine exposure status or level of cocaine exposure to child behavior (CBCL Externalizing and Internalizing scores or the eight CBCL subscale scores) with this caregiver report. A next step in this line of research is to secure standardized ratings from other informants including teachers as well as youth self-report given previous research findings indicate that discordance between child, parent, and teacher reports of symptoms is common. Accornero, V.H., Anthony, J.C., Morrow, C. E., Xue, L., and Bandstra, E.S. Prenatal Cocaine Exposure: An Examination of Childhood Externalizing and Internalizing Behavior Problems at Age 7 Years. Epidemiol Psychiatric Society, 15 (1), pp. 20-29, 2006.

Predicting Cognitive Control from Preschool to Late Adolescence and Young Adulthood

The purpose of this study was to investigate whether cognitive control in early life predicts cognitive control later in life. At approximately 4 years of age, children participated in a delay-of gratification assessment which measures the ability to control attention in the face of temptation. These same children performed the go/no-go task (a well-studied measure of cognitive control) 10 years later at a mean age of 18 years 2 months. The delay-of-gratification and go/no-go tasks are similar in that they both require controlling a prepotent response. The results indicated that those children who were able to direct their attention away from tempting aspects of the rewards (temptation focus) in the delay-of-gratification task were faster at performing the go/no-go task without making errors. Prior studies have indicated that poor performance on the go/no-go task is associated with immature development of frontal-striatal regions. The results of the current study indicate that the temptation focus measure in the delay-of gratification task may be a marker of the subsequent development of frontal-striatal circuitry. Eigsti, I.M., Zayas, V., Mischel, W., Shoda, Y., Ayduk, O., Dadlani, M., Davidson, M., Aber, J.L., and Casey, B.J. Predicting Cognitive Control from Preschool to Late Adolescence and Young Adulthood. Psychological Science, 17 (6), pp. 478-484, 2006.

Phonological Development and Frontal Cortex

The left inferior frontal gyrus has been previously identified as a key area in language production. Dr. Elizabeth Sowell and her colleagues examined whether changes in cortical gray matter thickness in this specific region of the brain are associated with developmental improvements in phonological processing (a linguistic skill) in normally developing children. Forty-five children (mean age of 6.7 years) were administered two measures of phonological processing (the Lindamood Auditory Conceptualization Test and the Elision subtest of the Comprehensive Test of Phonological Processing) and underwent magnetic resonance imaging (MRI). These same children were reassessed with these measures approximately 2 years later. Motor functioning tasks were also administered to establish specificity of the phonological processing tasks with the left inferior frontal gyrus. The results indicated a positive correlation between thickness increase in the left inferior frontal gyrus and improving phonological skills, but not with improving hand motor skills. Understanding brain-behavior relationships in children with normal language development may enhance our understanding of the reported language deficits and learning difficulties in children exposed in utero to drugs of abuse. Lu, L., Leonard, C., Thompson, P., Kan, E., Jolley, J., Welcome, S., Toga, A., and Sowell, E. Normal Developmental Changes in Inferior Frontal Gray Matter are Associated with Improvement in Phonological Processing: A Longitudinal MRI Analysis. Cerebral Cortex. pp. 1-8, June 16, 2006.

Neuroimaging and Prenatal Drug Exposure

This article is a summary report of a symposium that brought together researchers who are investigating effects of prenatal substance abuse in humans and primates, and who are utilizing neuroimaging techniques in their studies. The purpose of the symposium was to assess strengths and weaknesses of the neuroimaging and data processing techniques, and to discuss strategies that may facilitate collection of imaging data in exposed and comparison children. Various imaging techniques were discussed, i.e., magnetic resonance imaging (MRI), positron emission tomography (PET), diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), and molecular imaging. Papers were presented by five groups, and are provided in this article. While the findings in this report are very preliminary, they emphasize the potential that neuroimaging methodologies have for understanding how drug exposure may affect brain development. Dow-Edwards, D.L., Benveniste, H., Behnke, M., et al. Neuroimaging of Prenatal Drug Exposure. Neurotoxicology and Teratology, 28, pp. 386-402, 2006.

Depression, Sensation Seeking, and Maternal Smoking as Predictors of Adolescent Cigarette Smoking

This study examined maternal and adolescent depression, maternal and teen sensation seeking, and maternal smoking, and their associations with adolescent smoking. Data were collected from a sample of 47 male and 66 female adolescents (ages 11-18 years) and their mothers from three different health clinics. The findings indicate that maternal sensation seeking was linked indirectly with adolescent smoking through teen sensation seeking, both of which were significantly associated with teen smoking (beta = 0.29, p < 0.001 and beta = 0.32, p < 0.001, respectively). Teen depression was associated positively with teen smoking (beta = 0.24, p < 0.01) when controlling for sensation seeking behaviors. Maternal smoking was also directly linked to adolescent smoking (beta = 0.20, p < 0.05). These findings underscore a potentially important role of sensation seeking in the origins of adolescent smoking, and clarify pathways of influence with regard to maternal attitudes and behaviors in subsequent teenage nicotine use. van de Venne, J., Bradford, K., Martin, C., Cox, M., and Omar, H.A. Scientific World Jr., 6, pp. 643-652, 2006.

ADHD, Sensation Seeking, and Pubertal Changes

This pilot study was designed to examine the relationship of pubertal changes and sensation seeking (SS) in adolescents with Attention Deficit Hyperactivity Disorder (ADHD). Patients with current or past histories of uncomplicated stimulant medication use for ADHD between the ages of 11 and 15 were recruited from a Child Psychiatry and a General Pediatric Clinic. SS was measured using the SS Scale for Children. Pubertal development was measured using Tanner staging, free testosterone, and DHEAS. Subjects and their parent were interviewed with the Diagnostic Interview Schedule for Children (DISC). SS total score was correlated with Tanner stage, free testosterone, and DHEAS (p < or = 0.01). The combined parent and child reports of symptoms of Oppositional Defiant Disorder from the DISC were inversely related to age (p < or = 0.05). Understanding SS in ADHD adolescents as they move through puberty will aid clinicians in monitoring ADHD adolescents and their trajectory into substance abuse and other high-risk behaviors. Martin, C.A., Guenthner, G., Bingcang, C., Smith, W.J., Curry, T., Omar, H.A., Raynes, M.K., and Kelly, T.H. A Pilot Study: Attention Deficit Hyperactivity Disorder, Sensation Seeking, and Pubertal Changes. Scientific World Jr., 6, pp. 637-642, 2006.

Vitamin D Status in Adolescents and Young Adults with HIV Infection

Vitamin D status affects immune function and may affect the progress of HIV infection. In this study, Dr. Craig Wilson and his colleagues from the Adolescent Trials Network for HIV/AIDS Interventions, a co-operative agreement co-funded by NIDA , assessed vitamin D intake and status in subjects with HIV infection and in matched control subjects to determine whether HIV infection was associated with vitamin D insufficiency. Plasma 25-hydroxyvitamin D [25(OH)D] concentrations and vitamin D intake were measured in a cross-sectional study of members of the Reaching for Excellence in Adolescent Health (REACH) cohort. The subjects were aged 14-23 y; 74% were female, and 72% were black. Mean (+/-SE) vitamin D intake from food was 30% greater (P = 0.023) in HIV-positive subjects (295 +/- 18 IU/d; n = 237) than in HIV-negative subjects (227 +/- 26 IU/d; n = 121). The prevalence of vitamin D supplement use was 29% (104 of 358 subjects) and did not differ significantly by HIV status (P = 0.87). Mean plasma 25(OH)D did not differ significantly (P = 0.62) between the HIV-positive (20.3 +/- 1.1 nmol/L; n = 238) and HIV-negative (19.3 +/- 1.7 nmol/L; n = 121) subjects, nor was HIV status a significant predictor of plasma 25(OH)D when multiple regression analysis was used to adjust for other variables. The prevalence of vitamin D insufficiency [plasma 25(OH)D < or = 37.5 nmol/L] in the subjects was 87% (312 of 359 subjects). The results indicate that HIV infection did not influence vitamin D status. The prevalence of vitamin D insufficiency was high in both HIV-positive and HIV-negative REACH subjects, perhaps because these disadvantaged, largely urban youth have limited sun exposure. Stephensen, C.B., Marquis, G.S., Kruzich, L.A., Douglas, S.D., Aldrovandi, G.M., and Wilson, C.M. Vitamin D Status in Adolescents and Young Adults with HIV Infection, American Journal of Clinical Nutrition, 83 (5), pp. 1135-1141, 2006.