Research Findings - Behavioral and Brain Development Research

Age of Methylphenidate Treatment Initiation in Children with ADHD and Later Substance Abuse: Prospective Follow-Up Into Adulthood

The purpose of this study was to investigate whether the development of substance abuse disorders is related to the age at which stimulate treatment begins in children with attention deficit hyperactivity disorder (ADHD). Using a prospective longitudinal design, 176 methylphenidate-treated children were followed. Some of these children had begun stimulant treatment as early as age 6 and for others, the treatment did not begin until age 12. These Caucasian male children who were diagnosed with ADHD, but without conduct disorder, were reassessed at late adolescence (mean age=18.4 years) and adulthood (mean age=25.3). The study also included one hundred seventy-eight comparison subjects. Childhood predictor variables used in the Cox proportional hazards model included: age at initiation of methylphenidate treatment, total cumulative dose of methylphenidate, treatment duration, IQ, severity of hyperactivity, socioeconomic status, and lifetime parental psychopathology. Separate models examined a number of lifetime outcome measures which included: any substance use disorder, alcohol use disorder, non-alcohol substance use disorder, stimulant use disorder, antisocial personality, mood, and anxiety disorders. The results indicated a significant positive relationship between age of treatment initiation and non-alcohol substance use disorder. Specifically, the chance of developing a substance use disorder was greater the later in age that stimulant treatment began. Additional post hoc analyses showed that the relationship between age at stimulant treatment initiation and later substance use disorder was explained by the development of antisocial personality disorder which is often comorbid with substance abuse disorders. No relationship was found between the age at first methylphenidate treatment and mood and anxiety disorders. The results found in this study did not find that beginning stimulant treatment relatively early in the life of children with ADHD is associated with an increased risk for negative outcomes. Mannuzza, S., Klein, R., Truong, N., Moulton, J., Roizen, E., Howell K., and Castellanos, F. Age of Methylphenidate Treatment Initiation in Children with ADHD and Later Substance Abuse: Prospective Follow-Up into Adulthood. The American Journal of Psychiatry, 165 (5), pp. 604-609, 2008.

Fatty Acid Ethyl Esters in Meconium are Associated with Poorer Neurodevelopmental Outcomes to Two Years of Age

The aim of this study was to examine the relationship between fatty acid ethyl esters (FAEE) in meconium and neurodevelopment in infants at 6.5 months, 1 year, and 2 years of age who were exposed to alcohol in utero. The current study reports on a secondary analysis of the data collected in a prospective longitudinal study of high risk mothers and their infants. Meconium was collected from 219 newborns shortly after birth and neurodevelopment was assessed with the Bayley Scales of Infant Development (2nd edition) which included the Mental and Psychomotor scales. Increasing concentrations of FAEE were significantly correlated with poorer mental and psychomotor development at all follow-up visits even after controlling for a number of prenatal and maternal factors. The results of this study showed that elevated FAEE in meconium may be a marker in identifying newborn infants who may be at risk for mental and psychomotor delays from alcohol exposure in utero, but do not show the typical characteristic facies of FAS. Early intervention is critical in these children and the results of this study are important in that the meconium analysis described by these authors may be a reliable means of identifying these at-risk children at birth. Peterson, J., Kirchner, H., Xue, W., Minnes, S., Singer, L., and Bearer, C. Fatty Acid Ethyl Esters in Meconium are Associated with Poorer Neurodevelopmental Outcomes to Two Years of Age. Journal of Pediatrics, 152(6), pp. 788-792, June, 2008.

Meaningful Differences in Maternal Smoking Behavior during Pregnancy: Implications for Infant Behavioral Vulnerability

Dr. Laurie Wakschlag and her colleagues used the 9-month-old sweep of the Millennium Cohort Study, a cohort of over 18,000 infants born in 2000-2, to examine the effects of smoking during pregnancy on problem behavior in offspring. Prior research has shown that the prenatal exposure to maternal smoking is associated with problem behavior in infants, but it is not clear whether these effects are associated with maternal characteristics that distinguish persistent smoking from quitting or whether they are due to teratological effects. In this study, mothers were classified as pregnancy non-smokers, quitters and light or heavy smokers. The Carey Infant Temperament Scale was used to assess temperamental positive mood, receptivity to novelty and regularity. Mothers who smoked heavily during pregnancy had infants with the lowest scores of easy temperament and low positive mood. In contrast, mothers who quit smoking during their pregnancy had infants with the highest scores of easy temperament. There also appeared to be a protective effect of quitting during pregnancy in that these mothers' infants had a decreased risk of distress to novelty and irregularity in comparison to those mothers who had never smoked. The results of this study suggest that offspring behavior associated with pregnancy smoking is complex and multi-determined. Future research is needed to elucidate the differences in maternal personality characteristics between quitters and persistent smokers and how these differences help to predict early vulnerabilities and offspring behavioral patterns over time. Pickett, K., Wood, C., Adamson, J., DeSouza, L., and Wakschlag, L. Meaningful Differences in Maternal Smoking Behavior during Pregnancy: Implications for Infant Behavioral Vulnerability. Journal of Epidemiology and Community Health, 62(4), pp. 318-324, 2008.

Children's Cognitive-Behavioral Functioning at Age 6 and 7: Prenatal Drug Exposure and Caregiving Environment

This study examined the relationship of prenatal drug exposure (PDE) and caregiving environment to cognitive, academic, and behavioral performance. Participants included 111 with PDE that were part of a longitudinal randomized controlled trial of a home-based intervention among drug-using women and their infants. A total of 62 non-drug exposed children were recruited from the same community to serve as controls. At ages 6 and 7, children were administered the Stanford-Binet Intelligence Scales, Fourth Edition, the Wide Range Achievement Test and the Child Behavior Checklist. Numerous theoretically and empirically derived confounders that examined perinatal and environmental factors were included in the multivariate analyses. The results indicated that after adjustment for the confounding variables, there were no significant exposure-group differences on measures of cognitive, academic or behavior problems. Females had higher scores on overall IQ, higher reading achievement scores and fewer caregiver-reported attention and aggression problems. This gender difference was evident regardless of PDE status. The children who participated in this study were from low income families and scores obtained were well below normative expectations. Future studies examining the effects of prenatal exposure to drugs need to be aware of the influence that poverty has on cognitive and behavioral development of children so that attributions to PDE are accurate. Nair, P., Black, M., Ackerman, J., Schuler, M., and Keane, V. Children's Cognitive-Behavioral Functioning at Age 6 and 7: Prenatal Drug Exposure and Caregiving Environment. Ambulatory Pediatrics, 8(3), pp. 154-162, 2008.

Prenatal Cocaine Exposure: Drug and Environmental Effects at 9 Years

Dr. Sonia Minnes and her colleagues investigated the effects of prenatal cocaine exposure (CE) in a large sample of children with a high follow-up rate, controlling for a number of confounding variables such as polydrug exposure, blood lead levels, iron-deficiency anemia (IDA), quality of caregiving environment and foster/adoptive care. Three hundred and seventy one children in a longitudinal, prospective study from birth were assessed for IQ and school achievement at 9 years of age (192 cocaine exposure; 179 non-cocaine exposure). No effects were seen in school achievement measures. Poorer perceptual reasoning IQ was seen in CE children; the degree of impairment was linearly related to a cocaine metabolite. Effects were mediated by smaller birth head circumference, indicating a relationship with fetal brain growth. Positive effects of the home environment and negative effects of alcohol, lead, and marijuana exposure were additive. The most pervasive negative effects were associated with lead exposure, underscoring the need for stronger public health efforts. Lower lead levels and better home environments were seen in those CE children who were placed in foster/adoptive care. This study shows the importance of documenting environmental factors in behavioral teratology studies. Singer, L., Nelson, S., Short, E., Min, M., Lewis, B., Russ, S., and Minnes, S. Prenatal Cocaine Exposure: Drug and Environmental Effects at 9 years. Journal of Pediatrics, 153(1), pp. 105-111, 2008.

The Development of Corpus Callosum Microstructure and Associations with Bimanual Task Performance in Healthy Adolescents

Studies utilizing conventional magnetic resonance imaging studies have provided important information regarding the development of the corpus callosum (CC). This study used diffusion tensor imaging to examine the relationship of fine motor skills with white matter microstructural development of the CC in healthy children, adolescents, and young adults (ages 9 - 24 years). Fractional anisotropy (FA), which is a measure of white matter's structural organization, was the primary DTI variable. An alternating finger tapping test was used to assess interhemispheric transfer and motor speed. Relationships between behavioral performance on the tapping task and white matter microstructure, age, and gender were examined. Younger subjects performed the unilateral and bimanual finger tapping task significantly slower. Improved motor performance was correlated with increased white matter integrity in the splenium. The splenium of the CC is believed to be primarily involved in the transmission of interhemispheric signals from the posterior cortical regions. Gender differences were also noted in that males outperformed females. Decreases in alternating finger tapping time and increases in FA likely reflect increased myelination in the CC and more efficient neuronal signal transmission. The data from this study suggest that white matter integrity continues to develop until 18 years of age, which is consistent with findings from conventional MRI studies that show similar age related changes in splenium white matter volume. This study has expanded the utility of diffusion tensor imaging by using this method to demonstrate relationships between fine motor skills and underlying white matter microstructure in childhood and adolescence. Muetzel, R., Collins, P., Mueller, B., Schissel, A., Lim, K., and Luciana, M. The Development of Corpus Callosum Microstructure and Associations with Bimanual Task Performance in Healthy Adolescents. Neuroimage, 39(4), pp. 1918-1925, 2008.