Research Findings - Behavioral and Brain Development Research

Effects of Alcohol and Combined Marijuana and Alcohol Use During Adolescence on Hippocampal Volume and Asymmetry

During the period of adolescence, the hippocampus may be particularly vulnerable to the effects of alcohol and marijuana use. This study was designed to examine hippocampal volume and asymmetry in three groups of adolescents aged 15 - 18. An additional aim of the study was to examine the relationships between verbal memory functioning and hippocampal morphometry. The groups consisted of: 1) alcohol users, 2) alcohol + marijuana users and 3) non-substance-using controls. Differential effects on hippocampal morphometry were found for those adolescents abusing alcohol compared to those abusing both alcohol and marijuana. Alcohol abuse/dependence was associated with smaller left hippocampal volumes and increased right > left asymmetry compared to the alcohol + marijuana using teens and the non-substance-using controls. While a functional relationship was shown between verbal learning and hippocampal asymmetry in the healthy controls; this relationship was not found in adolescent substance abusers. Further research is needed to examine the potential interaction of marijuana and alcohol use on neurocognitive functioning among adolescent populations. Medina, K., Schweinsburg, A., Cohen-Zion, M., Nagel, B., and Tapert, S. Effects of Alcohol and Combined Marijuana and Alcohol Use During Adolescence on Hippocampal Volume and Asymmetry, Neurotoxicology and Teratology, 29(1), pp. 141-152, 2007.

Prenatal Marijuana Exposure and Marijuana Use at Age 14

In this longitudinal study conducted at the University of Pittsburgh, a cohort was recruited during the fourth prenatal month, and the mothers and their offspring were assessed at multiple ages from that time on. The assessments involved maternal psychological, social, and environmental factors, demographic status and substance use, and offspring cognitive, behavioral, psychological, and physical development. This report focuses on the association between prenatal marijuana exposure and marijuana use by the offspring at age 14 years. The analyses in this report are based on 563 offspring-mother pairs (74% of the original sample). The sample was half African American, half Caucasian, and mostly of lower socioeconomic status. Overall, at age 14 years, 30% of the adolescents reported using marijuana in the past year, and 7.5% reported using marijuana regularly (i.e., at least three to four times per week). Thirteen additional adolescents had initiated marijuana use but did not report use in the past year. Based on multivariate models of analysis, the authors conclude that prenatal marijuana exposure (i.e., average daily joints), in addition to other factors, predicts marijuana use at age 14 years. Specifically, they report a marginally significant association between prenatal marijuana exposure and age of onset of marijuana use, and a significant association between prenatal marijuana exposure and frequency of marijuana use at age 14 years. Variables controlled in these analyses include child's current alcohol and tobacco use, pubertal stage, delinquency, peer drug use, family history of drug use, and parental depression, current drug use, and strictness/supervision. Prenatal marijuana use did not predict age of onset or frequency of use for either alcohol or tobacco. The investigators discuss possible mechanisms by which prenatal marijuana exposure may predict marijuana use at age 14, and also discuss limitations on generalizability of the findings. Day, N.L., Goldschmidt, L., and Thomas, C.A. Prenatal Marijuana Exposure Contributes to the Prediction of Marijuana Use at Age 14. Addiction, 101, pp. 1313-1322, 2006.

Prenatal Cocaine Exposure and Child Behavior Outcomes Through Age 7 Years

Investigators from the Maternal Lifestyle Study, a multi-site longitudinal cohort study of development following prenatal exposure to cocaine and other substances, have reported on child behavior problems at ages 3, 5, and 7 years. The Child Behavior Checklist (CBCL) was administered to caregivers at all three ages, and data were reported for internalizing (e.g., social withdrawal, somatic complaints, anxiety), externalizing (e.g., delinquent and aggressive behaviors), and total behavior problems. Between 752 and 917 children were included in data analyses depending on the score category and the assessment age. Longitudinal hierarchical linear models were utilized to investigate relationships between prenatal cocaine exposure and behavior problem trajectories from 3 to 7 years. Statistical analyses included adjusting for a number of other prenatal exposures, and for time-varying covariates such as ongoing caregiver use of substances, demographic factors, family violence, and caregiver psychological distress. The authors report that high prenatal cocaine exposure was associated with trajectories of behavior problems (high exposure was defined as use > 3 times per week in the first trimester), independent of, and less than the significant combined effect of prenatal and postnatal tobacco and alcohol exposures. Caregiver depression and family violence were found to have independent negative association with all behavior outcomes. The investigators note that although the analyses are an important step in examining relationships between prenatal cocaine exposure and behavior outcomes, causality is far from being established. In addition, they point out that the findings highlight a need not only for continued prevention and treatment programs directed toward illegal drug use, but also for increased effort toward prevention and treatment of tobacco and alcohol use. Bada, H.M., Das, A., Bauer, C.R. et al. Impact of Prenatal Cocaine Exposure on Child Behavior Problems Through School Age. Pediatrics, 119, pp. e348-e359, 2007.

Maternal Depression, Prenatal Cocaine Use, and Infant Neurobehavior

Infant neurobehavior was assessed for 1053 infants at 1 month of age, and was studied in relation to prenatal cocaine use and postpartum maternal depression. The NICU Network Neurobehavioral Scale (NNNS) was used to measure infant neurobehavior, and the Addiction Severity Index (ASI) was used to assess present and past psychiatric history. These analyses were carried out within the context of the Maternal Lifestyle Study, a multi-site longitudinal cohort study of development following prenatal exposure to cocaine and other substances. Four groups were derived based on combinations of prenatal cocaine exposure/no prenatal cocaine exposure and current postpartum depression/no current postpartum depression. Analysis of covariance (with covariates birthweight, maternal age, SES, research site, and prenatal nicotine, marijuana, and alcohol) was utilized to examine infant neurobehavior in the four groups. Prenatal cocaine exposure by postpartum depression interactions were significant. A postpartum depression association was found for the non-cocaine-exposed infants (poorer self-regulation and more stress signs, excitability, and arousal than infants in the other groups). The combined prenatal cocaine exposure/current postpartum depression group did not differ on any of the neurobehavioral measures from the no-prenatal cocaine exposure/no current postpartum depression group. The investigators suggest that prenatal cocaine exposure may buffer or alter the relationship between postpartum depression and infant neurobehavior, with one possible explanation being prenatal cocaine exposure influences on developing monoamine systems. While cautioning that these analyses cannot determine if the observed depression effects are related solely to postpartum depression or if prenatal depression contributes to this relationship, the authors note that the findings do suggest the importance of considering maternal mood in studies of prenatal substance exposure. Salisbury, A.L., Lester, B.M., Seifer, R. et al. Prenatal Cocaine Use and Maternal Depression: Effects on Infant Neurobehavior. Neurotoxicology and Teratology, epub ahead of print, December 2006.

Prenatal Cocaine Exposure and Infant Regulation at 7 Months of Age

Using heart rate (HR) and respiratory sinus arrhythmia (RSA) as indices of reactivity and regulation during infancy, Drs. Schuetze, Eiden, and Coles report on assessments at 7 months of age in a sample of 154 infants (79 prenatally-exposed to cocaine and 75 not prenatally-exposed to cocaine). Data were collected during baseline and during tasks designed to elicit positive and negative affect. Analyses of covariance were carried out to examine group differences in change scores, with maternal alcohol and cigarette use during pregnancy, maternal age, measures of fetal growth, and gestational age as covariates. The investigators report that there was a significant suppression of RSA during the negative affect task for the non-exposed group but not for the exposed group. The response pattern of RSA suppression from baseline to environmental challenge is noted by the authors as being associated with more optimal state regulation in infancy, decreased behavior problems in preschool aged children, and more adaptive behavior during attention and affect eliciting tasks in preschool and school aged children. Based on their RSA suppression finding and other results, the authors conclude that their findings provide additional support for an association between prenatal cocaine exposure and dysregulation during infancy. Schuetze, P., Eiden, R.D., and Coles, C.D. Prenatal Cocaine and Other Substance Exposure: Effects on Infant Autonomic Regulation at 7 Months of Age. Developmental Psychobiology, 49, pp. 276-289, 2007.

Types of Violence, Protective Factors, Psychopathology, and Behaviors in Drug-Exposed Youth at 11 Years of Age

In this examination of violence and resilience among youth exposed to cocaine and other substances during pregnancy, four types of violence (community, domestic, violent friends, history of child abuse) were studied relative to the occurrence of several outcomes (delinquency, early drug use, symptoms of depression, diagnosis of conduct disorder or oppositional defiant disorder, diagnosis of ADHD) for 517 children at 11 years of age. Measurement of protective factors involved seven indicators of positive relationships and prosocial behavior to teachers, parents, friends, and peers, as well as indicators of effortful control (inhibitory control and attentional focusing). This work was conducted in the context of the Maternal Lifestyle Study, a multi-site longitudinal study of the development of children prenatally-exposed to cocaine and other substances. Mixed model regression analysis was used for each outcome, and all models were adjusted for research site effects. The results show various patterns of associations between specific types of violence and specific outcomes. For example, all forms of delinquency were associated with having violent friends, symptoms of depression were related to history of abuse, CD/ODD was more likely if exposed to domestic violence, and ADHD was not associated with any type of violence. Associations with protective factors also showed variation by outcome. For example, reduced occurrence of CD/ODD was associated with positive relatedness to others and with effortful control, while reduced school delinquency and reduced depression were related to positive relatedness. The authors conclude that the study provides new evidence on violence and protective factors relative to disruptive forms of psychopathology and behavior, and they comment on implications of the findings for interventions. Lagasse, L.L., Hammond, J., Liu, J., et al. Violence and Delinquency, Early Onset Drug Use, and Psychopathology in Drug-Exposed Youth at 11 Years. Annals of the New York Academy of Science, 1094, pp. 313-318, 2006.

Reliability and Validity of the Youth Version of the Balloon Analogue Risk Task (BART-Y) in the Assessment of Risk-Taking Behavior

Dr. Carl Lejuez and his colleagues examined the reliability and validity of the youth version of the Balloon Analogue Risk Task (BART-Y), a computer-based measure for assessing adolescent risk-taking propensity. In this sample of 98 inner-city African American adolescents (52% male, M age = 14.8, SD = 1.5), BART-Y demonstrated a significant relation with sensation seeking as well as a composite measure of risk behaviors across substance use, sexual behavior, delinquency, and health domains. BART-Y responding also explained unique variance in a composite of these risk behaviors above and beyond demographic variables and risk-related personality constructs, including sensation seeking and impulsivity. Lejuez, C.W., Aklin, W., Daughters, S., Zvolensky, M., Kayler, C., and Gwadz, M. Reliability and Validity of the Youth Version of the Balloon Analogue Risk Task (BART-Y) in the Assessment of Risk-Taking Behavior Among Inner-city Adolescents. Journal of Clinical Child and Adolescent Psychology, 36(1), pp. 106-111, 2007.

Improving Comprehension for HIV Vaccine Trial Information among Adolescents

Researchers from the Adolescent Trials Network for HIV/AIDS Interventions (ATN) developed and tested a simplified version of the HIV vaccine trial information provided to adults during the informed consent process by the HIV Network for Prevention Trials (HIVNET). The prototype was adapted for adolescents at risk for HIV/AIDS by: (1) reducing reading level; (2) reorganizing; (3) adding illustrations; and (4) obtaining focus group feedback. Adolescent participants (N = 187) at clinical sites in New York, Fort Lauderdale, and Los Angeles were randomly assigned to the standard or simplified version. Adolescents receiving the simplified version had significantly higher comprehension scores (80% correct vs. 72% correct), with 37% of items significantly more likely to be answered correctly and were also significantly more likely to recall study benefits and procedures. Overall, adolescents were less willing to participate in a potential HIV vaccine trial after presentation of information about the study than prior to presentation. The present study indicates the feasibility of adolescent participation in a vaccine trial, as simplification of vaccine information, combined with illustrations to depict key concepts, resulted in improved scores for adolescents on the comprehension and recall test. Murphy, D.A., Hoffman, D., Seage, G.R. 3rd, Belzer, M., Xu, J., Durako, S.J., and Geiger, M. Adolescent Trials Network for HIV/AIDS Interventions. Improving Comprehension for HIV Vaccine Trial Information Among Adolescents at Risk of HIV. AIDS Care, 19(1), pp. 42-51, 2007.

Unifying the Analyses of Anatomical and Diffusion Tensor Images Using Volume-Preserved Warping

Dr. Bradley Peterson and his colleagues at Columbia University Medical Center developed and tested an automated image analysis protocol that automatically identifies regions of anatomical abnormalities in anatomical magnetic resonance images and uses those regions as starting points for fiber tracking using diffusion tensor imaging. Their results showed that their methods could automatically identify regions of volumetric differences across groups of brains and, using those regions as seed points, identify differences in fiber tracts emanating from regions of known anatomical abnormalities. Xu, D., Hao, X., Bansal, R., Plessen, K.J., Geng, W., Hugdahi, K., and Peterson, B.S. Journal of Magnetic Resonance Imaging, 25, pp. 612-624, 2007.