Research Findings - Behavioral and Brain Development Research

Prenatal Methamphetamine Use and Neonatal Neurobehavioral Outcome

Neurobehavioral effects of prenatal methamphetamine exposure were examined in this study conducted by Dr. Barry Lester and his colleagues from the Infant Development, Environment and Lifestyle (IDEAL) study. Of 13,808 subjects screened, 1632 were eligible and consented and 166 (n=74 exposed) were enrolled in a longitudinal follow-up. Exposure was determined by meconium assay and self-report with alcohol, marijuana, and tobacco present in both groups. The NICU Network Neurobehavioral Scale (NNNS) was administered within the first 5 days of life. Analyses conducted on NNNS summary scores included exposure group effects, heavy MA use effects, association with frequency of use by trimester, and dose-response relationships with amphetamine metabolites. After adjusting for covariates, exposure to MA was associated with increased physiological stress. Heavy MA use was related to lower arousal, more lethargy, and increased physiological stress. First trimester MA use was related to elevated stress abstinence. Third trimester use was related to poorer quality of movement. Higher level of amphetamine metabolites in meconium was associated with increased CNS stress. Prenatal MA exposure was associated with neurobehavioral patterns of decreased arousal, increased stress, and poor quality of movement. The dose-response relationships may represent neurotoxic effects from MA. Smith, L.M., Lagasse, L.L., Derauf, C., Grant, P., Shah, R., Arria, A., Huestis, M., Haning, W., Strauss, A., Grotta, S.D., Fallone, M., Liu, J., and Lester, B.M., Prenatal Methamphetamine Use and Neonatal Neurobehavioral Outcome. Neurotoxicology and Teratology. Oct 3, 2007 (e-pub ahead of print).

Vagal Tone as a Resilience Factor in Children with Prenatal Cocaine Exposure

Researchers from the Maternal Lifestyle Study examined vagal tone (VT) as a resilience factor for children with prenatal cocaine exposure (CE). Presence of CE and other prenatal drugs was summed with postnatal risks in infancy to yield a 15-item risk index and children were classified as high versus low risk. High-risk children had lower IQ scores, more problem behaviors, and lower ratings of adaptive behaviors than low-risk children. VT was assessed during an infant exam at 1 month and toy exploration at 36 months (217 CE, 333 non-CE). Children were classified as having consistently high, consistently low, or fluctuating VT at 1 and 36 months. A significant risk by VT-stability interaction indicated that for high-risk children, those with stable low VT had higher ratings of adaptive behaviors at 36 months. This finding is consistent with theory linking reduced VT during tasks to adaptive regulation and indicates that such regulatory functioning may serve as a protective factor in prenatal CE. Sheinkopf, S.J., Lagasse, L.L., Lester, B.M., Liu, J., Seifer, R., Bauer, C.R., Shankaran, S., Bada, H., and Das, A. Vagal Tone as a Resilience Factor in Children with Prenatal Cocaine Exposure. Developmental Psychopathology, 19(3), pp. 649-673, 2007.

Predictors of Neonatal Abstinence Syndrome Severity in Methadone-Exposed Newborns

Investigators at Johns Hopkins University examined potential predictors of Neonatal Abstinence Syndrome (NAS), which is made up of symptoms reflecting dysfunction in autonomic and central nervous systems. Although infants born to mothers who experienced methadone-maintenance during pregnancy frequently show evidence of NAS, the signs and symptoms of NAS vary widely among infants. This study attempted to investigate some possible reasons behind such variation, with a focus on maternal vagal tone, a measure that reflects autonomic nervous system homeostasis, stress vulnerability, and self-regulation. Specifically, the investigators examined whether vagal tone responsivity to methadone administration in pregnant women provides insight into the pathophysiology and expression of NAS in the newborn. The expectation was that newborns born to mothers who show greater autonomic dysregulation, as reflected by increased levels of vagal suppression relative to methadone maintenance, would exhibit more severe NAS. At 36 weeks of gestation, electrocardiogram monitoring was carried out for 50 methadone-maintained pregnant women, at the times of trough and peak maternal methadone levels. NAS expression was related to maternal vagal activity; maternal vagal tone suppression and activation were associated with NAS symptomatology and treatment. NAS expression was not related to histories of maternal substance use or methadone maintenance, or to psychotropic medication exposure. The authors discuss potential mechanisms for interpretation of their findings. Jansson, L.M., DiPietro, J.A., Elko, A., and Velez, M. Maternal Vagal Tone Change in Response to Methadone is Associated with Neonatal Abstinence Syndrome Severity in Exposed Neonates. Journal of Maternal, Fetal and Neonatal Medicine, 20(9), pp. 677-685, 2007.

Marijuana Use Motives and Social Anxiety among Marijuana-Using Young Adults

A link between social anxiety and marijuana use has been found in both clinical and college samples. The purpose of this study was to examine the associations between social anxiety and marijuana use motives, and marijuana use problems in 159 undergraduate students. The results indicated that social anxiety predicted both coping motives (i.e., to regulate negative affective states) and conformity motives (i.e., using marijuana to avoid social censure) even after controlling for a number of other relevant factors. Future studies need to identify the social situations in which socially anxious individuals desire to use marijuana to help them alleviate their anxiety. It would also be important to better understand why some socially anxious individuals use marijuana to regulate their emotions while others do not. This study has implications for the prevention and treatment of this high-risk population. Buckner, J., Bonn-Miller, M., Zvolensky, M., and Schmidt, N. Marijuana Use Motives and Social Anxiety among Marijuana-Using Young Adults. Addictive Behaviors, 32, pp. 2238-2252, 2007.

Neuropsychological Functioning in Adolescent Marijuana Users: Subtle Deficits Detectable after a Month of Abstinence

Marijuana is the most commonly used illicit substance in the adolescent population. Although previous studies have observed neuropsychological deficits in adolescents who abuse marijuana, these studies included subjects with comorbid psychiatric disorders which may have contributed to the observed deficits. The purpose of this study was to examine whether marijuana use or extent of marijuana use was associated with neuropsychological functioning in an adolescent sample aged 16 - 18. Subjects were excluded if independent psychiatric, medical and neurologic disorders were noted. The results indicated that subtle deficits in psychomotor speed, complex attention, planning and sequencing, and verbal story memory were evident in adolescent marijuana users even after 23 days of monitored abstinence. Decreased performance in these areas was also associated with increased frequency of lifetime marijuana use. Longitudinal studies are needed to address the long-term trajectory of cognitive and brain functioning in adolescents who use marijuana. Medina, K., Hanson, K., Schweinsburg, A., Cohen-Zion, M., Nagel, B., and Tapert, S. Neuropsychological Functioning in Adolescent Marijuana Users: Subtle Deficits Detectable after a Month of Abstinence. Journal of the International Neuropsychological Society, 13, pp. 807-820, 2007.

Resting Cerebral Blood Flow in Adolescents with In Utero Cocaine Exposure

The aim of this study was to explore effects of in utero cocaine exposure on resting cerebral activation patterns in the brains of adolescents. The investigators employed arterial spin labeling (ASL) perfusion functional MRI (fMRI) to measure resting cerebral blood flow (CBF) in two groups of adolescents, one group that had been exposed to cocaine prenatally (N = 25), and one not prenatally-exposed (N = 24). A priori regions of interest of frontal lobe and limbic structures were defined, including the cingulate cortex, caudate, insula, and amygdala. The occipital lobe and thalamus were included as the lower-order sensory processing regions for compassion with the frontal lobe. Perfusion fMRI was combined with optimized voxel-based morphometry, a quantitative morphometric analysis of structural MRI, to compare gray matter between the two groups. Relative to the comparison group, cocaine-exposed adolescents showed significantly reduced global CBF, seen mainly in posterior and inferior brain regions, including the occipital cortex and thalamus. After adjusting for global CBF, a significant increase in relative CBF in cocaine-exposed adolescents was found in anterior and superior brain regions, including the prefrontal, cingulate, insular, amygdala, and superior parietal cortex. The investigators conclude that in utero cocaine exposure may reduce global CBF, which may persist into adolescence. They also point out that the relative increase in CBF in anterior and superior brain regions in cocaine-exposed adolescents suggests that compensatory mechanisms for reduced global CBF may develop during neurodevelopment. Rao, H., Wang, J., Giannetta, J., et al. Altered Resting Cerebral Blood Flow in Adolescents with in Utero Cocaine Exposure Revealed by Perfusion Functional MRI. Pediatrics, 120(5), pp. e1245-1254, 2007.

Prenatal and Adolescent Exposure to Tobacco Smoke Modulates the Development of White Matter Microstructure

Smoking during pregnancy is related to elevated risks of cognitive and auditory processing deficits. Preclinical studies have revealed that disruption in neurodevelopment by exposure to nicotine is likely linked to the disruption of the trophic actions of acetylcholine at nicotinic acetylcholine receptors. This study utilized diffusion tensor anisotropy and anatomical magnetic resonance images to examine white matter microstructure in 67 adolescent smokers and nonsmokers with and without prenatal exposure to maternal smoking. Auditory attention was assessed in all subjects. Adolescents with prenatal and/or adolescent exposure demonstrated increases in regional white matter fractional anisotropy (FA) primarily in anterior cortical and subcortical regions. Increased FA of regions of the internal capsule that contain auditory thalamocortical and corticofugal fibers was associated with adolescent smoking. Performance on the auditory performance task in smokers was positively correlated with FA of the posterior limb of the left internal capsule, but not in nonsmokers. The magnitude of tobacco exposure during adolescence was positively related to the FA of the genu of the corpus callosum further supporting the notion that the effects of nicotine on white matter maturation may be particularly significant during this developmental period. The results suggest that nicotine may disrupt the development of auditory corticofugal fibers which ultimately leads to reduced efficiency in the neurocircuitry that supports auditory processing. Jacobsen, L., Picciotto, M., Heath, C., Frost, S., Tsou, K., Dwan, R., Jackowski, M., Constable, R., and Menel, W. Prenatal and Adolescent Exposure to Tobacco Smoke Modulates the Development of White Matter Microstructure. The Journal of Neuroscience, 27(49) pp. 13491-13498, 2007.

Marijuana Use and HIV-Related Risk Factors

This study examined the role of early and current marijuana use as it relates to sexually transmitted infection (STI) risk in a sample of young women who had been pregnant teenagers. Pregnant adolescents (N= 279), ages 12-18, were recruited from an urban prenatal clinic as part of a study that was developed to evaluate the long-term effects of prenatal substance exposure. Six years later, they were asked about their substance use and sexual history. The association of early and late marijuana use to two HIV-related risk factors -- lifetime sexual partners and STIs --was examined, and then structural equation modeling (SEM) was used to illustrate the associations among marijuana use, number of sexual partners, and STIs. Bivariate analyses revealed a dose-response effect of early and current marijuana use on STIs in young adulthood. Early and current marijuana use also predicted a higher number of lifetime sexual partners. Using SEM, the effect of early marijuana use on STIs was mediated by lifetime number of sexual partners. African-American race, more externalizing problems, and a greater number of sexual partners were directly related to more STIs. Adolescent pregnancy, early marijuana use, mental health problems, and African-American race were significant risk factors for STIs in young adult women who had become mothers during adolescence. Pregnant teenage girls should be screened for early drug use and mental health problems, because they may benefit the most from the implementation of STI/HIV screening and skill-based STI and HIV prevention programs. DeGenna, N.M., Cornelius, M.D., and Cook, R.L. Marijuana Use and Sexually Transmitted Infections in Young Women Who Were Teenage Mothers. Women's Health Issues, 17(5), pp. 300-309, 2007.

Family Relationships and Sexual Activity among Hispanic Mid-Adolescents

Dr. Robles and her colleagues at the Universidad Central del Caribe examined the development of drug use and HIV/AIDS risk behaviors in a sample of 325 Hispanic 14 to 15-year old adolescents from a poor neighborhood in Puerto Rico. The study employed logistic regression analysis to identify variables associated with early sexual behavior. Adolescents whose parents reported poor communication and poor parent control were more likely to engage in early sexual activity than those peers who did not report this type of family relationship. Adolescents who reported poor parent bonding and lack of discipline were more likely to engage in early sexual relationships. Intervention and prevention programs need to be aware and address the role of family in early sexual activity in adolescence. Robles, R.R., Matos, T.D., Reyes, J.C., Colon, H.M., Negron, J., Calderon, J., Shepard, E.W. Correlates of Early Sexual Activity among Hispanic Children in Middle Adolescence. Puerto Rico Health Science Journal, 26(2), pp. 119-126, 2007.