Research Findings - Behavioral and Brain Development Research

Maternal Cocaine Use During Pregnancy and Physiological Regulation in 4- to 8-Week-Old Infants

In their report on associations between maternal cocaine use during pregnancy and physiological regulation in infants at 4 to 8 weeks of age, Drs. Schuetze and Eiden provided data for 141 mother-infant dyads (77 cocaine-exposed and 64 nonexposed) recruited at birth. Physiological measures of regulation included heart rate (HR) and respiratory sinus arrhythmia (RSA), assessed during a 15-minute period of sleep. Results indicated a dose-dependent relationship between prenatal exposure to cocaine and RSA. The analyses found no evidence that fetal growth or other prenatal exposure to substances mediated this association or that fetal growth or maternal age moderated this association. Analyses did indicate that birth weight (BW), but not birth length (BL), head circumference (HC) or other substance use mediated the association between prenatal exposure to cocaine and HR. In their conclusions, the researchers note that the findings highlight the importance of considering level of exposure when assessing infant outcomes. Schuetze, P. and Eiden, R.D. The Association Between Maternal Cocaine Use During Pregnancy and Physiological Regulation in 4- to 8-Week-Old Infants: An Examination of Possible Mediators and Moderators. Journal of Pediatric Psychology, 31, 2006 (Epub ahead of print, 2005).

Prenatal Drug Exposure and Mother-Infant Interaction

Based on data from the Maternal Lifestyle Study, a multi-site investigation of development following prenatal drug exposure, this report provides findings for mother-infant interactions observed at 4 months infant age. Specifically, the face-to-face still-face (FFSF) paradigm was used, a standardized procedure in which infants engage in face-to-face interaction with the caregiver, and also have to deal with a stressful interaction during which the caregiver becomes poker-faced as well as vocally and gesturally unresponsive. The sample involved 236 cocaine-exposed and 459 non-cocaine-exposed infants (49 were opiate-exposed and 646 non-opiate-exposed). No opiate exposure effects were observed. Mothers of cocaine-exposed infants showed more negative engagement than other mothers. The cocaine-exposed dyads also showed higher overall levels of mismatched engagement states than other dyads, including more maternal negative engagement when the infants were in states of neutral engagement. Infants exposed to heavier levels of cocaine showed more passive-withdrawn negative engagement and engaged in more negative affective matching with their mothers than other infants. The study authors conclude that although effect sizes were small, cocaine exposure, especially heavy cocaine exposure, was associated with subtly negative interchanges, which may have a cumulative impact on infants' later development and their relationships with their mothers. Tronick, E.Z., Messinger, D.S., Weinberg, M.K., et al. Cocaine Exposure is Associated with Subtle Compromises of Infants' and Mothers' Social-Emotional Behavior and Dyadic Features of Their Interaction in the Face-to-Face Still-Face Paradigm. Developmental Psychology, 41, pp. 711-722, 2005.

Prenatal Cocaine/Polydrug Use and Maternal-Infant Feeding Interactions During the First Year of Life

In research conducted at Case Western Reserve University, relationships between prenatal cocaine use and quality of maternal-infant interactions were examined. The Nursing Child Assessment Feeding Scale (NCAFS) was used with a sample of 341 mothers (155 with prenatal cocaine use and 186 without prenatal cocaine use) and their infants at 6.5 and 12 months infant age. Analyses included a number of sociodemographic and maternal covariates, including postnatal substance use. Women who used cocaine during pregnancy were found to be less sensitive to infant cues at 6.5 and 12 months than were non-cocaine-using women. At 6.5 months, heavier prenatal cocaine use was related to less maternal responsiveness to infants. In infants, prenatal cocaine exposure was related to poorer clarity of cues. The investigators found no significant cocaine effects on maternal social-emotional growth fostering, cognitive growth fostering, or infant responsiveness to mother. The study authors note implications of the findings for clinicians and intervention programs. Minnes, S., Singer, L.T., Arendt, R. and Satayathum, S. Effects of Prenatal Cocaine/Polydrug Use on Maternal-Infant Feeding Interactions During the First Year of Life. Developmental and Behavioral Pediatrics, 26, pp. 194-200, 2005.

Cocaine Use During Pregnancy and Preschool Development at 3 Years of Age

In this University of Florida longitudinal cohort study, 154 pregnant cocaine users were recruited and were matched on race, parity, socioeconomic status, and perinatal risk with 154 noncocaine users. The study protocol involves examining development of the children at multiple ages. This report presents findings for the children at 3 years of age based on two measures, the Bayley Scales of Infant Development, and the Vineland Adaptive Behavior Scales (the latter involving caregiver report). A preschool development variable was created, using the Bayley Mental and Psychomotor Development Indices, and the Communication and Motor Skills subscales of the Vineland. Based on structural equation modeling analyses, the researchers concluded that environmental factors accounted for most of the variance in the preschool development variable, and that prenatal cocaine exposure exerted an indirect effect on preschool development through its effect on birth head circumference. Behnke, M., Eyler, F.D., Warner, T.D., et al. Outcome from a Prospective, Longitudinal Study of Prenatal Cocaine Use: Preschool Development at 3 Years of Age. Journal of Pediatric Psychology, 31, 2006 (Epub ahead of print, 2005).

Aggression at Age 5 Years Relative to Prenatal Cocaine Exposure, Gender, and Environmental Risk

In a project conducted by researchers from Robert Wood Johnson Medical School, childhood aggression at age 5 years was examined using a multiple risk model that included prenatal cocaine exposure, environmental risk, and gender as predictors. Aggression was assessed in 206 children using multiple methods, including teacher report, parent report, child's response to hypothetical provocations, and child's observed behavior. Also examined was a composite score that reflected high aggression across contexts. Multiple aspects of the environment were assessed and quantified using a cumulative environmental risk score. Analyses indicated that a significant amount of variance in each of the aggression measures and the composite was explained by the predictors. The factors that were independently related differed depending on the outcome. Prenatal cocaine exposure, gender, and environmental risk were all related to the composite aggression score. The investigators concluded that prenatal cocaine exposure, being male, and living in a high-risk environment were all predictive of aggressive behavior at 5 years. They also suggested that it is this group of exposed boys at high environmental risk that is most likely to show continued aggression over time. Bendersky, M., Bennett, D. and Lewis, M. Aggression at Age 5 as a Function of Prenatal Exposure to Cocaine, Gender, and Environmental Risk. Journal of Pediatric Psychology, 31, 2006 (Epub ahead of print, 2005).

Mental Health Outcomes of Cocaine-Exposed Children at 6 Years of Age

Case Western Reserve University investigators assessed mental health outcomes for 6-year-old children who were either cocaine-exposed (CE) or not-cocaine-exposed (NCE) during the prenatal period. The sample of 322 children (169 CE and 153 NCE) were enrolled in this longitudinal study since birth. The children were assessed for mental health symptoms (not diagnoses) using the Dominic Interactive (DI), a child self-report measure, and the Child Behavior Checklist (CBCL), reflecting caregiver report of behavioral problems. Results indicated that CE children were more likely to self-report symptoms in the probable clinical range for oppositional defiant disorder (ODD) and attention deficit hyperactivity disorder (ADHD). In contrast, prenatal cocaine exposure was not related to child behavior based on the CBCL. When data were analyzed relative to type of caregiving environment, CE children in adoptive or foster care were rated as having more problems with aggression, externalizing behaviors, and total behavioral problems than NCE children and CE children in maternal or relative care. Also, CE children in adoptive or foster care self-reported more externalizing symptoms than CE children in maternal or relative care and NCE children. Findings could not be attributed to caregiver intelligence or depressive symptoms, or to the quality of the home environment. The investigators noted that although further studies are needed to understand the basis for the more negative ratings by adoptive or foster caregivers of their CE children, the self-report of symptoms by CE children indicates a need for psychological interventions. Linares, T.J., Singer, L.T., Kirchner, H.L., et al. Mental Health Outcomes of Cocaine-Exposed Children at 6 Years of Age. Journal of Pediatric Psychology, 31, 2006 (Epub ahead of print, 2005).

Prenatal Cocaine Exposure and Language Functioning at 6 and 9.5 Years: Moderating Effects of Child Age, Birthweight, and Gender

In this report from an ongoing longitudinal cohort study of development following prenatal drug exposure, results are presented for language functioning at 6 and 9.5 years relative to prenatal cocaine exposure (PCE) and other individual and environmental variables. Analyses involved data for 160 low-income, urban children who completed a standardized language assessment. Based on multivariate longitudinal analyses using generalized estimating equations (GEE), the authors concluded that age, birthweight, and gender moderated the relation between PCE and school-aged children's language. For example, children with PCE had lower receptive language than unexposed children at 6 but not at 9.5 years, lower expressive language if they had lower birthweight, and lower expressive and total language if they were female. Other risk (e.g., violence exposure) and protective factors (e.g., preschool experience) were related to language outcomes regardless of PCE status. Beeghly, M., Martin, B., Rose-Jacobs, R., et al. Prenatal Cocaine Exposure and Children's Language Functioning at 6 and 9.5 Years: Moderating Effects of Child Age, Birthweight, and Gender. Journal of Pediatric Psychology, 31, 2006 (Epub ahead of print, 2005).

Somatic Complaints in Children and Community Violence Exposure

Dr. Delaney-Black and her colleagues examined the relationship between witnessing or being a victim of community violence and somatic complaints (appetite, sleep, stomachache, and headache) in a sample of 6- and 7- year old urban African-American children recruited before birth. Participants (N= 268) were neighborhood controls from a larger longitudinal study on prenatal substance exposure and school age outcomes and were included in these analyses if they had no prenatal exposure to hard illicit drugs and resided with their biological mothers. Community violence exposure (Things I Have Seen and Heard), stress symptomatology (Levonn), and somatic complaints (teacher- and self-report items) were assessed. Community violence witnessing and victimization were associated with stress symptoms (r = .26 and .25, respectively, p < .001); violence victimization was related to decreased appetite (r = .16, p. < .01), difficulty sleeping (r = .21, p< .001), and stomachache complaints (r = .13, p < .05); witnessed violence was associated with difficulty sleeping (r = .13, p < .05), and headaches (r = .12, p < .05). All associations remained significant after controlling for confounding variables (SES, prenatal alcohol exposure, maternal: current alcohol use, age, marital status, education, psychopathology, life stress; child: gender, number of people living in child's home, history of child abuse, presence of a chronic medical condition, anxiety and depression). Community violence exposure accounted for 10% of the variance in child stress symptoms, and children who had experienced community violence victimization had a 28% increased risk of appetite problems, a 94% increased risk of sleeping problems, a 57% increased risk of headaches, and a 174% increased risk of stomachaches. Results suggest clinicians treating these physical symptoms in children take into consideration exposure to community violence. Bailey, B.N., Delaney-Black, V., Hannigan, J.H., Ager, J., Sokol, R.J., and Covington, C.Y., J Dev Behav Pediatrics, 26(5), pp. 341-348, 2005.

The Effects of Hepatitis C, HIV, and Methamphetamine Dependence on Neuropsycho-logical Performance

Dr. Scott Letendre and his colleagues at the San Diego HIV Neurobehavioral Research Center examined the important question of the effects of hepatitis C virus (HCV) infection on neuropsychological (NP) performance while taking into consideration HIV serostatus and methamphetamine dependence. The researchers performed a cross-sectional analysis of a prospectively enrolled cohort of 239 HIV-seropositive and 287 HIV-seronegative subjects. In this study HCV-seropositive subjects performed worse on neuropsychological testing and were almost twice as likely to be diagnosed as globally impaired, compared with those who were HCV seronegative. Notably, in a multivariate analysis, HCV, HIV, and methamphetamine dependence were independently associated with worse performance, even after adjusting for Centers for Disease Control stage and antiretroviral use. HCV-RNA levels in plasma were higher in those with memory, but not global, impairment. In cerebrospinal fluid, HCV RNA was below 100 copies/ml in all specimens. In HIV-infected subjects, HCV was associated with higher levels of HIV RNA in CSF, but not in plasma. HCV was also associated with higher levels of monocyte chemotactic protein 1, TNF-alpha, and soluble TNF receptor II. HCV-seropositive subjects did not appear to have advanced liver disease. The authors conclude that HIV, HCV, and methamphetamine independently injure the central nervous system, leading to global neuropsychological impairment. HCV may injure the brain by viral or immune-mediated mechanisms. HCV-associated brain injury may be preventable or reversible because HCV infection is potentially curable. Letendre, S.L., Cherner, M., Ellis, R.J., Marquie-Beck, J., Gragg, B., Marcotte, T., Heaton, R.K., McCutchan, J.A., and Grant, I., AIDS, Suppl 3, pp. S72-78, 2005.

Risk-Taking Propensity Across Adolescent Ever- and Never-Smokers

Dr. Carl Lejuez and his colleagues at the University of Maryland developed a computerized behavioral test to measure propensity for risk-taking called the Balloon Analogue Risk Task (BART). Recent research with the BART examined the relationship between risk propensity (measured by BART) and smoking status (ever-smoking (i.e., even one puff) versus never-smoking) in a sample of 125 predominantly African American high-school adolescents (M = 15.1, SD = 1.5). Results indicated that ever-smokers and never-smokers differed on risk-taking propensity; further risk-taking propensity was related to smoking status above and beyond both demographic variables (age and gender) and a measure of self-reported impulsive sensation seeking. Results point to the potential utility of a multimethod assessment approach (i.e., self-report measures and behavioral tasks) to identify adolescents' risk-taking susceptibilities and engagement in smoking and other risk-taking behaviors. Lejuez, C.W., Aklin, W., Bornovalova, M. and Moolchan, E.T., Nicotine Tobacco Research, 7(1), pp. 71-79, 2005.

Modeling Behavior in a Clinically Diagnostic Sequential Risk-Taking Task

As part of on-going research on the validity and clinical utility of the Balloon Analogue Risk Task (BART), researchers at the University of Maryland conducted analyses to model the cognitive processes underlying learning and sequential choice on this risk-taking task. These analyses were conducted to understand how these cognitive processes occur in a moderately complex environment and how these behaviors relate to self-reported real-world risk taking. The best stochastic model assumes that participants incorrectly treat outcome probabilities as stationary, update probabilities in a Bayesian fashion, evaluate choice policies prior to rather than during responding, and maintain constant response sensitivity. The model parameter associated with subjective value of gains correlates well with external risk taking. Both the overall approach, which can be expanded as the basic paradigm is varied, and the specific results provide direction for theories of risky choice and for understanding risk taking as a public health problem. Wallsten, T.S., Pleskac, T.J., and Lejuez, C.W., Psychological Review, 112(4), pp. 862-880, 2005.

fMRI Reveals Alterations in Spatial Working Memory Networks Across Adolescence

Dr. Susan Tapert and her colleagues at the University of California - San Diego have used functional neuroimaging to characterize the development of spatial working memory in adolescents. Their findings show that the frontal and parietal networks that are involved in working memory change over the course of adolescence, with activation of the left prefrontal and bilateral inferior posterior parietal regions increasing with age and activation of bilateral superior parietal cortex decreasing. Their data also demonstrate gender differences, with males showing greater activation of the anterior cingulate cortex and frontopolar cortex than females. Over the age range tested, there were no differences in performance on the working memory task, suggesting that the alterations in activation patterns with age represent the evolution of the strategies used in the task. Schweinsburg, A.D., Nagel, B.J. and Tapert, S.F. J. Int. Neuropsych. Soc. 11, pp. 631-644, 2005.

Event-related Potentials in Cocaine-Exposed Children During a Stroop Task

Dr. Linda Mayes and her colleagues used high-density event related potential (ERP) recording to compare the performance of 8 year old children exposed in utero to cocaine to non-drug exposed children on a task that measures frontal lobe function and inhibitory control. Their findings showed that children that had been exposed to cocaine during gestation committed more errors on the task and responded more slowly during the task than children that had not been exposed. The pattern of the evoked responses also differed in the 2 groups of 8 year olds, with the children that had been exposed to cocaine activating different brain areas, and having more extensive activation, than the non-exposed children. Dr. Mayes and her colleagues hypothesize that early cocaine exposure may alter the process of regional brain specialization leading to slower task processing, the involvement of more cortical areas in accomplishing a task, and more time to complete the task. Mayes, L.C., Molfese, D.L., Key, A.P.F. and Hunter, N.C. Neurotoxicology and Teratology. 27, pp. 797-813, 2005.

Axial Asymmetry of Water Diffusion in Brain White Matter

Dr. Andrew Alexander and colleagues at the University of Wisconsin-Madison have analyzed the directions of water diffusion in the white matter tracts of the human brain that are oriented orthogonal to the major diffusivity direction. Their analysis shows that differences in diffusion patterns of the minor diffusivity directions may be a function of the fine structure of the white matter tracts, such as merging or diverging or crossing fibers. These patterns may be useful in detecting subtle changes in white matter structure as a result of injury or disease. These authors have also shown that the methods developed are sensitive to changes in the structural organization caused by infiltrative disease. Lazar, M., Lee, J.H., and Alexander, A.L., Magnetic Resonance in Medicine. 54, pp. 860-867, 2005.

Contributions of the Hippocampus and the Striatum to Simple Association and Frequency-based Learning

Dr. B.J. Casey and colleagues used fMRI to investigate the regions of the brain that are involved in learning simple associations and frequency-based learning. Their data suggest that the caudate nucleus activates to signal that an unexpected (i.e., infrequent) stimulus has occurred, supporting the hypothesis that the caudate nucleus is tuned to detect the occurrence of an unexpected event. The hippocampus was activated preferentially when an unexpected stimulus pairing, or association, occurred and its activation diminished as the stimulus pairings became more frequent. Thus both structures are involved in learning but they activate in response to different learning contexts. Amso, D., Davidson, M.C., Johnson, S.P., Glover, G., and Casey, B.J. Neuroimage. 27, pp. 291-298, 2005.

Mapping Cerebellar Vermal Morphology and Cognitive Correlates in Prenatal Alcohol Exposure

A number of previous studies have documented alterations in cerebral morphology in individuals exposed prenatally to alcohol and related these alterations to cognitive deficits. In this study, Dr. Elizabeth Sowell and colleagues used sophisticated surface-based morphometric techniques and neuropsychological measures to characterize the cerebellar vermis in prenatally-exposed children and adolescents. Alcohol-exposed study participants had significant reductions in the anterior and posterior cerebellar vermis and the alterations in anterior vermal morphology were correlated with a reduction in performance in verbal learning and memory tasks. O'Hare, E.D., Kan, E., Yoshii, J., Mattson, S.N., Riley, E.P., Thompson, P.M., Toga, A.W. and Sowell, E.R. Neuroreport. 16, pp. 1285-1290, 2005.