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NIDA Home > Publications > Director's Reports > May, 2010 Index    

Director's Report to the National Advisory Council on Drug Abuse - May, 2010



Research Findings - Brain and Behavioral Development Research

Prenatal Exposure to Methamphetamine and Brain Volume: Differentiating Alcohol Effects

Dr. Elizabeth Sowell and her colleagues at UCLA investigated the effects of prenatal exposure to methamphetamine (MA) on local brain volume using magnetic resonance imaging. Because many women who use MA during pregnancy also use alcohol, a known teratogen, the team examined whether local brain volumes differed among 61 children (ages 5-15 years), 21 with prenatal MA exposure, 18 with concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but not MA exposure (ALC group), and 27 unexposed controls. Volume reductions were observed in both exposure groups relative to controls in striatal and thalamic regions bilaterally and in right prefrontal and left occipitoparietal cortices. Striatal volume reductions were more severe in the MAA group than in the ALC group, and, within the MAA group, a negative correlation between full-scale intelligence quotient (FSIQ) scores and caudate volume was observed. Limbic structures, including the anterior and posterior cingulate, the inferior frontal gyrus (IFG), and ventral and lateral temporal lobes bilaterally, were increased in volume in both exposure groups. Cingulate and right IFG volume increases were more pronounced in the MAA than ALC group. Discriminant function analyses using local volume measurements and FSIQ were used to predict group membership, yielding factor scores that correctly classified 72% of participants in jackknife analyses. These findings suggest that striatal and limbic structures, known to be sites of neurotoxicity in adult MA abusers, may be more vulnerable to prenatal MA exposure than alcohol exposure and that more severe striatal damage is associated with more severe cognitive deficit. Sowell ES, Leow AD, Bookheimer SY, Smith LM, O'Connor MJ, Kan E, Rosso C, Houston S, Dinov ID, Thompson PM. Differentiating prenatal exposure to methamphetamine and alcohol versus alcohol and not methamphetamine using tensor-based brain morphometry and discriminant analysis. J Neurosci. 2010 Mar 17; 30(11): 3876-3885.

Prenatal Methadone Exposure and Neonatal Neurobehavioral Functioning

Opioid-exposed infants display a wide and variable range of dysregulated neurobehavioral functioning, but the regulatory difficulties experienced by these infants outside the defined clusters of neonatal abstinence syndrome (NAS) have not been well described and may have implications for the infant's developmental course. This study by Dr. Lauren Jansson and her colleagues at Johns Hopkins University describes the neurobehavioral functioning of neonates prenatally exposed to methadone, using the NICU Network Neurobehavioral Scale (NNNS), and explores the relationships between maternal factors and infant functioning. The relationship between NNNS measures, NAS severity, and need for pharmacotherapy for NAS was also evaluated. Infants who required pharmacologic treatment for NAS showed more dysregulated behavior and signs of stress and abstinence as indicated by NNNS scores, but NNNS scores were not significantly correlated with maternal methadone dose. The determination of the range of the methadone-exposed infant's neurobehavioral repertoire could guide the optimal treatment of all such infants, particularly those requiring only nonpharmacologic care. Velez ML, Jansson LM, Schroeder J, Williams E. Prenatal methadone exposure and neonatal neurobehavioral functioning. Pediatr Res. 2009 Dec; 66(6): 704-709.

Effects of Prenatal Cocaine Exposure on School-aged Children

Studies through 6 years have shown no long-term direct effects of prenatal cocaine exposure (PCE) on children's physical growth, developmental test scores, or language outcomes. Little is known about the effects of PCE among school-aged children aged 6 years and older. Dr. Maureen Black and her colleagues reviewed articles from studies that examined the effects of PCE on growth, cognitive ability, academic functioning, and brain structure and function among school-aged children. Articles were obtained by searching PubMed, Medline, TOXNET, and PsycInfo databases from January 1980 to December 2008 with the terms "prenatal cocaine exposure," "cocaine," "drug exposure," "substance exposure," "maternal drug use," "polysubstance," "children," "adolescent," "in utero," "pregnancy," "development," and "behavior." Criteria for inclusion were (1) empirical research on children aged 6 years and older prenatally exposed to cocaine, (2) peer-reviewed English-language journal, (3) comparison group, (4) longitudinal follow-up or historical prospective design, (5) masked assessment, (6) exclusion of subjects with serious medical disabilities, and (7) studies that reported nonredundant findings for samples used in multiple investigations. Thirty-two unique studies met the criteria. Each article was independently abstracted by 2 authors to obtain sample composition, methods of PCE assessment, study design, comparison groups, dependent variables, covariates, and results. Associations between PCE and growth, cognitive ability, academic achievement, and language functioning were small and attenuated by environmental variables. PCE had significant negative associations with sustained attention and behavioral self-regulation, even with covariate control. Although emerging evidence suggests PCE-related alterations in brain structure and function, interpretation is limited by methodologic inconsistencies. Consistent with findings among preschool-aged children, environmental variables play a key role in moderating and explaining the effects of PCE on school-aged children's functioning. After controlling for these effects, PCE-related impairments are reliably reported in sustained attention and behavioral self-regulation among school-aged children. Ackerman JP, Riggins T, Black MM. A review of the effects of prenatal cocaine exposure among school-aged children. Pediatrics. 2010 Mar; 125(3): 554-565.

Structured Parenting of Toddlers at High versus Low Genetic Risk: Two Pathways to Child Problems

Little is known about how parenting might offset genetic risk to prevent the onset of child problems during toddlerhood. Dr. Jenae Neiderhiser and her colleagues used a prospective adoption design to separate genetic and environmental influences and test whether associations between structured parenting and toddler behavior problems were conditioned by genetic risk for psychopathology. The sample included 290 linked sets of adoptive families and birth mothers and 95 linked birth fathers. Genetic risk was assessed via birth mother and birth father psychopathology (anxiety, depression, antisociality, and drug use). Structured parenting was assessed via microsocial coding of adoptive mothers' behavior during a cleanup task. Toddler behavior problems were assessed with the Child Behavior Checklist. Controlling for temperamental risk at 9 months, there was an interaction between birth mother psychopathology and adoptive mothers' parenting on toddler behavior problems at 18 months. The interaction indicated two pathways to child problems: Structured parenting was beneficial for toddlers at high genetic risk but was related to behavior problems for toddlers at low genetic risk. This crossover interaction pattern was replicated with birth father psychopathology as the index of genetic risk. The effects of structured parenting on toddler behavior problems varied as a function of genetic risk. Children at genetic risk might benefit from parenting interventions during toddlerhood that enhance structured parenting. Such interventions may impact adolescent vulnerability to substance abuse. Leve LD, Harold GT, Ge X, Neiderhiser JM, Shaw D, Scaramella LV, Reiss D. Structured parenting of toddlers at high versus low genetic risk: Two pathways to child problems. J Am Acad Child Adolesc Psychiatry. 2009 Nov; 48(11): 1102-1109.

Cocaine Addiction in Mothers: Potential Effects on Maternal Care and Infant Development

Maternal cocaine addiction is a significant public health issue particularly affecting children, with high rates of reported abuse, neglect, and foster care placement. This paper by Dr. Linda Mayes and her colleague Dr. Lane Strathearn reviews both preclinical and clinical evidence for how cocaine abuse may affect maternal care and infant development, exploring brain, behavioral, and neuroendocrine mechanisms. There is evidence that cocaine affects infant development both directly, via in utero exposure, and indirectly via alterations in maternal care. Two neural systems known to play an important role in both maternal care and cocaine addiction are the oxytocin and dopamine systems, mediating social and reward-related behaviors and stress reactivity. These same neural mechanisms may also be involved in the infant's development of vulnerability to addiction. Understanding the neuroendocrine pathways involved in maternal behavior and addiction may help facilitate earlier, more effective interventions to help substance-abusing mothers provide adequate care for their infant and perhaps prevent the intergenerational transmission of risk. Strathearn L, Mayes LC. Cocaine addiction in mothers: Potential effects on maternal care and infant development. Ann N Y Acad Sci. 2010 Feb; 1187: 172-183.

Marijuana Use and Adherence to Doctor's Appointments among HIV-infected Female Youth

This project conducted in the Adolescent Trials Network for HIV/AIDS Interventions (ATN) identified factors associated with medical appointment-keeping among HIV-infected adolescents and young adults in five U.S. cities. Youth were followed for 18 months to examine adherence to scheduled clinic visits with their HIV care provider. Psychosocial and behavioral factors shown in other populations to influence appointment adherence (mood disorder, depressive symptoms, social network support, healthcare satisfaction, disease acceptance, HIV stigma, alcohol use, and marijuana use) were measured at baseline and follow-up visits using an audio computer-assisted self-interview questionnaire. CD4 count and prescription of antiretroviral therapy medication were also monitored to understand the influence of health status on appointment- keeping. Participants included 178 youth with a mean age of 20.6 years. Forty-two percent had clinically significant depressive symptoms, 10% had a diagnosable mood disorder, 37% reported marijuana use in the last 90 days, and 47% reported alcohol use. Overall, participants attended 67.3% of their scheduled visits. Controlling for age and health status, marijuana use was the only variable that was associated with appointment-keeping behavior. Considering the importance of appointment-keeping for maintaining personal health and preventing further transmission, screening HIV-infected adolescents for marijuana use could help alert providers of this specific barrier to visit compliance. Dietz E, Clum GA, Chung SE, Leonard L, Murphy DA, Perez LV, Harper GW, Ellen JM. Adherence to scheduled appointments among HIV-infected female youth in five U.S. cities. J Adolesc Health. 2010 Mar; 46(3): 278-283.

Recruiting and Retaining Mobile Young Injection Drug Users in a Longitudinal Study

Longitudinal studies that research homeless persons or transient drug users face particular challenges in retaining subjects. This paper reports on research methods that resulted in successful recruitment and retention of young ketamine injection drug users (IDUs), a population not previously tracked longitudinally. Between 2005 and 2006, 101 mobile young ketamine IDUs were recruited in Los Angeles into a 2-year longitudinal study. Several features of ethnographic methodology, including fieldwork and qualitative interviews, and modifications to the original design, such as toll-free calls routed directly to ethnographer cell phones and wiring incentive payments, resulted in retention of 78% of subjects for the first follow-up interview. Longitudinal studies that are flexible and based upon qualitative methodologies are more likely to retain mobile subjects while also uncovering emergent research findings. Lankenau SE, Sander B, Hathazi D, Bloom JJ. Recruiting and retaining mobile young injection drug users in a longitudinal study. Subst Use Misuse. 2010 Apr; 45(5): 684-699. Co-occurring Anxiety and Externalizing Disorders in Offspring of Mothers with Substance Abuse and/or Psychiatric Disorders This study used data from a study of 340 mothers with substance use and/or psychiatric disorders and their children to examine characteristics of children with co-occurring diagnoses of anxiety and externalizing disorders and compare them with children with a sole diagnosis or no diagnosis. Comparisons were made using 4 child-diagnostic groups: anxiety-only, externalizing-only, co-occurrence, and no-problem groups. Most mothers were characterized by low income and histories of substance use and/or affective/anxiety and/or antisocial personality disorder diagnoses during the child's lifetime. Analyses using multinomial logistic regressions found the incidence of co-occurring childhood disorders to be significantly linked with maternal affective/anxiety disorders during the child's lifetime. In exploring implications for developmental competence, the study found the co-occurrence group to have the lowest level of adaptive functioning among the 4 groups, faring significantly worse than the no-problem group on both academic achievement and intelligence as assessed by standardized tests. Findings underscore the importance of considering co-occurring behavior problems as a distinct phenomenon when examining children's developmental outcomes. Yoo JP, Brown PJ, Luthar SS. Children with co-occurring anxiety and externalizing disorders: Family risks and implications for competence. Am J Orthopsychiatry. 2009 Oct; 79(4): 532-540.

Neural Mechanisms of the Influence of Popularity on Adolescent Ratings of Music

It is well-known that social influences affect consumption decisions. Dr. Berns and his colleagues at Emory University School of Medicine used functional magnetic resonance imaging (fMRI) to elucidate the neural mechanisms associated with social influence with regard to music. The study population consisted of adolescents, age 12-17. Music is a common purchase in this age group, and it is widely believed that adolescent behavior is influenced by perceptions of popularity in their reference group. Using 15-s clips of songs from MySpace.com, behavioral measures of preferences and neurobiological responses to the songs were obtained. The data were gathered with, and without, the overall popularity of the song revealed. Song popularity had a significant effect on the participants' likability ratings of the songs. Imaging results showed a strong correlation between the participants' rating and activity in the caudate nucleus, a region previously implicated in reward-driven actions. The tendency to change one's evaluation of a song was positively correlated with activation in the anterior insula and anterior cingulate, two regions that are associated with physiological arousal and negative affective states. Sensitivity to popularity was linked to lower activation levels in the middle temporal gyrus, suggesting a lower depth of musical semantic processing. The results suggest that a principal mechanism whereby popularity ratings affect consumer choice is through the anxiety generated by the mismatch between one's own preferences and others'. This mismatch anxiety motivates people to switch their choices in the direction of the consensus. The data suggest that this is a major force behind the conformity observed in music tastes in some teenagers. Berns G, Capra C, Moore S, Noussair C. Neural mechanisms of the influence of popularity on adolescent ratings of music. NeuroImage 2010 49:2687-2696.


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