Copyright restrictions may apply JAMA Pediatrics Journal Club Slides: Prenatal Exposure to Cocaine and Tobacco Liu J, Lester BM, Neyzi N, et al. Regional brain morphometry and impulsivity in adolescents following prenatal exposure to cocaine and tobacco. JAMA Pediatr. Published online February 11, doi: /jamapediatrics

Copyright restrictions may apply Background –Animal studies suggest that prenatal cocaine exposure (PCE) exerts deleterious influences on the developing nervous system. –Human structural magnetic resonance imaging studies have begun to identify possible anatomical deficits following PCE. –One confounding factor in the study of PCE is that most PCE offspring are subject to gestational exposure to other substances of abuse, most notably tobacco. –There has been little information regarding the long-term effects of prenatal drug exposure on brain/behavior changes during adolescence. Study Objective –To examine the brain morphological features and associated impulsive behaviors in adolescents following PCE and/or prenatal tobacco exposure (PTE). Introduction

Copyright restrictions may apply Study Design –Magnetic resonance imaging data and behavioral measures were collected from adolescents followed up longitudinally. Setting –A hospital-based research center. Participants –A total of 40 adolescent participants aged years were recruited (20 without PCE; 20 with PCE) A subset of each additionally had PTE. –Participants were matched based on head circumference at birth, gestational age, maternal alcohol use, age, sex, race/ethnicity, IQ, family poverty, and socioeconomic status. Methods

Copyright restrictions may apply Methods Outcomes –Subcortical volumetric measures of the thalamus, caudate, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens. –Cortical thickness measures of the dorsolateral prefrontal cortex (DLPFC) and ventral medial prefrontal cortex (VMPFC). –Impulsivity assessed by Conners’ Continuous Performance Test and the Sensation Seeking Scale for Children. Limitations –Study is based on a modest sample size of affected adolescents. –Magnetic resonance–based brain imaging methods solely assessed brain morphometry. –Dichotomized indices of prenatal drug exposure preclude any dose- response analyses in brain morphometry.

Copyright restrictions may apply Results Subcortical Volumetric Measures –After adjustment for both intracranial volume and PTE, pallidum approached statistical significance, with PCE subjects showing relatively larger volumes (mean [SD], [195.88] vs [261.76] mm 3 ; P =.06). –After controlling for intracranial volume and PCE, PTE subjects exhibited significantly smaller pallidum (mean [SD], [247.67] vs [213.73] mm 3 ; P =.03). Cortical Thickness Measures VMPFCDLPFC

Copyright restrictions may apply The cortical thickness estimate for the right DLPFC was significantly reduced in PCE subjects compared with subjects with no PCE (mean [SD], 2.18 [0.15] vs 2.30 [0.14] mm; P =.03). Brain/Behavior Relationships –On the Sensation Seeking Scale for Children, more impulsivity was related to a larger thalamus in exposed subjects in both the PCE group (PCE: r = 0.47, P =.05; no PCE: r = 0.35, P =.14) and PTE group (PTE: r = 0.44, P =.04; no PTE: r = 0.22, P =.41). –Correlations between Conners’ Continuous Performance Test commission errors and caudate volume were of borderline significance in the PCE group (PCE: r = 0.44, P =.06; no PCE: r = −0.10, P =.68). Results

Copyright restrictions may apply Comment The lack of overall volumetric differences in subcortical regions in adolescents following PCE can result from a supranormal adolescent brain growth spurt and delayed pruning of redundant neuronal connections independently or together. This is the first report of cortical thinning in PCE offspring, resembling sustained changes in the brain in adults following chronic cocaine abuse. It remains unclear whether the thinner right DLPFC evident in the PCE group is a biomarker for adolescents at greater risk for drug experimentation or addiction. The finding of smaller pallidum in PTE adolescents matches decreased striatal volume from previous tobacco studies, presumably as the consequence of nicotine-mediated dopamine release in the striatum, individually or in concert with other neurotransmitter systems.

Copyright restrictions may apply Comment The positive correlations of volumetric measures and impulsivity in thalamus for both PCE and PTE groups suggest a structural basis for the behavioral deficits. Prenatal drug exposure changes brain development trajectories in a structure-specific pattern that plays out differentially during the second decade, a hypothesis that requires confirmation via future studies with iterative image acquisitions. Alternatively, deficits observed at early stages presumably diminished along with brain development. There may still be subtle deficits, but at a functional level, in the absence of overt morphometric deficits.

Copyright restrictions may apply If you have questions, please contact the corresponding author: –Barry E. Kosofsky, MD, PhD, Division of Child Neurology, Weill Cornell Medical College, New York Presbyterian Hospital, 525 E 68th St, Box 91, New York, NY Funding/Support This study was supported by grants U10-DA (Dr Lester), U10-HD (Dr Lester), K02-DA (Dr Kosofsky), and R01-DA (Dr Kosofsky) from the National Institutes of Health and by National Institute of Child Health and Human Development contract N01-HD (Dr Lester). Conflict of Interest Disclosures None reported Contact Information