Effects of heavy in utero cocaine exposure on adolescent caudate morphology.
We assess the effects of in utero cocaine and polysubstance exposure on the adolescent caudate nucleus through high-resolution magnetic resonance imaging. Cocaine exposure may compromise the developing brain through disruption of neural ontogeny in dopaminergic systems, effects secondary to fetal hypoxemia, or altered cerebrovascular reactivity. Cocaine exposure may also lead to neonatal lesions in the caudate. However, long-term or latent effects of intrauterine cocaine exposure are rarely found. We use T(1)-weighted magnetic resonance imaging to quantify caudate nucleus morphology in matched control and exposed groups. The literature suggests that in utero cocaine exposure consequences in adolescents may be subtle, or masked by other variables. Our comparison focuses on contrasting the control group with high-exposure subjects (mothers who reported 2 median of 117 days of cocaine use during pregnancy; 82% tested positive for cocaine use at term). We use advanced image registration and segmentation tools to quantify left and right caudate morphology. Our results indicate that the caudate is significantly larger in controls versus subjects (P < 0.0025), implying cocaine exposure-related detriments to the dopaminergic system. The right (P < 0.025) and left (P < 0.035) caudate, studied independently, show the same significant trend. Permutation testing and the false discovery rate were used to assess significance.
Avants
Brian B
BB
Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. avants@grasp.cis.upenn.edu
Hurt
Hallam
H
Giannetta
Joan M
JM
Epstein
Charles L
CL
Shera
David M
DM
Rao
Hengyi
H
Wang
Jiongjiong
J
Gee
James C
JC
D000293:Adolescent; D002421:Caudate Nucleus / Q000187:drug effects* / Q000473:pathology*; D003042:Cocaine / Q000008:administration & dosage* / Q000009:adverse effects*; D015331:Cohort Studies; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D018765:Dopamine Uptake Inhibitors; D003042:Cocaine