title: Prenatal cocaine exposure, illicit-substance use and stress and craving processes during adolescence.
abstract: BACKGROUND
  Prenatal cocaine exposure (PCE) is associated with increased rates of illicit-substance use during adolescence. In addition, both PCE and illicit-substance use are associated with alterations in cortico-striato-limbic neurocircuitry, development of which is ongoing throughout adolescence. However, the relationship between illicit-substance use, PCE and functional neural responses has not previously been assessed concurrently.
  
  
  METHODS
  Sixty-eight adolescents were recruited from an ongoing longitudinal study of childhood and adolescent development. All participants had been followed since birth. Functional magnetic resonance imaging (fMRI) data were acquired during presentation of personalized stressful, favorite-food and neutral/relaxing imagery scripts and compared between 46 PCE and 22 non-prenatally-drug-exposed (NDE) adolescents with and without lifetime illicit-substance use initiation. Data were analyzed using multi-level ANOVAs (pFWE<.05).
  
  
  RESULTS
  There was a significant three-way interaction between illicit-substance use, PCE status and cue condition on neural responses within primarily cortical brain regions, including regions of the left and right insula. Among PCE versus NDE adolescents, illicit-substance use was associated with decreased subcortical and increased cortical activity during the favorite-food condition, whereas the opposite pattern of activation was observed during the neutral/relaxing condition. Among PCE versus NDE adolescents, illicit-substance use during stress processing was associated with decreased activity in cortical and subcortical regions including amygdala, hippocampus and prefrontal cortex. Neural activity within cortico-striato-limbic regions was significantly negatively associated with subjective ratings of anxiety and craving among illicit-substance users, but not among non-users.
  
  
  CONCLUSIONS
  These findings suggest different neural substrates of experimentation with illicit drugs between adolescents with and without in utero cocaine exposure.
authors.affiliation: CASAColumbia, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States. Electronic address: sarah.yip@yale.edu.
authors.forename: Sarah W
authors.initials: SW
authors.lastname: Yip
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, United States.
authors.forename: Cheryl M
authors.initials: CM
authors.lastname: Lacadie
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States; Child Study Center, Yale University School of Medicine, New Haven, CT, United States; Department of Neurobiology, Yale University School of Medicine, New Haven, CT, United States.
authors.forename: Rajita
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Child Study Center, Yale University School of Medicine, New Haven, CT, United States; Departments of Epidemiology, Pediatrics and Psychology, Yale University School of Medicine, New Haven, CT, United States.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Mayes
authors.affiliation: CASAColumbia, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States; Child Study Center, Yale University School of Medicine, New Haven, CT, United States; Department of Neurobiology, Yale University School of Medicine, New Haven, CT, United States.
authors.forename: Marc N
authors.initials: MN
authors.lastname: Potenza
mesh_terms: D000293:Adolescent; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002648:Child; D003042:Cocaine / Q000008:administration & dosage / Q000009:adverse effects; D019970:Cocaine-Related Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000523:psychology; D015331:Cohort Studies; D066249:Craving / Q000187:drug effects; D005260:Female; D006801:Humans; D013287:Illicit Drugs / Q000009:adverse effects; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000175:diagnosis / Q000453:epidemiology* / Q000523:psychology; D013315:Stress, Psychological / Q000175:diagnosis / Q000453:epidemiology* / Q000523:psychology; D019966:Substance-Related Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000523:psychology
chemical_list: D013287:Illicit Drugs; D003042:Cocaine
keywords: Addiction; Cannabis; Cocaine; Development; Emotion; fMRI