Orbitofrontal Cortex and Drug Use During Adolescence: Role of Prenatal Exposure to Maternal Smoking and BDNF Genotype | Adolescent Medicine | JAMA Psychiatry | JAMA Network
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DiFranza  JRLew  RA Effect of maternal cigarette smoking on pregnancy complications and sudden infant death syndrome.  J Fam Pract 1995;40 (4) 385- 394PubMedGoogle Scholar
Huijbregts  SCSéguin  JRZoccolillo  MBoivin  MTremblay  RE Maternal prenatal smoking, parental antisocial behavior, and early childhood physical aggression.  Dev Psychopathol 2008;20 (2) 437- 453PubMedGoogle Scholar
Ernst  MMoolchan  ETRobinson  ML Behavioral and neural consequences of prenatal exposure to nicotine.  J Am Acad Child Adolesc Psychiatry 2001;40 (6) 630- 641PubMedGoogle Scholar
Weissman  MMWarner  VWickramaratne  PJKandel  DB Maternal smoking during pregnancy and psychopathology in offspring followed to adulthood.  J Am Acad Child Adolesc Psychiatry 1999;38 (7) 892- 899PubMedGoogle Scholar
Kenny  PJFile  SERattray  M Acute nicotine decreases, and chronic nicotine increases the expression of brain-derived neurotrophic factor mRNA in rat hippocampus.  Brain Res Mol Brain Res 2000;85 (1-2) 234- 238PubMedGoogle Scholar
Franke  RMPark  MBelluzzi  JDLeslie  FM Prenatal nicotine exposure changes natural and drug-induced reinforcement in adolescent male rats.  Eur J Neurosci 2008;27 (11) 2952- 2961PubMedGoogle Scholar
Perry  DCDávila-García  MIStockmeier  CAKellar  KJ Increased nicotinic receptors in brains from smokers: membrane binding and autoradiography studies.  J Pharmacol Exp Ther 1999;289 (3) 1545- 1552PubMedGoogle Scholar
Toro  RLeonard  GLerner  JVLerner  RMPerron  MPike  GBRicher  LVeillette  SPausova  ZPaus  T Prenatal exposure to maternal cigarette smoking and the adolescent cerebral cortex.  Neuropsychopharmacology 2008;33 (5) 1019- 1027PubMedGoogle Scholar
Bolla  KIEldreth  DALondon  EDKiehl  KAMouratidis  MContoreggi  CMatochik  JAKurian  VCadet  JLKimes  ASFunderburk  FRErnst  M Orbitofrontal cortex dysfunction in abstinent cocaine abusers performing a decision-making task.  Neuroimage 2003;19 (3) 1085- 1094PubMedGoogle Scholar
Everitt  BJHutcheson  DMErsche  KDPelloux  YDalley  JWRobbins  TW The orbital prefrontal cortex and drug addiction in laboratory animals and humans [published online December 18, 2007].  Ann N Y Acad Sci 2007;1121576- 597PubMed10.1196/annals.1401.02Google Scholar
Franklin  TRActon  PDMaldjian  JAGray  JDCroft  JRDackis  CAO’Brien  CPChildress  AR Decreased gray matter concentration in the insular, orbitofrontal, cingulate, and temporal cortices of cocaine patients.  Biol Psychiatry 2002;51 (2) 134- 142PubMedGoogle Scholar
Rolls  ET The orbitofrontal cortex and reward.  Cereb Cortex 2000;10 (3) 284- 294PubMedGoogle Scholar
Goldstein  RZVolkow  ND Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex.  Am J Psychiatry 2002;159 (10) 1642- 1652PubMedGoogle Scholar
Schultz  WTremblay  LHollerman  JR Reward processing in primate orbitofrontal cortex and basal ganglia.  Cereb Cortex 2000;10 (3) 272- 284PubMedGoogle Scholar
Pausova  ZPaus  TAbrahamowicz  MAlmerigi  JArbour  NBernard  MGaudet  DHanzalek  PHamet  PEvans  ACKramer  MLaberge  LLeal  SMLeonard  GLerner  JLerner  RMMathieu  JPerron  MPike  BPitiot  ARicher  LSéguin  JRSyme  CToro  RTremblay  REVeillette  SWatkins  K Genes, maternal smoking, and the offspring brain and body during adolescence: design of the Saguenay Youth Study.  Hum Brain Mapp 2007;28 (6) 502- 518PubMedGoogle Scholar
Fischl  BDale  AM Measuring the thickness of the human cerebral cortex from magnetic resonance images.  Proc Natl Acad Sci U S A 2000;97 (20) 11050- 11055PubMedGoogle Scholar
Desikan  RSSégonne  FFischl  BQuinn  BTDickerson  BCBlacker  DBuckner  RLDale  AMMaguire  RPHyman  BTAlbert  MSKilliany  RJ An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest.  Neuroimage 2006;31 (3) 968- 980PubMed10.1016/j.neuroimage.2006.01.021Google Scholar
Chiavaras  MMLeGoualher  GEvans  APetrides  M Three-dimensional probabilistic atlas of the human orbitofrontal sulci in standardized stereotaxic space.  Neuroimage 2001;13 (3) 479- 496PubMedGoogle Scholar
Lohoff  FWSander  TFerraro  TNDahl  JPGallinat  JBerrettini  WH Confirmation of association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene and bipolar I disorder.  Am J Med Genet B Neuropsychiatr Genet 2005;139B (1) 51- 53PubMedGoogle Scholar
Lucas  CPZhang  HFisher  PWShaffer  DRegier  DANarrow  WEBourdon  KDulcan  MKCanino  GRubio-Stipec  MLahey  BBFriman  P The DISC Predictive Scales (DPS): efficiently screening for diagnoses.  J Am Acad Child Adolesc Psychiatry 2001;40 (4) 443- 449PubMedGoogle Scholar
McReynolds  LSWasserman  GAFisher  PLucas  CP Diagnostic screening with incarcerated youths: comparing the DPS and Voice DISC.  Crim Justice Behav 2007;34 (6) 830- 845Google Scholar
Zoccolillo  MVitaro  FTremblay  RE Problem drug and alcohol use in a community sample of adolescents.  J Am Acad Child Adolesc Psychiatry 1999;38 (7) 900- 907PubMedGoogle Scholar
Lerner  RMLerner  JVAlmerigi  JTheokas  CPhelps  EGestsdottir  SNaudeau  SJelicic  HAlberts  AMa  LSmith  LBobek  DSimpson  IChristiansen  Evon Eye  A Positive youth development, participation in community youth development programs and contributions of fifth grade adolescents: findings from the first wave of the 4-H Study of Positive Youth Development.  J Early Adolesc 2005;25 (1) 17- 71PubMedGoogle Scholar
Séguin  JRFreeston  MHTarabulsy  GMZoccolillo  MTremblay  RECarbonneau  R Développement des comportements anxieux au préscolaire: de nouvelles mesures et influences familiales.  Presented at: Québec Mental Health Network Annual Meeting June 2, 2000 Montréal, Quebec
Steinberg  LMonahan  KC Age differences in resistance to peer influence.  Dev Psychol 2007;43 (6) 1531- 1543PubMedGoogle Scholar
Raudenbush  SWBryk  AS Hierarchical Linear Models: Applications and Data Analysis Methods. 2nd ed. Newbury Park, CA Sage Publications2002;
Hox  J Multilevel Analysis: Techniques and Applications.  London, England Lawrence Erlbaum Associates2002;
Rivkin  MJDavis  PELemaster  JLCabral  HJWarfield  SKMulkern  RVRobson  CDRose-Jacobs  RFrank  DA Volumetric MRI study of brain in children with intrauterine exposure to cocaine, alcohol, tobacco, and marijuana.  Pediatrics 2008;121 (4) 741- 750PubMedGoogle Scholar
Jacobsen  LKPicciotto  MRHeath  CJFrost  SJTsou  KADwan  RAJackowski  MPConstable  RTMencl  WE Prenatal and adolescent exposure to tobacco smoke modulates the development of white matter microstructure.  J Neurosci 2007;27 (49) 13491- 13498PubMedGoogle Scholar
Roy  TSSabherwal  U Effects of prenatal nicotine exposure on the morphogenesis of somatosensory cortex.  Neurotoxicol Teratol 1994;16 (4) 411- 421PubMedGoogle Scholar
Roy  TSSabherwal  U Effects of gestational nicotine exposure on hippocampal morphology.  Neurotoxicol Teratol 1998;20 (4) 465- 473PubMedGoogle Scholar
Slotkin  TAPinkerton  KESeidler  FJ Perinatal environmental tobacco smoke exposure in rhesus monkeys: critical periods and regional selectivity for effects on brain cell development and lipid peroxidation.  Environ Health Perspect 2006;114 (1) 34- 39PubMedGoogle Scholar
Fowler  JSVolkow  NDWang  GJPappas  NLogan  JMacGregor  RAlexoff  DShea  CSchlyer  DWolf  APWarner  DZezulkova  ICilento  R Inhibition of monoamine oxidase B in the brains of smokers.  Nature 1996;379 (6567) 733- 736PubMedGoogle Scholar
Franke  RMBelluzzi  JDLeslie  FM Gestational exposure to nicotine and monoamine oxidase inhibitors influences cocaine-induced locomotion in adolescent rats.  Psychopharmacology (Berl) 2007;195 (1) 117- 124PubMedGoogle Scholar
Volkow  NDFowler  JS Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex.  Cereb Cortex 2000;10 (3) 318- 325PubMedGoogle Scholar
Makris  NGasic  GPKennedy  DNHodge  SMKaiser  JRLee  MJKim  BWBlood  AJEvins  AESeidman  LJIosifescu  DVLee  SBaxter  CPerlis  RHSmoller  JWFava  MBreiter  HC Cortical thickness abnormalities in cocaine addiction: a reflection of both drug use and a pre-existing disposition to drug abuse?  Neuron 2008;60 (1) 174- 188PubMedGoogle Scholar
Russo  SJMazei-Robison  MSAbles  JLNestler  EJ Neurotrophic factors and structural plasticity in addiction.  Neuropharmacology 2009;56 ((suppl 1)) 73- 82PubMedGoogle Scholar
Bolaños  CANestler  EJ Neurotrophic mechanisms in drug addiction.  Neuromolecular Med 2004;5 (1) 69- 83PubMedGoogle Scholar
Pierce  RCBari  AA The role of neurotrophic factors in psychostimulant-induced behavioral and neuronal plasticity.  Rev Neurosci 2001;12 (2) 95- 110PubMedGoogle Scholar
Le Foll  BDiaz  JSokoloff  P A single cocaine exposure increases BDNF and D3 receptor expression: implications for drug-conditioning.  Neuroreport 2005;16 (2) 175- 178PubMedGoogle Scholar
Gorski  JAZeiler  SRTamowski  SJones  KR Brain-derived neurotrophic factor is required for the maintenance of cortical dendrites.  J Neurosci 2003;23 (17) 6856- 6865PubMedGoogle Scholar
Bath  KGLee  FS Variant BDNF (Val66Met) impact on brain structure and function.  Cogn Affect Behav Neurosci 2006;6 (1) 79- 85PubMedGoogle Scholar
Schofield  PRWilliams  LMPaul  RHGatt  JMBrown  KLuty  ACooper  NGrieve  SDobson-Stone  CMorris  CKuan  SAGordon  E Disturbances in selective information processing associated with the BDNF Val66Met polymorphism: evidence from cognition, the P300 and fronto-hippocampal systems [published online September 16, 2008].  Biol Psychol 2009;80 (2) 176- 188PubMed10.1016/j.biopsycho.2008.09.001Google Scholar
Sublette  MEBaca-Garcia  EParsey  RVOquendo  MARodrigues  SMGalfalvy  HHuang  YYArango  VMann  JJ Effect of BDNF val66met polymorphism on age-related amygdala volume changes in healthy subjects.  Prog Neuropsychopharmacol Biol Psychiatry 2008;32 (7) 1652- 1655PubMed10.1016/j.pnpbp.2008.06.009Google Scholar
Kim  TSKim  DJLee  HKim  YK Increased plasma brain-derived neurotrophic factor levels in chronic smokers following unaided smoking cessation.  Neurosci Lett 2007;423 (1) 53- 57PubMedGoogle Scholar
Terry  MBFerris  JSPilsner  RFlom  JDTehranifar  PSantella  RMGamble  MVSusser  E Genomic DNA methylation among women in a multiethnic New York City birth cohort.  Cancer Epidemiol Biomarkers Prev 2008;17 (9) 2306- 2310PubMedGoogle Scholar
Huizink  ACMulder  EJ Maternal smoking, drinking, or cannabis use during pregnancy and neurobehavioral and cognitive functioning in human offspring.  Neurosci Biobehav Rev 2006;30 (1) 24- 41PubMedGoogle Scholar
Original Article
November 2009

Orbitofrontal Cortex and Drug Use During Adolescence: Role of Prenatal Exposure to Maternal Smoking and BDNF Genotype

Author Affiliations

Author Affiliations: Brain and Body Centre (Drs Lotfipour, Toro, Pausova, and Paus) and School of Psychology (Dr Ferguson), University of Nottingham, United Kingdom; Montréal Neurological Institute, McGill University (Drs Leonard, Pike, and Paus), and Hospital Centre of the University of Montreal (Drs Perron, Veillette, and Pausova), and Department of Psychiatry (Dr Séguin) and University of Montreal, Montreal, Quebec, Canada; Department of Psychology, University of Quebec in Chicoutimi, Chicoutimi, Quebec (Dr Richer); and Cégep de Jonquière, Jonquiere, Quebec (Drs Perron and Veillette).

Arch Gen Psychiatry. 2009;66(11):1244-1252. doi:10.1001/archgenpsychiatry.2009.124

Context  Prenatal exposure to maternal cigarette smoking (PEMCS) may affect brain development and behavior in adolescent offspring.

Objective  To evaluate the involvement of the orbitofrontal cortex (OFC) in mediating the relationship between PEMCS and substance use.

Design  Cross-sectional analyses from the Saguenay Youth Study aimed at evaluating the effects of PEMCS on brain development and behavior among adolescents. Nonexposed adolescents were matched with adolescents exposed prenatally to cigarette smoking by maternal educational level.

Participants and Setting  A French Canadian founder population of the Saguenay–Lac-Saint-Jean region of Quebec, Canada.The behavioral data set included 597 adolescents (275 sibships; 12-18 years of age), half of whom were exposed in utero to maternal cigarette smoking. Analysis of cortical thickness and genotyping were performed using available data from 314 adolescents.

Main Outcome Measures  The likelihood of substance use was assessed with the Diagnostic Interview Schedule for Children Predictive Scales. The number of different drugs tried by each adolescent was assessed using another questionnaire. Thickness of the OFC was estimated from T1-weighted magnetic resonance images using FreeSurfer software.

Results  Prenatal exposure to maternal cigarette smoking is associated with an increased likelihood of substance use. Among exposed adolescents, the likelihood of drug experimentation correlates with the degree of OFC thinning. In nonexposed adolescents, the thickness of the OFC increases as a function of the number of drugs tried. The latter effect is moderated by a brain-derived neurotrophic factor (BDNF) genotype (Val66Met).

Conclusions  We speculate that PEMCS interferes with the development of the OFC and, in turn, increases the likelihood of drug use among adolescents. In contrast, we suggest that, among nonexposed adolescents, drug experimentation influences the OFC thickness via processes akin to experience-induced plasticity.