Orbitofrontal cortex and drug use during adolescence: role of prenatal exposure to maternal smoking and BDNF genotype.
BACKGROUND
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.


METHODS
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.


METHODS
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.


METHODS
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.
Lotfipour
Shahrdad
S
Brain and Body Centre, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom.
Ferguson
Eamonn
E
Leonard
Gabriel
G
Perron
Michel
M
Pike
Bruce
B
Richer
Louis
L
Séguin
Jean R
JR
Toro
Roberto
R
Veillette
Suzanne
S
Pausova
Zdenka
Z
Paus
Tomás
T
D000293:Adolescent; D000294:Adolescent Behavior / Q000523:psychology*; D001284:Atrophy / Q000473:pathology; D001931:Brain Mapping; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002540:Cerebral Cortex / Q000254:growth & development / Q000473:pathology*; D002648:Child; D016241:Child of Impaired Parents / Q000523:psychology / Q000706:statistics & numerical data; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006306:Health Surveys; D006801:Humans; D008279:Magnetic Resonance Imaging; D008425:Maternal Behavior / Q000523:psychology; D018811:Maternal Exposure / Q000009:adverse effects*; D009035:Mothers / Q000523:psychology* / Q000706:statistics & numerical data; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000473:pathology; D011792:Quebec / Q000453:epidemiology; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology / Q000235:genetics; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000235:genetics*
D019208:Brain-Derived Neurotrophic Factor