Effect of prenatal exposure to tobacco smoke on inhibitory control: neuroimaging results from a 25-year prospective study.
OBJECTIVE
There is accumulating evidence relating maternal smoking during pregnancy to attention-deficit/hyperactivity disorder (ADHD) without elucidating specific mechanisms. Research investigating the neurobiological underpinnings of this disorder has implicated deficits during response inhibition. Attempts to uncover the effect of prenatal exposure to nicotine on inhibitory control may thus be of high clinical importance.


OBJECTIVE
To clarify the influence of maternal smoking during pregnancy (hereafter referred to as prenatal smoking) on the neural circuitry of response inhibition and its association with related behavioral phenotypes such as ADHD and novelty seeking in the mother's offspring.


METHODS
Functional magnetic resonance imaging was performed for the offspring at 25 years of age during a modified Eriksen flanker/NoGo task, and voxel-based morphometry was performed to study brain volume differences of the offspring. Prenatal smoking (1-5 cigarettes per day [14 mothers] or >5 cigarettes per day [24 mothers]) and lifetime ADHD symptoms were determined using standardized parent interviews at the offspring's age of 3 months and over a period of 13 years (from 2 to 15 years of age), respectively. Novelty seeking was assessed at 19 years of age. Analyses were adjusted for sex, parental postnatal smoking, psychosocial and obstetric adversity, maternal prenatal stress, and lifetime substance abuse. A total of 178 young adults (73 males) without current psychopathology from a community sample followed since birth (Mannheim, Germany) participated in the study.


METHODS
Functional magnetic resonance imaging response, morphometric data, lifetime ADHD symptoms, and novelty seeking.


RESULTS
Participants prenatally exposed to nicotine exhibited a weaker response in the anterior cingulate cortex (t168 = 4.46; peak Montreal Neurological Institute [MNI] coordinates x = -2, y = 20, z = 30; familywise error [FWE]-corrected P = .003), the right inferior frontal gyrus (t168 = 3.65; peak MNI coordinates x = 44, y = 38, z = 12; FWE-corrected P = .04), the left inferior frontal gyrus (t168 = 4.09; peak MNI coordinates x = -38, y = 36, z = 8; FWE-corrected P = .009), and the supramarginal gyrus (t168 = 5.03; peak MNI coordinates x = 64, y = -28, z = 22; FWE-corrected P = .02) during the processing of the NoGo compared to neutral stimuli, while presenting a decreased volume in the right inferior frontal gyrus. These findings were obtained irrespective of the adjustment of confounders, ADHD symptoms, and novelty seeking. There was an inverse relationship between inferior frontal gyrus activity and ADHD symptoms and between anterior cingulate cortex activity and novelty seeking.


CONCLUSIONS
These findings point to a functional involvement of prenatal exposure to tobacco smoke in neural alterations similar to ADHD, which underlines the importance of smoking prevention treatments.
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Nathalie E
NE
Holz
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Regina
R
Boecker
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Sarah
S
Baumeister
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Erika
E
Hohm
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Katrin
K
Zohsel
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Arlette F
AF
Buchmann
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Dorothea
D
Blomeyer
Department of Biostatistics, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Christine
C
Jennen-Steinmetz
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Sarah
S
Hohmann
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany3Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim.
Isabella
I
Wolf
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Michael M
MM
Plichta
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Andreas
A
Meyer-Lindenberg
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Tobias
T
Banaschewski
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany5Department of Child and Adolescent Psychiatry, University of Zürich, Zürich, Switzerland.
Daniel
D
Brandeis
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany6Department of Psychology, University of Potsdam, Potsdam, Germany.
Manfred
M
Laucht
D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology* / Q000523:psychology; D002648:Child; D002675:Child, Preschool; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology; D059907:Functional Neuroimaging / Q000379:methods; D006801:Humans; D007223:Infant; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D009538:Nicotine / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology* / Q000523:psychology; D011446:Prospective Studies; D012907:Smoking / Q000009:adverse effects*; D055815:Young Adult
D009538:Nicotine