The present study examined the effects of dopamine receptor D2 genotype and PTE status on early infant neurobehavior

Espy, Kimberly A.

Huggenvik, Jodi

Jameson, Travis

Respass, Jennifer

Stopp, Christian

Wiebe, Sandra A.

English

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University of Nebraska - Lincoln 
DigitalCommons@University of Nebraska - Lincoln 
Developmental Cognitive Neuroscience 
Laboratory - Faculty and Staff Publications 
Developmental Cognitive Neuroscience 
Laboratory 
April 2008 
DRD2 Genotype and Prenatal Exposure to Tobacco Interact to 
Influence Infant Attention and Reactivity 
Sandra A. Wiebe 
University of Nebraska Lincoln, sandra.wiebe@ualberta.ca 
Kimberly A. Espy 
University of Nebraska-Lincoln, kespy2@unl.edu 
Christian Stopp 
University of Nebraska-Lincoln, cstopp2@unl.edu 
Jennifer Respass 
University of Nebraska-Lincoln 
Travis Jameson 
Southern Illinois University School of Medicine 
See next page for additional authors 
Follow this and additional works at: https://digitalcommons.unl.edu/dcnlfacpub 
 Part of the Neurosciences Commons 
Wiebe, Sandra A.; Espy, Kimberly A.; Stopp, Christian; Respass, Jennifer; Jameson, Travis; and Huggenvik, 
Jodi, "DRD2 Genotype and Prenatal Exposure to Tobacco Interact to Influence Infant Attention and 
Reactivity" (2008). Developmental Cognitive Neuroscience Laboratory - Faculty and Staff Publications. 39. 
https://digitalcommons.unl.edu/dcnlfacpub/39 
This Article is brought to you for free and open access by the Developmental Cognitive Neuroscience Laboratory at 
DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Developmental Cognitive 
Neuroscience Laboratory - Faculty and Staff Publications by an authorized administrator of 
DigitalCommons@University of Nebraska - Lincoln. 
Authors 
Sandra A. Wiebe, Kimberly A. Espy, Christian Stopp, Jennifer Respass, Travis Jameson, and Jodi 
Huggenvik 
This article is available at DigitalCommons@University of Nebraska - Lincoln: https://digitalcommons.unl.edu/
dcnlfacpub/39 
DRD2 Genotype and Prenatal Exposure to Tobacco Interact 
to Influence Infant Attention and Reactivity
Sandra A. Wiebe, Ph.D.1, Kimberly Andrews Espy, Ph.D.1 , Christian Stopp, M. A.1, 
Jennifer Respass, B.A.1, Travis Jameson, B.S.2, & Jodi Huggenvik, Ph.D.2
1. Developmental Cognitive Neuroscience Lab, University of Nebraska-Lincoln
2. Southern Illinois University School of Medicine
Acknowledgments
This work was funded by NIH grants MH 065668 and DA 014661 
to Kimberly Andrews Espy. We thank the Developmental 
Cognitive Neuroscience Lab teams at SIU Carbondale and UNL, 
and all of the mothers and infants who made this research possible. 
Correspondence regarding this poster may be addressed to Sandra 
Wiebe (swiebe2@unl.edu).
Method
?The sample was comprised of 119 infants (M = 4.24 
wks, range = 3.0 to 8.9 weeks)
?Mothers were prospectively enrolled during pregnancy 
(most before the 16th week)
?Prenatal tobacco exposure was quantified based on 
maternal self-report (timeline-followback interviews 
conducted at 16 weeks, 28 weeks, and 24-48 hours after 
birth), and verified by cotinine analysis of maternal urine 
and infant meconium
?All infants were genotyped on DRD2 TaqIA allele
?Infants were administered the Neonatal Temperament 
Assessment (NTA; Riese, 1983) when they were 4 
weeks old
?A principal components analysis of NTA rating scores 
yielded 3 summary component scores:
Attention: (e.g., auditory orienting to voice or rattle, visual following 
of bulls-eye)
Irritable Reactivity (e.g., irritability to visual/auditory stimuli, 
soothability after reflex elicitation)
Dysregulation to Stress (responsiveness to soothing techniques, 
soothability after pacifier withdrawal)
?Component scores were analyzed using SAS’s proc 
mixed, with PTE status, DRD2 allele, and their 
interaction entered as predictors, and covarying maternal 
education, sex, and age at assessment 
Introduction
?Prenatal tobacco exposure (PTE) results in activation 
of nicotinic acetylcholine receptors, changing the timing of 
neurodevelopmental processes (e.g., premature shift to 
differentiation at the expense of replication), and alteration 
in function of dopaminergic/serotonergic circuits (e.g., 
Levin & Slotkin, 1998; Muneoka et al., 1997)
?Previous studies have shown that PTE affects infant 
neurobehavior and temperament (Fried & Makin, 1987; 
Jacobson et al., 1984; Key et al., 2007)
?Candidate genes related to dopaminergic
neurotransmission have been implicated in individual 
differences in infant behavior/temperament (e.g., Auerbach
et al., 2001; Lakatos et al., 2003; Laucht, Becker, & 
Schmidt, 2006). 
?The impact of PTE on childhood outcomes (e.g., ADHD) 
has been shown to interact with genetic risk factors (e.g., 
Becker et al., 2008; Kahn et al., 2003; Neuman et al., 2007)
?Does PTE interact with genetic risk in infancy?
?The TaqIA polymorphism is located within a kinase gene 
upstream from the coding region of the D2 dopamine 
receptor (DRD2) gene (Neville, Johnstone, & Walton, 
2004)
?Presence of the A1 allele (in A1A1 homozygotes or 
A1A2 heterozygotes, collectively referred to as the A1+ 
genotype) is associated with differences in DRD2 receptor 
expression and availability in striatum (Pohjalainen et al., 
1998) and anterior cingulate activation when controlled 
attention is required (Fossella, Green, & Fan, 2006)
?The present study examined the effects of dopamine 
receptor D2 genotype and PTE status on early infant 
neurobehavior
Results
0.000
0.200
0.400
0.600
0.800
1.000
1.200
1.400
NE TE
Prenatal Tobacco Exposure Status
A
t
t
e
n
t
i
o
n
 
F
a
c
t
o
r
 
S
c
o
r
e
TaqIA Genotype A1-
TaqIA Genotype A1+
-1.000
-0.800
-0.600
-0.400
-0.200
0.000
0.200
0.400
0.600
0.800
NE TE
Prenatal Tobacco Exposure Status
I
r
r
i
t
a
b
l
e
 
R
e
a
c
t
i
v
i
t
y
 
F
a
c
t
o
r
 
S
c
o
r
e
TaqIA Genotype A1-
TaqIA Genotype A1+
0.000
0.100
0.200
0.300
0.400
0.500
0.600
0.700
0.800
Girls Boys
Sex
S
t
r
e
s
s
 
D
y
s
r
e
g
u
l
a
t
i
o
n
 
C
o
m
p
o
n
e
n
t
 
S
c
o
r
e
Attention
PTE: n.s.
DRD2: p < .05
PTExDRD2: p < .05
NE: A1+>A1-
TE: n.s.
Irritable Reactivity
PTE: n.s.
DRD2: p < .05
PTExDRD2: p < .05
NE: A1+<A1-
TE: n.s.
Dysregulation to Stress
PTE: n.s.
DRD2: n.s.
PTExDRD2: n.s.
Sex: p < .05
Conclusions
?Prenatal tobacco exposure appears to moderate the 
effect of genotype on infant attention and irritable 
reactivity
?Infants with the A1+ genotype were more attentive 
and less reactive, but only in the absence of PTE
?Infants with the A1+ genotype may have a heightened 
response to novelty (seen later in development: Berman 
et al., 2002), which could result in increased orienting 
and concomitant decreased irritability to novel stimuli
?In PTE infants with the A1+ genotype, response to 
novelty may then be dampened, as has been found in 
rhesus monkeys exposed to perinatal tobacco smoke 
(Golub, Slotkin, Tarantal, & Pinkerton, 2007); however, 
infants with the A1- genotype (who evidenced 
intermediate levels of attention and irritability regardless 
of PTE status) may be less susceptible to PTE’s effects
?These results exemplify the interplay between genetic 
and environmental factors in infant development
?Future studies should test these findings for replication 
and examine implications of early attention/orienting 
and irritability for later outcomes in samples with known 
prenatal histories and genetic risk



DRD2 Genotype and Prenatal Exposure to Tobacco Interact to Influence Infant Attention and Reactivity

DigitalCommons@University of Nebraska

University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Developmental Cognitive Neuroscience Laboratory - Faculty and Staff Publications Developmental Cognitive Neuroscience Laboratory April 2008 DRD2 Genotype and Prenatal Exposure to Tobacco Interact to Influence Infant Attention and Reactivity Sandra A. Wiebe University of Nebraska Lincoln, sandra.wiebe@ualberta.ca Kimberly A. Espy University of Nebraska-Lincoln, kespy2@unl.edu Christian Stopp University of Nebraska-Lincoln, cstopp2@unl.edu Jennifer Respass University of Nebraska-Lincoln Travis Jameson Southern Illinois University School of Medicine See next page for additional authors Follow this and additional works at: https://digitalcommons.unl.edu/dcnlfacpub  Part of the Neurosciences Commons Wiebe, Sandra A.; Espy, Kimberly A.; Stopp, Christian; Respass, Jennifer; Jameson, Travis; and Huggenvik, Jodi, "DRD2 Genotype and Prenatal Exposure to Tobacco Interact to Influence Infant Attention and Reactivity" (2008). Developmental Cognitive Neuroscience Laboratory - Faculty and Staff Publications. 39. https://digitalcommons.unl.edu/dcnlfacpub/39 This Article is brought to you for free and open access by the Developmental Cognitive Neuroscience Laboratory at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Developmental Cognitive Neuroscience Laboratory - Faculty and Staff Publications by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. Authors Sandra A. Wiebe, Kimberly A. Espy, Christian Stopp, Jennifer Respass, Travis Jameson, and Jodi Huggenvik This article is available at DigitalCommons@University of Nebraska - Lincoln: https://digitalcommons.unl.edu/dcnlfacpub/39 DRD2 Genotype and Prenatal Exposure to Tobacco Interact to Influence Infant Attention and ReactivitySandra A. Wiebe, Ph.D.1, Kimberly Andrews Espy, Ph.D.1 , Christian Stopp, M. A.1, Jennifer Respass, B.A.1, Travis Jameson, B.S.2, & Jodi Huggenvik, Ph.D.21. Developmental Cognitive Neuroscience Lab, University of Nebraska-Lincoln2. Southern Illinois University School of MedicineAcknowledgmentsThis work was funded by NIH grants MH 065668 and DA 014661 to Kimberly Andrews Espy. We thank the Developmental Cognitive Neuroscience Lab teams at SIU Carbondale and UNL, and all of the mothers and infants who made this research possible. Correspondence regarding this poster may be addressed to Sandra Wiebe (swiebe2@unl.edu).Method¾The sample was comprised of 119 infants (M = 4.24 wks, range = 3.0 to 8.9 weeks)¾Mothers were prospectively enrolled during pregnancy (most before the 16th week)¾Prenatal tobacco exposure was quantified based on maternal self-report (timeline-followback interviews conducted at 16 weeks, 28 weeks, and 24-48 hours after birth), and verified by cotinine analysis of maternal urine and infant meconium¾All infants were genotyped on DRD2 TaqIA allele¾Infants were administered the Neonatal Temperament Assessment (NTA; Riese, 1983) when they were 4 weeks old¾A principal components analysis of NTA rating scores yielded 3 summary component scores:Attention: (e.g., auditory orienting to voice or rattle, visual following of bulls-eye)Irritable Reactivity (e.g., irritability to visual/auditory stimuli, soothability after reflex elicitation)Dysregulation to Stress (responsiveness to soothing techniques, soothability after pacifier withdrawal)¾Component scores were analyzed using SAS’s proc mixed, with PTE status, DRD2 allele, and their interaction entered as predictors, and covarying maternal education, sex, and age at assessment Introduction¾Prenatal tobacco exposure (PTE) results in activation of nicotinic acetylcholine receptors, changing the timing of neurodevelopmental processes (e.g., premature shift to differentiation at the expense of replication), and alteration in function of dopaminergic/serotonergic circuits (e.g., Levin & Slotkin, 1998; Muneoka et al., 1997)¾Previous studies have shown that PTE affects infant neurobehavior and temperament (Fried & Makin, 1987; Jacobson et al., 1984; Key et al., 2007)¾Candidate genes related to dopaminergicneurotransmission have been implicated in individual differences in infant behavior/temperament (e.g., Auerbachet al., 2001; Lakatos et al., 2003; Laucht, Becker, & Schmidt, 2006). ¾The impact of PTE on childhood outcomes (e.g., ADHD) has been shown to interact with genetic risk factors (e.g., Becker et al., 2008; Kahn et al., 2003; Neuman et al., 2007)¾Does PTE interact with genetic risk in infancy?¾The TaqIA polymorphism is located within a kinase gene upstream from the coding region of the D2 dopamine receptor (DRD2) gene (Neville, Johnstone, & Walton, 2004)¾Presence of the A1 allele (in A1A1 homozygotes or A1A2 heterozygotes, collectively referred to as the A1+ genotype) is associated with differences in DRD2 receptor expression and availability in striatum (Pohjalainen et al., 1998) and anterior cingulate activation when controlled attention is required (Fossella, Green, & Fan, 2006)¾The present study examined the effects of dopamine receptor D2 genotype and PTE status on early infant neurobehaviorResults0.0000.2000.4000.6000.8001.0001.2001.400NE TEPrenatal Tobacco Exposure StatusAttention Factor ScoreTaqIA Genotype A1-TaqIA Genotype A1+-1.000-0.800-0.600-0.400-0.2000.0000.2000.4000.6000.800NE TEPrenatal Tobacco Exposure StatusIrritable Reactivity Factor ScoreTaqIA Genotype A1-TaqIA Genotype A1+0.0000.1000.2000.3000.4000.5000.6000.7000.800Girls BoysSexStress Dysregulation Component ScoreAttentionPTE: n.s.DRD2: p < .05PTExDRD2: p < .05NE: A1+>A1-TE: n.s.Irritable ReactivityPTE: n.s.DRD2: p < .05PTExDRD2: p < .05NE: A1+<A1-TE: n.s.Dysregulation to StressPTE: n.s.DRD2: n.s.PTExDRD2: n.s.Sex: p < .05Conclusions¾Prenatal tobacco exposure appears to moderate the effect of genotype on infant attention and irritable reactivity¾Infants with the A1+ genotype were more attentive and less reactive, but only in the absence of PTE¾Infants with the A1+ genotype may have a heightened response to novelty (seen later in development: Berman et al., 2002), which could result in increased orienting and concomitant decreased irritability to novel stimuli¾In PTE infants with the A1+ genotype, response to novelty may then be dampened, as has been found in rhesus monkeys exposed to perinatal tobacco smoke (Golub, Slotkin, Tarantal, & Pinkerton, 2007); however, infants with the A1- genotype (who evidenced intermediate levels of attention and irritability regardless of PTE status) may be less susceptible to PTE’s effects¾These results exemplify the interplay between genetic and environmental factors in infant development¾Future studies should test these findings for replication and examine implications of early attention/orienting and irritability for later outcomes in samples with known prenatal histories and genetic risk

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DRD2 Genotype and Prenatal Exposure to Tobacco Interact to Influence Infant Attention and Reactivity

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