Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Denmark Hill, London SE5 8AF
Section of Child and Adolescent Psychiatry, Department of Psychological Medicine, University of Wales College of Medicine, Cardiff
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Denmark Hill, London
Correspondence: Dr T. M. M. Button, Institute for Behavioral Genetics, 447 UCB, Boulder, CO80309-447, USA. E-mail: tanya.button{at}colorado.edu
Declaration of interest None. Funding detailed in Acknowledgement.
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ABSTRACT |
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Aims To examine the relationship between maternal smoking during pregnancy, antisocial behaviour and ADHD in offspring.
Method Questionnaires concerning behaviour and environmental factors were sent to twins from the CaStANET study and data analysed using a number of bivariate structural equation models.
Results Maternal prenatal smoking contributed small but significant amounts to the variance of ADHD and of antisocial behaviour. The best fitting bivariate model was one in which maternal prenatal smoking had a specific influence on each phenotype, independent of the effect on the other phenotype.
Conclusions Both antisocial behaviour and ADHD symptoms in offspring are independently influenced by maternal prenatal smoking during pregnancy.
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INTRODUCTION |
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The aim of the present study was to investigate whether maternal prenatal smoking contributes to the comorbidity between antisocial behaviour and ADHD, or whether the association between maternal prenatal smoking and antisocial behaviour is mediated by ADHD, given the evidence that ADHD may increase the risk of antisocial behaviour (Schachar & Tannock, 2002).
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METHOD |
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Measures
Parents were asked to complete the Rutter A scale
(Rutter, 1970), an extensively
used, parent report questionnaire with good validity, retest reliability and
interrater reliability. Antisocial behaviour in the twins was measured using
antisocial items from the scale, which were: does he ever steal
things?, often destroys own or other's belongings,
is often disobedient, often tells lies, and
bullies other children. Item scores were summed for each twin.
The presence of ADHD was assessed using a modified version of the DuPaul ADHD
rating scale (DuPaul, 1981), which contained 14 DSM-III-R ADHD symptoms
(American Psychiatric Association,
1987), and was augmented with four additional items to cover
ICD-10 symptoms of hyperkinetic disorder
(World Health Organization,
1993; Thapar et al,
2001). Scores were regressed for age and gender, and standardised
values were calculated prior to genetic analysis to eliminate any inflation of
common environment effects across same-gender twins
(McGue & Bouchard,
1984).
As a measure of maternal prenatal smoking, mothers were asked to retrospectively report how many cigarettes they smoked daily during their pregnancy according to four categories: non-smokers (0 cigarettes), light smokers (1-10), moderate smokers (11-20) and heavy smokers (over 20).
Statistical analysis
Initial statistical analyses were performed using the Statistical Package
for the Social Sciences, version 10 for Windows
(Kinnear & Gray, 2000). Data were double-entered to avoid any bias owing to birth order, and twin
order was then selected randomly. The structural equation modelling package Mx
(Neale, 1997) was used to test
a univariate model that enables us to estimate the proportion of the
phenotypic variance attributable to additive genetic effects, non-additive
genetic effects, and non-shared environmental effects and maternal prenatal
smoking (Fig. 1).
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RESULTS |
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Of the 29.1% (552) of mothers who reported smoking during pregnancy, 38.6% (213) smoked 1-10 cigarettes/day, 55.1% (304) smoked 11-20/day and 6.3% (35) smoked more than 20/day. The mean scores for both antisocial behaviour and ADHD increased with the number of cigarettes smoked. Means of 70.11 and 70.09 for antisocial behaviour and ADHD respectively were calculated for the non-smoking category, 0.15 and 0.11 were calculated for those smoking fewer than 10 cigarettes per day. Means were 0.35 and 0.24 for those smoking 11-20/day, and 0.24 and 0.30 for those smoking 20 or more cigarettes per day. Both antisocial behaviour and ADHD correlated significantly with amount of maternal prenatal smoking (antisocial behaviour: r=0.17, P < 0.001; ADHD: r=0.14, P < 0.001).
A gender limitation model was used to identify whether the parameter
estimates differed significantly across gender; for ADHD no such difference
was found (=2.823(4), P=0.588), although for
antisocial behaviour there was a small but significant difference
(
=24.206(4), P < 0.001.) However, as we
were not aiming to examine gender differences in these analyses we regressed
out both gender and age differences and included males, females and
opposite-gender twin pairs in our analyses.
Univariate models
The monozygotic and dizygotic correlations for ADHD were 0.74 and 0.45
respectively, and the respective correlations for antisocial behaviour were
0.68 and 0.44, suggesting a genetic contribution to both. The univariate
analyses showed ADHD to be moderately heritable, with both an additive and
non-additive genetic component. Neither of these parameters could be dropped
from the univariate analysis without significantly reducing the fit of the
model. The broad heritability of this phenotype is thus approximately 74%.
However, dropping non-additive genetic influences (D) from the antisocial
behaviour model did not result in a worse fit, although dropping additive
genetic influences (A) did. The AE model is thus the best fit, and the
heritability is 66% (Table
1).
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Bivariate models
A substantial correlation of 0.62 (P < 0.001) between
antisocial behaviour and ADHD was demonstrated, and the results of bivariate
model fitting are presented in Table
2. As it was possible to drop additive genetic effects specific to
antisocial behaviour, the best fitting Cholesky decomposition model is one in
which path a3 was dropped, thus setting the genetic correlation at
1.0. Thus there are no genetic effects specific to antisocial behaviour.
Non-shared environment also appears to influence the correlation between the
two phenotypes. Moreover, it is not possible to drop the two paths from
smoking to antisocial behaviour or ADHD, indicating that smoking is
significantly associated with both phenotypes, contributing approximately 2%
of the variance for ADHD and 3% for antisocial behaviour.
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Although it is not possible to directly compare the causal
model with the Cholesky model, the model in which the relationship between
maternal prenatal smoking and antisocial behaviour was mediated by ADHD did
not fit the observed data, judging by the large and significant
2 fit, whereas the Cholesky model does appear to
satisfactorily explain our data statistically.
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DISCUSSION |
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Contribution of maternal prenatal smoking to the phenotype
Consistent with previous studies, we found that maternal smoking during
pregnancy was associated with antisocial behaviour as well as ADHD,
contributing 3% to the variance of antisocial behaviour and 2% to the variance
of ADHD.
Relationship between maternal prenatal smoking, ADHD and antisocial behaviour
We investigated whether the relationship of maternal prenatal smoking with
antisocial behaviour was attributable to the association of maternal smoking
in pregnancy and ADHD and the covariation of the two childhood phenotypes.
However, the causal model did not fit the data at all whereas
the Cholesky model did, suggesting that smoking in pregnancy has a specific
influence on each, accounting for some of the covariance between them, rather
than resulting from this covariance. These findings suggest that the
association of smoking in pregnancy with antisocial behaviour is not
attributable to its association with ADHD.
Limitations
There are a number of limitations to this study. First, the age range of
the twins was large and the sample contained male, female and opposite-gender
twins. A larger twin data-set might allow more thorough investigation of the
relationships, controlling for differences in both age and gender. However,
according to this study and previous research, these differences may not be so
important. Second, all measures used in this study were rated by a single
individual, with mothers accounting for a large proportion of the raters.
Consequently shared rater effects may account for some of the covariance
between phenotypes. This is an especially important factor given that maternal
prenatal smoking may index antisocial behaviour in the mother
(Silberg et al,
2003), which may be associated with reporter bias. Using different
raters' accounts of the child's behaviour, such as the child him- or herself,
may help to overcome this problem. Finally, the data-set is cross-sectional;
the mother's report of her smoking during pregnancy is retrospective and a
memory of both smoking and the amount smoked between 5 and 18 years previously
was required. Consequently memory recall may have an effect on the outcomes of
the study.
Another limitation of this study is that it fails to account for the fact that maternal prenatal smoking may be an index of other latent risk variables transmitted from the mother to the children. For example, it has been suggested that maternal prenatal smoking may index a broader antisocial phenotype in the mother (Silberg et al, 2003). Consequently, antisocial behaviour of the offspring may partly or entirely result from genetic transmission of the propensity to antisocial behaviour from the mother to child (Fergusson et al, 1998; Brennan et al, 1999). Although it was not possible to test this hypothesis in the present study, lack of a significant contribution of shared environmental influences along with a significant influence of maternal prenatal smoking suggests an underlying genetic rather than environmental mediation, consistent with other studies (Maughan et al, 2004). Finally, maternal prenatal smoking may be indicative of other environmental risk factors for antisocial behaviour, such as poor family relationships (van den Bree et al, 2004) and low socio-economic status (Wakschlag et al, 2002). Longitudinal studies and children of twins studies may be more useful in differentiating these causal relationships.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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Received for publication June 15, 2004. Revision received November 5, 2004. Accepted for publication November 16, 2004.
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