The World Journal of Biological Psychiatry

ISSN: 1562-2975 (Print) 1814-1412 (Online) Journal homepage: https://www.tandfonline.com/loi/iwbp20

Is ADHD a risk for posttraumatic stress disorder

(PTSD)? Results from a large longitudinal study of
referred children with and without ADHD

Joseph Biederman, Carter Petty, Thomas J. Spencer, K. Yvonne Woodworth,

Pradeep Bhide, Jinmin Zhu & Stephen V. Faraone

To cite this article: Joseph Biederman, Carter Petty, Thomas J. Spencer, K. Yvonne
Woodworth, Pradeep Bhide, Jinmin Zhu & Stephen V. Faraone (2014) Is ADHD a risk for
posttraumatic stress disorder (PTSD)? Results from a large longitudinal study of referred
children with and without ADHD, The World Journal of Biological Psychiatry, 15:1, 49-55, DOI:
10.3109/15622975.2012.756585

To link to this article: https://doi.org/10.3109/15622975.2012.756585

Published online: 23 Apr 2013. Submit your article to this journal

Article views: 696 View related articles

View Crossmark data Citing articles: 8 View citing articles

Full Terms & Conditions of access and use can be found at

https://www.tandfonline.com/action/journalInformation?journalCode=iwbp20
The World Journal of Biological Psychiatry, 2014; 15: 49–55

ORIGINAL INVESTIGATION

Is ADHD a risk for posttraumatic stress disorder (PTSD)?

Results from a large longitudinal study of referred
children with and without ADHD

JOSEPH BIEDERMAN1,2, CARTER PETTY1, THOMAS J. SPENCER1,2,

K. YVONNE WOODWORTH1, PRADEEP BHIDE3, JINMIN ZHU3
& STEPHEN V. FARAONE4
1Clinicaland Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital,
Boston, MA, USA, 2Department of Psychiatry, Harvard Medical School, Cambridge, MA, USA, 3Department of
Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL, USA, and 4Departments of Psychiatry,
and of Neuroscience & Physiology, SUNY Upstate Medical University, Syracuse, NY, USA

Abstract
Objectives. Preclinical studies link prenatal nicotine exposure with the development of both ADHD-like phenotype in
rodents and blockade of extinction learning in a fear conditioning paradigm, a preclinical model of posttraumatic stress
disorder (PTSD). While these findings suggest that either ADHD, prenatal nicotine exposure, or both could be a risk
factor for PTSD, such associations have not been investigated in humans. Methods. Subjects were ascertained from
family-genetic, longitudinal studies of paediatrically and psychiatrically referred children with and without ADHD of both
sexes and their siblings followed for 10 years from childhood into adulthood (n  403 probands; n  464 siblings; mean
age at follow-up of probands and siblings  22.0 years). All subjects were comprehensively evaluated with structured
diagnostic interviews that included questions regarding prenatal use of cigarettes. Results. A total of 12% (104/867) of
the sample had been exposed to maternal smoking during pregnancy. There was no interaction effect between maternal
smoking during pregnancy and ADHD (z  0.01, P  0.99). Maternal smoking during pregnancy and ADHD were
independent, significant risk factors for PTSD at the 10-year follow-up (odds ratio  3.58 [1.35,9.48], z  2.57, P  0.01
and odds ratio  2.23 [1.06,4.69], z  2.11, P  0.04, respectively). Conclusions. These results suggest that both maternal
smoking during pregnancy and ADHD are significant predictors of PTSD in humans.

Key words: Nicotine, Smoking, Anxiety, PTSD, ADHD

Introduction
Preclinical studies have linked prenatal nicotine
exposure with the development of ADHD-like
behaviours in rodents (Zhu et al. 2012). Preclinical
studies have also linked prenatal nicotine exposure
with learning of trace-conditioned fear-associated
cues and blockade of extinction learning in a fear
conditioning paradigm (Eppolito et al. 2010), the
latter of which is considered to be a preclinical
model of posttraumatic stress disorder (PTSD).
These findings suggest that ADHD, prenatal
nicotine exposure, or both could be risk factors
for PTSD.
While a robust and bidirectional association
has been documented between ADHD and anxiety
disorders in both clinical and epidemiological studies
in both adult and paediatric samples (Biederman
et al. 1996; Biederman 2004; Kessler et al. 2006),
whether a specific link between ADHD and PTSD
exists has not been adequately investigated. A limited
literature suggests that youth with ADHD are more
likely than those without ADHD to develop PTSD
and vice versa (Riggs et al. 1995; Famularo 1996;
Husain et al. 2008; Daud and Rydelius 2009).
Consistent with this finding, Kessler et al. (2006)
identified a robust and bidirectional association

Correspondence: Joseph Biederman MD, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD,
Massachusetts General Hospital, YAW 6A, 55 Fruit Street, Boston, MA 02114-3139, USA. Tel:  1 617 726 1743. Fax:  1 617 724 3742.
E-mail: jbiederman@partners.org

(Received 8 March 2012 ; accepted 4 December 2012 )

ISSN 1562-2975 print/ISSN 1814-1412 online © 2014 Informa Healthcare
DOI: 10.3109/15622975.2012.756585
50 J. Biederman et al.
between ADHD and PTSD in a representative sam-
ple of the US adult population in the National
Comorbidity Replication Study.
Whether ADHD, prenatal nicotine exposure or
both are risk factors for PTSD in humans is of high
clinical, scientific, and public health relevance. If
ADHD or maternal smoking during pregnancy is
linked to PTSD, it could offer clinicians useful infor-
mation as to whether some children are at high risk
for manifesting PTSD and could aid in preventive
and early intervention strategies aimed at mitigating
this disorder. Scientifically, such knowledge could
lead to novel insights into the pathophysiology of
certain forms of PTSD. From a public health per-
spective, this knowledge could support public health
efforts aimed at smoking cessation in general and in
pregnant women in particular.
The main aim of this study was to examine whether
ADHD and maternal smoking during pregnancy are
associated with an increased risk for PTSD in humans.
To this end, we used data from a large, family genetic,
longitudinal study of referred children of both sexes
with and without ADHD and their siblings. Based on
data from animal models, we hypothesized that both
ADHD and maternal smoking during pregnancy
would be risks for PTSD. To the best of our knowl-
edge, this is the first and the most comprehensive
examination of these associations in humans.
Methods and materials
Subjects
Subjects were youth probands of both sexes and
their siblings derived from two identically designed,
longitudinal, case-control family studies conducted
at the Clinical and Research Programs in Pediatric
Psychopharmacology and Adult ADHD at
Massachusetts General Hospital (MGH). Detailed
study methodology has been previously reported
(Biederman et al. 2006a,b). Briefly, these studies
included male and female youth probands with and
without DSM-III-R ADHD and their first-degree
relatives (hereafter referred to as the Boys and Girls
ADHD study, respectively) ascertained from paedi-
atric and psychiatric sources. For both studies, poten-
tial probands were excluded if they had been adopted,
if their nuclear family was not available, if they had
major sensorimotor handicaps (paralysis, deafness,
blindness), if they had psychosis or autism, or if they
were unable to participate in the assessments due to
language barriers or an estimated IQ  80. After a
complete description of the study, parents provided
written informed consent for their children, and
children and adolescents provided written assent.
The IRB at MGH approved this study.
We used a three-stage ascertainment procedure to
select probands (Faraone and Tsuang 1994; Faraone
et al. 1999). For ADHD subjects, the first stage was
their referral, which resulted in a clinical diagnosis
of ADHD. The second stage confirmed the diagnosis
of ADHD through a telephone questionnaire admin-
istered to the mother. The third stage was a diagnos-
tic assessment with a structured interview. Only
patients who received a positive diagnosis at all three
stages were included. Controls were similarly selected
though a three-stage procedure. First, we ascertained
them from consecutive referrals to medical clinics for
routine physical examinations at both the psychiatric
and paediatric sources. In stage two, the control
mothers responded to the DSM-III-R ADHD tele-
phone questionnaire about their children. Eligible
controls meeting study entry criteria were recruited
for the study and received the third stage, a diagnos-
tic assessment with a structured interview. Only sub-
jects classified as not having ADHD at all three
stages were included in the control group.
We used data from male and female probands and
siblings from both studies who were assessed at the
10-year (Boys study) or 11-year (Girls study) fol-
low-up and had information regarding exposure to
maternal smoking during pregnancy (n  505 from
the Boys study and n  362 from the Girls study). In
the Boys study (Biederman et al. 2006b), the siblings
were assessed at baseline and at 4- and 10-year fol-
low-ups. In the Girls study (Biederman et al. 2010),
the siblings were assessed at baseline and at 5- and
11-year follow-ups. The age ranges of the samples at
follow-up were 8–47 (mean 22.3) and 8–38 (mean
21.7) for the Boys and Girls studies, respectively.
Assessment procedures
Psychiatric assessment. Psychiatric assessments relied
on the Kiddie Schedule for Affective Disorders and
Schizophrenia–Epidemiologic Version (K-SADS-E)
(Orvaschel 1994) for subjects less than 18 years of age
and the Structured Clinical Interview for DSM-III-R
(SCID) (Spitzer et al. 1992) (supplemented with
modules from the K-SADS-E to assess childhood
diagnoses) for subjects aged 18 and older. Diagnoses
were based on direct interviews with the mothers and
the offspring, except for children  12 years that
were not interviewed directly. Combining data from
direct and indirect interviews, we considered a diag-
nosis positive if it was endorsed in either interview.
All interviews conducted were blind to the subject’s
referral source or diagnostic status (ADHD or con-
trol, proband or sibling). Diagnoses were considered
positive if DSM-III-R criteria were unequivocally
met. A committee of board-certified child and
adult psychiatrists, who were blind to the subject’s
 ADHD and increased risk for PTSD 51

ascertainment status and all other data, resolved Statistical analysis

diagnostic uncertainties. Diagnoses presented for
First, we examined demographic characteristics, strat-
review were considered positive only if a consensus
ified by exposure status, using logistic, linear, or
was achieved that criteria were met to a degree that
ordered logistic regression, depending on the distribu-
would be considered clinically meaningful.
tion of the dependent variable. We controlled for any
All interviewers had undergraduate degrees in
demographic confounder that reached significance at
psychology and were trained to high levels of inter-
the 0.10 alpha level. Using logistic regression with
rater reliability. First, they underwent several weeks
lifetime PTSD as the dependent variable, we tested
of classroom style training, learning interview
exposure to maternal smoking during pregnancy and
mechanics, diagnostic criteria, and coding algo-
ADHD as predictors in separate logistic regression
rithms. Then, experienced raters and clinicians
models. We then tested the interaction effect of mater-
observed interviewers. They subsequently conducted
nal smoking during pregnancy and ADHD predicting
at least six practice (non-study) interviews and at
PTSD. If this interaction effect was not significant, we
least two study interviews while being observed by
examined the independent effects of maternal smok-
senior interviewers. The principal investigator (JB)
ing and ADHD using logistic regression. We used the
supervised the interviewers throughout the study. We
Wilcoxon rank-sum test to compare ages of PTSD
computed kappa coefficients of agreement by having
onset between subjects with and without exposure to
child and adult psychiatrists and clinical psycholo-
maternal smoking during pregnancy. We graphed
gists diagnose subjects from audio taped interviews.
Kaplan–Meier failure functions to display the devel-
Based on 500 assessments from interviews of chil-
opment of any anxiety disorders found to have a sig-
dren and adults, the median kappa coefficient was
nificant association with exposure to maternal
0.98. Kappa coefficients for individual diagnoses
smoking during pregnancy. Across all models, we
included: ADHD (0.88), separation anxiety (1.0),
used robust Huber–White estimates of variance to
agoraphobia (1.0), and panic (0.95). Socio-economic
account for the non-independence among subjects
status (SES) was measured with the five-point
due to the correlation between family members. All
Hollingshead scale (Hollingshead 1975), using the
tests were two-tailed and alpha was set at 0.05.
occupational and educational status of the parents.

Measurement of prenatal exposure to nicotine. During

the structured diagnostic interview, mothers com-
pleted a detailed pregnancy and delivery module
where mothers were directly questioned regarding
the pregnancy, delivery, and infancy complications
they experienced with each child. This interview
included direct questions regarding prenatal use of
cigarettes. Maternal smoking during pregnancy was
considered positive if endorsed during this module.
Results
Clinical and sociodemographic characteristics
Twelve percent (104/867) of the sample were
exposed to maternal smoking during pregnancy.
The demographic characteristics of this sample,
stratified by maternal smoking during pregnancy
exposure, are presented in Table I. As shown, we

Table I. Demographic characteristics of offspring (n  867) grouped by exposure to maternal smoking

during pregnancy.

Unexposed Exposed Test statistic,

Demographic characteristic (n  763) (n  104) P value

n (%) n (%)

Sex (male) 389 (51) 55 (53) χ2(1)  0.15, P  0.70

Study of origin χ2(1)  4.80, P  0.03
Boys ADHD study 429 (56) 76 (73)
Girls ADHD study 334 (44) 28 (27)
Referral status (Proband) 354 (46) 49 (47) χ2(1)  0.04, P  0.84
Prenatal exposure to alcohol/drugs 16 (5) 5 (8) χ2(1)  1.06, P  0.30
Mean SD Mean SD
Offspring age at baseline 12.1  4.6 12.2  3.8 t(409)  0.15, P  0.88
Offspring age at follow-up 21.9  5.5 23.0  4.3 t(411)  1.83, P  0.07
Parental social class at baseline1 1.6  0.8 2.3  1.1 χ2(1)  14.82, P  0.001
1Social class measurement ranges from 1 through 5; 1  most affluent social class, 5  least affluent.
52 J. Biederman et al.
found no statistically significant differences between
subjects with and without exposure to maternal
smoking during pregnancy on sex, age at baseline,
referral status, and prenatal exposure to alcohol/
drugs. However, the exposed group was significantly
more likely to be from the Boys study, was older at
follow-up, and had a lower family SES. The overall
rate of ADHD in the entire sample of ADHD and
Control probands and their siblings was 33%
(283/867).
Maternal smoking during pregnancy,
PTSD and ADHD
In separate logistic regression models, exposure to
maternal smoking during pregnancy and ADHD
were both significant predictors of PTSD at the
10-year follow-up (odds ratio  4.28 [1.58,11.53],
z  2.87, P  0.004 and odds ratio  2.68 [1.30,5.55],
z  2.66, P  0.008, respectively). Figure 1 displays
the rates of PTSD in subjects with and without
ADHD and exposure to parental smoking during
pregnancy.
To better understand the relationships between
maternal smoking during pregnancy, ADHD, and
PTSD, we tested the interaction effects between
these variables. Results showed no interaction effect
between maternal smoking during pregnancy and
ADHD (z  0.01, P  0.99). After removing the
interaction term from the model, further examina-
tion of the main effects revealed that maternal smok-
ing during pregnancy and ADHD were independent,
significant risk factors for PTSD at the 10-year
follow-up (odds ratio  3.58 [1.35,9.48], z  2.57,
P  0.01 and odds ratio  2.23 [1.06,4.69], z  2.11,
P  0.04, respectively). Because parental PTSD was
only assessed in the Girls study, we could not fully
assess the impact of parental PTSD on our findings.
Figure 1. Prevalence of PTSD in subjects with and without ADHD and exposure to maternal smoking during pregnancy. PTSD,
posttraumatic stress disorder; ADHD, attention-deficit/hyperactivity disorder.
In the Girls study, the associations between PTSD
and maternal smoking during pregnancy and
ADHD lost significance after controlling for
parental PTSD (both P  0.10), parental PTSD
was not a significant predictor of offspring PTSD
(z  1.10, P  0.27), and the odds ratios for mater-
nal smoking during pregnancy (2.45 [0.77, 7.81])
and ADHD (2.34 [0.84,6.56]) were modest but not
significant.
As depicted in Figure 2, the large majority of
PTSD onsets were in childhood and adolescence
(Figure 2). The age at onset of PTSD did not signifi-
cantly differ between offspring exposed or not expo-
sed to maternal smoking during pregnancy (11.2 
6.6 vs. 14.3  6.4, z  1.29, P  0.20) or ADHD status
(11.9  6.3 vs. 15.2  6.6, z  1.52, P  0.13).
Discussion
The main aim of this study was to examine whether
ADHD and/or maternal smoking during pregnancy
were associated with an increased risk for PTSD in
humans. Using data from a large, family-genetic,
longitudinal study of children referred to psychiatric
and paediatric clinics with and without ADHD of
both sexes, we found that children exposed to mater-
nal smoking during pregnancy were significantly
more likely to develop PTSD, compared to those not
exposed to maternal smoking. In addition, we also
found that ADHD was an independent risk factor
for PTSD. These results confirm our study hypoth-
esis linking ADHD and prenatal cigarette smoke
exposure to PTSD, and extend to humans the simi-
lar findings reported in animal models.
The association between prenatal nicotine expo-
sure and PTSD in humans is consistent with the
preclinical findings by Eppolito et al. (2010),

Figure 2. Kaplan–Meier failure functions of posttraumatic stress disorder. PTSD, posttraumatic stress disorder; ADHD, attention-deficit/
hyperactivity disorder.
who reported in rodents that prenatal exposure to
nicotine blocked extinction learning in a fear
conditioning paradigm. In that study, nicotine
exposure impaired fear extinction but did not alter
fear acquisition.
Although the reasons for the associations between
prenatal exposure to nicotine and the development
of PTSD are not entirely clear, preclinical studies
suggest that prenatal nicotine exposure could result
in lasting neurochemical effects on the cholinergic
system. Such effects could mediate cell death and
disrupt synaptic connections in the neural circuit
that mediates fear learning and extinction involving
prefrontal cortex and amygdala (LeDoux 1995;
Milad et al. 2006; Eppolito et al. 2010). More work
is needed to test these intriguing hypotheses.
Our findings linking paediatric ADHD with
PTSD are consistent with results identified in com-
munity and clinical studies. Kessler et al. (2006)
identified a robust and bidirectional association
between ADHD and PTSD in a representative
sample of the USA adult population in the National
Comorbidity Replication Study. These associations
in humans are consistent with preclinical studies
linking prenatal nicotine exposure with the devel-
opment of ADHD-like phenotype in rodents, char-
acterized by selectively smaller cingulate cortex
volumes, lower dopaminergic turnover in the fron-
tal lobe, and “hyperactivity” responsive to thera-
peutic oral doses of methylphenidate (Zhu et al.
2012). More preclinical work is needed to tease out
whether the risk for PTSD in rodent models is due
ADHD and increased risk for PTSD 53
to the nicotine exposure itself or it is mediated via
the development of an ADHD-like phenotype in
the exposed animal.
The findings linking prenatal exposure to nico-
tine and ADHD to the development of PTSD are
of high clinical, scientific and public health rele-
vance. This information could offer clinicians valu-
able clues as to whether some children are at higher
risk for manifesting PTSD based on their prenatal
exposure to nicotine via maternal smoking during
pregnancy, a history of ADHD or both. Consider-
ing the heterogeneity of PTSD, this knowledge
could lead to novel insights into the pathophysiol-
ogy of some forms of PTSD that could lead to new
therapeutic approaches to address more effectively
this serious disorder. From the public health per-
spective, this knowledge could further support pub-
lic health efforts aimed at smoking cessation in
pregnant women and early identification and inter-
vention for children with ADHD.
Our findings need to be viewed in light of some
methodological limitations. Since parental PTSD
was only assessed in the Girls study, we could not
adequately control for it. However, parental PTSD
was not a significant predictor of offspring PTSD
in our model. Statistical significance for maternal
smoking during pregnancy and ADHD as predic-
tors of PTSD was lost after parental PTSD was
considered in the regression analyses. While this
outcome could be the result of limited statistical
power, it also raises the possibility that parental psy-
chopathology may account for our findings. Future
54 J. Biederman et al.
studies should further examine the role of parental
psychopathology in analyses considering the impact
of smoking on offspring psychopathology. Our find-
ings were entirely based on self report of maternal
smoking during pregnancy. Future studies should
examine more objective measures of prenatal smok-
ing. Also, our measure of prenatal nicotine exposure
did not have details on dose, timing and duration.
More work is needed to further examine whether
severity, duration and timing of exposure to nico-
tine moderate the association between nicotine
exposure and the development of PTSD. Because
of limited statistical power, we did not correct for
comorbid psychiatric disorders. Future, better pow-
ered studies addressing the association between
ADHD and PTSD could benefit from such correc-
tions. Since the sample was largely Caucasian and
referred, we do not know whether the same asso-
ciation will generalize to community samples or
other ethnic groups. Future studies should deter-
mine if these results generalize to non-ADHD
samples or if ADHD is a key mediator or modera-
tor on the pathway from maternal smoking during
pregnancy to anxiety disorders. Although we did
not conduct a reliability study of PTSD diagnoses,
low diagnostic reliability would have added noise
to our findings and would not have created spuri-
ous group differences.
Despite these limitations, we found that children
exposed to maternal smoking during pregnancy and
those that suffered from ADHD were significantly
more likely to develop PTSD when compared to
subjects not exposed to maternal smoking and those
not affected with ADHD. If replicated in future stud-
ies, these findings can have large clinical, scientific
and public health relevance.
Acknowledgements
Dr Joseph Biederman is currently receiving research
support from the following sources: Elminda,
Janssen, McNeil, and Shire. In 2012, Dr. Joseph
Biederman received an honorarium from the
MGH Psychiatry Academy and The Children’s
Hospital of Southwest Florida/Lee Memorial
Health System for tuition-funded CME courses. In
2011, Dr Biederman gave a single unpaid talk for
Juste Pharmaceutical Spain, received honoraria
from the MGH Psychiatry Academy for a tuition-
funded CME course, and received an honorarium
for presenting at an international scientific confer-
ence on ADHD. He also received an honorarium
from Cambridge University Press for a chapter
publication. Dr Biederman received departmental
royalties from a copyrighted rating scale used for
ADHD diagnoses, paid by Eli Lilly, Shire and Astra-
Zeneca; these royalties are paid to the Department
of Psychiatry at MGH. In 2010, Dr Biederman
received a speaker’s fee from a single talk given at
Fundación Dr. Manuel Camelo A.C. in Monterrey
Mexico. Dr Biederman provided single consultations
for Shionogi Pharma Inc. and Cipher Pharmaceuti-
cals Inc.; the honoraria for these consultations were
paid to the Department of Psychiatry at the MGH.
Dr Biederman received honoraria from the MGH
Psychiatry Academy for a tuition-funded CME
course. In previous years, Dr Biederman received
research support, consultation fees, or speaker’s fees
for/from the following additional sources: Abbott,
Alza, AstraZeneca, Boston University, Bristol Myers
Squibb, Celltech, Cephalon, Eli Lilly and Co., Esai,
Fundacion Areces (Spain), Forest, Glaxo, Gliatech,
Hastings Center, Janssen, McNeil, Medice Pharma-
ceuticals (Germany), Merck, MMC Pediatric,
NARSAD, NIDA, New River, NICHD, NIMH,
Novartis, Noven, Neurosearch, Organon, Otsuka,
Pfizer, Pharmacia, Phase V Communications, Physi-
cians Academy, The Prechter Foundation, Quantia
Communications, Reed Exhibitions, Shire, the
Spanish Child Psychiatry Association, The Stanley
Foundation, UCB Pharma Inc., Veritas, and Wyeth.
Dr Thomas Spencer has received research support
from the following sources: Shire Laboratories Inc,
Cephalon, Eli Lilly & Company, Janssen, McNeil
Pharmaceutical, Novartis Pharmaceuticals, NIMH
and the Department of Defense. Dr Spencer has
been a speaker or on a speaker’s bureau for the fol-
lowing pharmaceutical companies: Shire Laborato-
ries, Inc, McNeil Pharmaceutical, and Novartis
Pharmaceuticals. Dr Spencer has been an advisor or
on an advisory board for the following pharmaceuti-
cal companies: Alcobra, Shire Laboratories Inc,
Cephalon, Eli Lilly & Company, Janssen, McNeil
Pharmaceutical, and Novartis Pharmaceuticals. Dr
Spencer receives research support from Royalties
and Licensing fees on copyrighted ADHD scales
through MGH Corporate Sponsored Research and
Licensing. Dr Spencer has a US Patent Application
pending (Provisional Number #61/233,686), through
MGH corporate licensing, on a method to prevent
stimulant abuse.
In the past year, Dr Faraone received consulting
income and/or research support from Shire, Otsuka
and Alcobra and research support from the National
Institutes of Health (NIH). He is also on the Clinical
Advisory Board for Akili Interactive Labs. In previ-
ous years, he received consulting fees or was on
Advisory Boards or participated in continuing med-
ical education programs sponsored by: Shire, McNeil,
Janssen, Novartis, Pfizer and Eli Lilly. Dr Faraone
receives royalties from books published by Guilford

Press: Straight Talk about Your Child’s Mental Health
and Oxford University Press: Schizophrenia: The
Facts.
Mr Carter Petty, Ms Yvonne Woodworth, Dr
Pradeep Bhide and Dr Jinmin Zhu report no finan-
cial interests or potential conflicts of interest related
to this manuscript.
This manuscript was supported in part by grants
to J. Biederman from the National Institute of Health
(R01 HD36317, R01 MH50657) and the Pediatric
Psychopharmacology Research Council Fund.
Statement of Interest
None.
References
Biederman J. 2004. Impact of comorbidity in adults with
attention-deficit/hyperactivity disorder. J Clin Psychiatry
65:(Suppl. 3):3–7.
Biederman J, Faraone S, Milberger S, Guite J, Mick E, Chen L,
et al. 1996. A prospective 4-year follow-up study of attention-
deficit hyperactivity and related disorders. Arch Gen Psychiatry
53(5):437–446.
Biederman J, Monuteaux M, Mick E, Spencer T, Wilens T,
Klein K, et al. 2006a. Psychopathology in females with
attention-deficit/hyperactivity disorder: A controlled, five-year
prospective study. Biol Psychiatry 60(10):1098–1105.
Biederman J, Monuteaux MC, Mick E, Spencer T, Wilens TE,
Silva JM, et al. 2006b. Young adult outcome of attention deficit
hyperactivity disorder: a controlled 10-year follow-up study.
Psychol Med 36(2):167–179.
Biederman J, Petty CR, Monuteaux MC, Fried R, Byrne D,
Mirto T, et al. 2010. Adult psychiatric outcomes of girls with
attention deficit hyperactivity disorder: 11-year follow-up in a lon-
gitudinal case-control study. Am J Psychiatry 167(4):409–417.
Daud A, Rydelius PA. 2009. Comorbidity/overlapping between
ADHD and PTSD in relation to IQ among children of trauma-
tized/non-traumatized parents. J Atten Disord 13(2):188–196.
ADHD and increased risk for PTSD 55
Eppolito AK, Bachus SE, McDonald CG, Meador-Woodruff
JH, Smith RF. 2010. Late emerging effects of prenatal and
early postnatal nicotine exposure on the cholinergic system
and anxiety-like behavior. Neurotoxicol Teratol 32(3):
336–345.
Famularo R. 1996. Psychiatric comorbidity in childhood
posttraumatic stress disorder. Child Abuse Neglect 20(10):
953–961.
Faraone S, Tsuang M. 1994. Measuring diagnostic accuracy in
the absence of a “gold standard”. Am J Psychiatry 151(5):
650–657.
Faraone SV, Tsuang MT, Tsuang D. 1999. Genetics and mental
disorders: a guide for students, clinicians, and researchers.
New York, NY: The Guilford Press.
Hollingshead AB. 1975. Four factor index of social status.
New Haven, CT: Yale Press.
Husain SA, Allwood MA, Bell DJ. 2008. The relationship between
PTSD symptoms and attention problems in children exposed
to the Bosnian war. J Emot Behav Disord 16(1):52–62.
Kessler RC, Adler L, Barkley R, Biederman J, Conners CK,
Demler O, et al. 2006. The prevalence and correlates of adult
ADHD in the United States: results from the National
Comorbidity Survey Replication. Am J Psychiatry 163(4):
716–723.
LeDoux JE. 1995. Emotion: clues from the brain. Annu Rev
Psychol 46:209–235.
Milad MR, Rauch SL, Pitman RK, Quirk GJ. 2006. Fear extinc-
tion in rats: implications for human brain imaging and anxiety
disorders. Biol Psychol 73(1):61–71.
Orvaschel H. 1994. Schedule for affective disorder and
schizophrenia for school-age children epidemiologic version.
Ft. Lauderdale: Nova Southeastern University, Center for
Psychological Studies.
Riggs P, Baker S, Mikulich S, Young S, Crowley T. 1995.
Depression in substance-dependent delinquents. Digest
Neurol Psychiatry (Fall):172.
Spitzer RL, Williams JB, Gibbon M, First MB. 1992. The
Structured Clinical Interview for DSM-III-R (SCID). I:
history, rationale, and description. Arch Gen Psychiatry 49(8):
624–629.
Zhu J, Zhang X, Xu Y, Spencer T, Biederman J, Bhide PG.
2012. Prenatal nicotine exposure mouse model showing
hyperactivity, reduced cingulate cortex volume, increased
dopamine turnover and responsiveness to oral methylpheni-
date treatment. Submitted.