Comorbidity of attention-deficit/hyperactivity disorder, Tourette's
syndrome and bipolar I disorder in an adolescent patient
Chou-Yu Yeh, M.D.a, Liang-Jen Wang, M.D., M.P.H.a,b,⁎, Yu-Chieh Huang, M.D.b,c
aDepartment of Psychiatry, Chang Gung Memorial Hospital at Keelung, Taiwan
bCollege of Medicine, Chang Gung University, Taoyuan, Taiwan
cDepartment of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, Taiwan
Received 25 October 2011; accepted 12 December 2011
There is compelling evidence for an association between structural brain deformities and psychiatric disorders. We report the case of an
adolescent boy who was diagnosed with both attention-deficit/hyperactivity disorder and Tourette's syndrome. A full-blown manic episode
occurred when he was 13 years old. During his admission to a psychiatric ward, closed-lip schizencephaly in the left frontal lobe and the right
parietal lobe was identified through brain imaging. Effective control of his manic symptoms was achieved with quetiapine monotherapy
within 3 weeks. This case report implies that the pathophysiology of psychiatric disorders, especially in young patients with multiple
comorbid conditions, may be associated with abnormalities in the anatomical and functional development of the brain.
© 2012 Elsevier Inc. All rights reserved.
Keywords: Mood disorder; ADHD; Tic; Brain development; Adolescent
Attention-deficit/hyperactivity disorder (ADHD) occurs
in 3% to 10% of children and adolescents . The core
symptoms of ADHD are inattention, hyperactivity and
impulsiveness. Tourette's syndrome (TS) is manifest as
multiple motor tics and one or more vocal tics. About half of
the patients with TS experience comorbid ADHD .
Bipolar disorder (BD) patients refer to those with both manic
and depressive episodes or patients with manic episodes
alone. Early-onset BD is likely to present poor prognosis and
outcome . Although a subject of debate, ADHD and TS
have been reported as frequent comorbid disorders in BD
patients [4,5]. Early developmental abnormalities in the
brain have been proposed as the pathogenesis of these
childhood psychiatric disorders .
Schizencephaly is a neurodevelopmental disorder char-
acterized by gray matter lined clefts extending from the
subarachnoid space to the ventricular system . Common
clinical manifestations include epilepsy, motor deficits and
mental retardation . Some case reports have demonstrated
psychiatric disorders such as psychosis [9–11] and bipolar
affective disorder [12,13] to be associated with schizence-
phaly. To the best of our knowledge, there has been no prior
report of an adolescent patient with schizencephaly and
concomitant ADHD, TS and BD.
2. Case report
A 14-year-old Taiwanese boy, a junior high school
student, had achieved normal developmental milestones.
There was no history of head trauma, epilepsy or other
neurological diseases. He suffered from fidgeting and a short
attention span beginning in preschool. In school, hyperac-
tivity, impulsivity and excessive talking were observed
during class. He was also very distracted and forgetful and
had difficulty in finishing his schoolwork. Frequent eyelid
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General Hospital Psychiatry 34 (2012) 702.e1–702e.3
⁎Corresponding author. Department of Psychiatry, Chang Gung
Memorial Hospital at Keelung, Anle District, Keelung City 204, Taiwan.
Tel.: +886 2 24329292x2725; fax: +886 2 24315931.
E-mail address: firstname.lastname@example.org (L.-J. Wang).
0163-8343/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
blinking, neck twisting and smacking sounds with clearing
the throat developed when he was 9. Because of impairments
a child psychiatrist. ADHD combined type and TS were first
diagnosed when he was 10. He was initially treated with
clonidine 75 µg at night and atomoxetine 25 mg per day. Due
to limited treatment response, the dose of atomoxetine was
gradually titrated up to 40 mg per day over 5 months, and 1
drug compliance to atomoxetine and clonidine was good, but
he adhered to risperidone treatment only half of the time due
ADHD and TS partially improved over the next 2 years.
At age 13, he had a manic episode characterized by an
elated and irritable mood, a decreased need for sleep,
hyperactivity, flight of ideas,grandiose delusions, wandering
behavior, excessive talking and auditory hallucinations.
There was no history suggestive of exposure to illicit drugs
or alcohol. Because these symptoms lasted for more than 10
days, he was diagnosed as a case of bipolar I disorder,
currently in a manic episode, severe with psychotic features.
He was admitted to an acute psychiatric ward in a general
hospital. Because of his early-onset manic episode, a
comprehensive assessment for organic etiology was under-
taken, and all medications were discontinued. No abnormal
results were observed in his hematological and biochemical
tests, except for elevated levels of serum transaminases
(glutamate oxaloacetate transaminase was 82 U/L; glutamic
pyruvic transaminase was 84 U/L). Computerized tomogra-
phy (CT) of the brain showed deep invagination of the gray
matter and gyrus characteristic of closed-lip schizencephaly
in the left frontal and right parietal lobes (Fig. 1). The
electroencephalograph did not reveal evidence of epilepsy or
cerebral cortical dysfunction. A neurologist was consulted,
but no specific neurological signs were identified.
Early in the admission, he was very agitated and restless
on the ward. Nevertheless, the psychotropic regimen was
relatively conservative because of his small body type (148
cm and 34.4 kg) and impaired liver function. Quetiapine
monotherapy was administrated, and the dosage was
gradually titrated from 50 mg to 300 mg per night, and his
manic symptoms improved substantially. His score on the
Young Mania Rating Scale was 47 in the first week, then
dropped to 26 two weeks later. The patient was discharged
after 3 weeks. On follow-up, he had no recurrence or further
interruption of school on quetiapine maintenance.
This patient developed a manic episode in addition to
ADHD and TS, and schizencephaly was discovered by
means of a neuroimaging study during admission. The
severity of neurological deficits associated with schizence-
phaly generally depends on the size and location of the clefts
of cerebral malformations . This patient presented with
closed-lip schizencephaly in the left frontal and right parietal
lobes. No apparent neurological signs, such as motor deficits
or epilepsy, were previously detected; however, this did raise
the question as to whether the comorbid psychiatric disorders
corresponded to his developmental brain malformations or
were merely a coincidence.
A growing body of neuroimaging studies has found
evidence for structural brain abnormalities in a variety of
psychiatric disorders, including ADHD and TS . Abnor-
malities in the prefrontal cortex and associated subcortical
structures are present in patients who have difficulty
Fig. 1. Brain CT findings. Closed-lip schizencephaly (noted by arrows) was
observed with deep invagination of the gray matter and gyrus in the right
parietal lobe (A) and the left frontal lobe (B).
702.e2 C.-Y. Yeh et al. / General Hospital Psychiatry 34 (2012) 702.e1–702e.3
controlling their thoughts, emotions and behaviors . In Download full-text
also been implicated in the pathophysiology, mostly with
regard to limbic hyperactivity and frontal hypoactivity .
A correlation between response inhibition and right parietal
gray matter volume has also been suggested . These
neuropsychiatric disorders, particularly when they occur
together, may share a joint underlying neurobiological
pathogenesis associated with anatomical disturbances in
brain structure .
It is noteworthy that our patient received atomoxetine and
risperidone treatment prior to the manic episode. The favor-
able safety and efficacy profile of atomoxetine has been
demonstrated in ADHD patients with comorbid conditions
; however, Henderson and Hartman reported that
mania/hypomania or mood dysregulation could occur in
4% of ADHD patients undergoing treatment with atomox-
etine . Although our patient had his first manic episode
after years of atomoxetine administration, the possibility of a
drug-induced mood disorder could not be completely
excluded. In addition, risperidone has demonstrated effects
on BD , but poor drug adherence might weaken its
still developed a manic episode even during risperidone
The co-occurrence of ADHD, TS, BP and schizencephaly
is uncommon. As suggested by the comorbidity of these
conditions in the case reviewed here, the pathophysiology of
psychiatric disorders may be linked to abnormalities in the
anatomical and functional development of the brain.
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