Tourette syndrome and comorbid early-onset schizophrenia
Jacob Kerbeshiana,c, Chun-Zi Pengb, Larry Burdb,c,⁎
aDepartment of Neuroscience, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202-9037, USA
bDepartment of Pediatrics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202-9037, USA
cAltru Health System, Grand Forks, ND, USA
Received 6 August 2009; accepted 6 August 2009
Objective: A study of the shared phenomenology between
Tourette syndrome (TS) and schizophrenia. Method: An illus-
trative case report is presented. We used a chart review of 399
clinically ascertained patients with TS to identify 10 cases meeting
criteria for schizophrenia. From our 10 patients, salient clinical
characteristics were then tabulated. We then extracted similar
clinical characteristics from a previously published series of
patients with comorbid TS and schizophrenia in order to combine
cases and allow for a comparison between childhood-onset
schizophrenia (COS), adolescent-onset schizophrenia (AdolOS),
and adult-onset schizophrenia (AduOS) cases in these groups.
Results: We found 10 cases of schizophrenia (all were males) in
the 399 TS patients for a prevalence rate of 2.5% (95% CI 0.96–
4.04). Mean age of tic onset for TS diagnostic criteria ranged from
2-14 years with a mean of 8.2 years. The mean age of diagnosis for
schizophrenia was 14.2 (range 9–23 years). We found six cases of
schizophrenia with onset of positive psychotic symptoms by 13
years of age, two cases with onset after 13 years of age and before
18 years of age, and two cases with onset after 18 years of age.
Attention deficit hyperactivity disorder was present at a higher rate
(70%) than one would expect in a clinically ascertained group of
patients with TS. Comparison between COS, AdolOS and AduOS
in our pooled cases noted a sex bias skewed toward males.
Catatonic symptoms may be more likely in child or adolescent
onset cases and negative symptoms more likely in AduOS cases.
Conclusions: The 2.5% prevalence of schizophrenia in our TS
sample exceeds the 1% expected rate of schizophrenia in the
general population (chi-square=9.14; P=.0025). The six cases of
COS (before 13 years of age) exceeds the expected rate of 1–2 per
100,000 (chi-square=4499; P=.0001). The 752-fold increase in
observed rates of comorbid TS and COS over expected rates
suggests a role for unknown common underlying etiologic factors.
Based on clinical features, patients with TS and comorbid COS,
AdolOS, or AduOS do not have different conditions. We conclude
with suggestions for further research.
© 2009 Published by Elsevier Inc.
Keywords: Tourette syndrome; Schizophrenia; Children; Comorbidity; Phenomenology
Tourette syndrome (TS) is a neuropsychiatric develop-
mental disorder, the hallmarks of which are multiple motor
and vocal tics of at least a year's duration . TS is thought
to represent a genetically mediated condition with a broad
range of severity, much of which may be attributable to the
neuropsychiatric comorbidities with which it commonly
occurs . Comorbid disorders including attention deficit-
hyperactivity disorder (ADHD) and obsessive–compulsive
disorder (OCD) are common . We have previously noted
additional patterns of comorbidity between TS and autistic
disorder, Asperger syndrome, and bipolar disorder [4–8].
We have also have examined the comorbidity between TS
and schizophreniform symptomatology, and TS and child-
hood-onset schizophrenia (COS) [8,9].
As conceptualized in the Diagnostic and Statistical
Manual of Mental Disorders, 4th Edition, Text Revision
(DSM-IV-TR), specific symptom criteria for schizophrenia
encompass positive symptoms such as delusions, hallucina-
tions, disordered thinking, and disorganized behavior. The
negative symptomsinclude flat affect, povertyof speech, and
lack of ability and persistence in goal directed activity .
Journal of Psychosomatic Research 67 (2009) 515–523
⁎Corresponding author. Department of Pediatrics, University of North
Dakota, School of Medicine and Health Sciences, 501 N. Columbia Road,
Grand Forks, ND 58202-9037, USA. Tel.: +1 701 777 3683; fax: +1 701
E-mail address: firstname.lastname@example.org (L. Burd).
0022-3999/09/$ – see front matter © 2009 Published by Elsevier Inc.
Although commonly cited in the literature, age of onset
criteria for COS vary widely. Prevalence rates of schizophre-
nia suggest that a childhood onset (based on age 14 or 13
years and younger) is very rare [10,11]. Studies in Sweden
reported a rate of COS of 1.6 per 100,000 [12,13]. Another
study in North Dakota found a prevalence rate of 1.9 per
under age 12 years were identified in a population of 130,000
. Thus, current prevalence estimates suggest a rate of 1 to
2 cases per 100,000 for COS (onset by 13 years of age).
In our clinical work, we have been struck by the
phenomenologic overlap in symptoms of our TS patients
and our schizophrenia patients. Our patients with schizo-
phrenia, particularly of the catatonic and disorganized
(hebephrenic) subtypes often exhibit motor or vocal tics,
including complex echophenomena, and palilalia. Similarly,
some of our patients with TS have engaged in complex
posturing reminiscent of catatonia, or in mirror gazing
reminiscent of disorganized schizophrenia. Many of our TS
patients report brief and fragmentary auditory hallucinations.
The vivid, eidetic imaging of echolalia and palilalia that
some patients with TS describe has considerable overlap
with the auditorization of thought, or “echo des pensees” of
Schneider's so-called first rank symptoms, which often
present with schizophrenia, but not exclusively so . One
of our TS patients interpreted his echokinesis in response to
the movement of others as those people having control over
his bodily movements, reminiscent of a delusion of somatic
passivity, another so called first rank symptom of schizo-
phrenia. These clinical similarities have caused us and others
to question just what the relationship between TS and
schizophrenia might be [9,17–24].
The onset of DSM-IV-TR Tourette's disorder, or TS, by
criterion definition is during the childhood or adolescent
years with a peak age of tic onset at 6–7 years of age .
Schizophrenia has a broader range of age of onset . COS is
thought to be symptomatically similar to and appears to be
continuous with adolescent-onset schizophrenia (AdolOS)
and adult-onset schizophrenia (AduOS), according to
Nicolson and Rapoport . However, their cohort of COS
patients had more premorbid developmental abnormalities,
more cytogenetic abnormalities, and a greater burden of
family history of paranoid and schizotypal personality
disorders than later onset cases, pointing to perhaps a greater
developmental neurobiologic vulnerability. Their finding
thatan earlier ageofonsetofschizophreniaisassociated with
more severe psychopathology and neurocognitive deficits
has been supported by others [26,27]. It has been hypothe-
sized that the typical age of onset of schizophrenia in later
adolescence to early adulthood is a manifestation of
neurotransmitter ontogeny interacting with neurobiological
with a developmental period of increased vulnerability to
neurobiological and genetic risk factors.
of G.K., a boy with “the tic syndrome” who later went on to
develop schizophrenia . In more recent decades, there
have been multiple case reports and small case series of
patients with comorbid TS and schizophrenia [9,17–
21,23,24]. From an epidemiologically defined sample in
North Dakota, we have published a prevalence rate of
schizophrenia in boys aged 2–12 years old with TS of 8.7%
. In a recent paper, Cavanna et al.  also noted that 15%
of patients in their clinical population with TS also met
criteria for schizotypal personality. They found increased
TS and schizotypal personality . Muller et al.  also
have reported on 5 adults with comorbid TS and schizophre-
nia. All of their patients first showed symptoms of TS,
adult onset of their schizophrenia, and one had an onset in
later adolescence. The course of the tic disorder was chronic
or worsening over time. They speculated that TS and
schizophrenia might co-occur at a rate greater than expected
by chance. In their review of the clinical and pathophysio-
logic similarities between TS and schizophrenia, they posited
that common biological mechanisms likely play a key role in
the shared phenomology between these clinical syndromes.
To date, the majority of case series reports of comorbidity
for TS and schizophrenia have focused on patients with
primarily later AdolOS/AduOS. In this study, we estimate
the prevalence rate for schizophrenia and shared phenomol-
ogy in a clinical population of primarily child and adolescent
patients with TS.
Case illustration from subjects of study
U.T. is a 14-year-old boy who has been in our care since
age 7. He was first seen for treatment of hyperactivity,
inattentiveness, and learning difficulties, not responsive to
stimulants. His pervasive hyperactivity dated back to his
earliest years. His tics preexisted the use of mixed salts of
amphetamine, but seemed to worsen following the start of
that medication. The patient's pattern of waxing and waning
multiple motor and vocal tics dates back to 5 years of age.
They have included the blinking of his eyes and pursing of
his lips. He would repeatedly clear his throat, causing the
parents often to wonder if he had allergies and was
congested. He had difficulties with swearing, usually in
anger, as well as episodic sexual exhibitionism. At age 7
years, his learning disability included a pattern of attempting
to read from right to left and letter and number reversals. He
would have rapid shifts in mood and sleep onset insomnia.
U.T. was treated with clonidine 0.05 mg qam and 0.2 mg
qhs, with some improvement in attention and tics. Due to
periods of brief blanking of consciousness, he had a
neurological evaluation and was diagnosed with epilepsy,
for which he was successfully treated with carbamazepine.
He admitted that since age 5 years, he has had 2 “imaginary
friends.” They had names, but he did not hear them or see
them. At age 8 years, the patient indicated that he was
hearing voices in his head when no one else was about. At
516 J. Kerbeshian et al. / Journal of Psychosomatic Research 67 (2009) 515–523
times, he would hear two voices in his head yelling at each
other. He noted at times he smelled odors that others did not
smell. At times, he would have “bad thoughts” that would
compel him to do things such a jumping from a moving
automobile. These thoughts did not feel as if they were his.
He discovered that if he hit his head with his fist, these
thoughts would dissipate. Risperidone 1 mg qhs was added
to U.T.'s treatment regimen. Subsequently, with the
emergence of depressive affect, citalopram 20 mg qd was
added. At age 11 years, U.T. had a psychiatric hospitaliza-
tion with symptoms of sleep disturbance, night terrors, fairly
rapid shifts in mood with explosive and unpredictable
laughter, and violence directed against his mother. There was
a resurgence of his psychotic ideation. Ziprasidone was
substituted for risperidone with good effect. The patient
continued with occasional facial grimacing and subtle
blinking of his left eye. During the subsequent 3 years, the
patient remained fairly stable, although he was markedly
withdrawn and shy at times. U.T. gained a considerable
amount of weight. He also developed a waxing and waning
pattern of hyperphagia, hypersomnolence, and irritability
consistent with Klein-Levin syndrome. Past medical history
is positive for complex partial seizures.
Family history is positive for ADHD on the part of an
older brother. Mother's father was diagnosed with paranoid
schizophrenia. Mother can recall her father driving along in
an automobile repetitively twitching his arm while staring,
and at the same time engaging in a guttural throat clearing
Data from 10 TS case reports in ascending order age of onset of schizophrenia
U.T. D.N.N.T.K.Q.T.T. S.H.D.R.U.M. E.I. Q.N.
Age motor tics
Age vocal tics
Meds before TS
Age-positive psychotic sx
Age dx schiz
Schiz-negative psychotic sx
Meds before Schiz
Klein, Klein Levin syndrome; Dep, depression; Enur, enuresis; Enco, encopresis; Meige, Meige syndrome; Gambl, gambling; TDys, tardive dyskinesia; EtOH,
alcohol abuse; Drugs, drug abuse; Degen CNS, degenerative disorders (progressive supranuclear palsy); Schiz, schizophrenia; Delus, delusional disorder; OC
sx's, obsessive compulsive disorders; Otitis, otitis media; Stim, stimulant; Meph, mephobarbital; Halo, haloperidol; Pheno, phenobarbital; Pim, pimozide;
Clon, clonidine; Li+, lithium; Triflu, trifluoperazine; CBZ, carbamazepine; Desip, desipramine; Flu, fluphenazine; sx, symtoms; hx, history; dx, diagnosis.
All 10 were males. All 10 were of average intelligence (+, present; −, absent).
517 J. Kerbeshian et al. / Journal of Psychosomatic Research 67 (2009) 515–523
sound. Since childhood, mother had had a pattern of
repetitively rolling her eyes, spasmodically closing her
eyes, pursing her lips, and making a slight vocalization.
Mother's brother at age 13 had recurrent suicide attempts.
Mother states that father may have some odd mannerisms,
which father denies.
U.T.'s diagnoses are schizophrenia, paranoid type, with
childhood-onset, TS, ADHD combined type, learning
disorder, and epilepsy.
For the purposes of our study, we adopted the age range
definitions of Kumra . COS was defined by an onset of
psychotic symptoms by 13 years of age. AdolOS was
defined as an onset of psychotic symptoms after age 13 years
and by age 18 years. AduOS had an age of onset of psychotic
symptoms after age 18 years.
We reviewed the charts of all 399 patients in our practice
with TS for cases meeting DSM-IV-TR criteria for schizo-
phrenia . This cohort was comprised of consecutive cases
collected over a 30-year time span. We examined age-related
variables for onset of tics, ADHD, psychotic symptoms, age
of onset and of diagnosis for TS and schizophrenia, rates of
comorbidities, and family history variables (Table 1). We
also reviewed phenomenology.
We then compared our patients with comorbid TS and
schizophrenia with the five patients reported by Muller et al.
 Of these, one had AdolOS and 4 had AduOS. We
abstracted data from these cases using the same format we
used for our cases. We excluded those data points for which
there was no mention in the Muller et al. cases. We inferred
that if no mention was made of use of medication prior to the
onset of TS, none had been used; that the use of psychoactive
medication prior to onset of schizophrenia would be
mentioned in the report (neuroleptic use was reported in
case number 2); that the age of onset of psychotic symptoms
was the same as the age of onset of schizophrenia; that if
catatonic symptoms were not reported that they were not
present; and that major neurologic events such as a seizures
and mental retardation were reported if they were present
We then combined data which allowed for contrast and
comparison between our cases and the cases of Muller et al.
and filtered the data points as a function of whether the
onset of schizophrenia for the 15 subjects with TS was
during childhood/adolescence (n=9) or adulthood (n=6)
(Tables 1 and 2).
Our results are in tabular form in Tables 1 through 4.
From our clinical cohort of 399 TS patients, we identified 10
cases (all were males) with comorbid DSM-IV-TR schizo-
phrenia, six of whom had COS, two of whom had AdolOS,
and two of whom had AduOS (Table 1). The prevalence rate
of schizophrenia in subjects with TS was 10/399=2.5% (95%
CI 0.96–4.039). The rate of comorbidity is 2.5 times the
population base rate for schizophrenia in adults which is 1%
(chi square=9.14; P=.0025) [1,31]. Previous prevalence
estimates suggest that the expected rate of COS to be 1–2 per
100,000 [4,10,12,13,15,32]. The finding of six cases of COS
(by 13 years of age) in 399 patients with TS exceeds
expected rates of 1–2 per 100,000 (chi square=4499;
P=.0001). The expected male to female preponderance for
COS was as would be expected. That all 6 of our COS cases
were males likely further increases the discrepancy between
the observed and expected rates for schizophrenia.
Case data from Muller et al.  in ascending order of age of diagnosis of schizophrenia
Age in report
Meds before TS
Meds before Schiz
Age motor tics
Age vocal tics
Age-positive psychotic sx
Age dx schiz
Sequence comorbidities TS
MR, Mental retardation; Avg, average intelligence; Y, present; N, absent; see footnote to Table 1.
518 J. Kerbeshian et al. / Journal of Psychosomatic Research 67 (2009) 515–523
Seven of our 10 cases were comorbid for ADHD a rate
somewhat greater than the 55% concordance rated expected
for TS and ADHD in clinical samples .
We found that 3 of our patients with comorbid ADHD
had exposure to stimulants prior to the onset of their TS. In 9
of the 10 cases, tics preceded the onset of psychotic
symptoms, perhaps reflective of age associated general risk
factors for the two conditions. Five of our 10 patients with
comorbid TS and schizophrenia had been exposed to
stimulants prior to the onset of their psychotic symptoms.
Exposure to stimulants may modify risk for psychotic
symptomatology . We also found 6 patients who had
been exposed to antipsychotic medications for treatment of
their TS prior to the onset of psychotic symptoms.
Four of our 10 patients exhibited catatonic symptoms.
This is not surprising as typical catatonic symptoms such as
posturing, the automatic compliance of echokinesis, echo-
lalia, and palilalia, when seen in TS are often categorized as
complex tics. Four patients exhibited obsessive compulsive
symptoms. We found that 5 of our 10 patients had an
unexpected preoccupation with knives.
Three of our patients had comorbid epilepsy. U.T. was
diagnosed with epilepsy at age 8 years, after the onset of his
tics and about the time of and possibly preceding the onset of
formal psychotic symptoms. His seizures were characterized
by brief blanking of consciousness, and he also endorsed
olfactory hallucinations. K.Q., at age 16, years complained
of blanking-out spells and was diagnosed with a generalized
seizure disorder with nonconvulsive epilepsy. His electro-
encephalography (EEG) disclosed a photoparoxysmal re-
sponse. TS and schizophrenia diagnoses preceded the
diagnosis of his epilepsy. E.I. was diagnosed with epilepsy
at age 4 years, prior to the onset of his tics and of his
schizophrenia. His first seizure followed a bout with
pneumonia and high fever. Repeated EEGs disclosed
polyspike activity. He was treated with mephobarbital.
After a few years of remaining seizure-free, his anticonvul-
sant was discontinued, and he has remained seizure-free
From our case studies, we have abstracted examples of
Schneiderian first-rank symptoms, or symptoms indicative
of so called nuclear schizophrenia, and specific tic
symptoms that may share a phenomenologic overlap with
schizophrenic symptoms, including catatonic symptoms,
and/or temporal lobe phenomena [34,35]. U.T.'s case study
is noted above. He auditorized two voices yelling at each
other, olfactory hallucinations, and a belief that his behavior
was controlled by thoughts that were not his. D.N. had
command auditory hallucinations causing a sense of external
control, and a belief that his body was externally controlled
by and was turning into a robotic toy called a “transformer.”
This was a manifestation of a delusion of somatic passivity,
was on a spectrum with catatonia, and may have reflected a
sensory precursor to a motor tic phenomenon. N.T. had a tic
Summary data from 10 subjects with TS and schizophrenia
Age at evaluation under 18 years 10
Onset of motor and vocal tics at same age
Use of stimulants before TS
Use of stimulants before schizophrenia
Use of antipsychotics before schizophrenia
Tics precede onset psychotic symptoms
Positive psychotic symptoms before age 18
Diagnosis of schizophrenia before age 18
Negative symptoms of schizophrenia
Obsessive compulsive symptoms
Preoccupation with knives
Family history of tics/TS
Family history of schizophrenia
Family history of ADHD
Family history of OCD
Family history of drugs/alcoholism
Developmental sequence of ADHD:TS:depression/OCD:schizophrenia
Comparison of combined patient groups from this study and Muller et al.  (n=5) by age of onset: COS+AdolOS=EOS vs. AduOS
No. of patients
Onset of motor and vocal tics at same age
Use of antipsychotics before schizophrenia
Tics precede onset psychotic symptoms
Negative symptoms of schizophrenia
Obsessive compulsive symptoms
Family history of schizophrenia
Family history of drugs/alcoholism
Developmental sequence (if present) of ADHD:TS:depression/OCD:schizophrenia
519 J. Kerbeshian et al. / Journal of Psychosomatic Research 67 (2009) 515–523
of significant palilalia, a symptom often present in
individuals with catatonia. He would engage in the complex
motor behavior of hitting his head in order to relieve the
sensory phenomenon of his command auditory hallucina-
tions, behavior perhaps on the spectrum with his TS. He had
olfactory hallucinations, and the delusion of somatic
passivity that contact with water would melt away his
body. K.Q. had auditory hallucinations commenting on his
actions. Prior to the onset of formal psychotic symptoms, he
had a delayed mental echolalia as a “mental tic,” more as
intense eidetic imagery. This preceded the onset of
command auditory hallucinations, voices referring to him
in the third person, and a sense of transmitting his thoughts
into the heads of others. T.T. believed he was being
magically externally controlled by a specific other student.
His vocal tic (or catatonic) behavior of echoing obscenities
uttered by this other student was perceived by him as being
controlled by an external agency. He also experienced
voices in conflict talking to each other in his head. S.H.
complained of uncomfortable somatic sensations interpreted
as small creatures crawling over his body, reminiscent of
sensory phenomena preceding motor tics. He had behaviors
reflecting a phenomenologic overlap between complex
motor tics and catatonia in which he would posture, holding
his right arm flexed and intermittently dragging his leg while
walking. He also had command auditory hallucinations.
D.R. complained that God was a “buzz-box” in his head. He
claimed powers of clairvoyance and was bizarrely silly. His
thought blocking was reminiscent of vocal tics manifested
by interruptive silences. He claimed he could not stop
himself from automatically whistling in the classroom. U.M.
had command hallucinations to harm others with a knife.
His making loud noises to drown out the auditory
hallucinations in his head had all the outward appearance
and function of a vocal tic. He had the sensation that others
were reading his mind, prior to his expressing those thoughts
in words. E.I. had complex sustained posturing involving his
upper extremities, again pointing to a phenomenologic
overlap between catatonia and complex motor tics. He had
erotic delusions of reference and that others were monitoring
his comings and goings. Q.N. had religious delusions and
was preoccupied with the belief that all his family members
None of our patients met criteria for a pervasive
developmental disorder. Although patients with a pervasive
developmental disorder may present with symptomatic
catatonia, the catatonic symptoms in our patients were
fellow travelers with more specific schizophrenic or TS
symptoms [36,37]. In addition, we have noted that, in
patients with TS and other developmental disorders,
schizophreniform symptoms may also be present [7,38].
Our profile of the patients of Muller et al.  is noted on
patients are summarized in Table 3. A comparison of COS
and AdolOS cases with AduOS utilizing a pooling of our 10
cases with Muller et al.'s 5 cases is noted on Table 4 .
Our clinical population of 399 TS patients is one the
largest reported to date to examine the rate of comorbidity of
schizophrenia in patients with TS. The prevalence rate of
2.5% exceeds the expected rate of schizophrenia in a general
population where it is typically reported to be 1% .
Of the 10 cases with TS and comorbid DSM-IV-TR
schizophrenia, six had a childhood onset by 13 years of age,
two had an adolescent onset by 18 years of age, and two had
an adult onset after 18 years of age. This suggests that the
rate of COS in subjects with TS is increased 752-fold. In
previous reports we have discussed increased rates of
schizophreniform symptomatology in TS patients who were
children . We found an 8.7% rate for schizophrenia
among TS boys aged 2–12 years, and 0% among girls with
TS . In our current study, all 10 cases were males, and
this supports an increase in risk for schizophrenia in males
In Table 3, we summarized the data for the 10 subjects
with TS and comorbid schizophrenia. Seven of our cases
were comorbid for ADHD, somewhat greater than the 55%
concordance rated expected for TS and ADHD in clinical
samples . Perhaps ADHD in the presence of TS confers a
somewhat greater risk for schizophrenia. With the exception
of one case, tics preceded the onset of psychotic symptoms,
suggesting periods of developmental vulnerability for the
two conditions. Due to the presence of comorbid ADHD, it is
not surprising that three of our patients had exposure to
stimulants prior to the onset of their TS. Five patients were
exposed to stimulants prior to the onset of their psychotic
symptoms, raising the question of kindling of those
symptoms . It is also not surprising that six patients
were exposed to antipsychotic medications for treatment of
their TS prior to the onset of psychotic symptoms. One might
have predicted a protective effect against the advent of
psychotic symptoms. This was not observed in our cases, but
might be operative in other cases of antipsychotic treated TS
patients, who do not go on to develop schizophrenia. Four of
our patients developed catatonic symptoms. This is of
interest since typical catatonic symptoms such as posturing,
the automatic compliance of echokinesis, echolalia, and
palilalia, when seen in TS are often categorized as complex
tics . Further research is required to define the
phenotypic boundaries of catatonia and complex tics in
children, as well as other aspects of shared phenomenology
between TS and schizophrenia. As catalogued in our results,
we selectively abstracted examples of Schneiderian first rank
symptoms, of catatonic symptoms, of possible temporal lobe
phenomena, of specific tic symptoms which may portend
transmutation to schizophrenic symptomatology, and of
schizophrenic symptoms which share a structural similarity
with complex tics. Command auditory hallucinations were
frequent, as were two or more voices, often in conflict,
talking to each other and referring to the patient in the third
person. Delusions of somatic passivity and a belief of being
520J. Kerbeshian et al. / Journal of Psychosomatic Research 67 (2009) 515–523
controlled by an external agent were also prominent. Themes
of somatosensory phenomena interfering with volition or
resulting in bizarre motor behavior or vocalizations were also
present. Some of our patients had a distinct intense eidetic
imagery phase as a precursor to their experiencing formal
hallucinations. “Mental tics” were also present. Reflex
bizarre motor or vocal behaviors were interpreted by patients
as terminating disturbing hallucinatory experiences. Themes
of thought broadcasting were also present. Our patients also
experienced olfactory hallucinations, raising the question of
temporal lobe phenomena.
Four patients exhibited obsessive compulsive symptoms,
which has been reported in both TS and in schizophrenia
[39,40]. The presence of learning disabilities in individuals
with TS and/or ADHD is also not surprising, nor is it so
with schizophrenia, especially in light of recent research
into the neurocognitive impairments present in that disorder
[41,42]. We found the 50% prevalence of preoccupation
with knives in our patients to be a most interesting clinical
tidbit. We know not what it means in its specificity, but it
could be related in general to the compelling disinhibition
noted in some patients with TS . It may also be a
precursor to or early manifestation of paranoid behavior.
Young people likely have greater access to knives than
The presence of three patients with seizures in our
cohort may reflect a greater neurobiologic risk for same
associated with the presence of schizophrenia and also
possibly by the concordance with TS . Two of these
three patients had the onset of their seizures contempora-
neous with or following the onset of their psychosis and
one prior to the onset of psychosis and of tics. One had
olfactory hallucinations, a phenomenon often associated
with temporal lobe abnormality. None of our three patients
had major motor seizures or lateralization of EEG
polyspike activity. Awareness of the greater risk for
schizophrenia or at least schizophrenia-like psychoses in
patients with epilepsy dates prior to the seminal work of
Slater et. al. . Typically patients with comorbid
epilepsy and schizophrenia have an earlier onset of
seizures, with seizures typically and often by years
preceding the onset of psychotic symptoms; more severe
seizures; vegetative seizure symptoms; frequently temporal
lobe discharges; and a likelihood of Schneiderian first rank
symptoms, fitting a picture of so-called nuclear schizo-
phrenia [34,35,46]. With the exception of the presence of
Schneiderian first rank symptoms in all three, the presence
of olfactory hallucinations in one, and an early age of onset
followed by psychosis in another, our patients did not
strongly fit the epilepsy/schizophrenia profile. Schneiderian
first-rank symptoms are often present in patients with
schizophrenic psychoses and with non-schizophrenic psy-
choses. Our patient with a preschool age onset of epilepsy
was treated with mephobarbital. It is tempting to speculate
whether that anticonvulsant may have played a part in
kindling a vulnerability for tics .
Our patients' family histories are not unexpected for the
conditions studied . The developmental sequence of onset
of comorbidities in nine of our patients is consistent with
age-related risk factors for these conditions.
Pooling our cases with those of Muller et al. , we
found the gender balance continues to be skewed toward
males even in adults with comorbid TS and schizophrenia
(Table 4). Exposure to antipsychotics prior to onset of
schizophrenia appears to be comparable, as does the
onset of tics preceding that of psychotic symptoms.
Catatonic symptoms may be more likely in COS and
AdolOS cases and negative schizophrenic symptoms
more likely in the AduOS group. A history of obsessive
compulsive symptoms may be more likely in the AduOS
group. The presence of seizures and a family history of
schizophrenia may be similar. As expected, the develop-
mental sequence of syndrome ontogenesis also appears to
The relationship between TS and schizophrenia is all
the more intriguing and elusive in light of our study. The
prevalence rate of schizophrenia in our clinic ascertained
sample of TS is at least suggestive of common underlying
etiologic factors. Assuming a shared underlying etiology,
by way of a chemistry analogy, TS might be seen as a
cation and schizophrenia as an anion in a neuropsychiatric
phenomenological solution, which is more than just the
sum of its constituent parts. Assuming an absence of
shared underlying etiology, an alternate chemistry analogy
would be of a mixture of the TS and the schizophrenia
phenotype emerging from a phenomenologic and neurobi-
ological final common pathway, with each condition
maintaining its overlapping but categorical integrity. At
least, in our TS patients, there appears to be no indication
based on symptomatic comparisons across studies that
concordant COS, AdolOS, and AduOS are different
conditions. Whatever the etiologic relationship might be
between TS and schizophrenia, it is likely similar for both
the COS and AdolOS type [early onset (EOS)] and the
AduOS type (Table 4).
With our admittedly small and clinically ascertained
population and resulting data set, we suggest a cautious
and conservative appraisal of our findings and conclusions.
Nonetheless, given the large caseload from which our
cases were extracted, and given the limited state of the
literature in regard to our topic, we believe that our
findings are worthy of consideration, at least from the
standpoint of clinical description and of hypothesis
generation. The generous proportion of child and adoles-
cent compared to adult TS cases in our cohort is not
unexpected as our practice has a referral bias toward
children and adolescents.
The agenda for marshalling additional epidemiologic
studies regarding the nature of concordance for TS and
521J. Kerbeshian et al. / Journal of Psychosomatic Research 67 (2009) 515–523
schizophrenia will be hampered by logistic obstacles,
especially for the case of COS for which the population
base rate is so low. It took our clinical center over 30 years to
collect this case series from North Dakota and surrounding
areas. Other approaches, such as genetic studies, or dynamic
imaging studies may point toward subgroups in which the
relevance of the concordance may be clarified, but that
would still leave open the question for the population at
large. In the meantime, we can only hope that our study has
added additional data to pique interest in future studies to
examine the role of the syndromal overlap between TS and
schizophrenia with its age-related subtypes.
 American Psychiatric Association. Diagnostic and Statistical Manual
of Mental Disorders. 4th ed. Text Rev. Washington, DC: American
Psychiatric Association, 2000.
 Freeman RD. Tic disorders and ADHD: answers from a world-wide
clinical dataset on Tourette syndrome. Eur Child Adolesc Psychiatry
 Freeman RD, Fast DK, Burd L, Kerbeshian J, Robertson MM, Sandor
P. An international perspective on Tourette syndrome: selected
findings from 3,500 individuals in 22 countries. Dev Med Child
 Burd L, Kerbeshian J. A North Dakota prevalence study of
schizophrenia presenting in childhood. J Am Acad Child Adolesc
 Kerbeshian J, Burd L, Klug MG. Comorbid Tourette's disorder and
bipolar disorder: an etiologic perspective. Am J Psychiatry 1995;152:
 Kerbeshian J, Burd L. Case study: comorbidity among Tourette's
syndrome, autistic disorder, and bipolar disorder. J Am Acad Child
Adolesc Psychiatry 1996;35:681–5.
 Kerbeshian J, Burd L. Are schizophreniform symptoms present in
attenuated form in children with Tourette disorder and other
developmental disorders. Can J Psychiatry 1987;32:123–35.
 Kerbeshian J, Burd L. Asperger's syndrome and Tourette
syndrome: the case of the pinball wizard. Br J Psychiatry 1986;
 Kerbeshian J, Burd L. Tourette disorder and schizophrenia in children.
Neurosci Biobehav Rev 1988;12:267–70.
 Remschmidt H, Theisen FM. Schizophrenia and related disorders in
children and adolescents. J Neural Transm Suppl 2005:121–41.
 Eggers C, Bunk D, Volberg G, Ropcke B. The ESSEN study of
childhood-onset schizophrenia: selected results. Eur Child Adolesc
Psychiatry 1999;8(Suppl 1):I21–8.
 Gillberg C. Infantile autism and other childhood psychoses in a
Swedish urban region. Epidemiological aspects. J Child Psychol
 Gillberg C, Steffenburg S. Outcome and prognostic factors in
infantile autism and similar conditions: a population-based study of
46 cases followed through puberty. J Autism Dev Disord 1987;17:
 Burd L, Fisher W, Kerbeshian J. A prevalence study of pervasive
developmental disorders in North Dakota. J Am Acad Child Adolesc
 WerryJS. Childand adolescent (earlyonset) schizophrenia: a reviewin
light of DSM-III-R. J Autism Dev Disord 1992;22:601–24.
 Nordgaard J, Arnfred SM,HandestP, ParnasJ. Thediagnosticstatus of
first-rank symptoms. Schizophr Bull 2008;34:137–54.
 Becker T, Laux G, Sofic E, Riederer P, Beckmann H. Schizophrenic
psychosis in a patient with Gilles de la Tourette syndrome. Nervenarzt
 Escobar R, Bernardo M. Schizophrenia, obsessive-compulsive disor-
der, and Tourette's syndrome: a case of triple comorbidity. J
Neuropsychiatry Clin Neurosci 1993;5:108.
 Fennig S, Fennig S, Pomeroy J, Calev A. Developmental disorder,
Tourette disorder and schizophrenia: a case study. Isr J Psychiatry
Relat Sci 1997;34:239–43.
 Muller N, Riedel M, Zawta P, Gunther W, Straube A. Comorbidity of
Tourette's syndrome and schizophrenia—biological and physiological
parallels. Prog Neuropsychopharmacol Biol Psychiatry 2002;26:
 Sandyk R, Bamford CR. Gilles de la Tourette's syndrome associated
with chronic schizophrenia. Int J Neurosci 1988;41:83–6.
 Sverd J, Montero G, Gurevich N. Brief report: cases for an association
between Tourette syndrome, autistic disorder, and schizophrenia-like
disorder. J Autism Dev Disord 1993;23:407–13.
 Takeuchi K, Yamashita M, Morikiyo M, Takeda N, Morita K, Tamura
T, et al. Gilles de la Tourette's syndrome and schizophrenia. J Nerv
Ment Dis 1986;174:247–8.
 Wagle AC, Staley CJ. Gilles de la Tourette syndrome with
schizophrenia and obsessive-compulsive disorder: a case report. J
Neuropsychiatry Clin Neurosci 1999;11:517.
 Nicolson R, Rapoport JL. Childhood-onset schizophrenia: rare but
worth studying. Biol Psychiatry 1999;46:1418–28.
 Bellino S, Rocca P, Patria L, Marchiaro L, Rasetti R, Di Lorenzo R,
et al. Relationships of age at onset with clinical features and cognitive
functions ina sampleof schizophreniapatients. J Clin Psychiatry2004;
 Luoma S, Hakko H, Ollinen T, Jarvelin MR, Lindeman S. Association
Finland 1966 birth cohort study. Eur Psychiatry 2008;23:331–5.
 Mahler MS, Luke JA. Outcome of the tic syndrome. J Nerv Ment Dis
1946;103:433–45 Ref Type: Generic.
 Cavanna AE, Robertson MM, Critchley HD. Schizotypal personality
traits in Gilles de la Tourette syndrome. Acta Neurol Scand 2007;116:
 Kumra S. Digging deeper: using neuroimaging tools reveals important
clues to early-onset schizophrenia. J Am Acad Child Adolesc
 American Academy of Child and Adolescent Psychiatry. Practice
parameter for the assessment and treatment of children and adolescents
with schizophrenia. J Am Acad Child Adolesc Psychiatry 2001;40(7
 Burd L, Fisher WW, Kerbeshian J, Arnold ME. Is development of
Tourettedisordera markerfor improvementin patientswithautismand
other pervasive developmental disorders? J Am Acad Child Adolesc
 Post RM, Kopanda RT. Cocaine, kindling, and psychosis. Am J
 Trimble MR. First-rank symptoms of Schneider. A new perspective?
Br J Psychiatry 1990;156:195–200.
 Gaitatzis A, Trimble MR, Sander JW. The psychiatric comorbidity of
epilepsy. Acta Neurol Scand 2004;110:207–20.
 Kakooza-Mwesige A, Wachtel LE, Dhossche DM. Catatonia in
autism: implications across the life span. Eur Child Adolesc Psychiatry
 Cavanna AE, Robertson MM, Critchley HD. Catatonic signs in Gilles
de la Tourette syndrome. Cogn Behav Neurol 2008;21:34–7.
 Burd L, Kerbeshian J, Fisher W, Gascon G. Anticonvulsant
medications: an iatrogenic cause of tic disorders. Can J Psychiatry
 BlochMH,PetersonBS,Scahill L,OtkaJ, KatsovichL,ZhangH, etal.
Adulthood outcome of tic and obsessive-compulsive symptom severity
in children with Tourette syndrome. Arch Pediatr Adolesc Med 2006;
 Nechmad A, Ratzoni G, Poyurovsky M, Meged S, Avidan G, Fuchs C,
et al. Obsessive-compulsive disorder in adolescent schizophrenia
patients. Am J Psychiatry 2003;160:1002–4.
522 J. Kerbeshian et al. / Journal of Psychosomatic Research 67 (2009) 515–523
 Burd L, Freeman RD, Klug MG, Kerbeshian J. Tourette Syndrome and Download full-text
learning disabilities. BMC Pediatr 2005;5:34.
 Fisher M, McCoy K, Poole JH, Vinogradov S. Self and Other in
Schizophrenia:a CognitiveNeuroscience Perspective.AmJPsychiatry
 Cohen AJ, Leckman JF. Sensory phenomena associated with Gilles de
la Tourette's syndrome. J Clin Psychiatry 1992;53:319–23.
 Sachdev PS. Alternating and postictal psychoses: review and a
unifying hypothesis. Schizophr Bull 2007;33:1029–37.
 Slater E, Beard A, Glithero E. The schizophrenialike psychoses of
epilepsy. Br J Psychiatry 1963;109:95–150.
 Schmitz EB, Robertson MM, Trimble MR. Depression and schizo-
phrenia in epilepsy: social and biological risk factors. Epilepsy Res
523 J. Kerbeshian et al. / Journal of Psychosomatic Research 67 (2009) 515–523