RESEARCH ARTICLE Open Access
Anti-NMDA-receptor antibody detected in
encephalitis, schizophrenia, and narcolepsy with
Ko Tsutsui1, Takashi Kanbayashi1*, Keiko Tanaka2, Shuken Boku3, Wakako Ito1,4, Jun Tokunaga1, Akane Mori1,
Yasuo Hishikawa1,5, Tetsuo Shimizu1and Seiji Nishino6
Background: Causative role of encephalitis in major psychotic features, dyskinesias (particularly orofacial), seizures,
and autonomic and respiratory changes has been recently emphasized. These symptoms often occur in young
females with ovarian teratomas and are frequently associated with serum and CSF autoantibodies to the NMDA
Methods: The study included a total of 61 patients from age 15 to 61 and was carried out between January 1,
2005, and Dec 31, 2010. The patients were divided into the following three clinical groups for comparison. Group A;
Patients with typical clinical characteristics of anti-NMDAR encephalitis. Group B; Patients with narcolepsy with
severe psychosis. Group C; Patients with schizophrenia or schizo-affective disorders.
Results: Ten out of 61 cases were anti-NMDAR antibody positive in typical encephalitis cases (group A: 3 of 5 cases)
and cases in a broader range of psychiatric disorders including narcolepsy (group B: 3 of 5 cases) and schizophrenia
(group C: 4 of 51 cases).
Conclusion: In addition to 3 typical cases, we found 7 cases with anti-NMDAR antibody associated with various
psychotic and sleep symptoms, which lack any noticeable clinical signs of encephalitis (seizures and autonomic
symptoms) throughout the course of the disease episodes; this result suggest that further discussion on the
nosology and pathophysiology of autoimmune-mediated atypical psychosis and sleep disorders is required.
Recently, causative role of encephalitis in major psychotic
features, dyskinesias (particularly orofacial), seizures, and
autonomic and respiratory changes has been emphasized
[1,2]. These symptoms often occur in young females with
ovarian teratomas, who have good responses to tumor
surgery and immunotherapy [3-6]. Anti-NMDA-receptor
(NMDAR) encephalitis is suggested in many of these cases
as they are frequently associated with serum and CSF
autoantibodies to the NMDA receptor (NMDAR) .
A stereotypical clinical course during phases is noted
for the patients with Anti-NMDAR encephalitis ; a
non-specific flu-like prodrome (subfebrile temperature,
headache, fatigue) is always followed by a psychotic stage
with bizarre behavior, disorientation, confusion, paranoid
thoughts, visual or auditory hallucinations and memory
deficits. Acute onsets of atypical psychosis are usually
considered initially, and the patients are often admitted to
psychiatric centers. Organic brain disease is considered
only after the patients develop seizures, autonomic instabil-
ity, dyskinesias, or decreased level of consciousness [6,8,9].
In the current study, we indentified 3 typical Japanese
anti-NMDAR encephalitis cases. In addition, we found 7
Japanese cases with anti-NMDAR antibody with various
psychotic and sleep symptoms, who lack any noticeable
clinical signs of encephalitis (seizures and autonomic
symptoms) throughout the courses of the disease episodes.
These patients exhibited two distinct clinical characteris-
tics, and we report clinical symptoms of these cases along
with the typical cases.
* Correspondence: email@example.com
1Akita University, Department of Neuropsychiatry, Akita, Japan
Full list of author information is available at the end of the article
© 2012 Tsutsui et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Tsutsui et al. BMC Psychiatry 2012, 12:37
The study included a total of 61 patients aged 15
to 61 years. They were studied in the Department of
Neuropsychiatry, Akita University Hospital and related
hospitals between January 1, 2005, and Dec 31, 2010. The
Group A had typical clinical characteristics of anti-
NMDAR encephalitis, beginning with psychiatric symp-
toms, followed by subsequently occurring seizures and
disturbances of consciousness (Table 1). In order to
examine the specificity of the anti-NMDAR antibody
involvement in these cases, we also examined the
prevalence of antibody positivity in other neurologic and
psychotic patients without signs of encephalitis. Five
narcolepsy with severe psychosis cases were examined
and also included (group B), because autoantibody-
mediated mechanisms (anti-Ma2, anti-aquaporine 4
antibodies) are suspected in some secondary narcolepsy
cases [10,11]. In addition, several research groups
recently reported that a swine flu (H1N1) vaccination
increased the incidence of hypocretin-deficient narco-
lepsy . The antibody levels of 10 narcolepsy cases
comparison with group B. We also examined the antibody
in 51 patients with schizophrenia or schizo-affective
disorders (group C). Group C was subdivided into (c-1)
schizophrenia accompanied with convulsion , (c-2)
atypical symptoms of psychosis, and (c-3) resistance to
pharmacological treatments with relatively good responses
to modified electric convulsion treatment (mECT).
Antibody detection was performed by Dr. Dalmau's
laboratory in cases 1, 2, 10 and by Dr. Tanaka’s laboratory
for the others in Table 1. Case reports for 1, 2, 4, 9, 10
were previously published [14-19].During the initial
study with Dr. Dalmau, we came across several patients
with positive antibody but without any symptoms of
encephalitis (in group C). We therefore extended the study
and measured the anti-NMDAR antibody in additional
cases by ourselves with a comparative method [20,21]. The
plasma and CSF were tested blind to diagnostic status.
The study was approved by the Akita University ethics
committee and all patients gave informed written consent
prior to the study.
3 clinicalgroups for
Each antibody positive case is described, while the negative
cases are summarized in Table 1. Psychiatric disorders,
behavioral disorders, movement disorders, or sleep disor-
ders are mainly presented. The DSM-IV diagnostic codes
are included. The details of the clinical characteristics of
the representative 3 cases of each group are presented in
the text. Ten cases were anti-NMDAR antibody positive;
3 of 5 cases of typical encephalitis (group A), 3 of 5 cases
with a broader range of psychiatric disorders including
narcolepsy (group B) and 4 of 51 cases with schizophrenia
or schizo-affective disorders (group C).
(Group A) Typical clinical pictures of anti-NMDAR
We reviewed a case of acute limbic encephalitis (NMDAR
antibody was detected retrospectively) diagnosed after
improvement of psychotic symptoms by mECT. This case
was first diagnosed as schizophrenia based on catatonia-
like symptoms, auditory hallucinations, and delusions.
Two other positive cases presented with psychosis,
convulsions and were treated with steroid pulse therapy.
The patient (case 3) was a 27-year-old female and had no
previous psychiatric, neurological, or family history of the
disease. After a common cold, the patient had hypobulia,
insomnia, and seizure-like episodes. In addition, the
patient exhibited strange and incoherent behaviors. During
her first visit to our department, she was substuporous.
After hospitalization, the existence of auditory halluci-
nation and persecutory delusions were also strongly
suggested. Blood examinations, brain MRI, and EEG
showed no abnormality. Therefore at first we diagnosed
the patient as having acute schizophrenia. Since her
psychotic symptoms were refractory to antipsychotic
medication and adverse effects were severe, we applied
mECT. The psychotic symptoms improved remarkably by
this treatment. Accessibility was also improved, and we
were able to identify various neurological and psychiatric
symptoms including aphasia, agraphia, constructional
apraxia, retrograde amnesia, personality change, and
disinhibition. Laboratory examinations involving CSF and
brain SPECT were performed. Brain SPECT showed
decreased blood flux in her left limbic system and in the
inside of the left temporal lobe. From the symptoms,
clinical course, rarenessof abnormality in various
examinations, and the findings of brain SPECT, we
diagnosed her as having limbic encephalitis. Thereafter her
symptoms naturally improved without antipsychotics, and
her mental condition has been kept stable and healthy.
Because her clinical picture resembled that of the
recently reported anti-NMDAR encephalitis, we examined
the possible association. An archived plasma sample from
her initial presentation was submitted to Kanazawa
Medical University, where the antibody against NMDAR
was detected in the sample; the final diagnosis was anti-
NMDAR encephalitis. Examinations for tumors were not
performed at initial hospitalization.
The discrimination between functional (endogenous)
psychosis and NMDAR encephalitis is sometimes very
difficult. Therefore, we have to consider the possibility of
Tsutsui et al. BMC Psychiatry 2012, 12:37
Page 2 of 9
Table 1 Characteristics and clinical features of 10 NMDAR antibody positive patients and negative controls
Group Age, SexDiagnosis Psychotic symptomsEpileptic
Treatments OthersLabolatory for
normal steroid pulse
slight high density
inside the bilateral
after m-ECT, ataxia,
were pointed out
N(A) type antibody-
59/F, 25/M Limbic encephalitis
61/M Narcolepsy, Parkinson's
delusion of jealousy
(-) short sleep
37/F Narcolepsy, Schizophrenia
(Paranoid type 295.30)(F20.0)
visual and auditory
(Paranoid type 295.30)(F20.0)
antipyschotics hypocretin deficient
N(B) type antibody-
25/F, 35/M Narcolepsy and psychosis
and Schizophrenia (35/M)
normalvalproic acidreccurent ovarian
Tsutsui et al. BMC Psychiatry 2012, 12:37
Page 3 of 9
Table 1 Characteristics and clinical features of 10 NMDAR antibody positive patients and negative controls (Continued)
oral dyskinesiaDr Tanaka(Kanazawa
depressive mood, hyper
(-) normal antipyschotics,
Dr Dalmau (University
N(C) type antibody-
hyper activity, bizzare
ovarian tumor (n=6),
Tsutsui et al. BMC Psychiatry 2012, 12:37
Page 4 of 9
anti-NMDAR encephalitis, especially when relatively young
women are suffering acutely from psychotic symptoms.
We provided immunotherapy in case 1 and 2 but not in
case 3 because non-herpes limbic encephalitis was initially
suspected for the former two cases.
Another two subjects presented typical clinical pictures
of anti-NMDAR encephalitis, beginning with psychotic
symptoms, followed by seizures and subsequent distur-
bances of consciousness. However, these two subjects with
similar clinical pictures to case 3 were negative for the
anti-NMDAR antibody (Table 1, group NA).
(Group B) Narcolepsy cases with severe psychosis
We had previously reported a case with Parkinson’s
disease (PD) comorbid with hypocretin (orexin) deficient
narcolepsy [16,17]. In this patient, severe psychosis
presented subsequently to the diseases above, and has
been treated by mECT in addition to anti-psychotics with
a successful outcome. NMDAR antibody was detected
retrospectively. The two other positive cases had narco-
lepsy with severe psychosis without neurodegenerative
A 58-year-old male (case 4) with mild PD for 15 years was
admitted to a hospital due to a sleep attack in 2004. He
suffered from excessive daytime sleepiness (EDS) at high
school, however, the patient had not been diagnosed or
treated at that time. The patient had never had cataplexy
(sudden loss of muscle tonus due to emotional trigger). At
age 43, the patient had tremors in his left fingers and at
age 45 was diagnosed with PD. The patient was hit by a
motor vehicle due to EDS at age 55 and started experienc-
ing frequent hypnagogic hallucinations with abnormal
limb movements. The patient had Hoehn-Yahr stage 2
Parkinsonism and scored 14 in the unified PD rating scale
part III. His epworth sleepiness scale result was 19/24
(normal range<11/24). In the multiple sleep latency test
(MSLT), mean sleep latency was shortened to 2 min
(normal range >8 min) and sleep onset REM periods were
present in all four naps. HLA was positive for DR15 (2) as
typical for idiopathic narcolepsy. CSF hypocretin (orexin)
concentration was very low (86 pg/ml, normal range
>200 pg/ml). The patient was treated with methylpheni-
date (MPH) for EDS in addition to medications for PD.
During the next two years, his condition was good.
Thereafter, the patient became delusional and suffered
from auditory hallucinations. MPH and medications for
PD were stopped, and anti-psychotics were used. However,
the serious psychotic symptoms persisted. Finally the
patient was treated by mECT in addition to anti-
psychotics with a successful outcome. The patient is
maintenance mECT every month. Later, at 63 years old,
the NMDAR antibody was detected in both the serum and
the CSF of this patient. The hypocretin level in the CSF
sample (92 pg/ml) was unchanged from the time of his
We found that 2 other narcolepsy patients (among 5
examined), who had severe psychotic symptoms occurring
3 to 30 years after the onset of narcolepsy, were positive
for the antibody (Table, group B). These cases were
hypocretin deficient, but no significant encephalitis signs
except predominant psychotic symptoms, were noted.
They were under stimulant medications, and their
hallucinations and delusions were unchanged when the
stimulants were withdrawn. Antipsychotics (3 out of 3
cases) and mECT (one case) were required to manage the
We also tested anti-NMDAR antibody in 10 hypocretin
deficient narcolepsy patients without psychotic symptoms,
and found 2 antibody positive patients (15/f, 22/f).
Although antibody positive cases were found both in
narcolepsy with and without psychotic symptoms, an
increase in antibody positivity in the patients with psychotic
symptoms was suggested (p=0.025, Chi-square test).
(Group C) Psychiatry cases
In addition to these cases, we also found 4 antibody
positive patients out of 51 patients with schizophrenia or
schizo-affective disorders (group C). The neurological
symptoms were mild in these cases, and mECT was
effective in 3 cases. These 4 cases were female, two cases
had convulsions (cases 7, 8), and two cases had ovarian
tumors (cases 8, 10).
A 26-year-old female patient (case 10) had normal devel-
opment during childhood . She had no problems with
friendships in elementary school and junior high school.
She was aware of depressive symptoms when she was
16 years old, although she had no emotional stress. She
was diagnosed with depression and received antidepres-
sants from a clinic. Her diagnosis was changed to bipolar
disorder because the patient presented a hypomanic
episode at age 17. After that, her mood was stable and
treatment was discontinued.
The patient had insomnia and hypobulia at age 22.
The patient tried to jump out of a window (of the upper
floor), and thus she was transferred to a closed ward. In
this hospital, the patient exhibited a variety of symptoms
including delusions of persecution and observation, self-
injury (head banging) and substupor. There were no
specific findings on brain MRI. The patient subsequently
was treated with various anti-psychotics based on a
schizophrenia diagnosis, however she was only in
Tsutsui et al. BMC Psychiatry 2012, 12:37
Page 5 of 9
The patient had been treated with mECT (a total of
ten times) since she was 23 years old, and her symptoms
almost disappeared. Therefore her therapy focused on
mECT, and she was transferred to our hospital. mECT
was needed every other week continuously. The patient
complained of atypical genital bleeding at age 24 years
old, and an ovarian tumor was detected by abdominal
ultrasonography. Pelvic MRI showed a cystic tumor in
the right ovary with low T1 and high T2. The diameter
and length were 4.7 × 3.4 cm and 4.3 cm, respectively.
She was positive for anti-NMDAR antibody. The
patient underwent oophorectomy at age 26 years. The
pathological diagnosis was ovarian cyst without teratoma.
After the operation, she has been treated only with oral
medication (antipsychotics) and follow-ups.
This patient showed atypical clinical history as a
schizophrenic and resistance to pharmacological treat-
ments, but responded relatively well to mECT. The
percentage of NMDAR positive cases of this group C
(4 out of 51 cases) is similar to that of Zandi’s report
(3 out of 46 cases).
Our results showed a number of cases with NMDAR
antibody positivity in a broader range of psychiatric
disorders, such as sleep disorders and schizophrenia
(group A: 3 out of 5 cases, B: 3 out of 5 cases & C: 4 out
of 51 cases). Although the causative relationship between
NMDAR antibody positivity and psychiatric symptoms
in these patients are unknown, they exhibit unique
demographic and clinical characteristics. Eight (out of
10) are female, the majority of cases are 20–30 year olds,
and ovarian tumors are found in 2 patients. Most of their
symptoms are resistant to pharmacological treatments
but respond relatively well to mECT, the clinical charac-
teristics often seen in psychotic symptoms associated
with NMDAR encephalitis [22,23].
NMDAR and psychiatric symptoms
Schizophrenia is a common, heterogeneous, and complex
disorder with unknown aetiology . There is established
evidence of NMDAR hypofunction  as a central
component of the functional dysconnectivity; this is one of
Moreover, autoimmune mechanisms have been proposed
to be involved, at least in subgroups of schizophrenia
patients [27,28]. In the last few years, a number of
antibodies to neuronal cell surface antigens have been
identified in cases of autoimmune encephalitis that
respond to immunotherapy [29,30]. Over two-thirds of
patients withNMDAR antibody
prominent psychiatric symptoms or may present to
psychiatric services in the first instance [23,29,31-33]. The
psychiatric symptoms are those seen in schizophrenia
including delusions, hallucinations, and catatonic move-
This characteristic clinical presentation resembles acute
psychosis followed by a rapid decline in the level of
consciousness, central hypoventilation, seizures, involun-
tary movements, and autonomic instability. Although anti-
NMDAR encephalitis is a potentially fatal condition, if
the diagnosis is made rapidly, effective treatments are
In fact, the most favorable outcome occurs with tumor
removal (e.g., teratoma), usually in combination with
immunotherapy (IV steroids, IV immunoglobulin, or
plasma exchange) [9,35]. Also, a good clinical outcome
was reported in patients treated with immunotherapy
without tumor removal [36,37]. Besides tumor removal
antiepileptic drugs and benzodiazepines may partially
relieve symptoms [5,36].
Our first three cases in group A had typical clinical
pictures of anti-NMDAR encephalitis, beginning with
psychiatric symptoms, followed by seizures and distur-
bances of consciousness (Table 1, group A). No tumors
were found in these cases, but two of them responded well
to steroid pulse treatments.
Hypersomnia and encephalitis
As far as we know, there has been no report of narcolepsy
with NMDAR antibody positivity. However, two studies
reported that some patients with contemporary Encepha-
litis Lethergica (EL) were positive for NMDAR antibodies
[23,38]. Ten out of twenty patients were positive and these
patients predominantly fit into the dyskinetic form of EL
. The five patients with the somnolent-Parkinsonian
form of EL, which is considered to be the classic form of
EL, were negative for NMDAR antibodies .
These results together with the fact that 3 out of 5
narcoleptic subjects who were positive for anti-NMDAR
antibodies exhibited severe psychiatric symptoms and
that 8 out of 10 conventional narcoleptic subjects studied
were negative for NMDAR antibodies (p=0.025, Chi-
square test), show that NMDAR antibody positivity
may be more specifically related with occurrences of
Nevertheless, it is possible that the immune mediated
mechanisms are more frequently involved in narcolepsy
and that these may also be responsible for their
associated symptoms, and further studies are warranted.
The prevalence of NMDAR positivity in group C
The occurrence rate of NMDAR positive cases in our
group C (4 out of 51 cases) is similar to that of Zandi’s
report (3 out of 46 cases).
Since there had been no reported cases of NMDAR
antibodies identified in patients with purely psychiatric
Tsutsui et al. BMC Psychiatry 2012, 12:37
Page 6 of 9
disorders, Zandi et al.  hypothesized that this antibody
would be present in a proportion of patients with early
schizophrenia, in the absence of overt seizures, movement
disorders, or other neurological signs. They found 3 cases
in 46 examined cases that fulfilled DSM IV criteria for
schizophrenia, and the patients were tested early in
the course of their illness. They also described the
first case of a patient with NMDAR antibodies and
a purely psychiatric presentation, that responded to
immunotherapy (plasmapheresis, oral prednisolone).
The term, “atypical psychosis” has been used, especially by
Japanese psychiatrists  as a possible clinical entity for
acute and transient psychotic disorders which cannot be
easily classified as either schizophrenia or a mood disorder
with psychotic features. Some of the important clinical
characteristics of atypical psychosis include acute onset,
emotional disturbances, psychomotor disturbances, alter-
nations of consciousness, high prevalence in women, and
oriented premorbid personality, characteristics that mirror
those of our psychotic cases. These authors had suspected
involvementsof brain organic changes
However, atypical psychosis, by its meaning, comprises
a widely varied and poorly understood collection of
disorders, and atypical psychosis was listed in DSM-III-R
under the heading Psychosis Not Otherwise Specified
(NOS); this does not define the nosological entity and
is rather used as a residual category. Consequently,
in DSM-IV, the term atypical psychosis is no longer
mentioned as a synonym for this category.
While schizophrenia and affective disorders have
dominated the psychiatric literature and research efforts
in psychotic disorders, several other atypical psychotic
conditions are emerging as significant. Included among
these are psychotic disorders secondary to medical
conditions . If NMDAR
functionally involved in pathophysiology of the disease in
the patients listed in group C, the disease will fit in the
category of psychotic disorders secondary to medical
Together with our present study, further determination
of whether the anti-NMDAR antibody plays functional
roles in these patients with schizophrenia, schizo-affective
disorders and atypical psychosis, is critical, since treatment
choices, including immunotherapy, are different from
those for classical psychosis and since the immune
mediated mechanisms may also be involved more
frequently in these psychotic patients.
antibody positivity is
We present cases to illustrate that anti-NMDAR encepha-
litis should be considered when diagnosing patients
with acute psychosis, and that mECT can possibly be
considered as an effective treatment option for these cases.
In our 5 out of 10 anti-NMDAR antibody positive cases,
mECT was effective. In one previous case series, one
patient was found to respond to ECT . Two patients
have been reported with paraneoplastic catatonia and
ovarian teratoma that partially improved with ECT, but
full recovery was only obtained after tumor removal [9,22].
Still, the remission may have been spontaneous and the
temporal association between ECT and recovery may have
been coincidental. Recently, Braakman  reported that
one patient (47 old male) deteriorated clinically in a period
of 10 weeks, and recovered in a period of 3 weeks after
ECT was started.
The mechanism of action of ECT remains largely
unclear. Still, in animal models ECT has been shown to
up-regulate NMDA receptors . This may, in part,
explain the efficacy of ECT in our patients, since NMDAR
was down-regulated during periods of anti-NMDAR
We report remarkable recoveries of our patients follow-
ing mECT. Psychosis, delusions, stupor, and catatonia
rapidly disappeared. Further clinical observation or studies
in patients with anti-NMDAR encephalitis are needed to
determine the significance of our observations .
Results of our study together with those by others
redefine this new class of psychotic disorders positive
for anti- NMDAR antibody. These include narcolepsy
with psychosis, EL , schizophrenia accompanied by
convulsion , atypical symptoms of psychosis and
psychotic patients who are drug resistant but respond
relatively well to mECT.
We are also aware of the limitations of the study. (1) We
did not include normal controls or typical schizophrenia
subjects. (2) The retrospective recollection of the clinical
data may favor the description of partial or isolated
symptoms of the disease because we could miss subtle
signs or symptoms associated with the predominant
manifestation. (3) We did not measure the CSF antibody
in the majority of our cases and future prospective studies
should include paired serum-CSF antibody measures.
In addition to 3 typical cases with NMDAR encephalitis,
we found 7 cases with anti-NMDAR antibody associated
with various psychotic and sleep symptoms, which lack
any noticeable clinical signs of encephalitis (seizures and
autonomic symptoms) throughout the course of the
disease episodes. These patients exhibited two distinct
clinical characteristics; narcolepsy with severe psychosis
(3 cases) or schizophrenia (4 cases). Further determination
if the anti-NMDAR antibody plays functional roles in these
patients is essential, since the immune mediated mecha-
nisms may be involved more frequently in nonencephalitic
Tsutsui et al. BMC Psychiatry 2012, 12:37
Page 7 of 9
atypical psychosis, schizophrenia accompanied with convul-
sion and sleep disorders than currently thought.
The authors declare that they have no competing interests.
Concept: KT, TK, TS; Data collection: KT, SB, WI, JK, AM; Data analysis: TK, KT,
SN; First draft: KT, TK, YH, TS, SN; Final revision: KT, TK, YH, TS, SN; All authors
read and approved the final manuscript.
The authors thank Professor Dalmau and his laboratory at the University of
Pennsylvania for analysis of anti NMDAR antibody in some of the case
reported. The authors also thank Ms. Sayumi Takahashi and Ms. Mari
Matsumura for editing the manuscript.
1Akita University, Department of Neuropsychiatry, Akita, Japan.2Kanazawa
Medical University, Department of Neurology, Ishikawa, Japan.3Hokkaido
University, Department of Neuropsychiatry, Sapporo, Japan.4University of
South Carolina, Department of Exercise Science, Columbia, SC, USA.5Akita
Kaiseikai Hospital, Department of Psychiatry, Akita, Japan.6Stanford University,
Sleep and Circadian Neurobiology Laboratory, Palo Alto, CA, USA.
Received: 27 September 2011 Accepted: 30 March 2012
Published: 8 May 2012
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Cite this article as: Tsutsui et al.: Anti-NMDA-receptor antibody detected
in encephalitis, schizophrenia, and narcolepsy with psychotic features.
BMC Psychiatry 2012 12:37.
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