Schizophrenia
Bulletin vol. 39 no. 4 pp. 815–819, 2013
Schizophrenia Bulletin
doi:10.1093/schbul/sbs037
doi:10.1093/schbul/sbs037
Advance Access publication March 13, 2012
How Frequent Are Radiological Abnormalities in Patients With Psychosis? A Review
of 1379 MRI Scans
Iris E. Sommer1,*, Gérard A. P. de Kort2, Anne Lotte Meijering1, Paola Dazzan3, Hilleke E. Hulshoff Pol1, René S. Kahn1,
and Neeltje E. M. van Haren1
1
Psychiatry Department University Medical Center Utrecht and Rudolf Magnus Institute for Neuroscience, A01.160, Heidelberglaan 100,
3485CX, the Netherlands; 2Radiology Department, University Medical Center Utrecht, Utrecht, the Netherlands; 3Department of Psychosis
Studies, Institute of Psychiatry, King’s College London, London, UK
*To whom correspondence should be addressed; tel: 31887556370, fax: 31887555443, e-mail: [email protected]
Background: The term psychosis refers to a combination of
symptoms, without pointing to the origin of these symptoms. In a subset of psychotic patients, symptoms are attributable to an organic disease. It is important to identify
these organic causes of psychosis early, as urgent treatment
of the primary disease may be required. Some of these underlying organic disorders can be identified on magnetic
resonance imaging (MRI) scans. Whether routine screening for all psychotic patients should therefore include MRI
scans is still a matter of debate. Methods: This study investigated the prevalence of clinically relevant abnormalities detected on MRI scans from psychotic patients and
a matched control group. We could include MRI scans
from 656 psychotic patients and 722 controls. The standard
radiological reports of these scans were classified as normal, as a nonrelevant abnormality or as a clinically relevant
brain abnormality by means of consensus, blind to diagnosis. Results: A normal aspect of the brain was reported in
74.4% of the patients and in 73.4% of the controls. We
found clinically relevant pathology in 11.1% of the patients
and in 11.8% of the controls. None of the neuropathological
findings observed in the patients was interpreted as a possible substrate for organic psychosis. Brain abnormalities
that were classified as not clinically relevant were identified
in 14.5% of the patients and in 14.8% of the controls.
Conclusions: This suggests that MRI brain scans are not
an essential part of routine screening for psychotic patients.
Key words: psychosis/screening/MRI/organic psychosis
Introduction
The term psychosis refers to a combination of symptoms,
without pointing to the specific origin of these symptoms.
While in many cases a specific underlying organic disorder is not identifiable (functional psychosis), it has long
been acknowledged that in a subset of psychotic patients,
symptoms are attributable to a medical or neurological
disease, such as sarchoidosis, porphyria, Cushing’s disease, acquired immune deficiency syndrome, carcinoid
tumor, toxic thyroid nodules, Wilson’s disease, neurosyphilis, Huntington’s disease, or multiple sclerosis. These
are the so called ‘‘secondary’’ or organic psychoses,1
which are included in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) under
the diagnostic category ‘‘psychosis due to a general
medical condition.’’ The exact percentage of organic
psychosis is not well known.2 In a group of 268 consecutive patients presenting with a psychotic episode,
Johnstone et al3 found evidence for systemic or neurological causes of psychosis in 6% of them. It is important
to identify these medical or neurological causes of
psychosis early, as urgent treatment of the primary
disease may be required. Unfortunately, the differentiation between ‘‘primary’’ and ‘‘secondary’’ (ie, organic)
psychosis on the basis of psychopathology alone is not
always possible.4
Psychiatric symptoms usually develop early in the
course of somatic or neurological disorders, often before
other symptoms become overt, which delays accurate
diagnosis.1 For this reason, most psychiatric centers
have established routine screening procedures for all
patients presenting with psychotic symptoms, including
for example syphilis serology and thyroid function tests.
In some developed countries (for example in Denmark
and Germany5), these protocols also include brain imaging for all patients presenting with psychotic symptoms,
while in others, this is still the subject of a debate (as for
example in the United Kingdom6). Whether such diagnostic scans should be included in standard screening
routine is open for discussion.2 The efficiency of diagnostic scans in detecting organic brain pathology underlying
psychosis is highly dependent on the chance of finding
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Sommeretetalal.
clinically relevant neuropathology on the brain scans.2
Several studies have systematically assessed the prevalence of neurological abnormalities that have therapeutic
implications in patients presenting with psychotic symptoms.7–14 However, these studies included only modest
sample sizes (the largest sample consisted of 242 patients
and 98 controls). Because clinically relevant neuropathology identified with magnetic resonance imaging (MRI)
may be rare (for example: 0.2% prevalence of brain
tumors in healthy subjects15), these studies may not
provide an accurate reflection of the prevalence of
neuropathology suggestive of an organic psychosis.
The aim of the present study is to estimate the prevalence of clinically relevant neuropathology in a large sample of patients presenting to services with psychotic
symptoms and compare these prevalence rates to those
of a matched group of healthy individuals from the community. The outcome may provide new evidence to the
debate as to whether screening procedures for psychotic
patients should include routine MRI scans. For this purpose, we have collected the standard radiological reports
of all patients presenting with a psychotic episode and the
matched healthy controls who have participated in MRI
studies of our center over the last 15 years.
Methods
Participants
The MRI’s used for the current study were performed as
part of a series of brain imaging studies carried out at the
Neuroscience Division of the University Medical Center
Utrecht (UMCU) between 1995 and 2010. We included
the MRI scans of all patients who presented with a psychotic episode, 656 in total. The inclusion criterion for the
MRI studies was a ‘‘psychotic episode’’ (for some studies,
a first psychotic episode) and not restricted to schizophrenia. Patients with an atypical presentation (for example,
without any negative symptoms) were therefore not
excluded.
DSM-IV diagnoses of this patient sample are summarized in table 1. The control group included subjects with
no history of psychotic disorders or other mental health
problems (N = 722) who were matched to the patient sample for age and sex. These controls were recruited by
newspaper advertisements and notice boards. An overview of the demographic and clinical characteristics of
the 2 groups is provided in table 1.
Image Acquisition
MRI scans were obtained using the Philips Intera and
Achiva 1.5 tesla (T) scanners (Philips, Best, the Netherlands) at the UMCU. A T2-weighted dual echo-turbo
spin echo (DE-TSE; TE1 = 9 msec, TE2 = 100 msec,
TR = 2200 msec, flip angle = 90, field of view = 250 3
250 mm2) scan with 17 axial 5-mm slices and 1.2-mm
2
816
Table 1. Demographic and Clinical Characteristics of the Study
Sample
Sociodemographic
and Clinical
Characteristics
Patients,
N = 656
Controls,
N = 722
Significance
Gender
Male
67%
56.4%
Female
33%
43.6%
Handedness
Right
85%
81%
Left
14%
18%
Ambidextrous
1%
1%
Age
31.1 SD: 11 33.8 SD: 13.8
Diagnoses
Schizophrenia
418
Schizoaffective
39
Schizophreniform
40
Psychosis NOS
38
Bipolar disorder
89
Autism/pervasive
30
developmental
disorder
Psychosis due to
5
substance use
First-episode patients
349
Multiple-episode
307
patients
.936
.431
.441
Note: NOS, not otherwise specified.
gap of the whole head was acquired for clinical neurodiagnostic evaluation.
Classification of Structural Brain Abnormalities
All MRI scans were assessed by neuroradiologists at the
UMCU. The radiologists were blind to subject status, although they were aware that these MRI scans could be
either from a patient with psychosis or from a healthy
individual who participated in research.
For the assessment of neuropathology, we excluded
noncerebral (ie, extracranial) abnormalities, such as sinus
abnormalities or pathology of the skin, face, or skull. For
all reports that made note of a brain abnormality, clinical
relevance was assessed according to the definition by
Katzman et al,15 ie, abnormal scans needing either routine,
urgent, or immediate referral. The categorization of each
scan report was based on a consensus decision between 2
of the authors: a radiologist (G.d.K.) and a psychiatrist
(I.E.S.), who were blind to diagnosis and subject status.
A complete list of all radiological findings classified as
not clinically relevant, and a list of all clinically relevant
radiological abnormalities can be found in the online supplementary material. Radiological abnormalities of the
brain that were considered clinically relevant were divided
into subgroups, depending on the nature of the pathology.
MRI Abnormalities
Abnormalities in
in Patients
Patients With
With Psychosis
Psychosis
MRI
Table 2. Classification of Radiological Abnormalities
Extracranial Lesions: Excluded
Not Clinically Relevant: Excluded
Clinically Relevant: Included
Sinus abnormalities
Skin or mucous membrane lesions
Skull or muscle abnormalities
Enlarged Virchow-Robin spaces
Cavum septum pellucidum
Increased/diminished asymmetry of ventricles,
lobes or brain
Deviant shape hippocampus
Accentuated or prominent ventricles
Deviant shape corpus callosum
Corpus callosum (partly) absent
Local/global atrophy
Tumors (benign/malignant)
Table 2 describes the subgroups of extracranial, not clinically relevant and clinically relevant abnormalities.
Statistical Analyses
Differences in the frequency of clinically relevant abnormalities for each of the 9 categories between the patients
and the controls were tested by means of a chi-square. In
the patient group, an independent sample t test was used
to test the difference in the number of clinically relevant
brain abnormalities between first- and multiple-episode
patients. Percentages of abnormalities were also calculated for patients with a diagnosis of schizophrenia
and for bipolar disorder. Statistical analyses were performed using the SPSS package software (Version
15.0; SPSS inc., Chicago, IL).
Results
A completely normal aspect of the brain was reported in
74.4% of the patients and in 73.4% of the controls. We
found evidence of clinically relevant pathology in
11.1% of the patients and in 11.8% of the controls.
Cysts (including Arnold-Chiari malformations)
White matter abnormalities
Vascular abnormalities
Pituitary gland abnormalities
Postischeamic lesions
Coarse ventricle abnormalities
The effect of diagnosis on the distribution of neuroradiological abnormalities was not significant (P = .285). None
of the neuropathological findings observed in the patient
group was interpreted as a possible substrate for organic
psychosis. The only tumor reported in this group was
a small lipoma. There was no difference in the number
of abnormalities on MRI scans between first- and
multiple-episode patients (P = .45). Brain abnormalities
that were classified as not clinically relevant were identified in 14.5% of the patients and in 14.7% of the controls.
A complete list of all observed abnormalities is provided
in the online supplementary material.
Detailed information about the clinically relevant abnormalities observed in both the patient and the control
groups, their percentages in each group, and the corresponding P values for differences between the groups
are provided in table 3. Several patients and controls
showed more than 1 abnormality on MRI (for example:
abnormal ventricle system and partly absent corpus callosum or global atrophy and white matter abnormalities).
We found no significant main effect of group (patient/
control): chi-square, 2-sided P = .45 in the frequency
of clinically relevant pathology. Significant group
Table 3. MRI Scans of Patients and Controls With Clinically Relevant Neuroradiological Abnormalities
Pathology Subgroups, % of Total
Patient Group, N = 656
Control Group, N = 722
White matter abnormalities
Atrophy
Tumors
Cysts
Vascular abnormalities
Ventricular abnormalities
Pituitary gland abnormalities
Postischeamic lesions
Abnormalities of corpus callosum
Any abnormality
6.9
1.8
0.2
1.8
0.2
0.9
0.5
0.5
0.3
11.1a
6.9
2.2
0.3
1.8
0.9
0.6
0.3
1.2
0.6
11.8a
Significance, 2-Sided P
1
.57
1
1
.07
1
1
.3
.69
.45
Note: MRI, magnetic resonance imaging.
a
Some participants have more than 1 abnormality, causing a discrepancy between the total number of pathologies and the total
percentage of participants with any pathology.
3
817
I.I.E.
E.Sommer
Sommeretetalal.
differences per category were absent; we only observed
a trend toward higher prevalence of vascular lesions in
the control group.
The patient group was split into several diagnostic categories. Only the groups with schizophrenia and the one
with bipolar disorder were large enough to investigate prevalences of abnormalities in these specific diagnostic groups.
In the schizophrenia group (n = 418), 63 patients had
a nonrelevant abnormality (14.9%) and 41 had a clinically
relevant neuroradiological abnormality (9.9%). These abnormalities consisted of 1 corpus callosum abnormality,
8 cases of atrophy, 8 cystes, 23 white matter abnormalities,
3 postischeamic lesions, and 3 ventricular abnormalities.
In the bipolar patients (n = 89), 12 had nonrelevant
abnormalities (13%) and 12 had a clinically significant
neuroradiological abnormality (13%). These consisted of
1 corpus callosum abnormality, 1 case of atrophy, 1 cyste,
9 white matter abnormalities, and 1 postischeamic lesions.
There was no significant difference in the distribution of
neuroradiological abnormalities between patients with
schizophrenia and bipolar disorder (Fischer’s exact test,
P = .297).
Discussion
This study estimated the frequency of clinically relevant
pathology on MRI scans of patients with psychosis and
healthy controls. We were particularly interested in the
frequency of neuropathology suggestive of an organic
psychosis because this may indicate the need for a routine
MRI screening in all patients with psychosis. We compared the frequency of neuropathological findings, diagnosed by standard neuroradiological examination, in the
MRI scans of 656 patients with psychosis and in 722 MRI
scans of healthy controls. The number of individuals with
signs of clinically relevant abnormalities was not higher
in the patients (11.1%) than in the controls (11.8%). In
addition, the number of not clinically relevant abnormalities was also similar in both groups: 14.5% in the patients
and 14.8% in the controls. From the 9 categories of clinically relevant neuropathology, only vascular abnormalities showed a trend toward a higher prevalence in the
controls, which we interpreted as a chance finding.
We found brain tumors in 0.2% of the patients and in
0.3% of the controls, which is in line with the findings of
Katzman et al,15 who also identified 0.2% tumors in 1000
scans of healthy controls. In this sample of 656 patients
with psychosis, we did not find signs of neuropathology
on MRI that was indicative for organic psychosis. There
was no significant effect of diagnosis on the distribution
of neuroradiological abnormalities. We could investigate
the distribution of neuroradiological abnormalities per
diagnosis only in schizophrenia and in bipolar patients
because the other groups were too small. We found 63
abnormalities in 418 patients with schizophrenia and
12 in 89 bipolar patients.
4
818
These findings may imply that the percentage of
psychotic patients identified as having an organic psychosis by means of MRI scans is low. These data therefore
suggest that MRI scanning should not be considered
a necessary component of routine screening in psychotic
patients.
Albon et al2 performed a costeffectiveness analysis for
routine MRI brain scans in psychotic patients and found
that neuroimaging as part of the standard screening procedure is cost-incurring if the prevalence of organic
causes of psychosis that can be identified with brain imaging is at least 1%. The findings of our study indicate
that this minimum rate is not met, ie, at least 6 patients
should have met criteria for organic psychosis in our
sample. This finding is in agreement with most other
studies that assessed series of MRI scans of psychotic
patients7–10,13,14 but not with Lubman et al11 who
identified 3 cases (1.2%) of possible organic psychosis
(1 patient with Moyamoya disease and 2 patients with
demyelination).
It should be kept in mind that the current study included patients who were referred to psychiatric services.
It is well possible that patients with a presentation suggestive of an organic psychosis, for example those with
comorbid neurological signs, had already been excluded
at entry into these services, and directly referred to a neurologist instead. If this was the case, we feel that our data
are even stronger because they specifically address the
issue of the utility of MRI screening ‘‘in the psychiatric
setting,’’ which is the aim of our study.
Limitations
A flaw of this study is that MRI scans were judged by
different neuroradiologists as part of a routine assessment. The study would have benefited from a systematic
examination of all MRI scans by the same radiologist.
However, as the UMCU is a teaching hospital, all
radiologists were trained similarly and were experienced
in the examination of MRI scans from psychiatric
patients.
In conclusion, in this series of 656 MRI scans from
patients with psychosis, we identified no more clinically
relevant neuropathology than in a sample of 722 controls. None of the abnormalities identified in the patients
was suggestive of an organic psychosis. This study, therefore, suggests that it is not essential to perform MRI
brain scans as part of the routine screening for psychotic
patients.
Funding
This work was supported by 2 grants of Dr I.E.S.: NWO/
ZonMW (Dutch Scientific Research Organization) Clinical Fellowship, number 40-00703-97-270 and NWO/
ZonMW Innovation Impulse (VIDI), number
017.106.301.
MRI Abnormalities
Abnormalities in
in Patients
Patients With
With Psychosis
Psychosis
MRI
Supplementary Material
Supplementary material is available
schizophreniabulletin.oxfordjournals.org.
at
http://
Acknowledgments
The authors have declared that there are no conflicts of
interest in relation to the subject of this study.
References
1. Falkai P. Differential diagnosis in acute psychotic episode. Int
Clin Psychopharmacol. 1996;11(suppl 2):13–17.
2. Albon E, Tsourapas A, Frew E, et al. Structural neuroimaging in psychosis: a systematic review and economic evaluation. Health Technol Assess. 2008;12:iii–iv, , ix-163.
3. Johnstone EC, Macmillan JF, Crow TJ. The occurrence of
organic disease of possible or probable aetiological significance in a population of 268 cases of first episode schizophrenia. Psychol Med. 1987;17:371–379.
4. Johnstone EC, Cooling NJ, Frith CD, Crow TJ, Owens DG.
Phenomenology of organic and functional psychoses and the
overlap between them. Br J Psychiatry. 1988;153:770–776.
5. Gaebel W, Falkai P, Weinmann S, Wobrock T. Behandlungsleitlinie Schizophrenie. Darmstadt, Germany: Steinkopff;
2006.
6. Agzarian MJ, Chryssidis S, Davies RP, Pozza CH. Use of
routine computed tomography brain scanning of psychiatry
patients. Australas Radiol. 2006;50:27–28.
7. Lieberman J, Bogerts B, Degreef G, Ashtari M, Lantos G,
Alvir J. Qualitative assessment of brain morphology in acute
and chronic schizophrenia. Am J Psychiatry. 1992;149:784–794.
8. Lewine RR, Hudgins P, Brown F, Caudle J, Risch SC. Differences in qualitative brain morphology findings in schizophrenia, major depression, bipolar disorder, and normal
volunteers. Schizophr Res. 1995;15:253–259.
9. Lawrie SM, Abukmeil SS, Chiswick A, Egan V, Santosh CG,
Best JJ. Qualitative cerebral morphology in schizophrenia:
a magnetic resonance imaging study and systematic literature
review. Schizophr Res. 1997;25:155–166.
10. Symonds LL, Olichney JM, Jernigan TL, Corey-Bloom J,
Healy JF, Jeste DV. Lack of clinically significant gross structural abnormalities in MRIs of older patients with schizophrenia and related psychoses. J Neuropsychiatry Clin
Neurosci. 1997;9:251–258.
11. Galderisi S, Vita A, Rossi A, et al. Qualitative MRI findings
in patients with schizophrenia: a controlled study. Psychiatry
Res. 2000;98:117–126.
12. Lubman DI, Velakoulis D, McGorry PD, et al. Incidental radiological findings on brain magnetic resonance imaging in
first-episode psychosis and chronic schizophrenia. Acta
Psychiatr Scand. 2002;106:331–336.
13. Borgwardt SJ, Radue EW, Götz K, et al. Radiological findings in individuals at high risk of psychosis. J Neurol Neurosurg Psychiatry. 2006;77:229–233.
14. Akhtar W, Naqvi HA, Hussain S, Ali A, Ahmad N. Magnetic
resonance imaging findings in patients with schizophrenia.
J Coll Physicians Surg Pak. 2010;20:167–170.
15. Katzman GL, Dagher AP, Patronas NJ. Incidental findings
on brain magnetic resonance imaging from 1000 asymptomatic volunteers. JAMA. 1999;282:36–39.
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