Abstract
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.
Keywords: 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 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.
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% | .936 |
| Female | 33% | 43.6% | |
| Handedness | |||
| Right | 85% | 81% | .431 |
| Left | 14% | 18% | |
| Ambidextrous | 1% | 1% | |
| Age | 31.1 SD: 11 | 33.8 SD: 13.8 | .441 |
| Diagnoses | |||
| Schizophrenia | 418 | ||
| Schizoaffective | 39 | ||
| Schizophreniform | 40 | ||
| Psychosis NOS | 38 | ||
| Bipolar disorder | 89 | ||
| Autism/pervasive developmental disorder | 30 | ||
| Psychosis due to substance use | 5 | ||
| First-episode patients | 349 | ||
| Multiple-episode patients | 307 |
Note: NOS, not otherwise specified.
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 × 250 mm2) scan with 17 axial 5-mm slices and 1.2-mm 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. Table 2 describes the subgroups of extracranial, not clinically relevant and clinically relevant abnormalities.
Table 2.
Classification of Radiological Abnormalities
| Extracranial Lesions: Excluded | Not Clinically Relevant: Excluded | Clinically Relevant: Included |
| Sinus abnormalities | Enlarged Virchow-Robin spaces | Corpus callosum (partly) absent |
| Skin or mucous membrane lesions | Cavum septum pellucidum | Local/global atrophy |
| Skull or muscle abnormalities | Increased/diminished asymmetry of ventricles, lobes or brain | Tumors (benign/malignant) |
| Deviant shape hippocampus | Cysts (including Arnold-Chiari malformations) | |
| Accentuated or prominent ventricles | White matter abnormalities | |
| Deviant shape corpus callosum | Vascular abnormalities | |
| Pituitary gland abnormalities | ||
| Postischeamic lesions | ||
| Coarse ventricle 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. 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 differences per category were absent; we only observed a trend toward higher prevalence of vascular lesions in the control 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 | Significance, 2-Sided P |
| White matter abnormalities | 6.9 | 6.9 | 1 |
| Atrophy | 1.8 | 2.2 | .57 |
| Tumors | 0.2 | 0.3 | 1 |
| Cysts | 1.8 | 1.8 | 1 |
| Vascular abnormalities | 0.2 | 0.9 | .07 |
| Ventricular abnormalities | 0.9 | 0.6 | 1 |
| Pituitary gland abnormalities | 0.5 | 0.3 | 1 |
| Postischeamic lesions | 0.5 | 1.2 | .3 |
| Abnormalities of corpus callosum | 0.3 | 0.6 | .69 |
| Any abnormality | 11.1a | 11.8a | .45 |
Note: MRI, magnetic resonance imaging.
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.
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.
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.
Supplementary Material
Supplementary material is available at http://schizophreniabulletin.oxfordjournals.org.
Acknowledgments
The authors have declared that there are no conflicts of interest in relation to the subject of this study.
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