Functional neuroimaging techniques such as single-positron emission computed tomography (SPECT) and positron emission tomography (PET) offer considerable scope for investigating disturbances of brain activity in psychiatric disorders. However, the heterogeneous nature of disorders such as schizophrenia limits the value of studies that group patients under this global label. Some have addressed this problem by considering schizophrenia at a syndromal level, but so far, few have focussed at the level of individual symptoms. We describe the first neuroimaging study of the specific symptom of religious delusions in schizophrenia. 99mTc HMPAO high-resolution SPECT neuroimaging showed an association of religious delusions with left temporal overactivation and reduced occipital uptake, particularly on the left.
The clinically heterogeneous nature of disorders such as schizophrenia limits the value of studies that group patients under this global label. One method of addressing such heterogeneity is to adopt a syndromal approach. However, while most syndromal structures, such as those of Liddle, 1987a and Liddle, 1987b, are essentially based on clinical rating-scale analyses, an alternative syndromal model that was originally founded on physiological measures, and that has subsequently been shown to have considerable etiological validity, is that of Gruzelier (Gruzelier and Manchanda, 1982, Gruzelier, 1996a and Gruzelier, 1999). The delineation by Gruzelier of a three-syndrome structure in schizophrenia, that is, the active, withdrawn and unreality syndromes (Gruzelier, 1991 and Gruzelier, 1994), was derived from studies of patterns of cerebral hemispheric imbalance using both electrophysiological and neuropsychological measures (Gruzelier, 1996b). Gruzelier's delineation of his ‘active syndrome’ consists of raised activity levels, accelerated cognition, positive thought disorder, positive labile affect and affective delusions, and is associated with a greater left than right functional asymmetry. In contrast, the opposite pattern of functional hemispheric imbalance (greater right than left hemispheric activation) is associated with the ‘withdrawn syndrome’, comprising the essential negative features of schizophrenia, including poverty of speech, blunted affect, social withdrawal and motor retardation. Gruzelier's third syndrome, the ‘unreality syndrome’, involving Schneiderian delusions and hallucinations, is not consistently associated with lateral imbalance, and can coexist with either the active or withdrawn syndromes.
Functional neuroimaging techniques, such as single-photon emission computerised tomography (SPECT) and positron emission tomography (PET), have considerable potential for furthering our understanding of the disturbances in brain activity that underlie schizophrenia syndromes. A particular advantage of the use of the radiotracer [99mTc]-d,l-hexamethylpropylene amine oxime (99mTc-HMPAO) with SPECT stems from the fact that this radiopharmaceutical displays regional cerebral blood-flow (rCBF)-dependent uptake, with little redistribution over time (Puri and Lewis, 1992). The lipophilic 99mTc complex has been demonstrated, in vitro, to convert slowly to a secondary complex, and this may underlie the relative lack of cerebral redistribution (Neirinckx et al., 1987); after crossing the blood–brain barrier on first pass, 99mTc-HMPAO enters brain cells, where the pH change renders the molecules lipophobic. Following the formation of the cerebral lipophilic 99mTc complex, a relatively high proportion of the radioactivity left in the blood is trapped in erythrocytes, possibly by a similar mechanism to that causing cerebral retention. However, as the total volume of blood in the adult human brain is of the order of 0.031 l, the contribution of photons from the blood to the total photon count from the brain is very small, being less than 2% at 1 h postinjection. Therefore, following injection of the radiotracer, the SPECT scan can be delayed for, say, up to 1 h; when scanned, the rCBF found will represent the blood flow pattern immediately following the injection.
By studying the differences in rCBF found by carrying out SPECT neuroimaging during the manifestation of a particular symptom of schizophrenia, and then repeating the examination in the same patient(s) when well, it is possible to localise those cerebral regions associated with that symptom. For example, using this methodology McGuire et al. (1993) found that auditory hallucinations in schizophrenia are associated with an increased blood flow in Broca's area.
Here, the case is described of a patient with the active syndrome of schizophrenia who underwent SPECT neuroimaging on two occasions: first, while suffering from florid religious delusions, and again during remission.
The SPECT images were analysed in detail on a workstation with relevant internal referencing and matched scaling between the serial scans. A representative image of the uptake of the 99mTc-HMPAO radiotracer by the brain during the first scan, when the patient was suffering from religious delusions, is shown in Fig. 1, while Fig. 2 shows a representative image of the radiotracer uptake during the second scan, 6 months later.
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Fig. 1.
Transverse reconstruction of the first scan carried out at the time the patient was suffering from prominent religious delusions.
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Full-size image (30 K)
Fig. 2.
Transverse reconstruction of the second scan carried out (under identical conditions to the first scan) when the patient had made a complete recovery, showing reduced uptake in frontal and left temporal regions and increased occipital uptake, particularly on the left.
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Compared with the second scan carried out when the patient was in remission (Fig. 2), the first scan, carried out when the patient was suffering from prominent religious delusions, showed increased uptake in frontal and left temporal regions, and reduced occipital uptake particularly on the left (Fig. 1). The maximum change in tracer uptake in the left temporal and (left) occipital lobes was of the order of 24–30%.
