Crichton Royal Hospital, Dumfries, UK
Schizophrenia Research Foundation (India), Chennai, India
Correspondence: Professor R.G. McCreadie, Crichton Royal Hospital, Dumfries DGI 4TG, UK. Tel: 01387 244000; fax 01387 257735; e-mail: rgmccreadie_crh{at}compuserve.com
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ABSTRACT |
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Aims To determine the prevalence of spontaneous dyskinesia and parkinsonism in a group of never-medicated, chronically ill patients with schizophrenia on two occasions separated by an 18-month interval.
Method Dyskinesia was assessed by the Abnormal Involuntary Movements Scale using Schooler and Kane criteria for its presence; parkinsonism by the Simpson and Angus scale; and mental state by the Positive and Negative Syndrome Scale for schizophrenia.
Results Thirty-seven patients were examined on two occasions. Nine (24%) had dyskinesia on both occasions, 12 (33%) on one occasion and 16 (43%) on neither occasion. Twenty-one (57%) had dyskinesia on at least one occasion. Thirteen patients (35%) had parkinsonism on at least one occasion.
Conclusions Spontaneous dyskinesia and parkinsonism fluctuate over time. The former was found on at least one occasion in the majority of patients. It is an integral part of the schizophrenic disease process.
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INTRODUCTION |
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METHOD |
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The patients' lifetime exposure to medication is determined from a number of sources which include discussion with patients and relatives, and examination of case records and prescription sheets. None of our never-treated patients had ever received antipsychotic medication. We also confirm that patients had not received any treatment from practitioners of indigenous systems of medicine. As we reported earlier (McCreadie et al, 1996), taking medication is an important and often expensive event in the lives of these patients and their families. We are confident of the accuracy of the medication histories. The participants in this study were drawn from a group of 108 patients who were assessed for a magnetic resonance imaging study (McCreadie et al, 2002). Attempts were made to trace and reassess these patients 18 months later.
Assessment
Dyskinesia at first assessment and followup was measured by the Abnormal
Involuntary Movements Scale (AIMS), which examines seven areas of the body
(US Department of Health, Education and
Welfare, 1976). Dyskinesia was defined as probably present
(Schooler & Kane, 1982) if
movements were mild in at least two areas, or
moderate in at least one. Parkinsonian symptoms were measured by
the Simpson and Angus scale (Simpson &
Angus, 1970); parkinsonism was defined as present if the mean
score was greater than 0.3. One psychiatrist (R.G.M.) carried out all
assessments of movement disorder with the help of an interpreter as required.
He was blind to age at onset and duration of illness, mental state assessments
(see below) and, at follow-up, to the assessment of movement disorders 18
months previously. The patients' mental state was assessed using the Positive
and Negative Syndrome Scale (PANSS) for schizophrenia
(Kay et al, 1987) by
three of us (R.T., R.P., T.N.S.) trained in the use of the instrument and
blind to the first assessment. This scale gives a total score, and scores on
positive, negative and general psychopathology sub-scales.
Ethical considerations
Many untreated patients assessed by SCARF remain untreated, owing to their
refusal of the offer of free antipsychotic medication. There is no question of
compulsory administration of psychotropic medication in community-dwelling
patients.
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RESULTS |
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The patients who were reassessed did not differ from the others in gender distribution or in numbers with dyskinesia at first assessment. However, those reassessed were older: mean age 52 (s.d. 13) years v. 38 (s.d. 15) years, t=3.45, d.f.=106, P=0.008; had been ill longer: mean 17 (s.d. 8) years v. 7 (s.d. 7) years, t=4.93, d.f.=106, P<0.0001; and had lower scores on the PANSS general psychopathology sub-scale: mean 23 (s.d. 11) v. 29 (s.d. 11), t=2.69, d.f.=106, P=0.008.
Dyskinesia
Dyskinesia, defined by Schooler and Kane criteria, was present in 17 (46%)
patients at first assessment and in 13 (35%) at follow-up. Nine patients had
dyskinesia on both occasions; 8 at first assessment but not at follow-up; 4 at
follow-up but not at first assessment; 16 did not have dyskinesia on either
occasion. Therefore 21 (57%) had dyskinesia on at least one occasion. When
those who had dyskinesia on both occasions (n=9) were compared on
social, demographic and clinical findings to those who had dyskinesia on
neither occasion (n=16), the only significant between-group
difference was that patients with dyskinesia had higher scores on the
follow-up rating of parkinsonism (mean 0.41 (s.d. 0.37) v. 0.12 (s.d.
0.29); t=2.19, d.f.=21, P=0.04).
Parkinsonism
Parkinsonism symptoms were not assessed in 3 patients at first assessment
and another 3 at follow-up. Parkinsonism was present in 7 (21%) patients at
first assessment and in 12 (35%) at follow-up. Five patients had parkinsonism
on both occasions; 2 at first assessment but not at follow-up; 6 at follow-up
but not at first assessment; 17 did not have parkinsonism on either occasion.
Therefore 13 of the 37 patients (35%) had parkinsonism on at least one
occasion.
Mental state assessment
When the PANSS scores at first assessment and follow-up were compared,
there was no significant change in mean positive and negative symptom
sub-scale scores. Mean scores on general psychopathology and total scales
decreased, indicating an improvement in mental state: paired t-test,
mean total score 61 (s.d. 19) v. 52 (s.d. 16), t=2.49,
d.f.=36, P=0.02. There was no significant correlation between scores
at first assessment and at follow-up on positive, general psychopathology and
total scales. There was a significant correlation in negative symptom
sub-scale scores (Pearson's r=0.45, P=0.006).
There was no significant correlation between, on the one hand, change in total scores on the AIMS between first assessment and follow-up, and, on the other hand, change in either parkinsonism, positive symptom, negative symptom, general psychopathology or total PANSS scores (Pearson's r ranged from 0.08 to 0.27).
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DISCUSSION |
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Dyskinesia
The finding that more than half of the patients had dyskinesia on at least
one occasion supports our view that dyskinesia is an integral part of the
disease process. We have recently gone further by proposing on the basis of
magnetic resonance imaging findings
(McCreadie et al,
2002) that there may be a subgroup of schizophrenia associated
with dyskinesia and striatal pathology (namely, an enlarged lenticular
nucleus, especially on the left side).
Of interest is the group of 12 patients in whom dyskinesia was present on one occasion only. This suggests that spontaneous dyskinesia may fluctuate over time. It has long been known that tardive dyskinesia, especially in its milder forms, shows temporal fluctuations (Bergen et al, 1989).
In our original study (McCreadie et al, 1996) we examined elderly patients in whom the prevalence of spontaneous dyskinesia was found to be 38%. We therefore suggested that antipsychotic drugs did not cause tardive dyskinesia, but rather brought forward in time a phenomenon that would occur inevitably when the illness had been present for decades, rather than years. We may need to revise that view, as in the present study more than half the group had dyskinesia even though they were not particularly elderly (mean age 52 years). It may be that spontaneous and tardive dyskinesia are indeed aetiologically different but phenomenologically similar. In this context it is noteworthy that we have recently found an excess of a dopamine D3 receptor gene variant in patients with tardive dyskinesia in Scotland (Steen et al, 1997) but not in never-treated patients with spontaneous dyskinesia in India (Løvlie et al, 2000). It may also be that what is taken to be tardive dyskinesia in treated younger patients is in fact spontaneous dyskinesia, raising the question posed by Crow et al (1983): does tardive dyskinesia exist?
Parkinsonism
Parkinsonism was present in about a third of our patients on at least one
occasion. As with dyskinesia, it fluctuated over time. The Simpson and Angus
scale places considerable emphasis on rigidity. It was this rather than tremor
that was most obvious in our patients; the latter was found in only 3 patients
and was rated as mild. Patients with spontaneous dyskinesia had higher
parkinsonism scores than those without dyskinesia; that is, there is probably
an association between the two movement disorders, a finding similar to that
in our larger study of 143 patients (details available from the author upon
request).
Over the 18 months between assessments not only did spontaneous dyskinesia and parkinsonism fluctuate, so also did the patients' mental state as measured by the positive and general psychopathology sub-scales of the PANSS. There was less change in negative symptoms. The fluctuations in different aspects of the illness appeared to be independent of each other.
Other studies of spontaneous dyskinesia and parkinsonism
Data from 14 studies of never-treated patients with schizophrenia were used
to generate age-adjusted estimates of the prevalence of spontaneous dyskinesia
(Fenton, 2000). Rates of 25%
for those aged 30-50 years and 40% for those aged 60 years or older were
estimated; these rates are similar to our follow-up rate of 35%. Apart from
the present study, we know of no other longitudinal study of spontaneous
dyskinesia.
Spontaneous parkinsonism has been described in never-treated patients experiencing their first episode of schizophrenia; prevalence rates have ranged from 4% (Puri et al, 1999) through 17% (Chatterjee et al, 1995) to 21% (Caligiuri et al, 1993). We know of no other reports, apart from our own, of parkinsonism in chronically ill, never-treated patients, from either cross-sectional or longitudinal studies.
We conclude that our findings in this longitudinal study provide further evidence that movement disorders, both dyskinesia and parkinsonism, are an integral part of the schizophrenic disease process. Our magnetic resonance imaging study (McCreadie et al, 2002) has suggested that there may be structural differences, namely striatal abnormalities, between the brains of those with and without spontaneous dyskinesia, and normal brains.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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REFERENCES |
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Received for publication November 27, 2001. Revision received April 4, 2002. Accepted for publication April 9, 2002.
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