Department of Clinical Research, Crichton Royal Hospital, Dumfries, UK
Schizophrenia Research Foundation, Chennai, India
Correspondence: Robin G. McCreadie, Department of Clinical Research, Crichton Royal Hospital, Dumfries DG1 4TG, UK. Tel: +44 1387 244000; Fax: +44 1387 257735; e-mail: rgmccreadie_crh{at}compuserve.com
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ABSTRACT |
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Aims To determine the prevalence of abnormal movements in first-degree relatives of people with schizophrenia who themselves do or do not have abnormal movements.
Method Chronically ill, never-treated people with schizophrenia in south India (n=70) and their first-degree relatives (n=181) were examined for dyskinesia using the Abnormal Involuntary Movements Scale (AIMS) and for parkinsonism by the Simpson and Angus scale.
Results Of all relatives, 25 (14%) had dyskinetic movements in at least one body area and 6 (3%) had parkinsonism. Siblings of people with schizophrenia and dyskinesia, compared with siblings of people without dyskinesia, had a higher total AIMS score and more had mild dyskinetic movements in at least one area (5/15 v. 3/34, P=0.04). There were no between-group differences in parkinsonism.
Conclusions Dyskinesia but not parkinsonism is more common in siblings of people with schizophrenia who have the corresponding movement disorder.
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INTRODUCTION |
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METHOD |
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Subjects
First-degree relatives of people with schizophrenia were recruited in two
ways. First, we had already identified and examined never-treated people with
schizophrenia from previous studies in 1997
(McCreadie et al,
2002a) and 2000
(McCreadie et al,
2002b). In August 2001 their first-degree relatives were
identified in the villages and examined in their homes. Second, also in August
2001, we recruited from the villages newly identified people with
schizophrenia and their first-degree relatives, specifically for this
study.
As before, people with schizophrenia were recruited if they fulfilled the DSMIV criteria for schizophrenia (American Psychiatric Association, 1994) and had never received antipsychotic medication. The diagnosis was made through mental state assessment, using the Positive and Negative Syndrome Scale (PANSS) for schizophrenia (Kay et al, 1987), and a history was obtained from those with schizophrenia and their relatives. The diagnosis was made by one of three psychiatrists (R.T., R.P. or T.N.S.), all of whom had a postgraduate qualification in psychiatry and had been practising clinicians for more than 15 years. People with schizophrenia were excluded if there was a history of seizures. None of the people with schizophrenia was misusing street drugs and none had ever received psychotropic medication. Analgesics and antipyretics were taken as needed.
None of the relatives included had a history of schizophrenia, any psychotic illness, seizures or brain injury. Also, none had ever taken psychotropic medication or abused alcohol or drugs. Those included were parents, siblings and children aged 18 years and over.
The study was approved by the ethical review board at SCARF. Written consent was inappropriate because almost all subjects were illiterate. All people with schizophrenia and their relatives gave informed consent, witnessed by a SCARF staff member. Oral consent was recorded in the case record of the person with schizophrenia.
Assessment
Relatives and newly identified people with schizophrenia (see above) were
assessed for the presence of dyskinesia using the Abnormal Involuntary
Movements Scale (AIMS; US Department of
Health, Education and Welfare, 1976). This assesses movements in
seven areas of the body and in each area movements are assessed on a
five-point scale ranging from 0 (absent) to 4 (severe). A total score (AIMS
17) can also be obtained. Probable dyskinesia is said to be present if
movements are rated as mild (=2) in at least two areas, or
moderate (=3) in at least one area
(Schooler & Kane, 1982).
In addition to dyskinesia, parkinsonism was assessed using the Simpson and
Angus scale (Simpson & Angus,
1970). This assesses ten areas and in each area the score ranges
from 0 (absent) to 4 (severe). A total score also can be obtained (PARK
110). Parkinsonism is said to be present if the mean score is > 0.3
(Simpson & Angus,
1970).
The following information about people with schizophrenia was also known or recorded: gender, age and length of illness (as estimated from first appearance of positive psychotic symptoms). In the case of relatives, in addition to gender, age, relationship to the person with schizophrenia, and the use of alcohol and/or tobacco was recorded two factors that may be associated with dyskinesia in the general population (Nilsson et al, 1997).
Blindness
All assessments of dyskinesia and parkinsonism were made by one
psychiatrist (R.G.McC.). With regard to the relatives and people with
schizophrenia who had been identified in the previous studies (McCreadie
et al,
2002a,b),
he was completely blind as to which relative was related to which person with
schizophrenia. With regard to relatives of newly identified people with
schizophrenia specifically recruited for the present study, there were two
groups: for those who lived in the same house as the person with
schizophrenia, he always rated the relatives before the person with
schizophrenia; for those who lived in a different place to the person with
schizophrenia, he was blind as to who was related to whom.
Statistical analysis
We made an a priori decision to report the following results in
relatives: the median AIMS 17 score, the proportion with at least
mild movements in at least one area, the proportion with
probable dyskinesia (Schooler & Kane,
1982), the median PARK 110 score, the proportion with a
score of at least 2 in at least one area and the proportion with parkinsonism
(Simpson & Angus,
1970).
It was originally agreed that we would compare the prevalence of movement disorders in all relatives of people with schizophrenia with and without probable dyskinesia and with and without parkinsonism. However, during our collation of results an authoritative report of the prevalence of neurological signs in siblings of people with schizophrenia was published (Egan et al, 2001), which stated that in order to avoid inflating the degrees of freedom, only one selected sibling per family was used for group comparisons. Also, if only one sibling was used, each patient would make the same contribution to the results. Thus, in the interests of transparency, we report an analysis of the comparison between siblings but also make reference to an analysis of all relatives.
Differences between groups were measured by 2,
Fishers exact, MannWhitney and t-tests, as appropriate.
Multivariate analysis explored the significance of predictor variables.
Two-sided significance tests were used.
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RESULTS |
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Comparison of siblings
Dyskinesia
One sibling, the nearest in age to the person with schizophrenia, was
identified for each person with schizophrenia (49 siblings in total; 21 people
with schizophrenia had no siblings). When siblings of people with
schizophrenia and dyskinesia were compared with siblings of those with
schizophrenia but no dyskinesia there were no significant differences in
gender distribution (Table 2)
or proportions smoking or drinking alcohol. Siblings of people with
schizophrenia and dyskinesia were significantly older, had a higher total AIMS
17 score and more had mild movements in at least one area
(Table 2 and
Fig. 1). Two of the four
siblings with probable dyskinesia were siblings of people with schizophrenia
and probable dyskinesia.
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Multiple linear regression was used to examine the simultaneous effect of two predictor variables sibling age and dyskinesia status of people with schizophrenia on a dependent variable the sibling total AIMS 17 score. The dyskinesia status of people with schizophrenia remained independently significantly associated with the sibling total AIMS 17 score (P=0.02). Logistic regression was used to examine the effect of the same two predictor variables on the presence of mild movements in at least one area (the dependent variable). The dyskinesia status of people with schizophrenia remained independently significantly associated with the presence of mild symptoms in at least one area in siblings (P=0.05).
Parkinsonism
When siblings of those with schizophrenia and parkinsonism were compared
with siblings of those with schizophrenia but no parkinsonism (14 and 35,
respectively) there were no significant differences in gender distribution,
age, proportions smoking or drinking alcohol, median parkinsonism score,
proportions with a score of at least 2 in one area and proportions with
parkinsonism.
All relatives
Twenty-five relatives (14%) had mild dyskinetic movements in at least one
body area and six (3%) had parkinsonism. As with the siblings, differences
between all relatives of people with schizophrenia with and without dyskinesia
and with and without parkinsonism were examined. The statistically significant
differences were the same as with the siblings but with the following
exception: there was no difference in the age of relatives of those with
schizophrenia with and without dyskinesia.
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DISCUSSION |
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We are also satisfied that the abnormal movements rated were indistinguishable from tardive dyskinesia. The rater (R.G.McC.) has had extensive experience in the use of the AIMS scale in tardive dyskinesia and has made more than 1500 ratings using this scale.
Methodological limitations
There are, however, limitations to our study. Those with schizophrenia who
were eventually recruited to the study had first to agree to come with
outreach workers to the SCARF centre for assessment. They had to agree to be
examined by clinicians and then, in one study
(McCreadie et al,
2002a), travel with their relatives to the city (up to
100 km) for an MRI scan. All this demanded a high degree of cooperation from
those with schizophrenia and their families. We cannot be certain, therefore,
that those individuals with schizophrenia are representative of the large
numbers of never-treated people with schizophrenia in and around
Thiropuror.
Also, we did not examine all first-degree relatives of patients. Some had left the village to work in the city and some female siblings who had married were living in distant places.
Another limitation is that the diagnosis of schizophrenia was made on clinical grounds, albeit by experienced clinicians, using the PANSS assessment and history from those with schizophrenia and their families. A structured diagnostic interview was not carried out.
With regard to assessment, a strength is that all ratings of movement disorders were made by the same psychiatrist. A potential drawback to the assessment is that in those with schizophrenia recruited specifically for the present study, although the rater, in his assessment of relatives, was blind to the dyskinesia status of those with schizophrenia, he was not always blind to the dyskinesia status of the relatives when he rated the person with schizophrenia.
Dyskinesia
When the siblings of those with schizophrenia with and without dyskinesia
were compared, we found dyskinetic movements to be significantly more common
and more severe in the siblings of those with schizophrenia and dyskinesia. We
believe that this is the first study to report this finding. In contrast, a
study of dyskinesia in treated individuals with schizophrenia and
neuroleptic-naïve siblings (Ismail
et al, 2001) found little co-occurrence of dyskinesia in
the siblings and the person with schizophrenia in the same family. Another
study (Egan et al,
2001), using the AIMS, found a higher dyskinesia rating in
siblings when compared with normal controls, but the significance level was
reduced (P=0.06) when subjects who were taking neuroleptics or
selective serotonin reuptake inhibitors were excluded.
If spontaneous dyskinesia in schizophrenia runs in families, then either environmental or genetic factors may be responsible. With regard to the environment, all those with schizophrenia and their relatives were recruited from the same group of villages in south India, with very similar lifestyles and dietary habits. However, one possible environmental factor studied in tardive (drug-induced) dyskinesia is obstetric complications. One small study (Cantor-Graae et al, 2000; Ismail et al, 2001) found that the rate of obstetric complications was increased by 65% in siblings with signs of dyskinesia compared with those having no signs. We now plan to examine further the obstetric histories of never-treated individuals with schizophrenia and their siblings with and without dyskinesia.
With regard to genetic factors, in those with schizophrenia with and without spontaneous dyskinesia we have already reported no variations in the dopamine D3 receptor gene (Lovlie et al, 2001), a variation found in those with schizophrenia with and without tardive dyskinesia (Lerer et al, 2002).
Parkinsonism
There were no significant differences in parkinsonian symptoms when
siblings of those with schizophrenia with and without parkinsonism were
compared. The findings, therefore, do not suggest any familial basis to
parkinsonian symptoms.
Our present results suggest that spontaneous dyskinesia but not parkinsonism runs in families and is further evidence that there may be a subgroup of schizophrenia, namely schizophrenia with dyskinesia. A previous study (McCreadie et al, 2002a) suggests that such patients may have striatal pathology. Whether genetic factors are responsible for both the schizophrenic illness and the dyskinesia or whether environmental factors contribute to the latter is not yet known.
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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 August 21, 2002. Revision received February 28, 2003. Accepted for publication April 9, 2003.
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