University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh, UK
Correspondence: Eve Johnstone, University Department of Psychiatry, Kennedy Tower, Royal Edinburgh Hospital, Morningside Park, Edinburgh EH10 5HF, UK
Declaration of interest This study was financed by the Medical Research Council, which supports S.M.L. and R.C.
* Presented in part at the European First Episode Schizophrenia Network
Meeting, Whistler BC, Canada, 27 April 2001.
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ABSTRACT |
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Aims To compare groups of good and poor outcome from the Edinburgh High-Risk Study and clarify the nature of the change from the state of vulnerability to that of developing psychosis.
Method The recruitment procedure is described. Good and poor outcome are defined. These groups are compared in terms of genetic liability and of baseline and change in neuropsychology and neuroanatomy.
Results Demographic characteristics and genetic liability do not differ between the groups. The good outcome group perform better at baseline in some neuropsychological tests, but there is little neuroanatomical difference. The poor outcome group show consistently impaired memory function and a tendency to reduction in temporal lobe size.
Conclusions In genetically predisposed subjects, the change from vulnerability to developing psychosis may be marked by a reduced size and impaired function of the temporal lobe.
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INTRODUCTION |
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METHOD |
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Definition of outcome categories
As previously described (Johnstone
et al, 2000), to simplify consideration of the
psychopathology as determined by PSE, a simplified classification was drawn up
on the basis of the PSE profiles whereby a score of 4=Catego S+ together with
a clinical diagnosis of schizophrenia; 3=fully rated psychotic symptom(s)
55-92 and/or fully rated behavioural item(s) 128, 129, 135, 136, 137; 2=3, but
features partially rated or features 49-54 partially or fully rated and/or
108, 109, 118, 125, 126 fully and 133 partially or fully rated; 1=none of the
above, but any other items fully rated; 0=none of the above. For the purposes
of this study, those with the best outcome were those who have never achieved
any fully rated score on any psychopathological item at PSE on any occasion of
assessment (i.e. they always scored 0 on the study score), and who, in
addition, had a record of sustained employment (or successful study towards
employment) at a level higher or at least as high in terms of the Registrar
General's ratings (Her Majesty's Stationery
Office, 1991) of social class as their parents. Furthermore, at
interview they were noted to have no abnormalities of social presentation and
gave an account of unimpaired social performance. Within the context of the
high-risk study, these individuals are referred to as the
perfects. Those with the worst outcomes have developed
schizophrenia, i.e., they achieved a score of 4 on the study score at the last
time of assessment and in addition all fulfilled the diagnostic criteria for
schizophrenia according to ICD-10 (World
Health Organization, 1993).
Comparisons
The perfects and the individuals with newly developed
schizophrenia were compared in terms of basic demographics, degree of genetic
liability, baseline neuropsychology and neuroanatomy, and in those where there
were at least two assessments before development of illness, change in
neuropsychology and change in neuroanatomy. It will be appreciated that
whereas most of the perfects provided at least two assessments
the numbers of individuals with newly developed schizophrenia were reduced by
the fact that some of them became unwell before the second assessment could be
carried out.
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RESULTS |
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Genetic liability
Genetic liability was assessed categorically in terms of the numbers of
relatives of first and second degree known to be affected but this does not,
of course, take account of the entire numbers of relatives that the subjects
had, and a continuous measure of genetic liability was devised by Professor
Pak Sham at the Institute of Psychiatry. It has been described by Lawrie
et al
(2001a) and takes
account of the total number of relatives ill and well of each subject and
their degree of relationship to the high-risk individual. On this scale, a
higher score indicates a greater degree of genetic liability. The mean score
of the perfects was 0.25 (range -0.02 to +0.70) and that of
those with new schizophrenia 0.16 (-0.01 to +0.40) but this difference is not
significant. In the perfects, 18 had a genetic liability from
the maternal side and 6 from the paternal. As far as those with new
schizophrenia are concerned, six are known to have maternal genetic liability
and five paternal. In the remaining two cases, it is possible that the
inheritance is from both sides, but we do not have complete data on both
maternal and paternal branches of these families.
Baseline measures
An extensive programme of neuropsychological tests was carried out at
baseline on all entrants to the study and these are compared between the
perfects and those with new schizophrenia. Many of these tests
showed no differences between these two groups
(Table 1). Differences that
were present were always in the direction that those who were destined to
develop schizophrenia performed less well
(Table 1). Baseline scans were
available on 23 of the perfects and 10 of those destined to develop
schizophrenia. Reasons for non-availability include pregnancy as well as
reluctance to be scanned. The results are shown in
Table 2. The significant
difference in whole brain relates to the fact that there are more males in the
newly developed schizophrenia group and where correction is made for gender
and height, this difference disappears.
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Differences between first and second assessments
We then examined the relationship between the first and second
neuropsychological assessment and compared this between the
perfects and those of the newly developed schizophrenia group on
whom we had two assessments (eight cases). The significant findings are shown
in Table 3. There is
consistently poorer performance in memory tests in those who will develop
schizophrenia and an improvement in function in the Stroop tests in those
patients but not in the perfects. All other tests were
non-significant. Similarly, we compared the difference between the first and
second scan in the perfects and those with newly developed
schizophrenia for whom two scans were available before they became ill. Most
comparisons showed no tendency to significance. In particular, the
amygdalahippocampus, which has shown clear-cut findings such that this
is smallest in the control schizophrenia group, next in the generality of the
high-risk cases and largest in the normal controls (Lawrie et al,
1999,
2001a), showed no
tendency to a difference between the perfects and those with new
schizophrenia. By contrast, there was an apparent difference in the change in
temporal lobe size between scans 1 and 2 (see
Table 4). This does not achieve
significance because of the small numbers and high variance but is of
interest.
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DISCUSSION |
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The interest of the impaired memory function that we see before the manifestation of psychosis in those destined to develop schizophrenia is enhanced by the tendency of these subjects to show a reduction in temporal lobe size over the same period because, of course, memory function is most localisable to the temporal lobe. This finding reflects our earlier result (Cosway et al, 2000) of a pre-psychotic decline in memory. We have already shown that the neuropsychological impairments in subjects at enhanced risk of schizophrenia are widespread and affect many more individuals than are likely to develop the condition (Byrne et al, 1999). We suggest that the findings may indicate that the feature that marks the change from vulnerability to developing psychosis is a reduction in size and impairment of function of the temporal lobe. Cognitive change seems to be a precursor and not a consequence of psychosis in people who have schizophrenia.
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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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