Cognitive performance in presumed obligate carriers for psychosis
Timothea Toulopoulou, PhD,
Francesca Mapua-Filbey, PhD,
Seema Quraishi, MSc and
Eugenia Kravariti, PhD
Division of Psychological Medicine, Institute of Psychiatry, London,
UK
Robin G. Morris, PhD
Department of Psychology, Institute of Psychiatry, London, UK
Colm McDonald, MRCPsych,
Muriel Walshe, BA,
Elvira Bramon, MD and
Robin M. Murray, MD
Division of Psychological Medicine, Institute of Psychiatry, London,
UK
Correspondence:
Dr Timothea Toulopoulou, Section of General Psychiatry, Box 63, Division of
Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London SE5
8AF, UK. Tel: +44 (0) 207 848 0061; fax: +44 (0) 207 701 9044; e-mail:
t.toulopoulou{at}iop.kcl.ac.uk
Declaration of interest None.
Funding detailed in Acknowledgements.
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ABSTRACT
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We report cognitive performance of a group of individuals who are likely to
have transmitted liability to psychosis to their offspring. Out of 230
relatives of patients with psychosis, 27 met our criteria for a presumed
obligate carrier, that is a non-psychotic individual who had a parent or a
sibling as well as an offspring with psychosis. The presumed obligate carriers
showed impairments in verbal memory and in visuospatial manipulations,
suggesting that these individuals transmit vulnerability for psychosis to
their offspring in terms of a disability to recall verbal information and an
impaired capacity to perceive spatial relations.
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INTRODUCTION
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Deficits in cognition may represent a genetic vulnerability for
schizophrenia because cognitive deficits, particularly in verbal learning and
memory, are found in both individuals with schizophrenia and their healthy
relatives (Byrne et al,
2003; Toulopoulou et al,
2003a,
b). A similar pattern
has emerged in bipolar disorder, with both patients and their healthy
relatives showing decreased performance in certain aspects of cognition
(Keri et al, 2001).
The distinction of psychosis into schizophrenia and bipolar disorder has been
increasingly questioned, with recent evidence suggesting that the two
disorders share some common characteristics in terms of cognition and genetic
liability (Murray et al,
2004). We explore further the idea that specific cognitive
dysfunction may be a marker of genetic susceptibility to psychosis by
assessing a very selected group of relatives derived from a large sample of
pedigrees containing multiple cases of psychosis. The relatives had passed the
normal age threshold for developing psychosis (mean age=57.2 years, s.d.=6.5)
and, although healthy themselves, the structure of their pedigrees suggests
that they are likely carriers of susceptibility genes for psychosis.
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METHOD
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Participants and procedures
Our sample comprised a subgroup of first-degree relatives (n=27)
of individuals with schizophrenia or bipolar I disorder with psychotic
features. The subgroup had been identified as being more likely to have
transmitted the liability to schizophrenia and/or bipolar disorder (obligate
carriers for psychosis) because, although healthy themselves, they have a
parent or sibling, as well as an offspring, with schizophrenia or bipolar I
disorder. The sample constitutes a sub-population of a larger cohort of
relatives of individuals with schizophrenia, bipolar disorder and controls
from the Maudsley Family Study of Psychosis (Toulopoulou et al,
2003a,
b,
2005;
McDonald et al, 2004).
The 27 presumed obligate carriers were from a total of 230 non-psychotic
relatives who were neurocognitively assessed, and derived from 27 separate
families. Eleven of these non-psychotic relatives were from families with
documented multiple cases of schizophrenia, six from families with documented
multiple cases of bipolar disorder (with at least one member with bipolar I
disorder with psychotic features), and ten from families with documented cases
of both bipolar I disorder with psychotic features and schizophrenia. After
complete description of the study to the participants, written informed
consent was obtained. The study was approved by the South London and Maudsley
NHS Trust/Institute of Psychiatry Ethical Committee (Research). A control
group comprised 32 individuals with no family history of schizophrenia or
bipolar disorder, matched for age, gender, education and handedness.
Structured diagnostic interviews were administered to all participants
using the Schedule for Affective Disorders and SchizophreniaLifetime
version (Spitzer et al,
1978). Information regarding the timing and nature of any
psychopathology was collected to enable DSMIV diagnoses to be made
(American Psychiatric Association,
1994). Eight of the presumed obligate carriers had fulfilled
criteria for a DSMIV Axis I disorder at some point in their lives, five
for a major depressive disorder, two for panic disorder and one for anxiety
disorder; one also fulfilled criteria for schizotypal personality disorder.
Three of the controls had also fulfilled criteria for a major depressive
disorder at some point in their lives. All participants were recovered and
were not in treatment at the time of assessment.
The neuropsychological tests assessed:
- IQ, as measured by a five sub-test short form (vocabulary, similarities,
comprehension, block design, object assembly) of the Wechsler Adult
Intelligence ScaleRevised (WAISR);
Wechsler, 1981; and
- verbal and visual memory and learning, as measured by (i) immediate recall,
(ii) 30-min delayed recall and (iii) saving scores of two stories and designs
two procedures taken from the Wechsler Memory Scale (WMS;
Wechsler & Stone,
1945).
The savings score was calculated using the following formula: saving score=
(delayed recall/immediate recall)x100.
Data analyses
All data were analysed with independent-samples two-tailed t-tests
except for handedness and gender where Pearsons
2 tests
were used. Analyses were performed primarily to compare the presumed obligate
carriers with the controls. We also re-ran all the analyses after excluding
all those with a history of psychiatric disorder. We report findings without
correcting for multiple testing as we consider Bonferroni corrections too
conservative since many of the tests are correlated and not independent.
Furthermore, although the presumed obligate sample is abstracted from a very
large population of relatives, the numbers are sufficiently low to warrant
initially less-stringent criteria.
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RESULTS
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The groups were matched and therefore compatible in terms of age
(t=0.66, d.f.=58, P=0.51), gender
(
2=0.06, d.f.=1, P=0.81), education
(t=0.88, d.f.=57, P=0.38) and handedness
(
2=2.5, d.f.=1, P=0.12). We found no differences
between the presumed obligate carriers for psychosis and the controls in
estimated IQ and visual memory (Table
1). However, the presumed obligate carriers scored lower than the
controls on object assembly, a task that assesses perception of visual
relationships, and on the delayed recall of verbal memory. A trend was also
found for immediate recall of verbal memory to be poorer in obligate carriers.
This became significant after excluding all those with a history of
psychiatric disorder (t=2.86, d.f.=42, P=0.007). The
differences in delayed recall of verbal memory remained significant even after
excluding all those with a history of psychiatric disorder (t=2.5,
d.f.=41, P=0.02), but the significant difference in the object
assembly disappeared after excluding those with a history of psychiatric
disorder (t=1.8, d.f.=44, P=0.08).
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Table 1 Current general intellectual and verbal and visual memory function
(means (s.d.)) for presumed obligate carriers and normal controls
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DISCUSSION
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The presumed obligate carriers for psychosis represent a group who,
although not suffering from psychosis themselves, are likely to have
transmitted to their offspring a liability to psychosis. This group had a
similar IQ and educational attainment to controls, with both groups falling
within the average range of ability. However, they performed worse on object
assembly, a test that evaluates visual motor speed and visuospatial
manipulation. Furthermore, the presumed obligate carriers showed decreased
performance in delayed recall of the logical memory sub-test, a test that
assesses long-term verbal memory. These findings remained statistically
significant when we excluded those with any Axis I disorder; moreover, when we
excluded those with an Axis I disorder differences between the immediate
recall of the logical memory sub-test also became statistically significant.
Consistent with some studies of those with bipolar disorder and their
relatives (Quraishi & Frangou,
2002) and of the relatives of those with schizophrenia
(Laurent et al, 2000),
visual memory was not impaired among our presumed obligate carrier subjects,
suggesting that this does not reflect genetic liability to psychosis.
To conclude, our data suggest that presumed obligate carriers for psychosis
transmit liability to their offspring in the form of impairments in verbal
memory and ability to perceive spatial relationships. These impairments cannot
be explained by an overall decreased level of general intellectual ability or
by deprivations related to education.
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ACKNOWLEDGMENTS
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E.B. and C.McD. were supported by research training fellowships from the
Wellcome Trust.
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Received for publication September 14, 2004.
Revision received February 17, 2005.
Accepted for publication February 19, 2005.
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