University of Oslo, Norway
Rikshospitalet University Hospital, Oslo, Norway
University of Oslo, Norway
Yale University, USA
Correspondence: Professor Svein Friis, Department of Research and Education, Division of Psychiatry, Ullevål University Hospital, N-0407 Oslo, Norway. Tel: +47 22 11 84 40; fax: +47 22 11 78 48; e-mail: svein.friis{at}psykiatri.uio.no
Declaration of interest The study was supported by the Norwegian Research Council and by NIMH 01654 (T.H.M.).
This paper is part of the Tidlig Intervensjon ved Psykoser (TIPS: Early Intervention in Psychosis) project with the following research group: T.H.M.; P.V.; S.F.; Ulrik Haahr; Jan Olav Johannessen; Tor Ketil Larsen; Ingrid Melle; Stein Opjordsmoen; Bjørn Rishovd Rund; and Erik Simonsen.
* 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 We aimed to identify the main dimensions of an assessment battery for patients with first-episode psychosis and to estimate the relationship between dimension scores and gender, age, education, diagnosis and symptoms.
Method Eight frequently used neuropsychological tests were used. We tested 219 patients 3 months after start of therapy or at remission, whichever occurred first.
Results We identified five dimensions: working memory (WM); verbal learning (VL); executive function (EF); impulsivity (lm); and motor speed (MS). Significant findings were that the MS score was higher for men, and the WM and VL scores were correlated with years of education.
Conclusions Neurocognitive function in first-episode psychosis is described by at least five independent dimensions.
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INTRODUCTION |
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In this paper we present the results of eight neuropsychological tests in a group of stabilised patients with first-episode psychosis. We used data-reducing techniques to try to identify the main dimensions of an assessment battery for a group of patients with first-episode psychosis. We wanted to answer the following questions:
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METHOD |
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Subjects
This paper is based on a sample of 219 patients. Diagnostic and demographic
characteristics and symptom scores at 3 months are presented in
Table 1.
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Because our intention was to measure neurocognitive traits and not be biased by acute effects of the psychotic episode, patients were tested 3 months after start of therapy or at remission, whichever occurred first. As seen from Table 1, this strategy seems to have been successful as the symptom level was fairly low at 3 months.
Neurocognitive tests
Eight neuropsychological tests were chosen for assessing neurocognitive
function. We selected elected tests used frequently and shown to be sensitive
for diagnostic and prognostic issues in schizophrenia. The tests were
administered by a trained test technician or approved neuropsychologist. The
tests were administered in the following order.
California Verbal Learning Test (CVLT)
The CVLT (Delis et al,
1987) measures capacity for explicit verbal memory. The test
consists of oral presentation of a 16-word shopping list (list
A) for five immediate recall trials, followed by a single presentation and
recall of a second 16-word interference list (list B). The words
on both lists consist of four items from each of four categories. Free- and
category-cued recall of list A is elicited immediately after recall of list B
(short delay) and again 20 minutes later (long delay). Finally, a recognition
trial is run, involving oral presentation of 44 shopping items
of which subjects are asked to identify the 16 list A items. Scoring of the
test involves computing several parameters of learning strategies in addition
to the number of words recalled at the various stages of learning. Based on
scores from 286 normal subjects and 113 neurological patients, Delis et
al (1988) found support
for a 6-component model of the CVLT. Subsequent research has confirmed the
multi-dimensional nature of the test (e.g.
Vanderploeg et al,
1994) and has suggested qualitative differences in the way
psychiatric patients solve the task compared with normal controls
(Kareken et al,
1996). Our study did not involve computerised scoring of test
protocols and only measures of immediate and delayed recall, recognition,
perseverations and intrusions are reported.
Backward Masking Test (BMT)
The BMT (Spaulding et al,
1981; Rund, 1993;
Green et al,
1994a,b)
assesses the earliest phases of visual information processing. A standard
target duration procedure in which pairs of digits (target stimuli) are
presented for 16.5 ms on the monitor was used. The stimuli are followed by a
patterned mask of Xs of equal duration, covering the image of the digits on
the monitor. The task consists of 30 stimulus presentations: 10 with a 33 ms
stimulus onset mask (short); 10 with a 49.5 ms stimulus onset mask (long); and
10 with no mask. The three test trials are assigned randomly. Identification
of each digit in the pair is scored separately, yielding a maximum score of 20
correct for each of the three conditions. In the present report, the no-mask
condition is excluded for the final analysis and the mean of the two mask
conditions are used in order to improve the reliability of the measure.
Finger Tapping Test (FTT)
The FTT (Lezak, 1995)
requires that the subject tap as rapidly as possible with the index finger on
a small lever, which is attached to a mechanical counter. The test is
basically a test of simple motor speed, although some degree of coordination
is required. The subject is given 5 consecutive 10-s trials with the preferred
hand and then 5 consecutive trials with the non-preferred hand. Mean number of
taps for each hand is computed. Because no lateralised motor deficits were
expected, mean score of the two hands are used in the component analysis.
Wisconsin Card Sorting Test (WCST)
The WCST (PC-version, Heaton et
al, 1993) is a test of abstract thinking that requires the
ability to form a hypothesis and check it out. The test is the most commonly
used measure of executive functioning in schizophrenia research
(Green, 1998) and provides
estimates of perseverative thinking and distractibility. The subject is asked
to sort a series of cards to one of four key cards that vary in shape, colour
and number of shapes. Feedback after each response provides information
whether or not the correct matching rule is being followed. After 10
consecutive correct sorts, the test shifts without warning to reinforce a new
sorting rule. The test terminates after 128 trials or when the subject has
completed the three correct sorting rules twice. Studies by Bell et
al (1997) and Koren et
al (1998) find evidence
for a three-factor structure in the WCST (perseveration, idiosyncratic
sorting/non-perseverative errors and failure to maintain set). The same
pattern is generally concluded in normal control subjects or subjects with
traumatic brain injuries (Wiegner &
Donders, 1999). Recent research has suggested that impaired scores
may be explained by reduced intellectual capacity rather than executive
dysfunction (Laws, 1999) but
the cause-and-effect question has still to be solved.
Controlled Oral Word Association task (COWA)
The COWA (Spreen & Strauss,
1998) is a measure of verbal fluency requiring the ability to
generate words beginning with specific letters (F, A and S) for 1 minute each.
The instructions followed are identical to those used by Spreen & Benton
(1969).
Trail Making Test (TMT)
The TMT (Lezak, 1995)
consists of two parts (A and B). Each part measures speed of visual scanning
with a motor component. Part A requires the subject to connect series of
numbered circles arrayed randomly on a sheet of paper using a pencil. In part
B the array consists of both numbers and letters, and the subject must connect
them in alternating order. Part B demands simultaneous processing capacity for
two sets of mental operations (number and letter sequencing) as well as a
rule-following instruction to alternate between the sets. It is a sensitive
measure of disturbances in both attention and executive function.
Digit Span Distractibility Test (DSDT)
In the DSDT (Oltmanns & Neale,
1975; Rund, 1983)
the subjects hear short strings of digits with and without distractors and are
asked to recall the digits in correct order. The test measures short-term
memory, selective attention and distractibility. Neutral and distractor items
are interspersed randomly. The distraction and neutral digit strings are
matched for difficulty level and reliability to avoid problems associated with
differential discrimination power (Chapman
& Chapman, 1978). The total number of correctly recalled
digits for the neutral and distractor lists is divided by a maximum score for
comparison between conditions. The score (percentage of correctly recalled
digits) for each condition is used in the analysis.
Continuous Performance Test, Identical Pairs version
(CPTIP)
The CPTIP is a multi-dimensional CPT task that systematically varies
type of stimulus, distraction and stimulus exposure time
(Cornblatt et al,
1989). Four stimuli conditions are used: numbers; shapes; numbers
presented with distractors; and shapes presented with distractors. The test
consists of both a slow and a fast condition for each of the four conditions.
Computer-generated stimuli are presented on a monitor. The subject is asked to
respond as fast as possible by lifting the index finger from a reaction time
key whenever two identical stimuli follow each other. For each condition, a
series of 150 trials are continually flashed on the screen, with stimulus
onset time of 50 ms and dark interval between stimuli of 950 ms.
A subset of measures were selected from each test to be entered as input variables in an overall second-generation principal component analysis. The selection of measures from each test was based on a combination of the theoretical foundation of the essential quality of the test, clinical experience and principal component analysis. For example, for the CPT a factor analysis indicated that the best solution was to use the average of hits, false alarms and reaction time across all conditions.
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RESULTS |
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The intercorrelations between the 17 variables are given in Table 3. As seen from this table, all four WCST variables were strongly to moderately intercorrelated, and so were the CVLT scores except for perseverations. TMT, COWA, DSDT and CPT hits were also strongly to moderately intercorrelated. CPT false alarms and CPT reaction time were moderately intercorrelated, whereas FTT was basically uncorrelated with all the other variables.
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The 17 tests were included in a factor (principal component) analysis with varimax rotation. We wanted to be sure that the factor solution could account for a considerable proportion of the variance of the included variables. We therefore chose to exclude variables with communalities <0.50. The first analysis gave six factors with eigenvalue >1. Two variables (CVLT perseverations and WCST failure to maintain sets) had communalities <0.50. We reran the analysis with the 15 remaining variables and found five factors with eigen-value >1. From this factor solution two more variables (BMT and TMT) had to be excluded because of communality <0.50. We finally ended with 13 variables, for which the factor analysis again gave five factors with eigenvalue >1. Together, the five factors explained nearly 72% of the variance. The communalities and the factor loadings are given in Table 4.
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Based on the factor analysis we chose to make an index score for each of the five dimensions. A variable was included in an index if:
We z-transformed the variables and calculated the mean of the items of each index (with negative sign if items were reversed).
This gave us the following five index scores:
For the first four indices the internal consistency could be calculated. It had a median of 0.73 (range: 0.54 (impulsivity) to 0.82 (executive function)).
The correlations between the index scores and the factor scores had a median of 0.95 (range 0.87 to 0.98), indicating that the index scores could replace the factor scores without substantial loss of information.
The intercorrelations between the index scores are shown in Table 5. As seen from the table, the five scores seemed to represent fairly independent dimensions.
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We also looked at the relationship between the dimension scores and age, gender, education, diagnosis and GAF symptom and function scores. Because of multiple comparisons and the fairly high number of patients, we chose a significance level of 0.001. No dimensions were significantly correlated with age. The difference between genders was clearly significant for motor speed (P <0.0005), with women having lower scores. Years of education were significantly correlated with working memory (=0.29, P<0.005) and verbal learning (r=0.30, P<0.0005).
We did not find any significant relations between any of the neurocognitive dimensions and core/non-core diagnosis, GAF symptom or GAF function scores.
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DISCUSSION |
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Can the CPT measure impulsivity?
The impulsivity sub-scale is a new construction. In the present sample
there was a clear inverse relationship between the CPT false alarm and the CPT
reaction time, and when combined they seemed to give a measure of impulsivity.
However, the relationship between the two variables could prove to be a more
complex one, as a comparison with normals seemed to indicate that the patients
had both a higher percentage of false alarms and a longer reaction time.
Relationship with other variables
Our second main finding was that the dimension scores were weakly related
to factors such as education, gender, age, diagnosis and symptom level. We
cannot rule out the possibility that more specific findings may be obtained in
future analyses of our data, when we go into details of the specific
neurocognitive tests and look at diagnostic subgroups and variables such as
DUP. By contrast, the five dimensions explained most of the variance in our
data-set, and the fact that the group as a whole scored below average on most
of the dimensions might imply that the level of neurocognitive functioning is
compromised even in a basically remitted sample of patients with first-episode
psychosis. If this finding is replicated in our total sample, it could
indicate that neurocognitive deficiencies are vulnerability factors for
psychosis, more than a result of the psychotic process. However, it might be
that neurocognitive function can improve over time, but that such an
improvement takes a longer time than symptomatic remission. Only a follow-up
investigation can tell us whether this is the case or not. Such a study is
under way as part of the Tidlig Intervensjon ved Psykoser (TIPS: Early
Intervention in Psychosis) project.
Limitations
Even if this study is based on a considerable number of patients, the
results have to be regarded as preliminary. Replicatory studies are needed to
demonstrate the robustness of the identified dimensions.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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