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Keywords:

  • cognitive impairment;
  • cross-national difference;
  • functional outcome;
  • schizophrenia;
  • Wechsler Adult Intelligence Scale-III

Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References
  8. Supporting Information

Aim

Patients with schizophrenia have been reported to perform worse than non-schizophrenic populations on neuropsychological tests, which may be affected by cultural factors. The aim of this study was to examine the performance of a sizable number of patients with schizophrenia on the Japanese version of the Wechsler Adult Intelligence Scale-III (WAIS-III) compared with healthy controls.

Methods

Performance on the WAIS-III was evaluated in 157 Japanese patients with schizophrenia and in 264 healthy control subjects.

Results

All IQ scores and four indices from the WAIS-III were impaired for patients with schizophrenia compared with healthy controls. Processing Speed was markedly disturbed, approximately 2 SD below that of the healthy control group. Among the 13 subtests, Comprehension (z = −1.70, d = 1.55), Digit Symbol Coding (z = −1.84, d = 1.88), and Symbol Search (z = −1.85, d = 1.77) were profoundly impaired relative to the healthy controls.

Conclusion

These results indicate that the pattern and degree of impairment, as evaluated by the WAIS-III, in Japanese patients are similar to those previously reported in English-speaking patients and that the deficits of some neuropsychological domains relevant to functional outcomes are universally characteristic of schizophrenia.

Schizophrenia is characterized by positive (e.g., delusions and hallucinations) and negative (e.g., blunted affect and withdrawal) symptoms as well as cognitive deficits.[1] Specifically, various domains of cognitive function, such as several types of memory, attention, executive function, fluency, and information processing, are impaired in patients with schizophrenia.[2-8] Cognitive disturbances are regarded as a core feature of schizophrenia and have been reported to profoundly alter everyday social functioning.[9] Most patients with schizophrenia fail to reach their expected level of cognitive functioning estimated from educational level and premorbid intelligence.[10] Cognitive impairment appears to be independent of other aspects of the symptomatology of schizophrenia, for example, positive symptoms.[11] Although other psychiatric disorders, such as bipolar disorder, also present with cognitive degradation to some degree, patients with schizophrenia exhibit more global and more severe impairment.[12-14]

Cognitive impairments in schizophrenia are also known to affect everyday functioning and social abilities.[15] For these reasons, efforts have been made to enhance cognitive functioning, such as by cognitive rehabilitation, to encourage the patients’ social adjustment.[16-18]

The Wechsler Adult Intelligence Scale-III (WAIS-III)[19] has been developed to assess intellectual ability and is frequently used in studies of cognitive abilities in patients with schizophrenia.[20-22] Several modifications have been incorporated in the update from the WAIS-Revised (previous version of the WAIS-III) into the WAIS-III. In addition to Full-Scale IQ (FSIQ), Verbal IQ, and Performance IQ, four new indices have been included: Verbal Comprehension (VC), Perceptual Organization (PO), Working Memory (WM), and Processing Speed (PS). VC is a measure of the ability to understand and provide oral explanations corresponding to certain tasks and to identify abstract concepts. PO measures non-verbal thinking, such as the manipulation of designs and pictures, fluid reasoning, and spatial processing. WM measures the ability to retain information temporarily to perform a designated task. PS measures the ability to perform given tasks quickly and efficiently based on the presented information. Upon adopting these four indices, new subtests have been included in the WAIS-III. Brief descriptions of these tasks and other tasks are provided in Table S1. The reliability of the Japanese version of the WAIS-III was confirmed through a standardization study. The reliability coefficients of the Japanese version of the WAIS-III were calculated using the split-half method and test–retest reliabilities. The mean reliability coefficients across all age groups were 0.81–0.92 for all subtests and 0.91–0.97 for indices and IQs, which showed good reliabilities.[23]

Despite the accumulation of studies, performance on the WAIS-III has only been grossly reported, and no study has clarified the comprehensive profile of the WAIS-III in populations of patients with schizophrenia. The aim of this study was to examine the performance on the Japanese version of the WAIS-III in patients with schizophrenia compared with healthy controls.

Methods

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References
  8. Supporting Information

Subjects

A total of 157 patients with schizophrenia (97 male, 60 female) and 264 healthy control subjects (153 male, 111 female) were included in this study. The patients consisted of inpatients and outpatients treated at the Department of Psychiatry, Osaka University Hospital. A consensus diagnosis, according to the DSM-IV[1] criteria, was made by experienced senior psychiatrists using the Structured Clinical Interview for DSM-IV (SCID) for schizophrenia. Psychotic symptoms (positive symptoms, negative symptoms, and general psychopathology) were evaluated using the Positive and Negative Syndrome Scale (PANSS).[24]

Healthy control subjects were recruited from the community through local advertisements at Osaka University. The healthy control subjects were evaluated psychiatrically, medically, and neurologically, and the DSM-IV-Non-Patient version of the SCID was used to exclude individuals who had current or past contact with psychiatric services or had previously received psychiatric medications.

Subjects were excluded from this study if they had neurological or medical conditions that could affect the central nervous system, such as atypical headache, head trauma with loss of consciousness, chronic lung disease, kidney disease, chronic hepatic disease, thyroid disease, cancer in an active stage, cerebrovascular disease, epilepsy, seizures, substance-related disorders, and mental retardation.

All participants provided written informed consent after the study procedures were fully explained. All procedures were conducted according to the Declaration of Helsinki and approved by the Ethical Committee of Osaka University.

Measures

The Japanese version of the WAIS-III[23] was used. It comprises three IQ categorical scores: Full Scale IQ (FSIQ), Verbal IQ, and Performance IQ. Verbal IQ consists of seven subtests: Vocabulary, Similarities, Arithmetic, Digit Span, Information, Comprehension, and Letter–Number Sequencing. Performance IQ consists of six subtests: Picture Completion, Digit Symbol Coding, Block Design, Matrix Reasoning, Picture Arrangement, and Symbol Search. The subtests of the WAIS-III are grouped into four index scores as follows: VC (Vocabulary, Similarities, and Information), PO (Picture Completion, Block Design, and Matrix Reasoning), WM (Arithmetic, Digit Span, and Letter–Number Sequencing), and PS (Digit Symbol Coding and Symbol Search) (Table S1). The raw scores of these subtests were converted to scaled scores.

Premorbid IQ was estimated using the Japanese Adult Reading Test (JART).[25, 26]

Statistical analysis

Statistical analyses were performed using spss 17.0 (spss Japan, Tokyo, Japan). Group comparisons of demographic variables were performed using t-tests or χ2-tests, as appropriate. The effects of a psychiatric diagnosis on IQ scores and the WAIS-III indices were analyzed using t-tests. To control for confounding factors, analyses of covariance (ancova) were performed with sex and JART scores as covariates (the significance level was set at two-tailed P < 0.05). A strong correlation is known to exist between JART and years of education; thus, only the former, the index of premorbid intelligence, was included as a covariate.

The premorbid and WAIS-III IQ scores and the scores of the four indices and subtests of the WAIS-III were transformed to standardized z-scores on the basis of the means and SD of the healthy control group. In addition, effect size (Cohen's d) was calculated; the mean difference between the healthy controls’ scores and the patients’ scores was divided by the pooled SD (weighted by n of each group).

Pearson's correlations were calculated for the patients to examine the correlations between clinical variables and the performance on the WAIS-III.

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References
  8. Supporting Information

Table 1 summarizes the demographic and clinical information of the subjects. Patients and healthy controls did not differ significantly in age, sex, and education years (Ps > 0.05).

Table 1. Comparisons of healthy controls and schizophrenia patients on demographic variables
 Healthy controls (n = 264)Schizophrenia patients (n = 157)StatisticsP-value
MeanSDMeanSD
  1. CPZeq, chlorpromazine equivalent of total antipsychotics; PANSS, Positive and Negative Syndrome Scale.

Age37.512.935.912.2t342.9 = 1.2310.219
Sex (Male/Female)153/11197/60χ2(1) = 0.5980.439
Education (years)14.12.013.92.5t267.9 = 0.8950.372
Age at onset24.19.4
Duration of untreated psychosis (years)2.04.1
Duration of illness (years)11.89.7
CPZeq (mg/day)589.7537.4
PANSS positive19.65.6
PANSS negative20.15.9
PANSS general psychopathology42.710.3

Table 2 presents premorbid IQ, FSIQ, Verbal IQ, Performance IQ, the four indices, and the scaled scores of the WAIS-III subtests. All the IQ scales and scores of the four indices were significantly lower for the patients with schizophrenia than for the healthy controls (all Ps < 0.001). In contrast to a relatively small decline in premorbid IQ, the patients’ FSIQ, Verbal IQ, and Performance IQ fell between 1.34 and 1.90 SD below normal values (Fig. 1, upper). Performance IQ was 8.4 points below Verbal IQ in the patient group. PS was markedly disturbed, being approximately 2 SD below the healthy control group (z = −2.16, d = 2.06). In contrast, the three other index scores demonstrated a decline of approximately 1 SD (Fig. 1, lower).

Table 2. Comparison of healthy controls and schizophrenia patients on premorbid IQ, WAIS-III IQ, indices, and subtests
 Healthy controlsSchizophrenia patientst-testancovazd
(n = 264)(n = 157)
MeanSDMeanSDtd.f.P-valueF1, 419P-value
  1. Scores of subtests were scaled scores.

  2. ancova (covariate = sex, premorbid IQ [Japanese Adult Reading Test]).

  3. WAIS-III, Wechsler Adult Intelligence Scale-III.

Premorbid IQ106.78.0101.710.25.23269.13.46 × 10−7NANA−0.620.56
Full Scale IQ108.012.485.516.614.77259.82.90 × 10−36246.55.61 × 10−44−1.821.60
Verbal IQ108.413.490.516.111.77282.12.84 × 10−26136.31.92 × 10−27−1.341.24
Performance IQ105.812.482.116.315.67263.51.54 × 10−39238.86.45 × 10−43−1.901.69
Indices           
Verbal Comprehension106.113.493.215.78.57287.36.47 × 10−1649.67.94 × 10−12−0.960.90
Perceptual Organization105.313.286.317.911.56256.73.77 × 10−25121.46.02 × 10−25−1.441.26
Working Memory105.715.688.216.510.75314.53.74 × 10−2390.11.77 × 10−19−1.121.10
Processing Speed106.813.178.414.819.80297.13.18 × 10−56356.46.61 × 10−58−2.162.06
Subtests           
Vocabulary11.43.08.83.28.13310.51.06 × 10−1436.53.36 × 10−9−0.860.83
Similarities11.02.48.53.18.75272.02.26 × 10−1651.43.46 × 10−12−1.030.94
Information10.82.99.03.05.97314.06.58 × 10−911.57.60 × 10−4−0.620.61
Comprehension12.22.87.53.414.56275.85.07 × 10−36191.83.75 × 10−36−1.701.55
Arithmetic11.63.08.03.211.60315.03.76 × 10−26113.81.18 × 10−23−1.211.19
Digit Span10.83.29.33.05.00342.29.10 × 10−712.25.29 × 10−4−0.490.50
Letter–Number Sequencing10.73.27.53.39.71319.11.08 × 10−1968.12.03 × 10−15−1.000.99
Picture Arrangement10.53.47.23.79.22304.95.01 × 10−1862.12.91 × 10−14−0.980.95
Picture Completion10.42.67.63.48.82261.51.70 × 10−1664.88.80 × 10−15−1.080.95
Block Design11.03.18.23.78.18281.29.89 × 10−1553.31.48 × 10−12−0.940.86
Matrix Reasoning11.42.87.83.510.84271.45.66 × 10−23101.41.69 × 10−21−1.281.16
Digit Symbol Coding11.32.86.12.718.95343.22.49 × 10−55294.12.86 × 10−50−1.841.88
Symbol Search11.32.86.23.117.10299.43.33 × 10−46262.14.37 × 10−46−1.851.77
figure

Figure 1. Scores of premorbid IQ and the Wechsler Adult Intelligence Scale-III IQ and four indices. (image) Controls, (image) Patients. Each score was transformed to standardized z-scores based on the means and SD of the healthy controls. Therefore, the means of the healthy controls are represented by the zero line (SD = 1).

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Performance on the subtests revealed that scores fell significantly below normal (Ps < 0.001). Among the 13 subtests, the deficits of Information (z = −0.62, d= 0.61) and Digit Span (z = −0.49, d = 0.50) were relatively mild, whereas Comprehension (z = −1.70, d = 1.55), Digit Symbol Coding (z = −1.84, d = 1.88), and Symbol Search (z = −1.85, d = 1.77) were markedly impaired relative to the healthy controls (Fig. 2).

figure

Figure 2. Wechsler Adult Intelligence Scale-III subtests scores. (image) Controls, (image) Patients. The subtest scores were transformed to standardized z-scores based on the means and SD of the healthy controls.

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Correlations between clinical variables and WAIS-III indices are shown in Table 3. Age at onset, duration of untreated psychosis, and duration of illness were not correlated with the indices. Correlations between antipsychotic medications and indices were mild to moderate. Positive symptoms were partly correlated with the indices. Correlations between negative symptoms and the indices were moderately correlated. General psychopathology was mildly correlated with the indices. Correlations between clinical variables and the WAIS-III subtests are presented in Table S2 (Supporting Information), representing similar results of the indices.

Table 3. Correlations between clinical variables and WAIS-III indices in patients with schizophrenia
 FSIQVIQPIQVCPOWMPS
  1. *P < 0.05, ** P < 0.01, *** P < 0.001 (2 tailed).

  2. CPZeq, chlorpromazine equivalent of total anti psychotics; FSIQ, Full-Scale IQ; PANSS, Positive and Negative Syndrome Scale; PIQ, Performance IQ; PO, Perceptual Organization; PS, Processing Speed; VC, Verbal Comprehension; VIQ, Verbal IQ; WAIS-III, Wechsler Adult Intelligence Scale-III; WM, Working Memory.

Age at onset0.0790.0840.0540.0450.0160.0100.025
Duration of untreated psychosis0.018−0.0200.054−0.0700.030−0.034−0.015
Duration of illness0.0580.0440.0590.0340.0270.0230.123
CPZeq (mg/day)−0.311***−0.267***−0.325***−0.218**−0.320***−0.352***−0.251**
PANSS positive−0.184*−0.151−0.199*−0.094−0.204*−0.152−0.084
PANSS negative−0.434***−0.428***−0.379***−0.381***−0.327***−0.352***−0.312***
PANSS general psychopathology−0.290***−0.268***−0.271***−0.207**−0.249**−0.239**−0.190*

Discussion

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References
  8. Supporting Information

This study evaluated the complete profile of the performance of a sizable number of subjects with schizophrenia on the Japanese version of WAIS-III. Performances on the subtests associated with functional outcome and sensitivity to language systems were closely examined.

Profile of the Japanese version of the WAIS-III

Generally, patients with schizophrenia performed significantly worse on the Japanese WAIS-III, as was reported by previous studies with the English version of the WAIS-III,[20, 27] even though the patients were demographically equivalent to the normal controls. Impairment of the patients’ premorbid IQ was relatively mild (z = −0.62, d = 0.56), whereas the performance on the FSIQ was severely disturbed (z = −1.82, d = 1.60), indicating a large decrement from the expected level of cognitive functioning.[10] Consistent with previous studies,[22, 28, 29] Performance IQ tended to be below Verbal IQ in patients with schizophrenia. VC was most preserved (z = −0.96, d = 0.90), followed by WM (z = −1.12, d = 1.10) and PO (z = −1.44, d = 1.26). PS was markedly impaired in schizophrenic patients (z = −2.16, d = 2.06). Previous studies have reported that VC and PS were associated with community functioning and vocational functioning.[27, 30] Specifically, PS is one of the most negatively affected cognitive abilities in schizophrenia.[6, 31, 32]

Generally, scores of the 13 subtests were slightly lower than those of a previous study;[33] however, the profile pattern in the patients studied here was similar to those reported in the literature. Among the 13 subtests, Comprehension (z = −1.70, d = 1.55), Digit Symbol Coding (z = 1.84, d = 1.88), and Symbol Search (z = −1.85, d = 1.77) were severely impaired, as was shown in studies using the WAIS-R.[6] Comprehension and Digit Symbol Coding were closely associated with functional outcome in patients with schizophrenia and first-episode psychosis.[27, 30, 34] The Information (z = −0.62, d = 0.61) and Digit Span (z = −0.49, d = 0.50) subtests were relatively preserved, consistent with a previous study.[21, 35] The former subtest is considered to reflect crystallized intelligence, which may not be largely affected by the illness.

Negative symptoms and general psychopathology were moderately correlated with all indices of WAIS-III, as reported in WAIS-R.[36] Although the association between cognitive performance and psychiatric symptoms are consistent in a number of studies, whether there is a causal link between these variables remains unclear.[37] Further investigation may provide a comprehensive model for key linkages to cognition and symptoms.

In summary, the results obtained in this study are consistent with previous studies of the English version of the WAIS-III in patients with schizophrenia.[20, 27, 33]

Performance in letter–number sequencing

Generally, the WAIS-III subtests are designed in a culture- or language-independent manner and thus require some minor adjustments in translations. Letter–Number Sequencing needs a relatively large modification to equalize the cognitive demands among different language users. The cognitive demand for the manipulation of letters is considered to be more complex in the Japanese kana (a two-dimensional structure by vowels and consonants, approximately 50 letters) than in the English alphabet (a one-dimensional sequence of phonemes, 26 letters). Consequently, the Japanese version of Letter–Number Sequencing was modified to reduce the level of difficulty by adding extra practice tasks and restricting the types of letters used in the task.[23] In the current study, the degree of deficits in Letter–Number Sequencing was similar to that reported in a previous study for English users.[33] This result indicates that the Japanese version of Letter–Number Sequencing is adequately adjusted, in terms of difficulty level, compared with the English version.

In addition to the WAIS-III, the Letter–Number Sequencing task is also included in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). Although the method of Letter–Number Sequencing in the Japanese version of the MCCB partially differs from that of the Japanese version of the WAIS-III, Japanese kana have also been adopted in the MCCB, and the letters have been selected in a similar manner.[38] Kaneda et al. preliminarily examined the validity of the Japanese version of the MCCB.[39] Further investigation will be needed to adequately validate the Japanese WAIS-III version of Letter–Number Sequencing.

Limitations

The present study had several limitations that should be noted. Although all of the patients had FSIQ of 70 or more to exclude the possibility of mental retardation, some patients may have had difficulty completing the WAIS-III. Therefore, the results of the current study might only be relevant to a subgroup of patients with relatively higher-level capacities. Cognitive impairment in patients with schizophrenia can be affected by combining multiple antipsychotic medications, negatively influencing cognition in a dose-dependent manner.[40] However, cognitive impairments were also observed in drug-naïve patients with schizophrenia.[41] Therefore, cognitive impairment could be a core feature of patients with schizophrenia. This study was cross-sectional, and treatment response and temporal changes in performance were not considered. Future longitudinal studies will be needed to investigate the role of cognitive functioning for the treatment outcome and social functioning. Despite these limitations, this study was the first to examine the performance of schizophrenic patients on the Japanese version of WAIS-III and compare that performance with that of normal controls.

The current study has reported the profile of the performance on the Japanese version of WAIS-III in a sizable number of patients with schizophrenia and in healthy control subjects. Analyses of the results indicate that the profile and degree of cognitive impairment of Japanese patients are similar to those of English-speaking patients.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References
  8. Supporting Information

We would like to thank all of the individuals who participated in this study. This work was supported in part by research grants from the Japanese Ministry of Health, Labor and Welfare (H22-seishin-ippan-001); the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) KAKENHI (22390225-Grant-in-Aid for Scientific Research (B), 23659565-Grant-in-Aid for Challenging Exploratory Research and 221S0003-Grant-in-Aid for Scientific Research on Innovative Areas [Comprehensive Brain Science Network]); and the Japan Foundation for Neuroscience and Mental Health. Additionally, this work was supported by the Strategic Research Program for Brain Sciences (Development of Biomarker Candidates for Social Behavior) of the Ministry of Education, Culture, Sports, Science, and Technology, Japan. No additional external funding was received for this study. The funders had no role in the study design, data collection and analyses, decision to publish, or preparation of the manuscript. All authors declare that they had no conflict of interest.

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  6. Acknowledgments
  7. References
  8. Supporting Information
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Supporting Information

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References
  8. Supporting Information
FilenameFormatSizeDescription
pcn12165-sup-0001-tableS1.doc38K

Table S1. Subtests descriptions and indices of the Wechsler Adult Intelligence Scale-III.

pcn12165-sup-0002-tableS2.doc42K

Table S2. Correlations between clinical variables and Wechsler Adult Intelligence Scale-III subtests in patients with schizophrenia.

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