SEARCH

SEARCH BY CITATION

Keywords:

  • cognitive function;
  • extrapyramidal symptom;
  • schizophrenia

Abstract

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

Aims

The purpose of the present study was to investigate the correlation between cognitive function and clinical variables in people with schizophrenia.

Methods

The subjects were 61 stabilized outpatients with schizophrenia (DSM-IV). Their mean age was 40.1 (SD = 12.2) years. All subjects gave written informed consent to participate in the research. Cognitive function was evaluated using the Brief Assessment of Cognition in Schizophrenia. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, and the Drug-Induced Extrapyramidal Symptoms Scale.

Results

The Positive and Negative Syndrome Scale Negative syndrome score was significantly correlated with verbal memory score (r = −0.37, P < 0.01), working memory score (r = 0.38, P < 0.01), attention and speed of information processing score (r = −0.51, P < 0.01), verbal fluency score (r = −0.39, P < 0.01), and composite score (r = −0.54, P < 0.01). In addition, the Drug-Induced Extrapyramidal Symptoms Scale score was significantly correlated with attention and speed of information processing (r = −0.45, P < 0.01), and composite score (r = −0.41, P < 0. 01). Dose of antipsychotics and anti-Parkinson drugs was not significantly correlated with the Brief Assessment of Cognition in Schizophrenia scores.

Conclusions

These results indicate that cognitive dysfunction of people with schizophrenia might be associated with negative and drug-induced extrapyramidal symptoms, suggesting that their minimization would be important for improving cognitive dysfunction.

COGNITIVE DYSFUNCTION IS thought to be a core feature of schizophrenia.[1] It has recently been the subject of great attention because it can lead to poor social functioning[2] and impair patients' quality of life (QOL).[3, 4] Several studies have investigated the cognitive dysfunction of schizophrenia patients using various neuropsychological tests and found that their cognitive functions were of the order of one to two SD below the mean of healthy controls in several cognitive dimensions, in particular memory, attention, verbal fluency and executive function.[1, 2, 5-9]

Clinical factors associated with cognitive dysfunction of schizophrenia patients have also been studied. Thurston-Snoha et al.[10] reported that executive function measured by the Wisconsin Card Sorting Test (WCST) was inversely related to negative symptom. Winograd-Gurvich et al.[11] found that negative symptom was related to poor working memory. Hughes et al.[12] reported that severity of negative symptom predicted poor neuropsychological performance on verbal fluency and memory task. Several researchers have reported that antipsychotics and anti-Parkinson drugs can impair cognitive function.[13, 14] In addition, Wciórka et al.[15] found that age, duration of illness and the number of previous hospitalizations significantly correlated with cognitive dysfunction.

However, there are questions regarding the validity of the tests used in these studies because they are not standardized for use with schizophrenia. Additionally, in many previous studies, researchers assessed cognitive function using only one or a few neuropsychological tests. This means that cognitive functions were not assessed comprehensively in the studies. Therefore, a more comprehensive assessment is needed to investigate in detail the relation between cognitive function and clinical factors in schizophrenia patients.

Keefe et al. constructed the Brief Assessment of Cognition in Schizophrenia (BACS)[7] to more comprehensively and briefly evaluate the cognitive function of schizophrenia patients. The BACS assesses the six neurocognitive domains of verbal memory, working memory, motor speed, verbal fluency, attention and speed of information processing, and executive function. These six domains are reported to be severely disturbed in schizophrenia patients. The BACS is easy to use because it takes only half an hour to administer. Several neuropsychological batteries, such as the Cambridge Neuropsychological Test Automated Battery,[16] the Cognitive Drug Research Cognitive Assessment System,[17] the CogTest Battery,[18] and the Measurement and Treatment Research to Improve Cognition in Schizophrenia consensus cognition battery[19] can assess cognitive function comprehensively. However, they take more than 1 h to administer, which may be a significant burden to subjects. Thus, we chose the BACS as a cognitive test battery in the present study.

In many previous studies focusing on the correlation between cognitive function and clinical factors, subjects included patients with schizoaffective disorder or schizoid personality disorder besides patients with schizophrenia.[20, 21] In addition, many researchers investigated schizophrenia patients in a variety of stages, which might lead to uncertain findings. As cognitive dysfunction is observed not only in schizophrenia patients but also in other psychiatric disorders, such as mood disorders or anxiety disorders,[6, 22] it is thought that cognitive function can be influenced by various clinical states. Therefore, it seems to be important to choose only schizophrenia patients in a certain stage as subjects for an improved investigation.

Thus, in the present study, we chose clinically stabilized outpatients with schizophrenia who did not have other psychiatric disorders, and explored the relations between cognitive function and clinical factors.

Methods

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

Subjects

Sixty-one outpatients with a DSM-IV diagnosis of schizophrenia were recruited from the Department of Psychiatry, Tokushima University Hospital, between 1 October 2007 and 31 March 2009. Patients with any organic central nervous system disorders, epilepsy, mental retardation, substance-related disorders or severe somatic disorders were excluded. All the subjects gave written consent to participate in this study. The study was approved by the Ethics Committee of the University of Tokushima.

All subjects were Japanese, of whom 33 were men and 28 women. Their mean age was 40.1 years (SD = 12.2), ranging from 20 to 60 years old. All had been receiving regular outpatient treatment and had not been hospitalized in the previous 6 months, including 13 who had never received inpatient treatment. Forty-five subjects had followed the same antipsychotic regimen for at least 6 months before recruitment. Although 16 had had slight changes in their regimen, they were judged as clinically stabilized by the treating psychiatrists.

Procedure

To assess cognitive function, we used the BACS. It has been developed for clinical trials with a brief battery of tests for measuring the cognitive functions of schizophrenia patients. The domains of cognitive functions evaluated by the BACS are verbal memory, working memory, motor speed, verbal fluency, attention and speed of information processing, and executive function. It is fully portable,[7, 23, 24] and it was already reported that the Japanese version was fully reliable to evaluate the cognitive functions of schizophrenia patients.[24, 25] In the present study, data were collected using the Japanese version of the BACS by clinical psychologists who were experienced and well trained for the use of the test.

Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS). It was originally designed to assess the positive and negative symptoms and the general psychopathology in schizophrenia.[26, 27] The score ranges from 30 to 210 for the global score, with higher score indicating a greater level of symptom severity. Interviews were conducted by experienced psychiatrists according to the Evaluation Manual for the PANSS.[27]

Depressive symptom was specifically assessed with the Calgary Depression Scale for Schizophrenia (CDSS).[28] The scale was specifically developed to distinguish depressive symptom from positive symptom, negative symptom or antipsychotic-induced side-effects. It is a nine-item questionnaire (depression, hopelessness, self-deprecation, guilty ideas of reference, pathological guilt, morning depression, early awakening, suicidality, and observed depression), with higher scores corresponding to greater levels of depression. The reliability and validity of the Japanese version was verified by Kaneda et al.[29]

Drug-induced extrapyramidal adverse effects were assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), which is composed of nine items, including eight individual parameters (gait, bradykinesia, sialorrhea, muscle rigidity, tremor, akathisia, dystonia, and dyskinesia) and one global severity scale. It uses a 5-point scale that ranges from 0 to 4, with higher scores indicating greater levels of extrapyramidal adverse effects. In this study, the sum of eight individual parameters was used as the index of the extrapyramidal symptoms. Ratings were performed according to the Rater's Manual for the DIEPSS.[30]

Statistical analysis

Spearman rank correlation coefficients were calculated to study the correlation between the BACS and other clinical variables, including the PANSS Positive and Negative syndrome scores, the CDSS score, the DIEPSS score, age, years of education, duration of illness, number of hospitalizations, dose of antipsychotics, and dose of anti-Parkinson drugs. As several data showed non-normal distribution, we used non-parametric test for correlation analysis. The statistical significance was regulated for multiple comparisons by Bonferroni corrections. Statistical analyses were carried out with spss, version 14.0J for Windows (spss Japan, Tokyo, Japan).

Results

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

Table 1 presents the demographic characteristics and clinical variables of the subjects.

Table 1. Demographic characteristics of subjects (mean ± SD)
  1. Chlorpromazine equivalent. Biperiden equivalent.

  2. BACS, Brief Assessment of Cognition in Schizophrenia; CDSS, Calgary Depression Scale for Schizophrenia; DIEPSS, Drug-Induced Extrapyramidal Symptoms Scale; PANSS, Positive and Negative Syndrome Scale.

n (men/women) 61 (33/28)
Age (years) 40.1 ± 12.2
Duration of illness (years) 15.5 ± 9.3
Number of hospitalizations 2.1 ± 2.3
Dose of antipsychotics (mg/day) 642.3 ± 501.7
Dose of anti-Parkinson drugs (mg/day) 2.4 ± 2.4
Type of schizophrenia (n)Paranoid38
Residual13
Disorganized5
Catatonic4
Undifferentiated1
Marital state (n)Married6
Never married52
Divorced2
Widowed1
Social state (n)Full-time14
Part-time8
No employment39
PANSSTotal61.3 ± 16.4
Positive syndrome13.4 ± 4.8
Negative syndrome18.0 ± 6.6
General psychopathology29.9 ± 7.9
CDSS (Total) 3.2 ± 3.1
DIEPSS (Total) 1.6 ± 2.4
BACSVerbal memory33.6 ± 13.1
Working memory17.1 ± 6.4
Motor speed66.9 ± 18.5
Attention and speed of information processing50.8 ± 12.9
Verbal fluency37.3 ± 10.6
Executive function14.9 ± 5.3
Composite score−1.4 ± 1.0

The performance of subjects on each BACS test was standardized by creating z-scores whereby the healthy control mean was set to zero and the SD set to one. The control data used to compare the performance of our subjects with that of healthy controls were collected by Kaneda et al.[25] The mean age of healthy control subjects (n = 76) was 38.3 years (SD = 14.2). Z-scores calculated based on the mean scores of healthy control subjects were −1.68 (SD = 1.28) for verbal memory, −1.23 (SD = 1.78) for working memory, −1.81 (SD = 1.64) for motor speed, −1.66 (SD = 1.19) for attention and speed of information processing, −0.82 (SD = 1.11) for verbal fluency, and −1.20 (SD = 1.95) for executive function. In a second step, the BACS composite score was calculated to provide a measure for overall cognitive performance by averaging Z-scores of six primary measures.

Table 2 shows the result of the correlation analyses between the BACS domain scores and clinical variables (age, years of education, duration of illness, number of hospitalizations, dose of antipsychotics, and dose of anti-Parkinson drugs). Attention and speed of information processing score was significantly correlated with age. However, there was no other significant correlation between the BACS domain scores and clinical variables.

Table 2. Correlation between BACS and clinical indices
 BACS
Verbal memoryWorking memoryMotor speedAttention and speed of information processingVerbal fluencyExecutive functionComposite score
  1. *P < 0.05, Spearman rank correlations (Bonferroni correction).

  2. BACS, Brief Assessment of Cognition in Schizophrenia.

Age−0.271−0.056−0.212−0.356*0.098−0.190−0.100
Education0.3300.1410.1950.2970.1210.1830.272
Duration of illness−0.228−0.013−0.168−0.2710.186−0.022−0.007
Number of hospitalizations−0.0440.166−0.088−0.0430.055−0.0140.049
Dose of antipsychotics−0.267−0.119−0.239−0.2970.061−0.298−0.182
Dose of anti-Parkinson Drugs−0.196−0.136−0.010−0.1370.115−0.239−0.065

Table 3 illustrates the correlations between the BACS and clinical symptom scales (the PANSS Total score, the PANSS Positive syndrome score, the PANSS Negative syndrome score, the PANSS General psychopathology score, the CDSS score, and the DIEPSS score). The PANSS total score was significantly correlated with verbal memory, attention and speed of information processing, and composite score. The PANSS Negative syndrome score was significantly correlated with verbal memory, working memory, attention and speed of information processing, verbal fluency, and composite score. In addition, the DIEPSS score showed significantly negative correlation with attention and speed of information processing and composite score. On the other hand, the PANSS Positive syndrome score and the CDSS score had no significant correlation with the BACS scores.

Table 3. Correlation between BACS and clinical symptoms
 BACS
Verbal memoryWorking memoryMotor speedAttention and speed of information processingVerbal fluencyExecutive functionComposite score
  1. *P < 0.05; **P < 0.01, Spearman rank correlations (Bonferroni correction).

  2. BACS, Brief Assessment of Cognition in Schizophrenia; CDSS, Calgary Depression Scale for Schizophrenia; DIEPSS, Drug-Induced Extrapyramidal Symptoms Scale; PANSS, Positive and Negative Syndrome Scale.

PANSS       
Total−0.342*−0.252−0.166−0.375*−0.229−0.153−0.350*
Positive syndrome−0.241−0.091−0.166−0.226−0.006−0.094−0.151
Negative syndrome−0.379*−0.384*−0.316−0.509**−0.389*−0.228−0.541**
General psychopathology−0.189−0.142−0.074−0.226−0.195−0.107−0.229
CDSS−0.1110.106−0.034−0.0910.1230.0720.084
DIEPSS−0.275−0.318−0.174−0.448**−0.318−0.293−0.411*

Discussion

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

In the present study, Z-scores for all tests of the BACS ranged from −0.82 to −1.81, which suggests that even symptomatically stabilized outpatients who are able to live in the community have prominent cognitive dysfunction. Based on reports that cognitive dysfunction is associated with lowered social function and quality of life,[3, 4, 31] treatment for improving cognitive dysfunction will be a fundamental requirement.

There are many studies investigating the relation between cognitive dysfunction and negative symptoms. For example, Klingberg et al.[32] assessed cognitive function with some neuropsychological tests and reported that there was a weak correlation between cognitive dysfunction and negative symptoms. Villalta-Gil et al.[33] found that schizophrenia patients who had serious negative symptoms expressed lowered performance of verbal memory tasks, attention tasks and operative memory tasks. It is also reported that severity of negative symptoms was associated with audible attention problem[34] and lowered performance of the Digit Span task.[35] On the other hand, Daban et al.[36] investigated two groups that had different symptom severity and reported that there was no significant difference in attention performance, suggesting that psychotic symptoms, including negative symptoms, would not influence attention performance. In many previous studies, the illness stage of the subjects was not controlled, and researchers used a variety of diverse tests, which led to complex findings and made it difficult to compare the results. To solve the problem, we recruited schizophrenia patients who had been symptomatically stabilized as subjects; and we used the BACS because it has the overall index called composite score to assess overall cognitive function of schizophrenia patients. We found moderate correlation between the BACS composite score and the PANSS Negative syndrome score. This result clearly shows that cognitive dysfunction is more strongly related to negative symptoms than previous studies reported. Our findings also seem to partly support the findings from the studies of Bozikas et al. and Linfsbergs et al. in terms of the relation between negative symptom and cognitive dysfunction in the attention domain.

We also found another important finding that there was a significant correlation between the DIEPSS score and the BACS composite score and attention and speed of information processing score. Sachdev et al.[37] investigated cognitive function in chronic schizophrenia patients with akathisia and found that they had lowered scores of Symbol Digits Modalities Test and Trail Making Test. Palmer et al.[38] reported a significant correlation between drug-induced extrapyramidal symptoms and global neuropsychological scores. However, all the subjects of their study were older than 45 years old, and the subjects had severe dyskinesia. Those factors might have a negative influence on a performance of neuropsychological tests. Although it is reported that anti-Parkinson drugs have negative effects on attention and verbal memory,[13] there was no significant correlation between the dose of anti-Parkinson drugs and any scores of the BACS. These findings suggest that there is a possibility that drug-induced extrapyramidal symptoms may be directly related to poor cognitive performance. In spite of the fact that the score of the DIEPSS of our subjects was very low (average score of the DIEPSS = 1.6), there was a significant correlation between cognitive dysfunction and drug-induced extrapyramidal symptoms. This means that even relatively mild extrapyramidal symptoms due to antipsychotics can lead to poor cognitive performance, especially in the domain of attention and speed of information processing. The finding suggests that efforts should be made to minimize drug-induced extrapyramidal symptoms in daily practice in order to improve cognitive dysfunction of schizophrenia patients.

In the present study, cognitive dysfunction was independent of age, length of illness duration, medication, positive symptoms, general psychopathology symptoms and depressive symptoms. Although there are some reports that age affects cognitive function,[15] some studies using the BACS do not show a significant correlation between age and the composite score.[39, 40] Our study shows that age correlates significantly with the attention and speed of information processing but not with the composite score. Inconsistent with the previous findings showing that depressive symptoms had significant correlation with cognitive dysfunction in schizophrenia patients, there was no significant correlation between them in the present study. A possible reason for the[41, 42] inconsistency is the fact that the depressive symptom scores of our subjects were relatively low. It is also suggested that as scores of cognitive function obtained from the present study are not influenced by depressive symptoms, they may reflect relatively pure cognitive function of schizophrenia patients.

The current study has some limitations. As the sample size was relatively small, we did not have an opportunity to investigate subgroups of patients. In addition, the PANSS scores showed relatively mild psychotic symptoms in our patients, who may therefore be unrepresentative of schizophrenia patients generally. However, it was evident that cognitive dysfunction is a major problem even in schizophrenia patients who have relatively mild and stabilized psychotic symptoms and are able to live in the community.

In conclusion, our results suggest that cognitive dysfunction in people with schizophrenia is associated with negative and drug-induced extrapyramidal symptoms, and that minimizing them may be important to improve cognitive dysfunction.

Acknowledgments

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

We wish to thank Mr Hiromasa Adachi and Ms Ayaka Nouchi for their help with data processing. This work was supported in part by a Health and Labor Science Research Grant from the Japanese Ministry of Health, Labor and Welfare, and Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The authors declare no conflict of interests.

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Results
  5. Discussion
  6. Acknowledgments
  7. References
  • 1
    Kraus MS, Keefe RSE. Cognition as an outcome measure in schizophrenia. Br. J. Psychiatry 2007; 191: 4651.
  • 2
    Keefe RSE, Poe M, Walker TM, Harvey PD. The Relationship of the Brief Assessment of Cognition in Schizophrenia (BACS) to functional capacity and real-world functional outcome. J. Clin. Exp. Neuropsychol. 2006; 28: 260269.
  • 3
    Yamauchi K, Aki H, Tomotake M et al. Predictors of subjective and objective quality of life in outpatients with schizophrenia. Psychiatry Clin. Neurosci. 2008; 62: 404411.
  • 4
    Ueoka Y, Tomotake M, Tanaka T et al. Quality of life and cognitive dysfunction in people with schizophrenia. Prog. Neuropsychopharmacol Biol. Psychiatry 2011; 35: 5359.
  • 5
    Heinrichs RW, Zakzanis KK. Neurocognitive deficits in schizophrenia; A quantitative review of the evidence. Neuropsychology 1998; 12: 426445.
  • 6
    Glahn DC, Bearden CE, Barguil M et al. The neurocognitive signature of psychotic bipolar disorder. Biol. Psychiatry 2007; 62: 910916.
  • 7
    Keefe RSE, Goldberg TE, Harvey PD, Gold JM, Poe MP, Coughenour L. The Brief Assessment of Cognition in Schizophrenia: Reliability, sensitivity, and comparison with a standard neurocognitive battery. Schizophr. Res. 2004; 68: 283297.
  • 8
    Matsuoka H. Clinical issues of cognitive dysfunction in schizophrenia. Jpn J. Clin. Psychopharmacol. 2007; 10: 11531160 (in Japanese).
  • 9
    Savilla K, Kettler L, Galletly C. Relationships between cognitive deficits, symptoms and quality of life in schizophrenia. Aust. N. Z. J. Psychiatry 2008; 42: 496504.
  • 10
    Thurston-Snoha BJ, Lewine RR. Intact Wisconsin Card Sorting Test performance: Implications for the role of executive function in schizophrenia. Br. J. Clin. Psychol. 2007; 46: 361369.
  • 11
    Winograd-Gurvich C, Fitzgerald PB, Georgiou-Karistianis N, Millist L, White O. Inhibitory control and spatial working memory: A saccadic eye movement study of negative symptoms in schizophrenia. Psychiatry Res. 2008; 157: 919.
  • 12
    Hughes C, Kumari V, Soni W et al. Longitudinal study of symptoms and cognitive function in chronic schizophrenia. Schizophr. Res. 2003; 59: 137146.
  • 13
    Minzenberg MJ, Poole JH, Benton C, Vinogradov S. Association of anticholinergic load with impairment of complex attention and memory in schizophrenia. Am. J. Psychiatry 2004; 161: 116124.
  • 14
    Peuskens J, Demily C, Thibaut F. Treatment of cognitive dysfunction in schizophrenia. Clin. Ther. 2005; 27: 2537.
  • 15
    Wciórka J, Bembenek A, Hintze B, Kühn-Dymecka A. Schizophrenic disorders – does cognitive dysfunction relate to characteristics of course and psychopathology of the illness? Psychiatr. Pol. 2006; 40: 867884.
  • 16
    Robbins TW, James M, Owen AM, Sahakian BJ, McInnes L, Rabbitt PM. A neural systems approach to the cognitive psychology of aging: Studies with CANTAB on a large sample of the normal elderly population. In: Rabbitt PM (ed.). Methodology of Frontal and Executive Function. Lawrence Erlbaum Associates, Hove, 1996; 215238.
  • 17
    Hunter R, Cameron S, Perks S, Wesnes K. The cognitive profile of unmedicated schizophrenic patients in relation to controls. J. Psychopharmacol. 1997; 11 (Suppl.): A74.
  • 18
    Cogtest plc. Cogtest(tm): Computerised Cognitive Battery for Clinical Trials. 2002. [Cited 8 Nov 2002.] Available from URL: http://www.cogtest.com
  • 19
    Nuechterlein KH, Barch DM, Gold JM, Goldberg TE, Green MF, Heaton RK. Identification of separable cognitive factors in schizophrenia. Schizophr. Res. 2004; 72: 2939.
  • 20
    Twamley EW, Woods SP, Zurhellen CH et al. Neuropsychological substrates and everyday functioning implications of prospective memory impairment in schizophrenia. Schizophr. Res. 2008; 106: 4249.
  • 21
    Tschacher W, Dubouloz P, Meier R, Junghan U. Altered perception of apparent motion in schizophrenia spectrum disorder. Psychiatry Res. 2008; 159: 290299.
  • 22
    Boldrini M, Del Pace L, Placidi GP et al. Selective cognitive deficits in obsessive-compulsive disorder compared to panic disorder with agoraphobia. Acta Psychiatr. Scand. 2005; 111: 150158.
  • 23
    Bralet MC, Falissard B, Neveu X, Lucas-Ross M, Eskenazi AM, Keefe RS. Validation of French version of the BACS (the brief assessment of cognition in schizophrenia) among 50 French schizophrenia patients. Eur. Psychiatry 2007; 22: 365370.
  • 24
    Kaneda Y, Sumiyoshi T, Keefe R, Ishimoto Y, Numata S, Ohmori T. Brief assessment of cognition in schizophrenia: Validation of the Japanese version. Psychiatry Clin. Neurosci. 2007; 6: 602609.
  • 25
    Kaneda Y, Sumiyoshi T, Nakagome K et al. The Brief Assessment of Cognition in Schizophrenia Japanese version (BACS-J). Seishin Igaku (Clinical Psychiatry) 2008; 50: 913917 (in Japanese).
  • 26
    Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr. Bull. 1987; 13: 261276.
  • 27
    Kay SR, Opler LA, Fiszbein A. Positive and Negative Syndrome Scale (PANSS) Rating Manual. Seiwa Pub, Tokyo, 1991.
  • 28
    Addington D, Addington J, Maticka-Tyndale E. Assessing depression in schizophrenia: The Calgary Depression Scale. Br. J. Psychiatry 1993; 22: 3944.
  • 29
    Kaneda Y, Fujii A, Ohmori T. Psychometric properties of the Japanese version of the Calgary Depression Scale for Schizophrenics. J. Nerv. Ment. Dis. 2000; 188: 237239.
  • 30
    Inada T. Evaluation and Diagnosis of Drug-Induced Extrapyramidal Symptoms: Commentary on the DIEPSS and Guide to Its Usage. Seiwa Pub, Tokyo, 1996 (in Japanese).
  • 31
    Matsui M, Sumiyoshi T, Arai H, Higuchi Y, Kurachi M. Cognitive functioning related to quality of life in schizophrenia. Prog. Neuropsychopharmacol Biol. Psychiatry 2008; 32: 280287.
  • 32
    Klingberg S, Wittorf A, Wiedemann G. Disorganization and cognitive impairment in schizophrenia: Independent symptom dimensions? Eur. Arch. Psychiatry Clin. Neurosci. 2006; 256: 532540.
  • 33
    Villalta-Gil V, Vilaplana M, Ochoa S et al.; NEDENA Group. Neurocognitive performance and negative symptoms: Are they equal in explaining disability in schizophrenia outpatients? Schizophr. Res. 2006; 87: 246253.
  • 34
    Bozikas VP, Kosmidis MH, Kioperlidou K, Karavatos A. Relationship between psychopathology and cognitive functioning in schizophrenia. Compr. Psychiatry 2004; 45: 392400.
  • 35
    Lindsberg J, Poutiainen E, Kalska H. Clarifying the diversity of first-episode psychosis: Neuropsychological correlates of clinical symptoms. Nord. J. Psychiatry 2009; 14: 18.
  • 36
    Daban C, Amado I, Bourdel MC et al. Cognitive dysfunctions in medicated and unmedicated patients with recent-onset schizophrenia. J. Psychiatr. Res. 2005; 39: 391398.
  • 37
    Sachdev P, Hume F, Toohey P, Doutney C. Negative symptoms, cognitive dysfunction, tardive akathisia and tardive dyskinesia. Acta Psychiatr. Scand. 1996; 93: 451459.
  • 38
    Palmer BW, Heaton RK, Jeste DV. Extrapyramidal symptoms and neuropsychological deficits in schizophrenia. Biol. Psychiatry 1999; 15: 791794.
  • 39
    Kishi T, Moriwaki M, Kawashima K et al. Investigation of clinical factors influencing cognitive function in Japanese schizophrenia. Neurosci. Res. 2010; 66: 340344.
  • 40
    Woon PS, Chia MY, Chan WY, Sim K. Neurocognitive, clinical and functional correlates of subjective quality of life in Asian outpatients with schizophrenia. Prog. Neuropsychopharmacol Biol. Psychiatry 2010; 34: 463468.
  • 41
    Seghers JP, Docherty NM. Cognitive impairments, emotion, stress, and language in schizophrenia. Psychiatry Res. 2009; 170: 97102.
  • 42
    Mutsatsa SH, Joyce EM, Hutton SB, Barnes TR. Relationship between insight, cognitive function, social function and symptomatology in schizophrenia: The West London first episode study. Eur. Arch. Psychiatry Clin. Neurosci. 2006; 256: 356363.