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Keywords:

  • cognitive;
  • neuropsychological;
  • progressive;
  • schizophrenia;
  • thought disorder

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

Abstract  It is unclear whether the severity of positive formal thought disorder, a core clinical feature of schizophrenia, is stable or worsening through the chronic course of the illness. The neurocognitive basis for positive thought disorder also remains unclear. The aim of the present paper was to examine the relationship between thought disorder as measured by the Thought Disorder Index (TDI) and duration of illness and neuropsychological indices in 79 patients with schizophrenia. TDI scores increased in proportion to illness duration. TDI scores were not associated with verbal memory or executive functioning. These results indicate an ongoing worsening of positive thought disorder through the course of illness in schizophrenia.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

Positive formal thought disorder is considered one of the core features of the psychopathology of schizophrenia and a number of rating scales have been developed to assess its presence and severity.1,2 One such scale that has proved useful in objectively and quantitatively assessing positive formal thought disorder in patients with schizophrenia is the Thought Disorder Index (TDI).3

However, it remains unclear whether patients with schizophrenia exhibit progressive worsening of positive formal thought disorder through the course of the illness. A limited number of studies have addressed this question. Marengo and Harrow found a persistence of positive formal thought disorder in first-hospitalized patients with schizophrenia during a 4-year follow-up period.2 A cross-sectional study indicated that positive thought disorder was less severe in geriatric patients than in young patients in a group of chronically hospitalized patients with schizophrenia.4 Later, the same research group conducted a 2-year follow-up study in geriatric patients and found a stability of positive thought disorder.5 Additionally, an 11-year follow-up study of high- and low-risk adoptees for schizophrenia indicated stability of positive thought disorder.6

Another important but unanswered question is the neuropsychological basis of positive thought disorder in schizophrenia. Nestor et al. found a correlation between more severe positive thought disorder and lower verbal memory as assessed on the Wechsler Memory Scale-Revised (WMS-R) and executive functioning as assessed on the Wisconsin Card Sorting Test (WCST) in 15 patients with schizophrenia.7 Goldberg et al. reported an association between severity of positive thought disorder and disturbed semantic fluency in patients with schizophrenia (n = 23), while working memory function as assessed on WCST was unrelated.8

Accordingly, the aim of the present study was to evaluate the relationship between positive formal thought disorder as assessed using TDI and duration of illness, and neuropsychological functioning (verbal memory and executive functioning) in a larger sample of Japanese patients with schizophrenia.

METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

Subjects

Seventy-nine outpatients with schizophrenia (43 men and 36 women) were recruited from the Department of Neuropsychiatry, University Hospital of Tokyo, Japan. Diagnosis of schizophrenia was made through the Structured Clinical Interview for DSM-IV Axis I Disorders by an experienced psychiatrist (K.K.). The mean patient age was 32.3 years (range, 16–56 years; SD, 8.9). The onset of illness was defined as onset of the full positive syndrome, and the mean duration of illness was 7.7 years (range, 0.1–29.0 years; SD, 7.1). The mean years of education was 13.4 years (SD, 2.4), and the mean neuroleptic dose was 672.3 mg/day (chlorpromazine equivalents; SD, 582.5).9 Verbal IQ was evaluated using Wechsler Adult Intelligent Scale–Revised (WAIS-R; mean, 90.1; SD, 16.6). Clinical symptoms were rated with the Positive and Negative Syndrome Scale (PANSS). The mean score was 14.1 ± 5.0 for the positive scale, 18.9 ± 5.9 for the negative scale and 33.2 ± 6.9 for the general psychopathology scale scores. This study was approved by the ethical committee of Faculty of Medicine, University of Tokyo. After complete description of the study to the subjects, written informed consent was obtained.

Assessment of thought disorder

The TDI10 was used to assess the presence and severity of positive thought disorder in patients with schizophrenia. Rorschach tests were administered to the patients with schizophrenia, using the full 10-card procedure. The subjects' responses were tape-recorded and transcribed verbatim. The transcribed protocols for all cases were scored according to the Japanese version of the scoring manual for TDI11 by a trained clinical psychologist (K.M.), who was blind to other neuropsychological and clinical data. One of the authors (A.H.), who was the first author of the Japanese version of TDI and had expertise with the scoring of TDI, provided extensive training for the rater (K.M.). Two raters (K.M and A.H.) independently scored TDI on 20 randomly selected cases, resulting in a high interrater reliability (intraclass correlation coefficient: 0.97). The TDI includes 23 categories of thought disorder rated at four different levels of severity, and these categories were further classified into four factors: associative looseness, combinatory thinking, disorganization, and idiosyncratic verbalization. The total TDI score was computed as the following formula: 100× cumulative TDI score/total number of responses in the Rorschach test. Then the total TDI was converted to logarithmic-scaled score according to the method of Shenton et al.,12 and the number of subjects was reduced to n = 72 because the total TDI score was 0 for seven subjects.

Neuropsychological measures

We evaluated verbal memory using WMS-R and executive functioning using WCST based on the results of a previous study on an association between TDI and neuropsychological test battery.7 Verbal memory was assessed using the WMS-R (n = 78; mean, 79.3 ± 18.5). Executive functioning was assessed using the computerized version of the WCST.13 The calculated index was percentage perseverative errors (no. perseverative errors divided by total no. responses; n = 65; mean, 23.4 ± 16.4%).

Statistical analysis

For the first step, Pearson's product moment coefficients were calculated between logarithmic-scaled total TDI and duration of illness, verbal memory score on the WMS-R, and percentage perseverative error on the WCST, respectively. For confirmation stepwise multiple regression was performed using logarithmic-scaled total TDI as the dependent variable, and age, gender, years of education, duration of illness, medication dosage, verbal IQ, WMS-R verbal memory, and WCST percentage perseverative errors as the independent variables. Also, logarithmic-scaled total TDI score was compared between patients with longer duration of illness (≥15 years) and those with shorter duration (<15 years) on t-test.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

The logarithmic-scaled total TDI score was significantly correlated with duration of illness (r = 0.259, n = 72, P = 0.028; Fig. 1). Due to a skewed data distribution of duration of illness, Spearman's non-parametric correlation was also computed, which remained significant (ρ = 0.243, P = 0.040). Neither verbal memory (r =−0.050, n = 71, P = 0.68) nor percentage perseverative error (r = 0.149, n = 61, P = 0.25) were correlated with logarithmic-scaled total TDI score.

image

Figure 1. Correlation between duration of illness and thought disorder index (logarithm scale), r = 0.259, n = 72, P = 0.028.

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Stepwise multiple regression confirmed the results; only the duration of illness significantly predicted logarithmic-scaled total TDI scores (r = 0.334, r2 = 0.11, adjusted r2: 0.096; F = 7.03, P = 0.010; t = 2.65).

Moreover, patients with longer duration (n = 13) had higher scores on logarithmic-scaled total TDI than those with shorter duration (n = 59; t70 = 2.26, P = 0.027).

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

The present study found a significantly positive correlation between positive formal thought disorder and duration of illness in a large sample of Japanese patients with schizophrenia. We failed to find a significant correlation between positive thought disorder and neuropsychological functioning.

With respect to the neuroanatomical basis of positive thought disorder, Shenton et al. found an inverse relationship between total scores on TDI and gray matter volume of left posterior superior temporal gyrus in chronic patients with schizophrenia.12 Moreover, recent longitudinal magnetic resonance imaging (MRI) studies have shown a progressive decrease of superior temporal gyrus gray matter at peri-onset14 and in chronic patients with schizophrenia.15 These findings are consistent with the present observations. Longitudinal evaluation of both thought disorder and MRI will be necessary to look for more direct evidence of progressive worsening of thought disorder coupled with its neuroanatomical substrates.

We did not find a significant relationship between positive thought disorder and verbal memory and executive functioning in the present sample, in contrast to the Nestor et al. study in which a relationship was seen between positive thought disorder and these indices using a smaller sample size (n = 15).7 The present study found that positive thought disorder increased in proportion to duration of illness. In contrast, previous studies have indicated stability of neuropsychological indices in schizophrenia.16 Thus, one possible explanation may be that the progressive nature of positive thought disorder and the stable nature of neuropsychological functioning may have resulted in a lack of association between the two indices in the present study.

We must note a limitation of this type of cross-sectional investigation. Schizophrenia may be more severe in patients with longer duration of illness recruited in the university hospital setting than in individuals with schizophrenia who live a relatively independent life in the community setting, who thus were not included in the study. We cannot fully rule out a possibility that this sample bias may have driven a spurious correlation between the positive thought disorder and duration of illness in the present study. Longitudinal studies will definitely be necessary for obtaining more direct evidence of progression of thought disorder in patients with schizophrenia.

In conclusion, the present study identified evidence, albeit indirect due to the cross-sectional design, of an ongoing worsening of positive formal thought disorder through the course of illness in schizophrenia.

ACKNOWLEDGMENTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES

This study was supported in part by grants-in-aid for scientific research (No. 18019009 and 18390319 to KK, no. 17-5234 to MAR) from Japan Society for the Promotion of Science and the Ministry of Education, Culture, Sports, Science and Technology, Japan, and by grants-in-aid (H17-Kokoro-Ippan 009, H18-Shi 7, H17-Koh 2) from the Ministry of Health, Labor and Welfare, Japan.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGMENTS
  8. REFERENCES
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