J Med Dent Sci 2010； 57： 83－94

Original Article Reliability and Diagnostic Validity for Schizophrenia of the Japanese Version of the Bonn Scale for Assessment of Basic Symptoms (BSABS) Kazunari Oshima1), Tsukasa Okimura2), Tomoaki Yukizane1), Katsuhiro Yasumi3), Astushi Iwawaki4), Toru Nishikawa1) and Seiichi Hanamura1) 5)

1) 2) 3) 4) 5)

Section of Psychiatry and Behavioral Science, Tokyo Medical and Dental University Graduate School Inagidai Hospital, Health Service Center,Tokyo Institute of Technology Kanuma Hospital Tokyo University of Social Welfare

Schizophrenia is defined by operative diagnostic criteria in DSM-IV with some typical symptoms as hallucinations and duration of the disease. Huber focused on the subjective experience of patients and coined the term “basic symptoms” and created BSABS. Our study investigated the reliability and the diagnostic validity of the 5 clusters of BSABS for DSM-IV-based diagnosis of schizophrenia with a cohort of 105 patients. Good inter-rater reliability was obtained except for one item D.10. As evaluated by Spearman’s rank correlation coefficients, among the 5 clusters excluding Cluster 2, internal consistency was good. This suggests that, although each cluster is heterogeneous, cluster symptoms are the expression of physiological and biological disturbances of schizophrenia. Receiver Operating Characteristic Curve analysis was also used to show the ability of each cluster to discriminate schizophrenia. Results showed that the area representing the powers in discriminate schizophrenia of Cluster 4 “Adynamia”, which is considered related to the dynamic aspect of thinking,was highest, at 0.739. Cluster 1 “Information processing disturbances” which has a predictive ability for schizophrenia showed 0.714 and Cluster 3 “Impaired tolerance to normal stress”

Corresponding Author：Kazunari Oshima Yushima 1-5-45, Bunkyo-ku, Tokyo, 113-8519, Japan Tel: 03-5803-5673　Fax: 03-5803-0245 E-mail: [email protected] Received September 30；Accepted November 13, 2009

showed 0.711. Our findings suggest that, although these clusters symptoms differ from DSM-Ⅳ criteria, they are related to fundamental process of schizophrenia. Use of some of these three clusters with other neurophysiological markers could allow clinical evaluation of schizophrenia from a new perspective. Key words: s  chizophrenia, reliability, diagnostic validity, BSABS, DSM-IV (1) Introduction Schizophrenia is an illness causing dysfunction marked by repeated hallucinations and delusions, disorganized speech, and catatonic behavior. Historically, Kraepelin saw the importance of course of illness in the classification of mental disorders, while Bleuler focused on loosening of association and disturbance of thought, and Schneider developed “firstrank symptoms” considered characteristic of 1) schizophrenia . Based on this pathognomy, DSM-IV was completed in 1994 as a set of operative diagnostic criteria in the U.S. 2) In DSM-IV, schizophrenia is defined by operative diagnostic criteria specifically derived through statistical verification 2) :Criterion A: Two (or more) of the following, each present for a significant portion of time during a 1-month period: (1) Delusions, (2) Hallucinations, (3) Disorganized speech, (4) Grossly disorganized or catatonic behavior, and/or (5) Negative symptoms. Criterion B: Social/occupational dysfunction. Criterion C: Duration (Continuous signs of the disturbance persist for at least 6 months, including

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periods of prodromal, active, or residual symptoms.) Schizophrenia is likewise defined by exclusion of other mental illnesses and the direct physiological effects of a substance. 2) These DSM-IV criteria can be used to diagnose schizophrenia in a straightforward, operational manner. Despite national differences in traditional psychiatry, these criteria have high diagnostic reliability, and the majority of current schizophrenia research worldwide proceeds on the basis of the DSM-IV diagnostic criteria. Although DSM-IV has high reliability in diagnosis, Criteria A symptoms do not account for all schizophrenia symptoms, and the validity of DSM-IVbased diagnosis of schizophrenia has correspondingly become a topic of recent concern. 3) In the treatment of schizophrenia, importance is laid on improvement of social function and increased interpersonal capability following acute-phase drug treatment, and there is a like focus on negative symptoms in the residual phase. Negative symptoms are defined only in terms of symptom complexes including affective flattening, alogia (poverty of speech), and avolition, and the Scale for the Assessment of Negative Symptoms (SANS) 4)5) is based on these clusters. In the residual phase, however, a more detailed symptomatic scale relating to recovery is needed. In the U.S., where DSM-IV was created, a task force for DSM-Ｖ discussed certain dimensions of categorization of psychiatric disorders, 6)7) namely: 1) causalismdescriptivism, 2) essentialism-nominalism, 3) objectivism-evaluativism, 4) internalism-externalism, 5) entities-agents, and 6) categories-continua. In this context, there is a focus on incorporating Patients’ subjective experiences. 8) In Germany, the center of descriptive phenomenology, beginning in the 1960s Huber noted the fact that many schizophrenia patients were aware of their own deficits and could also state what they were during most phases of long-term progression. 9) He regarded this as evidence of fundamental disturbances akin to organic factors and coined the term “basic symptoms.” 10) In 1982, Gross et al. provided a description and extensive listing of basic symptoms, after which the Bonn Scale for the Assessment of Basic Symptoms (BSABS) 11) was completed in 1987. Klosterkötter, the successor of Huber, redefined basic symptoms as “self-perceivable” neuropsychological deficits representing subtle, subclinical signs of illness. The BSABS is a symptom assessment scale based on description of a variety of self-experienced symptoms related to drive, stress-tolerance, emotion, thought,

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perception, and motor function, and covers several phases in the course of schizophrenia from subclinical signs in the prodrome, through progression to acutephase symptoms, to residual-phase symptoms. In the dimensions of causalism-descriptivism and objectivism-evaluativism, and in the context of patientoriented psychiatry, BSABS could focus on a new perspective on schizophrenia research. Leading research using the BSABS includes the following. In a follow-up study on development of symptoms, Klosterkötter 12) followed the course of development from basic symptoms to first-rank symptoms in 121 inpatients. Klosterkötter et al. then examined the diagnostic validity of the BSABS 13) in 1996. They applied a simplified version of the BSABS to a group of 79 healthy individuals and a patient group of 243 individuals with disorders classified by WHO Classification of Diseases (ICD-10) categories as F0 Organic mental disorders; F1 - Mental and behavior disorders due to psychoactive substance use; F2 Schizophrenia, schizotypal, and delusional disorders; F3 - Mood (affective) disorders; F4 - Neurotic, stressrelated, and somatoform disorders; and F6 - Disorders of adult personality and behavior. Through cluster analysis, they extracted 5 BSABS clusters and demonstrated that these clusters served as indicators discriminating ICD-10 categories F0-F4 and F6. Our research is original in the following two respects: First, it is the first to investigate the reliability and the diagnostic validity of a simplified Japanese version of the BSABS by trial application among Japanese patients. Second, it is also the first study using DSM-IV to investigate the validity of the BSABS in the diagnosis of schizophrenia, although Klosterkötter used ICD-10 diagnosis in his study of the diagnostic validity of BSABS. (2) Subjects and Methods Instrument The BSABS was translated in its entirety, and a simplified Japanese version of the BSABS was created from 53 items divided into 5 clusters extracted on the basis of cluster analysis of cases with diagnosis ICD-10 13) categories F0-F4 and F6 by Klosterkötter : Cluster 1 – thought, language, perception, and motor disturbances (Information processing disturbances). Cluster 2 – Impaired bodily sensations (coenaesthesias), Cluster 3 – Impaired tolerance to normal stress, Cluster 4 –

Reliability and Diagnostic Validity for Schizophrenia of BSABS

Adynamia (disorders of emotion and affect, disturbance of short-term memory and disturbance of immediate recall, disturbance of thought process), and Cluster 5 – Increased emotional reactivity (Interpersonal irritation). The 5 clusters and 53 items are shown in Table Ⅰ. Subjects The subjects included a total of 109 cases: A cohort of patients hospitalized in the Department of Psychiatry of the University Hospital of Medicine, Tokyo Medical and Dental University from 1998 to 2005 and diagnosed with schizophrenia based on DSM-IV at admission, and another cohort of patients with suspected schizophrenia in which confirmative diagnosis could not be made at admission. The latter group was selected with the following criteria: (1) Psychotic symptoms such as hallucinations, delusions, or catatonic symptoms present in attenuated form or persisting less than 1 month; or subtle disturbance of thought. Alternatively, (2) A state demonstrating sudden deterioration in social or occupational function requiring hospitalization. Cases in the latter cohort fulfilled some criteria in the diagnosis of schizophrenia according to DSM-IV but did not satisfy all criteria of the diagnostic standard. However, they were characterized by the onset or relapse of mental illness leading to hospitalization and exhibited symptoms corresponding to “incomprehensibility” and “discontinuity of meaning” 1) as described by Jaspers. Procedure for data assessment The simplified Japanese-language BSABS was tested in 109 cases. Four cases with missing values were excluded, making the total number in the sample 105. We obtained informed consent in written form for BSABS interviews and use of data for research. All cases received a confirmatory diagnosis by DSM-IV during the observational evaluation phase of hospitalization. The schizophrenia cohort consisted of 65 cases, including 63 with schizophrenia and 2 with simple deteriorative disorder (simple schizophrenia), while the non-schizophrenia cohort included 40 cases. All cases were also evaluated for social function at admission and discharge using the GAF (Global Assessment of Functioning) Scale. Table Ⅱ presents the composition of confirmatory diagnoses of 105 patients by DSM-IV at discharge. Among 105 patients, we have followed carefully 19 patients with the other psychotic disorders among the non-cohort schizophrenia to reconfirm if they develop

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schizophrenia. Of these 19 cases, 15 cases whom we have followed did not develop schizophrenia. Among 4 cases with schizophreniform disorder, 3 cases have still the same diagnostic and one case stopped to come to consultation. Among 4 cases with delusional disorder, any case did not develop schizophrenia. Among 2 cases with brief psychotic disorder, 1 case still have the same diagnostic and another case stopped to come to consultation. Among 9 cases with psychotic not otherwise specified, 7 cases still have the same diagnostic and 2 cases did not come to the consultation. . To evaluate the inter-rater reliability of BSABS, two raters had a interview with 35 patients among total sample of 105 patients. The distribution of diagnoses of 35 patients are as follows: 28 schizophrenia, 1 schizophreniform disorder, 2 delusional disorders, 2 psychotic disorders not otherwise specified, 2 major depressive disorders.. The BSABS raters consisted of 3 psychiatrists with clinical experience of more than 10 years in the Department of Psychiatry, University Hospital of Tokyo Medical and Dental University, who had each undergone 10 sessions of BSABS training. One rater conducted a semi-structured interview with the patient in the presence of another psychiatrist, and two raters performed blinded evaluation of BSABS symptoms. The two raters scored self-perceivable symptoms mentioned by the patient, with scoring on three levels as: (1) Present (2 points), (2) Doubtful (1 point), and (3) Absent (0 point) and determined the total score for each cluster. Statistical procedures First, to investigate inter-rater reliability between the two raters, Cohen’s k coefficient was determined for each BSABS item using SPSS15.0 statistical software. Inter-rater reliability was determined in 35 cases among 105 cases of a cohort of this study. Next, to examine the internal consistency of the BSABS, product-moment correlation was determined for each cluster by Spearman’s rank correlation coefficient. Cronbach’s α coefficient was also determined. Finally, to determine concurrent validity with the DSMIV in the diagnosis of schizophrenia by BSABS, Receiver Operating Characteristic Curves (ROC curves) were determined with horizontal plotting of falsepositive rates (1 – specificity) and vertical plotting of

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Table Ⅰ. S  ymptoms of the Bonn Scale for the Assessment of Basic Symptoms (BSABS) and their clusteranalytical grouping by Klosterkötter 13)17) Note: The original names of 5 Clusters revised by Klosterkötter are noted in parentheses at the end of each Cluster. The number of each symptom in the original BSABS 11) by Huber is noted at left columns of this table.

D.1s1

Somatopsychic bodily depersonalization

D.2

Bodily sensations of motor weakness, ‘paralysis’

Cluster 1：Thought, language, perception and motor disturbances ( Information processing disturbances)

D.3

Unusual bodily sensations of pain in a distinct area

D.4

Migrating bodily sensations ‘wandering’ through the body

A.6.2

Decreased capacity to discriminate between different kinds of emotions

D.5

Electric bodily sensations, feelings of being electrified

C.1.1

Thought Interference

D.6

Thermal bodily sensations, unusual coldness or warmth

C.1.2

Thought perseveration

D.7

C.1.3

Thought pressure

Bodily sensations of movement, pulling or pressure inside the body or on its surface

C.1.4

Thought blockage

D.8

Sensations of the body or parts of it being abnormally heavy, light, empty, falling or sinking

C.1.6

Disturbances of receptive language, either heard or read

C.1.7

Disturbances of expressive language

D.9

Sensations of the body or parts of it extending, diminishing, shrinking, enlarging, growing, constricting

C.1.10

Disturbances of retrieval of presently required knowledge from long-term memory

D.10

Vestibular sensations, pseudomovements of the body

D.11

C.1.15

Decreased ability to discriminate between ideas and perception, fantasy and true memories

Kinesthetic sensations like vertigo, unsure gait, walking on moving ground

C.1.16

Disturbance of abstract thinking ( ‘concretism’ )

D.14

Dysesthetic crises(unusual bodily sensation plus centralvegetative disturbance or fear of dying any minute)

C.2.1s1

Blurred vision

C.2.1s3

Partial seeing incl. tubular vision

C.2.2s1

Hypersensitivity to light or certain optic stimuli

C.2.2s2

Photopsia

C.2.3s1

Near and tele-vision

C.2.3s2

Micropsia, macropsia

C.2.3s3

Metamorphopsia

C.2.3s4

Changes in color vision

C.2.3s5

Changed perception of the face/body of others

C.2.3s6

Changed perception of the patient’s own face

C.2.3s7

Pseudomovements of optic stimuli

A.6.1

Change in mood and emotional responsiveness

C.2.3s8

Diplopsia, oblique vision

A.6.4

Decrease in the need for contact with others

C.2.3s9

Disturbances of the estimation of distances or sizes

C.1.5

Difficulties concentrating

C.2.3s10

Disturbances of perception of straight lines or contours

C.2.3s12

Maintenance of optic stimuli, ‘visual echoes’

C.1.8

Difficulties to hold things in mind for seconds ( immediate recall)

C.2.4s1

Hypersensitivity to sounds or noise

C.1.9

C.2.4s2

Acoasms

Difficulties to hold things in mind for less than half an hour (short-term memory)

Changes in the perceived intensity or quality of acoustic stimuli

C.1.12

Slowed-down thinking

C.2.5s1

C.1.13

Lack of ‘thought energy’ or goal-directed thoughts

C.2.5s2

Maintenance of acoustic stimuli , ‘acoustic echoes’

C.2.6

Disturbances of olfactoric, gustatoric or sensible perception

C.2.8

Feeling overwhelmed by stimuli, hyperdistractibility

C.2.9

Captivation of attention by details of the visual field

C.2.11

Derealization

C.3.1

Motor interference exceeding simple lack of coordination

C.3.2

Motor blockages

C.3.3

Loss of automatic skills

No.of items

Basic Symptoms

Cluster ３：Impaired tolerance to normal stress (Vulnerability) B.1.1

Impaired tolerance to everyday stress or routine work

A.8.1 ＋ B.1.2

Impaired tolerance to unusual, unexpected or specific novel demands

A.8.2 ＋ B.1.3

Impaired tolerance to certain social situations of everyday life that are primarily emotionally neutral

A.8.3 ＋ B.1.4

Impaired tolerance to working under pressure or time or rapidly changing different demands

A.8.4

Inability to divide attention

Cluster ４： Disorders of emotion and affect (Adynamia)

Cluster5：Increased emotional reactivity ( Interpersonal irritation) A.7.1

Decrease in the ability to maintain or initiate social contacts

A.7.2

Disturbances of emotional responsiveness as characterized by a decrease in facial expression, intonation and communication gestures

B.2.1

Increased emotional reactivity in response to everyday events

B.2.2

Increased emotional reactivity in response to routine social interactions

Cluster ２：Impaired bodily sensations ( Coenaesthesias )

B.2.3

Increased emotional reactivity in response to misfortune to strangers

D.1

C.1.17

Unstable ideas of reference

Unusual bodily sensations of numbness or stiffness

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Reliability and Diagnostic Validity for Schizophrenia of BSABS Table Ⅱ. The composition of diagnoses of schizophrenia cohort and of non-schizophrenia cohort by DSM-Ⅳ

A Schizophrenia Cohort

65 cases

295 Schizophrenia

63 cases

295.30 Paranoid type

29 cases

295.10 Disorganized type

4 cases

290.20 Catatonic type

1 case

295.90 Undifferentiated type

27 cases

295.60 Residual Type

2 cases

Simple deteriorative disorder

2 cases

B Non-schizophrenia Cohort

40 cases

Diagnoses on Axis Ⅰ Other psychotic disorders 295.40 Schizophreniform disorder

4 cases

297.1 Delusional disorder

4 cases

298.8 Brief Psychotic disorder

2 cases

298.9 Psychotic disorder Not otherwise Specified

9 cases

Mood disorders

7 cases

Anxiety Disorders

3 cases

Somatoform Disorders

1 case

Eating disorders

2 case

Adjustment disorders

5 case

Conduct disorder

1 case

Psychiatric disorder

1 case

Not otherwise Specified No diagnosis on AxisⅠ, Diagnosis on AxisⅡ：schizotypal personality disorder

sensitivity corresponding to cut-off points for each cluster in the diagnosis of schizophrenia for the schizophrenia cohort (65 cases) and non-schizophrenia cohort (40 cases). The diagnostic validity of BSABS for schizophrenia, which is not influenced by the choice of cut-off points, can be assessed by a geometric approach using the area under the corresponding ROC curve. A nonparametric method of this approach for related samples was used to compare the diagnostic validity for schizophrenia of 5 clusters of BSABS. (3) Results All 105 cases receiving a confirmatory diagnosis by DSM-IV were divided into two groups by diagnosis on Axis I: a schizophrenia cohort (65 cases) and a nonschizophrenia cohort (40 cases). Descriptive statistical characteristics of the two groups are shown in Table Ⅲ

1 case

Although the two groups exhibited similar age at examination, age at onset, and number of hospitalization, the schizophrenia cohort had longer duration of disease and duration of hospitalization, and also had more number of hospitalization. On GAF at admission, the schizophrenia group was approximately 8 points lower, but at discharge no substantial difference was observed between the groups. 1) First, inter-rater reliability for the BSABS was determined based on Cohen’s κ coefficient. Missing values of the item C.2.11(Derealization) prevented assessment of 1/53 items in the simplified Japanese BSABS, but good consistency was obtained among 52 items and overall except for the item D.10 of Cluster2. Table Ⅳ shows the values of Cohen’s κ coefficient for each item of BSABS. 2) Next, to examine the internal consistency of the

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Table Ⅲ. General Data of Sample(N ＝ 105)

Schizophrenia (n ＝ 65) Non-schizophrenia (n ＝ 40) Mean±SD(Median) Mean±SD(Median) Age at Examination, y

31.3 ± 10.3

29.0 ± 8.87

Age at onset, y

22.5 ± 7.64

24.3 ± 7.50

Duration of Disease, y

8.42 ± 8.39

4.75 ± 4.50

Number of hospitalization

2.57 ± 2.92

1.80 ± 1.86

Duration of hospitalization, day 144.0 ± 90.1

74.0 ± 46.3

GAF in admission

33.9 ± 11.0

41.8 ± 12.3

GAF at discharge

56.4± 11.3

57.8 ± 15.4

BSABS, the product-moment correlation was determined for each cluster based on Spearman’s rank correlation coefficient, as shown in Table Ⅴ. Results of statistical analysis of product-moment correlations among the 5 clusters evaluated by Spearman’s rank correlation coefficient were as follows. Cluster 1 correlated highly with Clusters 2, 3, and 5, and also correlated moderately with Cluster 4. Cluster 2 demonstrated high correlation with Cluster 1, and moderate correlation with Cluster 3, but exhibited low correlations with Clusters 4 and 5. Cluster 3 was highly correlated with Clusters 1, 4, and 5, and was moderately correlated with Cluster 2. Cluster 4 demonstrated high correlation with Cluster 3, and moderate correlation with Clusters 1 and 5. Cluster 5 also demonstrated high correlations with Clusters 1 and 3, and moderate correlation with Cluster 4. Furthermore, Cronbach’s α coefficient was also 0.788 for standardized items, indicating good internal consistency. 3) Finally, Figure 1 presents Receiver Operating Characteristic Curves (ROC curves) with horizontal plotting of false-positive rates (1 – specificity) and vertical plotting of sensitivity corresponding to cut-off points for each cluster in schizophrenia diagnosis for the schizophrenia cohort (65 cases) and nonschizophrenia cohort (40 cases). The areas under the corresponding ROC curve for the 5 clusters are as follows; The largest area under the ROC curve was 0.739 for Cluster 4, followed by 0.714 for Cluster 1, and 0.711 for Cluster 3. That of Cluster 5 was low, at 0.638, and that of Cluster 2 was very low, at 0.561.

(4) Discussion To test the diagnostic validity of BSABS for schizophrenia, we first evaluated inter-rater reliability and investigated the internal consistency of BSABS and the powers in discriminating schizophrenia of the 5 clusters of the BSABS. We first translated the BSABS in entirety and then created a simplified Japanese version of the BSABS from a total of 53 items divided into 5 clusters extracted on the basis of cluster analysis with ICD-10 13) diagnosis by Klosterkötter et al. 1) Inter-rater reliability Gross et al. first 14) studied the reliability of BSABS in 1989, and found that inter-rater consistency was good, with a correlation coefficient of 0.808. In our study, inter-rater reliability was reflected in 34 items with a κ coefficient of 0.8 or higher and 48 items with a κ coefficient of 0.7 or higher, accounting for most items. Only 4 items had a value less than 0.7, a good result overall except for D10 (Kinesthetic sensation) in Cluster 2. . In 2007, Vollmer-Larsen et al. 15) determined Cohen’s κ coefficient for 79 BSABS items by the same method we used, and while κ exceeded 0.6 for 68 items (86%), we achieved higher inter-rater reliability. The BSABS is a semi-structured interview including many questions and requiring a long interview time. However, through training of experienced psychiatrists, our results exhibited good inter-rater reliability. 2) Internal consistency of BSABS Our study used Spearman’s rank correlation

Reliability and Diagnostic Validity for Schizophrenia of BSABS

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Table Ⅳ. Cohen’s κ coefficient of each item of BSABS

Cluster 1

Cluster 3

A.6.2

0.93

B.1.1

0.77

C.1.1

0.74

A8.1B1.2

0.90

C.1.2

0.85

B3

0.85

C.1.3

0.95

B4

0.95

B5

0.83

C.1.4

0.95

C.1.6

0.91

C.1.7

0.85

C.1.10

0.86

Cluster 4

C.1.15

1.00

A.6.1

0.79

C.1.16

0.83

A.6.4

0.74

C.2.1

0.88

C.1.5

0.85

C.2.2

0.83

C.1.8

0.85

C.2.3

0.75

C.1.9

0.90

C.2.4

0.90

C.1.12

0.85

C.2.5

0.86

C.1.13

0.90

C.2.6

0.83

C.2.8

0.80

C.2.9

1.00

Cluster 5

C.3.1

0.75

A.7.1

0.76

C.3.2

0.90

A.7.2

0.65

C.3.3

0.88

B.2.1

0.76

B.2.2

0.91

B.2.3

0.90

C.1.17

0.75

Cluster 2 D.1

0.82

D.1S1 D.2

0.69 0.84

D.3

0.76

D.4

0.90

D.5

0.64

D.6

0.94

D.7

0.76

D.8

0.77

D.9

0.75

D.10

0.38

D.11

0.83

D.14

0.71

Cohen’s κ coefficient

κ

Number of items

0.9 ≤ κ

9

items

0.8 ≤ κ＜ 0.9

25

items

0.7 ≤ κ＜ 0.8

14

items

4

items

κ ＜ 0.7

coefficient, because the order among status in each symptom is important and the observations are referred to as ordinal data. Results of statistical analysis of product-moment correlations among the 5 clusters evaluated by Spearman’s rank correlation coefficient were as follows. To discuss about the internal consistency, we use for simplicity, the descriptions, small (Correlation

Coefficient 0.1-0.3), moderate(0.3-0.5)and high(0.5-0.7) as Cohen 16) proposed. Cluster 1 correlated highly with Clusters 2, 3, and 5, and also correlated moderately with Cluster 4. Cluster 2 demonstrated moderate correlation with Cluster 3, and low correlations with Clusters 4 and 5. Cluster 3 was highly correlated with Clusters 1, 4, and 5. Cluster 4 demonstrated high correlation with Cluster 3, and

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Table Ⅴ. Internal consistency of Bonn Scale for the Assessment for Basic Symptoms

1. Spearman’s rank correlation coefficient of 5 Clusters of BSABS Cluster 1 Spearman’s rank correlation coefficient

Cluster 1

Cluster 2

Correlation coefficient Level of significance (bilateral)

–

N Cluster 2

Correlation coefficient Level of significance (bilateral)

Cluster 3

Correlation coefficient Level of significance (bilateral) N

Cluster 4

.613(**)

.462(**)

.569(**)

.000

.000

.000

.000

105

105

105

105

.346(**)

.189

.199( * )

.000

.054

.042

105

105

105

.543(**)

.501(**)

.000

.000

105

105

. –

. –

Correlation coefficient Level of significance (bilateral) N

Cluster 5

Cluster 5

.548(**)

N Cluster 3

Cluster 4

.468(**) –

.000 105

Correlation coefficient Level of significance (bilateral)

–

N ** Correlation is significant in the 1% level (bilateral). * Correlation is significant in the 5% level (bilateral). 2. Cronbach’s α of 5 Clusters of BSABS Cronbach’s α of 5 clusters of BSABS is 0.788.

moderate correlation with Clusters 1 and 5. Furthermore, Cronbach’s α coefficient was also 0.788 for standardized items, indicating good internal consistency. In long-term follow-up research by Klosterkötter et al. 17) about predictive ability of BSABS for schizophrenia, prospective study of cases free of positive symptoms of the early prodrome revealed that Cluster 1 (Information processing disturbances) had high prognostic accuracy for schizophrenia onset. In addition, in another follow-up study 12), Klosterkötter observed during hospitalization that some symptoms of Cluster 1; thought interference, thought preservation

and thought blockage shifted to first “rank” symptoms of experience of “passivity”, and that another type of symptom in Cluster 1; thought pressure and decreased ability to discriminate ideas and perceptions, could develop hallucinations. These results suggest that Cluster 1 symptoms could shift to complexes of schizophrenic symptoms, and are compatible with the result that Cluster 1 is highly correlated with other clusters. Each of the 5 clusters of the BSABS is homogeneous. After Huber created the original BSABS, 11) there was criticism by Janzarik 18) that the BSBAS includes heterogeneous symptoms and that many symptoms of

Reliability and Diagnostic Validity for Schizophrenia of BSABS

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Figure 1 : Receiver Operating Caracteristics (ROC) Curves of 5 clusters of BSABS (N = 105) The horizontal plotting indicates false-positive rates (1 – specificity) and the vertical plotting indicates sensitivity, corresponding to cut-off points for each cluster in schizophrenia diagnosis for the schizophrenia cohort (65 cases) and non-schizophrenia cohort (40 cases). Areas under the ROC curve of each Cluster is as follows: Cluster1; 0.714, Cluster 2; 0.561, Cluster 3; 0.711, Cluster 4; 0.739, Cluster 5; 0.638, Sum; 0.732

the category “dynamic deficiencies” have two aspects: basic deficiency symptom and its effect: To respond to this point, Huber thinks the dynamic deficiency is the central psychopathology of schizophrenia and created a category of “dynamic deficiencies with direct or indirect minus symptoms” to clarify the effects of dynamic deficiencies. In the end, Klosterkötter revised these categories using cluster analysis, which yielded 5 clusters. Cluster 1 represents information processing disturbances, Cluster 2 impaired bodily sensations, Cluster 3 impaired tolerance to normal stress, Cluster 4 disorders of emotion and affect which also include disturbance of memory, and Cluster 5 increased emotional reactivity. Although the 5 clusters are psychopathologically heterogeneous and the items in each cluster are homogeneous, clusters other than Cluster 2 exhibited high or moderate correlation with each other as determined by Spearman’s correlation coefficient. Furthermore, Cronbach’s α coefficient was

also 0.788, indicating good internal consistency. These findings suggest that, although symptom expression differs in each cluster, with the exception of Cluster 2, each cluster is the expression of common process of 12) demonstrated that schizophrenia as Klosterkötter complexes of complaints of cognitive thought disturbances developed first “rank” symptoms like hallucinations or experience of passivity. That is why Huber named this fundamental disturbance “basic”. 3) D  iagnostic validity for schizophrenia of 5 clusters of BSABS Our study investigated the discriminating power of each of the 5 clusters of the simplified version of BSBAS in the DSM-IV diagnosis of schizophrenia. Multivariate analysis by Klosterkötter 13) in the first study concerning the diagnostic validity of BSABS showed the ability of each cluster to discriminate illness, as follows. In all 5 clusters, there was discrimination of F6 (disorders of adult personality and

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behavior), F4 (neurotic, stress-related and somatoform disorders), and F1 (mental and behavioural disorders due to psychoactive substance use) from what are termed the traditional psychosis groups of F2 (schizophrenia, schizotypal, and delusional disorders), F0 (organic, including symptomatic, mental disorders), and F3 (mood 《affective》 disorders). Results also showed that Cluster 1 – Information processing disturbances discriminated schizophrenic disorders and organic mental disorders from other groups, and that Cluster 5 – Interpersonal irritation discriminated schizophrenic disorders from all other groups.This study demonstrated the ability of each cluster to discriminate F2 from other psychiatric disorders including F0, F1, F3, F4, and F6, which are etiologically different. Our research focused on the power of BSABS in the DSM-IV diagnosis of schizophrenia of discriminating it from other psychotic disorders and related mental disorders. We evaluated the ability of the BSBAS to distinguish a schizophrenia cohort from a non-schizophrenia cohort exhibiting attenuated hallucinations, delusions, catatonic symptoms, or subtle thought disturbances, or acute social or occupational dysfunction requiring inpatient treatment. Diagnostically, 19 of 40 cases in the non-schizophrenia cohort represented other psychotic disorders (schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, and psychotic disorders not otherwise specified), while the remaining cases varied in diagnosis but shared the feature of acute dysfunction. The non-schizophrenia cohort was characterized by the onset or relapses of mental illness, corresponding in German psychiatry to the “incomprehensibility” and “discontinuity of meaning” described by Jaspers. Schizophrenia differs from non-schizophrenic diseases in that the durations of prodromal, acute, and residual phases are defined. 4) ROC curves of 5 clusters of BSABS The diagnostic validity of BSABS for schizophrenia is assessed by the area under ROC curves. The areas under ROC curves were 0.739 for Cluster 4, the largest, followed by 0.714 for Cluster 1, and 0.711 for Cluster 3. That of Cluster 5 was low, at 0.638, and that of Cluster 2 was very low, at 0.561. Cluster ４ Adynamia is characterized by 5 items that Huber had initially included in the category “thought disturbances”, and 2 items initially included in the

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category “impairment of affect and social contact” among the 6 categories of the original BSABS. More recently, Klosterkötter et al. completed a cluster analysis of BSABS items with regard to ICD-10 diseases and concluded, based on the results of determination of squared correlations among items, that these 7 items fit 13) into one cluster, “adynamia” , which they revised. Cluster ４ Adynamia, also named “disorders of emotion and affect” which includes disturbance of memory, and some of them are related to negative symptoms. Cluster 4 Adynamia has been considered related to the dynamic aspects of thinking and comprises 1) change in mood and emotional responsiveness, 2) decrease in the need for contact with others, 3) difficulties concentrating, 4) difficulties to hold things in mind for seconds(immediate recall), 5) difficulties to hold things in mind for less than half an hour (short-term memory), 6) slowed-down thinking, and 7) lack of ‘thought energy’ or goal-directed thoughts. In the past, thought disturbance was regarded as a single symptom including phenomena such as loosening of association and alogia 4), but theories in the U.S. and U.K. 12) hold that the fundamental deficit in schizophrenia is an inability to produce planned thought activity and speech activity, and adynamia is evaluated with respect to several functions relating to production of such volitional thought activity. The finding that adynamia viewed in this light had a powerful ability to distinguish schizophrenia from other psychotic disorders and psychiatric disorders which had a sudden social dysfunction after onset, is of great interest. It suggests that disturbance of dynamic aspects of thinking is a fundamental disturbance in schizophrenia. Considering in another aspect, some symptoms of Cluster 4 is similar to negative symptoms: affective flattening, alogia and avolition. It is possible that Cluster 4 symptoms have an influence of neuroleptic-induced secondly negative symptoms. We don’t discuss about this point further in this study and we need another investigation. In the study by Klosterkötter 17) which investigates predictive ability for schizophrenia, only Cluster 1 Information processing disturbance has high predictive power for schizophrenia. Subjects are patients who don’t have positive symptoms and are at risk state or early prodromal phase. On the other hand, in our study, subjects are patients in true prodromal phase, after onset or at relapse. For the latter cohort of subjects, Cluster 4 could have the most discriminating power for schizophrenia.

Reliability and Diagnostic Validity for Schizophrenia of BSABS

In Cluster 1 – Information processing disturbances, we also rated a wide range of information processing items relating to thought, language, perception, and motor disturbances. As we discussed about the internal consistency, Cluster 1 has a strong predictive value for schizophrenia and some symptoms of Cluster 1 could develop first “rank” symptoms. In our study, Cluster 1 is also important to discriminate schizophrenia after onset or at relapse. In Cluster 3 – Impaired tolerance to normal stress, we rated dysfunction occurring primarily during work and other such mental and physical activity, Huber thinks symptoms of Cluster 3 are direct or indirect effect of dynamic deficiencies, and in DSM-Ⅳ terminology this cluster is related to negative symptoms and social dysfunction. It is plausible that Clusters 3 could distinguish schizophrenia with regard to the level of social dysfunction and its cause “dynamic deficiencies ”. These results seem to be different from that of the study by Klosterkötter with Cluster analysis which indicates that Cluster5(interpersonal irritation) distinguish F2 from other psychiatric disorder. Although ICD-10 diagnosis F2 includes F20 schizophrenia, F21 schizotypal disorder, F22 Persistent delusional disorders, F23 acute and transient psychotic disorders, F24 Indeced delusional disorder, F25 schizoaffective disorders and other nonorganic psychotic disorders, the study by Klosterkötter did not focus on discriminating power of each Cluster for F20, schizophrenia. It is plausible to think that, F2 includes schizophrenia and other psychotic disorders marked by a typical symptom; “idea or delusion of reference”, and that’s why Cluater 5 could distinguish F2 from other psychiatric disorder. Cluster 2-Impaired bodily sensation lacked power in discriminating schizophrenia from other mental disorders. Impaired bodily sensations are thought to be “active” symptoms and related to positive symptoms. Accordingly, they could represent a “state” rather than a “trait” of schizophrenia. Clusters 4, 1, and 3 are able to discriminate schizophrenia from other psychotic disorders or related mental disorders close to schizophrenia in symptomatology. This means that symptoms corresponding to these clusters are related to fundamental and basic disturbances in schizophrenia differing from those of other psychotic disorders. There is a exploratory eye movement study with

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19) The responsive search score(RSS) in the BSABS. exploratory eye movement indicators can be a vulnerability marker of schizophrenia. The RSS has significant correlations with Cluster 4 and Cluster 3. This study support the result that Clusters 4, 1, and 3 are able to discriminate schizophrenia.

5) Future directions of application of BSABS With regard to diagnostic validity, Robins and Guze 20) as long ago as 1970 proposed levels of diagnostic validity including: 1) clinical description, 2) laboratory data research, 3) delimitation from other disorders, 4) follow-up study, and 5) family investigation. In 1990, Kendler 21) built on this concept to segment, advance validity, present validity (psychological/biological data), and predictive validity (e.g., diagnostic consistency, longitudinal variation in function, and responsiveness to treatment).3） The BSABS derives from descriptive phenomenology, i.e., detailed description by the patient of neuropsychological deficit symptoms, and its clinical descriptions differ from those of the DSM-IV. Our research, which focused on distinction from other diseases, investigated the concurrent validity in diagnosis of schizophrenia of DSM-Ⅳ and the BSABS, which feature differing clinical descriptions of schizophrenia. Although DSM-Ⅳ defines schizophrenia with typical symptoms (hallucinations, delusions, disorganized speech and catatonic behavior and negative symptoms), social dysfunction and duration of disease, BSABS could describe and define schizophrenia just with subjective experience symptoms of Cluster4 (adynamia), Cluster 1(Information processing disturbances) and Cluster3 (Impaired tolerance to normal stress). The simplified Japanese version of the BSABS is a psychopathological documentation tool which allows evaluation in every stage of schizophrenia, in particular, evaluation of symptoms that differ from those of DSM-Ⅳ schizophrenia in prodrome to the onset, and in recovery phase In addition, early detection and early intervention in schizophrenia is another topic of current importance in psychiatry, making prodromal symptoms a focus of 22) In DSM-IV, however, prodromal symptoms interest. are not fully defined, and concepts such as ARMS (At Risk Mental State) and UHR (Ultra High Risk) are treated primarily as no more than psychotic symptoms such as transient, weak auditory hallucinations. Prodromal schizophrenia requires highly sensitive indices with greater early utility.

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Recently, some neurophysiologial studies focus on at risk or prodromal stage of schizophrenia. There are findings that auditory evoked potential P50 suppression 23) was significantly impaired in patients in at-risk state, prodromal phase, first episode and chronic schizophrenia. On the other hand. auditory evoked potential N100 suppression was significantly reduced in almost stages, but not at-risk subjects. This auditory gating theory is related to some symptoms of Cluster 1. The exploratory eye movement research 19) also focus on BSABS. The responsive search score(RSS) in the exploratory eye movement indicators can be a vulnerability marker of schizophrenia. The RSS has significant correlations with Cluster 4 and Cluster 3. RSS is thought to be a trait marker of schizophrenia and Cluster 4 and Cluster 3 could represent traits of schizophrenia. Use of some clusters of BSABS with other neurophysiological markers like the auditory evoked potential or the exploratory eye movement indicators could make detection of schizophrenia possible in the very early prodromal phase and allow clinical evaluation of schizophrenia from a new perspective.

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(5) Acknowledgements We thank Professor Koichi Yoshioka of Kokusikan University for his helpful advice on statistical analysis. This study was partly supported by a research grant from the Research Group for Schizophrenia of Astellas Pharm Inc.

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