Schizophrenic syndrome and Wisconsin Card Sorting Test dimensions

PSYCHIATRY RESEARCH Psychiatry Research 58 (1995) 45-51

ELSEVIER

Schizophrenic syndrome and Wisconsin Card Sorting Test dimensions Manuel J. Cuesta*a, Victor Peraltaa, Francisco Caroa, Jose .de Leonb “Psychiatric Unit I, ‘*Virgen de1 Camino” Hospital. Iruniarrea 4. 31008 Pamplona, Spain ‘~e~rtment of Psychiatry, Oedipal College of Pe~~y~~a~ia at Eastern Penns_~~vania Psyehiatri~ ~~titute, 3200 Henry Avenue, Philadelphia, PA 19129, USA

Received 26 April 1994;revision received 5 December 1994;accepted 27 February 1994

Abstract

A principal component analysis of Wisconsin Card Sorting Test (WCST) scores has recently shown three factors. Only the Perseveration factor may measure the activity of the dorsolateral prefrontal cortex in schizophrenic patients. Liddle has hypothesized that a dysfunction in this area is specifically related to the negative syndrome and not to other schizophrenic syndromes (positive and disorganization). The factor analysis of the WCST was replicated with similar results in 38 schizophrenic or schizoaffective patients. In the total group, the correlation between the negative syndrome and the Perseveration factor did not reach significant levels. In the patients with a ~~~-rZI-~ diagnosis of schizophrenia (n = 30), the correlations did reach significant levels. Keywords: Frontal lobe; Positive and negative symptoms of schizophrenia; Factor analysis; Schizoaffective disorder; Neuropsychology

1. In~~uction The Wisconsin Card Sorting Test (WCST) is a neuropsychological instrument frequently used to evaluate executive functions in psychiatric patients, including those suffering from schizophrenia. It has been traditionally hypothesized that this test measures the function of the dorsolateral area of the prefrontal cortex. Unfortunately, the presence of an executive syndrome need not imply the presence of a distinct focal lesion, but may be a relatively common consequence

* Corresponding author, Fax: 948 170515

of global cerebral deterioration (Goldberg and Seidman, 1991). Recently, Sullivan et al. (1993) have examined the association between poor performance on the WCST and dysfunction of the dorsolateral area of the prefrontal cortex in a mixed group of 58 subjects, including normal comparison subjects, patients with schizophrenia or chronic alcoholism, and seven patients with frontal lobe lesions invading the dorsolateral area. They entered 11 of the 14 WCST scores described by Heaton (1981) in a principal component analysis and found the following three factors: Perseveration, Ineffkient Sorting, and Nonperseverative Errors. The following seven categories had high loadings on the

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M.J. Cuesta et al. /Psychiatry Research 58 (1995) 45-51

Perseveration factor: all perseverative responses, total perseverative errors, percent perseverative errors, total number of errors, total number of correct responses, percent of conceptual responses, and number of categories achieved. The Inefficient Sorting factor had contributions from two high loading categories: failure to maintain set and total correct minus 10 per categories achieved. The Nonperseverative Errors factor had high loadings from nonperseverative errors and unique responses. In the study of Sullivan et al., the performance of the seven patients with frontal lobe lesions provided criterion validity for the Perseveration factor and, less strongly, for the Inefficient Sorting factor. The schizophrenic and frontal lobe groups had the highest Perseveration factor scores, whereas the alcoholic group had the highest Inefficient Sorting factor scores. The Nonperseverative Errors factor did not show significant group differences. Only within the schizophrenic patients did the Perseveration factor (but not the other two factors) show convergent and discriminant validity suggesting that only in these patients, and not within the alcoholic patients, can this factor be measuring the activity of the dorsolateral prefrontal cortex. Although schizophrenic patients tend to perform worse than normal comparison subjects on most neuropsychological tests, schizophrenia is believed to be associated with a dysfunction in the medial temporal and frontal lobes (Randolph et al., 1993). The heterogeneity of schizophrenic patients contributes to the difficulty in replicating neuropsychological findings across studies. One of the major factors contributing to schizophrenia’s heterogeneity is symptomatology. Crow (1980) published an influential article proposing two types of schizophrenia, I and II, characterized’by positive and negative symptoms, respectively. Type II schizophrenia would be associated with cognitive deficits. Exploratory factor analyses have shown that schizophrenic symptoms are better classified in three syndromes (or dimensions): positive, negative, and disorganization (Arndt et al., 1991; Peralta et al., 1992). These three syndromes have been found to have different neuropsychological correlates. Bilder et al. (1985) found that only the disorganization syndrome was

associated with neuropsychological deficits. In this study, poverty of speech loaded on the disorganization factor. Later, Liddle (1987b) replicated the three syndromes, with the difference that poverty of speech loaded on the negative factor. In a neuropsychological study, Liddle (1987a) proposed that the negative syndrome is associated with dorsolateral frontal dysfunction; the disorganization syndrome, with mediobasal frontal dysfunction; and the positive syndrome, with medial temporal dysfunction. More recently, Liddle and Morris (1991) found that the negative syndrome was associated with slowness of mental activity, while the disorganization syndrome was associated with difficulty in inhibiting inappropriate responses. In a regional cerebral blood flow study, Liddle et al. (1992) confirmed that the negative syndrome was associated with a left-sided dysfunction of the fronto-subcortical system; the disorganization syndrome, with a right-sided ventral prefrontal abnormality; and the positive syndrome, with a left medial temporal dysfunction. Several studies that examined the negative syndrome in the context of the positive/negative symptom dichotomy have also linked this syndrome to frontal lobe dysfunction. Other studies, however, have not replicated this finding (Morrison-Stewart et al., 1992). Brain-imaging studies have also tested the existence of a frontal lobe dysfunction in psychotic and schizophrenic patients and tend to converge with the neuropsychological studies. Hypofrontality in schizophrenic patients was originally described in a study of regional cerebral flow (Ingvar and Franzen, 1974). Increased attention has been paid to this dysfunction since Weinberger et al. (1986) described schizophrenic patients performing poorly on the WCST while concurrently showing hypofrontality in a regional cerebral blood flow scan. Replication studies of the factor-analytic study of the WCST by Sullivan et al. (1993) have not previously been reported. If the Perseveration factor were replicated and continued to have criterion validity for dorsolateral prefrontal dysfunction, this WCST factor would be confirmed as a good measure for the evaluation of dysfunction of the dorsolateral area of the prefrontal cortex in

M.J. Cuesta et al. /Psychiatry Research 58 (1995) 45-51

47

schizophrenic patients. Therefore the WCST Perseveration factor could be a valuable test of Liddle’s hypothesis that the negative syndrome is associated with a dysfunction of this area of the brain. We have attempted to replicate the WCST three-factor solution found by Sullivan et al. (1993) and to test whether the negative syndrome versus the positive and the disorganization syndromes is correlated with the Perseveration factor (which may be measuring dysfunction of the dorsolateral area of the prefrontal cortex). The three syndromes have been measured as continuous variables (Green and Walker, 1985) in schizophrenic and schizoaffective patients. These three syndromes are not specific to schizophrenia. Schizoaffective patients may also show negative, positive, or disorganization syndromes. It would be reasonable to expect that the pathophysiology of the syndromes is similar across these allegedly different illnesses. The negative symptoms should be associated with a dysfunction of the dorsolateral area of the prefrontal cortex in the schizophrenic patients as well as in those who have schizoaffective disorder.

symptomatology with the Scale for the Assessment of Positive Symptoms (SAPS; Andreasen, 1984b) and the Scale for the Assessment of Negative Symptoms (SANS; Andreasen, 1984a). Interrater reliability and scoring of positive, negative, and disorganization syndromes have been reported elsewhere (Peralta et al., 1992). Delusions and hallucinations load on the positive factor. Affective flattening, alogia, avolition, and anhedonia load on the negative factor. Positive formal thought disturbances, inappropriate affect, and attentional impairment load on the disorganization factor. The WCST was administered by a rater (F.C.) without knowledge of psychiatric diagnosis and symptom ratings. Thirteen of the 14 Heaton rating criteria for the WCST were introduced in the factor analysis. We included all 11 items used by Sullivan et al. (1993) and two categories that they excluded because of missing data: prior category perseverations and trial to the first category. Learning-to-learn, which was not used by Sullivan et al., could not be included in our analysis because some patients did not reach the three needed categories.

2. Methods

2.3. Stai~stical analyses Statistical analyses were performed with the computerized Statistical Package for Social Sciences (Norusis, 1986). A principal component analysis with varimax rotation was carried out for the 13 WCST variables. Pearson correlations were calculated between WCST factor scores and factor scores obtained from the exploratory factor analysis of the SANSSAPS to test whether the Perseveration factor was correlated to the negative syndrome. One-tailed tests were used to assess significance. Partial correlations to eliminate the effect of variables such as education or duration of illness were not calculated since they may be influenced by the schizophrenic illness. An analysis of variance was used to compare WCST factor scores across two diagnoses.

2.1. Subjects All psychotic patients consecutively hospitalized in an acute psychiatric unit were included if they had schizophrenia or schizoaffective disorder. Patients were excluded if they had a history of alcohol or drug abuse, neurological disorders (including head injury), or age of onset of psychosis > 45 years. The sample included 30 patients with the following ~~~-III-R (American Psychiatric Association, 1987) diagnoses: schizophrenia (n = 30) and schizoaffective disorder (n = 8). Diagnoses were made using a semistructured interview for schizophrenia (Landmark, 1982). Table 1 describes the clinical and demographic characteristics of the patients. None of them had received electroconvulsive therapy. 2.2. Procedures Two psychiatrists (M.J.C. and V.P.M.) rated

3. Results 3. I. Factor analysis Table 2 presents the three factors with eigen-

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48

Table I Demographic and clinical characteristics Total (N = 38)

Schizophrenia (n = 30)

Schizoaffective disorder (n = 8)

30.8 f 8.0 19-50 10.0 f 2.4 5-15 22.3 i 5.6 15-37 8.5 f 6.2 l-25 197 f 640 O-3050 2.4 f 2.9 O-8 21.0 f 10.4 4-55 57.0 f 12.6 36-90

29.2 f 6.8 19-45 IO.1 Z+Z 2.6 S-15 21.1 f 5.0 15-34 8.1 f 5.4 l-20 887 f 671 O-3050 2.5 f 2.9 O-8 21.6 f 10.7 9-55 54.1 f 10.6 36-76

36.8 f 24-50 9.5 f 8-12 26.6 f 20-37 10.1 f l-25 463 f 0-1000 2.0 l O-8 18.8 l 4-32 68.0 f 52-90

Mean f SD Range Mean f SD Range Mean f SD Range

0.88 f 1.11 o-5 1.94 f 1.07 o-4.25 0.79 f 0.75 O-2.33

0.93 f I.21 o-5 2.08 * I.04 O-4.25 0.86 f 0.75 O-2.33

0.69 f 0.65 O-l.5 1.41 l 1.04 O-2.75 0.54 f 1.33 O-2.00

(%) (W

14 26

77 23

63 37

(W (W W)

84 5 II

87 0 I3

25 0

(“/) W) (W

37 21 42

40 20 40

25 25 50

(1%) (W (W W)

82 5 3 IO

84 3 3 IO

75

Variables

Age (years) Education (years) Age at onset (years) Illness duration (years) Antipsychotic dose Biperiden dose (mgday) GAF at admission GAF for last year

Mean f Range Mean f Range Mean f Range Mean f Range Mean f: Range Mean f Range Mean f Range Mean f Range

SD SD SD SD SD SD SD SD

9.8 1.3 6.1 8.8 367 3.0 9.5 14.0

SAPUSANS

Positive factor Negative factor Disorganization factor Sex Male Female Marital status

Single Married Divorced

75

Family history

Absent Schizophrenia Other Handedness

Right Left Ambidextrous Untested

13 0 12

Note. SAPS/SAN& Scale for the Assessment of Positive Symptoms/Scale for the Assessment of Negative Symptoms, GAF. Global Assessment Functioning. Antipsychotic dosage is given in chlorpromazine equivalents. Handedness was assessed by the Edinburgh Inventory (Old~eld, 1971)

values > 1. The terminology applied by Sullivan et al. (1993) was used because the factors were almost identical. The order of the factors differed, however, since our second factor (Inefficient Sorting) corresponded to their third factor. Prior category

perseverations and trial to the first category, which were not included by Sullivan et al., loaded on our first factor. Two factors showed significant correlations with demographic and clinical variables. The

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M.J. Cuesto et al. /Psychiatry Research 58 (1995) 45-51

Table 2 Factor analysis of scores on the Wisconsin Card Sorting Test (WCST)

Table 3 Pearson correlations between Wisu;onsin Card Sorting Test factors and clinical syndromes

Factors

Perseveration

Nonpersever- Inefficient alive Errors Sorting

Variance (“/0) Eigenvalues

52 6.8

15 1.9

WCST scores

Perseveration

I2 I.6

-0.13

0.90(P) -0.83(P) -0.60(P) -0.85(P) -0.28

-0.19 -0.18 0.31 -0.10 -0. I I -0.26 -0.15

0.15 (P = 0.19)

-0.09 Disorganization syndrome

0.93(P) 0.94(P)

0.22 (P = 0.10)

Positive syndrome 0.95(P)

-0.10 -0.07

0.10 -0.11 0.84 0.78

0.18

O.Sl(NE) 0.87(NE) -0.10 0.17

-0.01

(P = 0.22)

(P = 0.49)

-0.12

-0.30

(P = 0.25)

(P = 0.03)

0.09

0.03

-0.12

(P = 0.45)

(P = 0.25)

Negative syndrome Positive syndrome

-0.01 0.41 0.36

-0.13

(P = 0.31) Schizophrenic group (n = 30)

Disorganization syndrome

0.3 I

-0.09

-0.06

(P = 0.05)

(P = 0.33)

(P = 0.38)

0.12 (P = 0.26) 0.12 (P = 0.26)

-0.15 (P = 0.22) -0.01 (P = 0.48)

-0.33 (P = 0.04)

-0.13 (P = 0.26)

Schizoafictive group (n = 8)

-0.25 0.70(B)

Negative syndrome

0.23 (P = 0.29)

0.23

Nonperseverative Errors

Total group (N = 38)

Negative syndrome

Factor loadings

Total perseverative errors All perseverative responses % Perseverative errors Total errors Total correct % Conceptual responses Categories Failure to maintain set Total correct - IO per category achieved Unique responses Nonperseverative errors Prior category perseverations Trial to tirst category

lneflicient Sorting

Positive syndrome

0.9l(IS)

Disorganization syndrome

-0.15 0.15

0.50 (P=O.ll) 0.15 (P = 0.36)

-0.43 (P=O.l5) 0.08 (P = 0.43) 0.15 (P = 0.36)

0.27 (P = 0.26)

-0.18 (P = 0.34)

-0.07 (P = 0.43)

-0.07 0.14

Note. The name of the factor on which the item had the highest loading (terminology follows the study of Sullivan et al., 1993) appears in parentheses: P, Perseveration; NE, Nonperseverative errors; IS, Inefficient Sorting.

Perseveration factor was significantly correlated to age (r = 0.45, P = O.OOS), number of years of education (r = -0.37, P = 0.020), and duration of the illness (r = 0.43, P = 0.008). The Inefficient Sorting factor showed correlations that bordered on significance with years of education (r = -0.30, P = 0.068) and duration of illness (r = 0.31, P = 0.059). 3.2. Correlations schizophrenic In the 30

between syndromes

WCST

factors

and

schizophrenic patients, the negative syndrome showed a significant correlation with

-I

Negative

Syndrome

Fig. I. Scatterplot: Perseveration factor and negative syndrome factor scores in the total group of patients. I indicates one subject, and 2 indicates two subjects.

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M. J. Cuesta et al. /Psychiatry Research 58 (I 995) 45-51

the Perseveration factor. Unexpectedly, the positive syndrome showed a negative correlation with the Inefficient Sorting factor (Table 3). In the total group of patients, the correlation between the negative syndrome and the Perseveration factor did not reach significance, while the negative correlation between the positive syndrome and the Inefficient Sorting factor remained within significant levels. Fig. 1 presents the scatterplot for the Perseveration factor and the negative syndrome factor scores. The correlation of the negative syndrome with the first WCST factor was partially attributable to the effect of age, education, and illness duration. 3.3. WCST factor scores across diagnosis Across diagnoses, there were no significant differences in the WCST Perseveration (F = 1.60; df = l/36; P = 0.21), Nonperseverative Errors (F = 0.13; df = l/36; P = 0.72), and Inefficient Sorting factors (F= 0.02; df = 1136; P = 0.91). 4. Discussion Despite the limitations and differences of our study, the factor structure of the WCST was surprisingly similar to that described by Sullivan et al. (1993). The most impo~ant Iimitation was that our group of patients contained too few subjects for the number of variables. There were two methodological differences in the statistics since Sutlivan et al. used two fewer WCST criteria and composite scores obtained by adding scores of items with high loadings instead of direct factor scores. We studied 30 schizophrenic and 8 schizoaffective patients, and Sullivan et al. studied 22 schizophrenic patients, 20 patients with chronic alcoholism, and 16 normal subjects. As hypothesized, schizophrenic patients displayed an association between the negative syndrome and the Perseveration factor, which may be related to dorsolateral prefrontal dysfunction. However, the amount of variance of the negative syndrome accounted for by the Perseveration factor was rather small, c 10%. This correlation may be partially explained by the effects of age, education, and duration of illness. Unfortunately, these factors may be influenced by the severity of the

schizophrenic illness. Therefore, the impairment of the Perseveration factor reflects the effects of the schizophrenic illness, age, and educational level, but a correlational analysis does not permit us to establish the causality of the interrelationships of the three variables. Unexpectedly, an association was found between the positive syndrome and the Inefficient Sorting factor of the WCST. The correlation was negative, suggesting that the positive syndrome was related to fewer errors and more efficient sorting. In the study of Sullivan et al., this factor did not appear to be related to frontal or temporal dysfunctions. The correlation between the positive syndrome and the Inefficient Sorting factor was not hypothesized, however, and may be a chance finding. If the association is replicated in future studies, it may suggest that schizophrenic patients in whom positive symptoms predominate do better cognitively than other schizophrenic patients or that preserved frontal lobe function may be associated with the positive syndrome. McKenna et al. (1994) have suggested that positive symptoms may be explained by a heightened, biased, or distorted neuropsychological function. The three WCST factors may have clinical meaning since the Perseveration factor measures the tendency to persist in spite of frequent errors. It includes the two measures that traditionally are used to assess the results of the WCST: number of categories and the percentage of perseverative errors. This Perseveration factor showed convergent and discriminant validity in the schizophrenic patients studied by Sullivan et al. (1993), suggesting that it may measure the activity of the dorsolateral prefrontal cortex in schizophrenia. IneffIcient Sorting reflects an inadequate set or mechanism of selection. Nonperseverative Errors do not appear to be an important dimension in schizophrenic patients and may merely reflect lack of motivation or cooperation. In conclusion, despite the limitations of our study and methodological differences that distinguished it from the study of Sullivan et al. (1993), results of the two factor-analytic studies were remarkably similar. Like Sullivan et al., we found three factors - Perseveration, IneffIcient Sorting, and Nonperseverative Errors - which had a very

M.J. Cuesta et al. /Psychiatry Research 58 (1995) 45-51

similar item composition. A larger group of subjects will be needed to confirm that the these factors are an appropriate summary of the WCST items described by Heaton (1981). New studies need to establish whether the three schizophrenic syndromes (positive, negative, and disorganization) are consistently related to specific neuropsychological findings which suggest brain localization. The WCST, particularly the Perseveration factor which may be related to dysfunction in the dorsolateral area of the prefrontal cortex, provides an important tool for these studies. Acknowledgments

The authors are grateful to Blaine Cloud, M.A., for his critiques and to Amy McGrory, B.A., for her help with editing the article. Recognition is owed to Albert R. Di Dario, Superintendent of Norristown State Hospital, who provides administrative support for the Clinical Research Center at Norristown State Hospital. References

51

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