wisconsin card sorting test performance in obsessive-compulsive disorder: no evidence for...

Psychiatry Research 58 (1995) 37-43

PSYCHIATRY

RESEARCH

Wisconsin Card Sorting Test performance in obsessive-compulsive disorder: no evidence for involvement of

dorsolateral prefrontal cortex

Massimo Abbruzzese*, Stefano Ferri, Silvio Scarone

Psychiatric Branch, Department of Biomedical and Technological Sciences, University of Milan Medical School, IRCCS at S. Raffaele Hospital, via Luigi Prinetti 29, Milan, 20127 Italy

Received 3 June 1994; revision received 8 March 1995; accepted 26 April 1995

Abstract

Wisconsin Card Sorting Test (WCST) performances were studied in 33 patients with obsessive-compulsive disorder (OCD) and 33 age-, sex-, and education-matched normal comparison subjects; the OCD patients were divided into four subgroups on the basis of their symptomatology. Neither the two groups of subjects nor the four OCD subgroups differed on any of the WCST neuropsychological indices. No relationship was demonstrated between test performance and clinical-epidemiological characteristics of the OCD patients. All of the OCD patients were being treated with fluvoxamine maleate, which improves OCD symptoms and could also improve WCST performances. Nevertheless, no remarkable differences in the WCST indices were observed in patients treated with fluvoxamine when compared with patients who had not received a specific therapy for at least 3 weeks. Since the WCST is widely considered sensitive to dysfunction of the dorsolateral prefrontal cortex, our results do not support the involvement of that brain region in OCD.

Keywords: Neuropsychology; Frontal lobe; Perseveration

1. Introduction

The hypothesized link between the psycho- pathology of obsessive-compulsive disorder

(OCD) and the frontal lobes has received renewed emphasis as a result of recent studies of the rela- tionships between frontal regions and subcortical

l Corresponding author, Tel: +39 2 2643 3300; Fax: +39 2 2643 3375.

structures such as the basal ganglia. Magnetic res- onance imaging studies reported modifications in the size of the head of caudate nucleus (Kellner et al., 1991; Scarone et al., 1992) in OCD patients. Moreover, analyses of frontal cortical metabolism, through positron emission tomography (PET), have reported modifications of glucose metabo- lism in OCD patients (Baxter et al., 1987; Nordahl et al., 1989). This evidence is in accord with the most widely accepted psychophysiological model

0165-1781/95/%09.50 0 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0165-1781(95)02670-R

38 M. Abbruxese et al. /Psychiatry Research 58 (1995) 37-43

of OCD (Alexander et al., 1986; Wise and Rapoport, 1989), also supported by metabolic studies (Baxter et al., 1987; Benkelfat et al., 1990), which suggests that a dysfunction in the circuits connecting frontal cortex-basal ganglia-thalamus- subthalamic regions produces the thinking and motor abno~alities of OCD patients.

On the other hand, the neuropsychological data relevant to this model are still not detinitive. In fact, neuropsychological studies of tests sensitive to frontal regions have provided discordant results (Insel et al., 1983; Behar et al., 1984; Malloy, 1987; Bellini et al., 1989; Christensen et al., 1992; Abbruzzese et al., 1993, 1995). Two investigations conducted recently in our laboratory in two independent groups of OCD patients failed to fur- nish concordant results on tasks sensitive to fron- tal lobe functioning (Gambini et al., 1993; Abbruzzese et al., 1995).

It is possible that such discordant results could depend on a particular heterogeneity of OCD. In fact, it is still not clear if checking and washing symptoms can be considered as an expression of the same psychopathological status; moreover, the outcome of OCD can depend on the coexistence of other psychiatric illnesses; neuropsychological test performance may likewise be related to some of these features.

The present study was carried out as a replica- tion of previous studies. Our aim was to examine the Wisconsin Card Sorting Test (WCST) in a larger and more exhaustively assessed group of OCD patients. We focused on the effects on test performance of other clinical variables: age at onset of OCD, sex differences, symptomatological characteristics, illness severity, and comorbidity with mood or other anxiety disorders. Moreover, we examined WCST performance in an indepen- dent group of untreated OCD patients.

2. Methods

2.1. Subjects Sixty-six subjects (33 OCD patients and 33 nor-

mal comparison subjects matched for age, sex, educational level, and handedness) participated in the study. Table 1 presents the demographic characteristics of the sample. The 33 OCD patients

Table 1 Demographic characteristics of 33 fluvoxamine-treated ob~ssive~ompulsive disorder (OCD) patients, I4 unmedicated OCD patients, and 33 normal comparison subjects

Characteristics Medicated Unmedicat- Normal OCD ed OCD subjects patients patients

Mean SD Mean SD Mean SD

Age (years)” 30.9 10.2 29.8 7.8 28.4 5.5 Education (years)b 10.8 3.4 10.9 3.2 12.1 3.5 Wechsler Adult 102.5 14.6 100.9 11.3 109.3 10.5

Intelligence Scale scoreC

Sex (Male/female)d 19114 717 16117

“Analysis of variance (ANOVA): F = I. 15; df= I, 78; P = NS. bANOVA: F= 2.84; df= I, 78; P = NS. ‘ANOVA: F= 4.05; df=1,78;P=NS. d~2=0.15~df=2.P=0.70

were consecutively recruited from the Anxiety In- patients Unit at the psychiatric branch of S. Raf- faele Hospital. The diagnosis of OCD was made with a computerized version of the Diagnostic In- terview Schedule (Robins et al., 1989) which follows DSM-III-R criteria (American Psychiatric Association, 1987), and confirmed by two psychiatrists. The obsessive-compulsive symp- tomatology was assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS; Goodman et al., 1989b, 1989~). The Y-BOCS is a clinical semistructured interview that assesses the severity of obsessional symptoms, compulsions, and other important features of OCD, as well as avoidant behaviors, pathological doubt, interference of OCD symptoms with daily life, time spent in obsessions or compulsions, and resistance to these symptoms. Four OCD subgroups were formed on the basis of the Y-BOCS results according to the most characteristic symptoms: checkers, washers, mental checkers, and mixed symptoms. The Y- BOCS evaluations were carried out before patients began pharmacological treatment.

Table 2 shows the clinical characteristics and sex distribution in the four OCD subgroups. At the time of their neuropsychological evaluation, all of the OCD patients had been treated with fluvox- amine maleate in doses 5300 mg/day for at least 6 weeks. No subjects had taken benzodiazepines in

M. Abbruzzese et al. / ~syehiafry Research 58 (19951 37-43 39

Table 2 Clinical characteristics of patients with obsessive-compulsive disorder

Characteristics Sex Age at onset”

Duration of illnessb

Mean SD Mean SD

Checkers (6M/3F) 22.1 8.1 11.5 9.8 Washers (6M/4F) 25.4 10.7 5.4 4.5 Mental checkers (3M14F) 23.6 14.8 9.0 4.3 Mixed (4Mi3F) 22.4 8.1 7.4 6.4

Nofe. Mean scores on the Yale-Brown Ob~ssive-Compulsive Scale were as follows: obsessions 13.4 (SD = 3.0); compulsions 13.5 (SD = 3.3); total 26.9 (SD = 3.2). M, male; F, female. “Analysis of variance (ANOVA): F = 0.14; df = 3, 60; P = 0.93, NS. bANOVA: F= 1.10; df= 3, 60; P = 0.36, NS

the 2 weeks preceding the neuropsychological assessment. In addition, an independent group of 14 untreated OCD patients, who were diagnosed according to ~~~-III-~ criteria and were assessed with the Y-BOCS, were also studied. The 33 nor- mal comparison subjects were recruited from hos- pital employees, nursing staff, and medical students; the exclusion criteria for recruitment were a personal history of neurological or psychiatric illness or alcohol abuse. All the sub- jects had a complete physical and neurological examination to exclude any somatic illness. Fur- thermore, no subjects had any history of documented head injuries, loss of consciousness, neurosurgical treatment, or perinatal trauma. All subjects were right-handed as determined by a standardized questionnaire (Raczkowskj et al., 1974). Intellectual level was assessed with the Wechsler Adult Intelligence Scale (Wechsler, 1981). Informed consent for the study was obtain- ed from each subject before testing began.

2.2. Procedures The WCST is one of the most widely used tasks

in neuropsychological evaluation of frontal lobe function. Originally proposed as a test for the assessment of frontal cortical malfunction in neurosurgical patients (~ilner, 1963; Robinson et al., 1980), the WCST has shown a particular sensi- tivity to damage to the dorsolateral prefrontal cor-

tex (DLPC) (Weinberger et al., 1986; Goldberg et al., 1987; Berman et al., 1988).

The WCST was administered according to stan- dardized criteria (Heaton, 1981) by a trained neuropsychologist in a quiet laboratory. All sub- jects completed the test session.

Four stimulus cards with symbols differing in color, shape and number are placed in front of the subject who is given a pack of 128 response cards, four of which are identical to the stimulus cards. The subject is instructed to place each response card under one of the four stimulus cards and is told that the examiner will say if the coupling criterion is right or wrong.

According to the examiner’s responses, the sub- ject has to get as many cards right as possible. After coupling 10 cards with the first criterion (color), the subject is required to shift to the sec- ond one (shape) and then to the third one (num- ber). The procedure is repeated twice or until all 128 cards have been placed. The indices con- sidered for the test evaluation are as follows: (I) SN: Number of categories completed by the sub- ject. (2) TE: Total errors made during the task. (3) PE: Perseverative errors score; a perseverative error is one in which the subject continues to sort the cards in the same way - according to color - after the examiner says the card is wrong or changes criteria. (4) LS: Loss of set or failure to maintain set is defined by the number of times that the subject makes at least five correct responses in a row, but fails to complete the category. (5) CL: Percent conceptual level responses; this index represents the number of times in which correct responses occur consecutively in runs of three or more divided by the number of trials in the test. (6) NT: Number of trials to complete the first category.

2.3. Statistical analysis The raw data obtained from the WCST indices

(PE, TE, SN, LS, CL, and NT) were z-transformed to normalize their distribution before statistical analysis. Data transfo~ation was made after a spread-level examination of the variables and a subsequent power transformation (Statistical Package for Social Sciences, 1988). Six analyses of

40 M. Abbruxese et al. /Psychiatry Research 58 (1995) 37-43

variance (ANOVAs) were performed with all the single WCST indices according to diagnosis.

Mann-Whitney U tests were used to compare the WCST indices in the OCD patients according to sex and comorbidity. A Kruskal-Wallis one- way ANOVA was performed to compare WCST performance in the OCD patients according to clinical subtype (checkers, washers, mental checkers, and mixed). Nonparametric analyses were chosen because of the small number of sub- jects in each subgroup.

3. Results

Table 3 shows the mean values of WCST-SN, WCST-TE, WCST-PE, WCST-LS, WCST-CL, and WCST-NT after their z-transformation and summarizes the results of the ANOVA according to diagnostic categories. The z-transformation was

Table 3

WCST scores and ANOVA results in OCD patients and nor-

mal subjects

OCD patients Normal ANOVA

subjects (d.= 1, 64)

Mean SD Mean SD F P

WCST-SN

Raw score

* score

WCST-PE

Raw score

z score

WCST- TE

Raw score

z score WCST-LS

Raw score

z score WCST-CL

Raw score

z score WCST-NT

Raw score z score

5.45 1.34 5.87 0.33

-0.22 1.36 0.21 0.33 0.13

9.33 15.74 5.39 6.12

0.19 I.14 -0.18 0.80 2.30

16.09 18.70 12.45 11.55

0.10 I.16 -0.09 0.8 I 0.64

2.39 3.51 I.15 2.37

0.20 1.15 -0.20 0.78 2.82

0.79 0.12 0.75 0.13

0.14 0.95 -0. I 1 1.03 0.88

14.92 4.74 15.13 5.58 -0.02 0.91 0.02 1.08 0.02

NS Table 4

WCST mean ranks and Kruskal-Wallis one-way ANOVA re-

sults in OCD clinical subgroups

NS

NS

NS

NS

NS

WCST-SN 18.89 16.09 18.08 15.07 1.55 NS

WCST-PE 16.72 17.18 14.00 19.64 1.12 NS

WCST-TE 16.72 18.36 13.50 18.21 I.12 NS

WCST-LS 18.94 16.59 13.83 17.86 1.32 NS

WCST-CL 15.64 15.14 16.92 18.23 1.52 NS

WCST-NT 18.63 16.10 17.98 15.21 0.77 NS

required because the WCST values were not nor- mally distributed. No significant differences were found between the two diagnostic groups on the six WCST indices. Sex did not affect test perfor- mances.

Table 4 shows the WCST mean ranks and sum- marizes the results of the Kruskal-Wallis one-way ANOVA in OCD clinical subgroups. No signiti- cant differences were founded among the four OCD subgroups (checkers, washers, mixed, and mental checkers) on the six WCST indices.

Table 5 presents the WCST mean ranks in the OCD group and summarizes the Mann-Whitney U-test results according to comorbidity. No signif- icant differences were found between OCD pa- tients with and without comorbid mood disorders for any of the WCST indices.

No significant differences were found between males and females in the OCD group for any of the WCST indices. Y-BOCS scores and WCST perfor- mance did not reveal any positive or negative cor- relations in the regression analysis. As far as the effects of psychopharmacological treatment are concerned, untreated patients showed a significantly higher number of WCST total errors and CL responses compared with fluvoxamine- treated patients (WCST-TE: F = 4.56; df = 1, 45;

Check- Washers Mental Mixed Kruskal-

ers checkers Wallis

ANOVA

(n=9) (n=lO) (n=7) (n=7)

x2 P

Note. OCD, obsessive-compulsive disorder; ANOVA, analysis Nore. OCD, obsessive-compulsive disorder; ANOVA, analysis

of variance; WCST, Wisconsin Card Sorting Test; WCST in- of variance; WCST, Wisconsin Card Sorting Test; WCST in-

dices: SN, number of categories completed; PE, perseverative dices: SN, number of categories completed; PE. perseverative

errors; TE, total errors; LS, loss of set; CL, percent conceptual errors; TE. total errors; LS. loss of set; CL, percent conceptual level responses; NT number of trials to complete first category. level responses: NT. number of trials to complete first category.

M. Abbruzzese et a/. /Psychiatry Research 58 (1995) 37-43 41

Table 5 WCST mean ranks in OCD group and Mann-Whitney U-test

results according to comorbidity

WCST-SN

WCST-PE

WCST-TE WCST-LS

WCST-CL WCST-NT

Comorb+ Comorb- Mann-Whitney U test

(n = 17) (n = 16)

z P

17.21 16.25 -0.60 0.54

14.85 19.28 -1.32 0.18

15.26 18.84 -1.06 0.28

15.82 18.25 -0.80 0.42

14.04 18.75 -0.44 0.66

15.10 19.05 -0.20 0.83

Note. OCD, obsessive-compulsive disorder; Comorb+ =

presence of comorbidity for mood or other anxiety disorders;

Comorb- = absence of comorbidity; WCST, Wisconsin Card

Sorting Test; WCST indices: SN, number of categories com-

pleted; PE, perseverative errors; TE, total errors; LS, loss of set;

CL, percent conceptual level responses; NT, number of trials to

complete first category.

P < 0.05; WCST-CL: F = 6.68; df = 1, 45; P <

0.05); the other values were not significantly different.

4. Discussion

The WCST performance in the OCD group did not differ significantly from that of the normal

comparison group. In fact, no differences were found in TE, PE, or SN. The other three WCST variables (LS, CL, and NT) did not show statistically significant differences between the two

groups. Each member of the two groups was matched

for age and sex, and selected from a larger popula- tion; moreover, since WCST performance could

depend on educational level (Gambini et al., 1992) the two groups were also matched for education to exclude this possible source of variance. The results seem to confirm our previous study

(Abbruzzese et al., 1995) which also did not demonstrate a significant WCST impairment in OCD patients.

The 33 OCD patients were being treated with

the same medication, fluvoxamine maleate, an antidepressant drug that is considered one of the most effective in the control of obsessive symp- tomatology (Goodman et al., 1989a; Jenike et al.,

1990). Moreover, no patients were taking benzo-

diazepines or undergoing behavioral desensitiza- tion therapy.

Although there are no reports that fluvoxamine

treatment is associated with improved perfor- mance on the WCST and other neuro- psychological tests sensitive to frontal lobe function, it is possible that clinical improvement of

OCD symptoms could also improve WCST perfor- mance. Therefore, our fluvoxamine-treated OCD patients were compared with a group of unmedicated OCD inpatients. The comparison of

WCST performance in the two OCD groups revealed slightly poorer performance of the unmedicated group on two WCST indices: TE and CL. Since the two OCD groups did not differ in

age, education, age at onset, duration of illness, or symptom severity (mean f SD Y-BOCS total scores were 27.21 f 5.20 in the medicated group

vs. 28.25 f 5.18 in the unmedicated group; F = 0.35; df= 1, 45: P = NS), we think that the slightly better WCST performance in the

medicated group may be more related to im- provements in sustained attention and/or mental flexibility as a result of medication rather than to remediation of a specific frontal lobe dysfunction.

In fact, no differences were found in the WCST PE index, which is considered a good indicator of DLPC dysfunction (Milner, 1963). The slightly better neuropsychological performance associated

with medication may be linked to a generalized enhancement of frontal functioning attributable to actions of antidepressant drugs that improve cog- nitive abilities. There is insufficient evidence, how-

ever, that antidepressant medication corrects a preexisting specific deficit of the DLPC in OCD. The drug-related changes probably reflect some components of the state of illness (e.g., symptoms

like anxiety, fear of inadequacy, inattention. and mood disorders that are not assessed by the Y- BOCS) and do not constitute trait markers specific to OCD.

Since previous neuropsychological studies in

OCD patients have found inconsistent results, it is possible that OCD may be a heterogeneous condi- tion that involves a number of still-to-be-identified biological and clinical factors. Our attempt to sub-

divide the OCD group was based on certain symp- tomatological characteristics of the patients, and

42 M. Ahbrazzese et al. I Psychiatry Research 58 (1995) 37-43

analyses did not reveal significant differences in WCST performance among the four clinical subgroups. Other attempts to uncover differences related to clinical heterogeneity were also unsuc- cessful. No differences were found between OCD patients with or without comorbid anxiety or mood disorders. Moreover, we did not find signifi- cant differences between OCD patients who show- ed early phobic symptoms (e.g., fear of dirty objects, oil, or bacteria) and OCD patients who were characterized by checking symptoms or sexual/religious thoughts at the onset of their illness.

The major conclusions of our study can be sum- marized as follows: (1) OCD patients did not demonstrate failures in comprehension or ability to solve a neuropsychological test, the WCST, when compared with a matched group of normal subjects. (2) Evaluation of WCST indices did not reveal significant differences among clinical subgroups. This finding suggests that the clinical, symptomatological, and demographic character- istics of OCD are not related to WCST perfor- mance. Similarly, pha~acolo~cal treatment did not significantly improve overall WCST perfor- mance. (3) Since OCD patients did not differ from normal subjects in their performance of the WCST, which has been reported in the neurological and psychiatric literature to be highly sensitive to dysfunctions of the DLPC (Milner, 1963; Robinson et al., 1980; Goldberg et al., 1987; Bellini et al., 1991), a lesion in the DLPC does not appear to be etiologically implicated in OCD.

The increased glucose metabolism in the frontal lobes and the basal ganglia reported in PET stud- ies of OCD patients (e.g., Baxter et al., 1987) could suggest a certain type of “hyperfrontality” in OCD patients, while findings of “hypofrontality” have been reported in a number of metabolic studies of schizophrenic patients (e.g., Buchsbaum et al., 1984; Wolkin et al., 1988; for review, see Buchsbaum, 1990). A recent study (Abbruzzese et al., 1995) that compared WCS?: performance in OCD patients, normal subjects, and schizophrenic patients revealed that only the schizophrenic pa- tients had impaired performance and that OCD patients showed a WCST profile similar to that of normal subjects.

The inconsistent results obtained in studies of frontal lobe involvement in the pathophysiology of OCD may also reflect an inadequate sensitivity of test procedures. Further investigations will be needed to clarify the discrepancies. A more com- prehensive assessment of OCD heterogeneity should encompass additional biological, psycho- logical, and clinical variables, which may prove more informative.

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