- Email: [email protected]
The effects of typical antipsychotics, clozapine, and risperidone on neuropsychological test performance in schizophrenia
Schizophrenia Research 40 (1999) 255–261 www.elsevier.com/locate/schres
Letters to the Editors The effects of typical antipsychotics, clozapine, and risperidone on neuropsychological test performance in schizophrenia Dear Editors, Evidence has begun to emerge that atypical antipsychotic medications differ from typical antipsychotics in their effects on memory and executive function in schizophrenia. Specifically, administration of typical antipsychotics has generally been found to produce no significant change in memory or executive functioning (see Goldberg and Weinberger, 1996 for a review). In contrast, clozapine, the prototype of atypical antipsychotics, has been shown to have positive effects on schizophrenic patients’ verbal recall and verbal fluency, and possible adverse effects on visuospatial memory (Goldberg et al., 1993; Hagger et al., 1993; Buchanan et al., 1994; Hoff et al., 1996). More recently, the effects of a new antipsychotic medication, risperidone, on schizophrenic patients’ cognitive functioning have been examined, and risperidone has been found to have beneficial effects on verbal memory, visuospatial memory, and executive function (Daniel, 1994; Green et al., 1997; McGurk et al., 1997). We compared schizophrenic inpatients (N=30) who were non-randomly, naturalistically assigned to treatment with typical antipsychotics, clozapine, or risperidone, on neuropsychological measures of memory and executive function. Verbal memory was assessed using the Selective Reminding Test and the Verbal Paired Associates subtest of the Wechsler Memory Scale ( WMS), and visuospatial memory was measured using the Visuospatial Reproduction subtest of the WMS. Executive function was assessed using the Controlled Oral Word Association Test (COWAT ), Trails B, and the
Wisconsin Card Sorting Test ( WCST ). The typical antipsychotic, clozapine, and risperidone groups were compared on each of these tests using a Kruskal–Wallis ( K–W ) one-way analysis of variance (ANOVA). Neuropsychological test scores for each of the three groups are shown in Table 1. The group main effect was significant for the Long-Term Storage (LTS) score from the Selective Reminding Test, K– W=6.99, p=0.03. Follow-up analyses revealed that risperidone patients had significantly higher scores on LTS than clozapine patients, p<0.02. The differences between risperidone and typical patients and between clozapine and typical patients were not statistically significant. Also, the group main effect for the Continuous Long-Term Retrieval (CLTR) score from the Selective Reminding Test was significant, K–W=6.11, p<0.05. Follow-up analyses revealed no statistically significant differences between groups, although the mean for the risperidone group was the highest. In addition, the group main effect for the WMS Verbal Paired Associates subtest approached significance, K–W=5.15, p<0.08, with the mean for the risperidone group being higher than the means for the typical and clozapine groups. There were no significant differences among the groups on the WMS Visual Reproduction subtest, COWAT, Trails B, number of categories achieved on the WCST, or the number of perseverative errors made on the WCST. These preliminary findings suggest that patients taking risperidone exhibit better verbal memory function than patients on clozapine. Future studies are needed to replicate these findings in a larger sample, to examine functional correlates of improved verbal memory, and to assess the longterm effects of different medications on verbal memory.
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Letters to the Editors / Schizophrenia Research 40 (1999) 255–261
Table 1 Performance on neuropsychological testsa Typical
Verbal memory LTS CLTR WMS Paired Assoc. Visuospatial memory WMS Visual Executive function COWAT WCST categories WCST pers. Errors Trails B
Clozapine
Risperidone
K–W
( p)
n
Score
n
Score
n
Score
6 6 7
65.67±12.50 56.33±3.27 62.29±11.27
8 8 7
55.13±0.35 57.00±4.90 69.14±13.89
12 12 12
73.92±16.46 67.58±16.63 82.42±20.26
6.99 6.11 5.15
(0.03) (0.047) (0.076)
7
85.14±23.02
7
81.71±15.04
12
83.08±19.82
0.02
(0.989)
6 5 5 7
99.33±27.62 82.00±24.65 86.20±25.23 89.71±24.35
9 7 7 8
93.67±23.45 70.43±16.74 68.57±11.69 65.75±19.25
10 10 10 11
77.50±17.59 84.30±18.55 75.40±18.00 74.09±19.79
4.28 2.39 1.63 3.34
(0.118) (0.302) (0.442) (0.188)
a Neuropsychological test scores are standardized scores. See text for abbreviations.
References Buchanan, R.W., Holstein, C., Breier, A., 1994. The comparative efficacy and long-term effect of clozapine treatment on neuropsychological test performance. Biol. Psychiatry 36, 717–725. Daniel, D.G., 1994. Comparison of risperidone and clozapine on clinical and cognitive functions in psychotic disorders. Biol. Psychiatry 35, 667 Goldberg, T.E., Greenberg, R.D., Griffin, S.J., Gold, J.M., Kleinman, J.E., Pickar, D., Schulz, S.C., Weinberger, D.R., 1993. The effect of clozapine on cognition and psychiatric symptoms in patients with schizophrenia. Br. J. Psychiatry 162, 43–48. Goldberg, T.E., Weinberger, D.R., 1996. Effects of neuroleptic medications on the cognition of patients with schizophrenia: a review of recent studies. J. Clin. Psychiatry 57, 62–65. Green, M.F., Marshall, B.D., Wirshing, W.C., Ames, D., Marder, S.R., McGurk, S., Kern, R.S., Mintz, J., 1997. Does risperidone improve verbal working memory in treatmentresistant schizophrenia? Am. J. Psychiatry 154, 799–804. Hagger, C., Buckley, P., Kenny, J.T., Friedman, L., Ubogy, D., Meltzer, H.Y., 1993. Improvement in cognitive functions and psychiatric symptoms in treatment-refractory schizophrenic patients receiving clozapine. Biol. Psychiatry 34, 702–712. Hoff, A.L., Faustman, W.O., Wieneke, M., Espinoza, S., Costa, M., Wolkowitz, O., Csernansky, J.G., 1996. The effects of clozapine on symptom reduction, neurocognitive function, and clinical management in treatment-refractory state hospital schizophrenic inpatients. Neuropsychopharmacology 15, 361–369. McGurk, S.R., Green, M.F., Wirshing, W.C., Ames, D., Marshall, B.D., Marder, S.R., Mintz, J., 1997. The effects of risperidone vs haloperidol on cognitive functioning in treatment-resistant schizophrenia: The Trail Making test. CNS Spectrums 2, 60–64.
Kelly S. Earnst * Psychology Service, Ann Arbor Veterans Administration Medical Center, Ann Arbor, MI, USA E-mail address: [email protected] ( K.S. Earnst) Stephan F. Taylor Irma C. Smet Department of Psychiatry, University of Michigan Medical Center, Ann Arbor, MI, USA Robert S. Goldman Long Island Jewish Medical Center/ Hillside Hospital, New York, NY, USA Rajiv Tandon Stanley Berent Department of Psychiatry, University of Michigan Medical Center, Ann Arbor, MI, USA * Corresponding author. Present address: University of Alabama at Birmingham, Department of Neurology, 1216 Jefferson Tower, 625 19th Street South, Birmingham, AL 35233-7340, USA. 0920-9964/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved. PII: S0 9 20 - 9 96 4 ( 9 9 ) 00 0 6 4 -X
Letters to the Editors / Schizophrenia Research 40 (1999) 255–261
Span of apprehension in adolescents with schizophrenia or ADHD Dear Editors, Despite increasing evidence of attentional deficits in patients with schizophrenia and patients with ADHD, few studies have directly compared the two groups. Several studies have shown that performance on the partial-report version of span tasks is sensitive to schizophrenia (Asarnow et al., 1991). Regarding the specificity of span of apprehension to schizophrenia, research data are still inconclusive (Rund et al., 1992; Addington and Addington, 1997; Buchanan, 1997). Span tasks have been used only to a limited degree in research on subjects with ADHD. Denton and McIntire (1978) demonstrated a decreased accuracy on a span task in hyperactive boys compared to normal boys. McIntire et al. (1978) showed that the span performance of hyperactive and normal boys was affected equally by variations in signal-noise similarity and noise redundancy. Only Asarnow et al. (1994) have compared the span performance of subjects with schizophrenia and ADHD. They compared children with schizophrenia, children with ADHD, and mental agematched normal children. The schizophrenia patients detected significantly fewer targets than the ADHD children on some conditions, but did not differ from them on others. Adults or adolescents with schizophrenia have never been compared to ADHD patients. The aim of the present study was to assess the specificity and sensitivity of two span of apprehension tasks in relation to schizophrenia. This was done by comparing the performance of firstepisode schizophrenic patients with that of both age-matched healthy controls, and another neuropsychiatric group characterized by attentional dysfunctions, namely ADHD. Nineteen subjects with a DSM-III-R (American Psychiatric Association, 1987) diagnosis of a schizophrenic disorder were included: 14 males, five females. The mean age was 16.2 years (s.d.= 1.1). Twenty subjects fulfilled the DSM-III-R cri-
257
teria for ADHD. All were males, with a mean age of 14.1 years (s.d.=1.5). Fourteen schizophrenia patients were drug-free. Twelve ADHD subjects used stimulant medication. The medication was discontinued at least 24 h before testing. The ADHD group was significantly younger than the two other groups. This group also consisted of more males than females, as did the group of patients with schizophrenia. The comparison group consisted of 30 healthy adolescents. Sixteen subjects were males, and 14 were females. The mean age was 15.7 years (s.d.=1.6). Two span of apprehension tasks were applied. One of them (SPAN; Asarnow and Nuechterlein, unpublished test) is a forced-choice version in which sets of three or 12 letters are flashed for a period of 83 ms on the screen. The other task, SAT (Spaulding et al., 1981), consists of three different conditions. The subject is instructed to watch the screen for a specified digit and to press a button when it appears. The second and third condition scores were summarized and are those reported here. In these two conditions, an array of eight digits are presented which may or may not contain the target. Responses are scored for the number of hits and commission errors. In addition, an accuracy score was computed, consisting of the number of hits plus correct rejections. SPAN results. The means and standard deviations of the correct identification of target letters are shown in Table 1. Data were analyzed by a 3 (groups)×2 (array size) analysis of variance with repeated measures. There were significant effects of groups on correct responses, F(2,66)=3.63, p= 0.03. Post-hoc comparisons (Duncan) between groups revealed that the schizophrenia patients performed significantly worse than the normal comparison group ( p<0.05). A hit sum score provided a significant distinction between schizophrenic subjects and normal controls: x2 (1)=6.41, p=0.01. Twelve of the 19 schizophrenic subjects scored 107 or below, and 22 of the 30 normal controls scored above 107. The two patient groups did not differ in hit rate, with 11 out of 20 ADHD subjects scoring 107 or less. SAT results. The mean number of SAT hit scores, errors of commission scores, and accuracy
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Letters to the Editors / Schizophrenia Research 40 (1999) 255–261
Table 1 Group means and standard deviations for SPAN and SAT performance SPAN Score
Normal control (n=30) Schizophrenia (n=19) ADHD (n=20)
SAT
Three-letter hit
Three-letter hit RT (ms)
12-letter hit
12-letter hit RT (ms)
Hit (cond. 2+cond. 3)
Commision error (cond. 2+cond. 3)
Accuracy score
Mean
s.d.
Mean
s.d.
Mean
s.d.
Mean
s.d.
Mean
s.d.
Mean
s.d.
Mean
s.d.
61.46
2.08
705.30
131.11
49.53
6.16
1000.17
239.63
16.20
2.30
2.97
2.95
73.23
3.96
58.36
5.89
773.31
109.13
46.47
5.57
1064.84
216.61
15.74
2.83
5.11
5.27
70.63
5.79
59.70
3.06
794.15
168.76
45.90
6.63
1085.70
210.50
15.50
2.86
6.95
7.68
68.55
9.42
scores are shown in Table 1. An overall analysis of variance with the three groups was performed for the hit scores and the commission score. On the correct hits condition, the groups did not differ significantly from each other. No single cut-off score resulted in a significant distinction of subjects. Regarding errors of commission, there was a significant difference between groups, F(2,66)= 3.43, p=0.04. The ADHD group was significantly ( p<0.05) more impaired than the normal comparison group. When comparing the schizophrenia group to the normal comparison group, a difference at trend level was found: t(1,47)=1.82, p= 0.075, with the schizophrenia group having more commission errors. No single cut-off score of commission resulted in a significant distinction of subjects. An ANOVA with the three groups was performed for the accuracy score. A significant group effect was found: F(2,66)=3.25, p=0.045. Posthoc comparisons between groups showed that the ADHD group performed significantly worse than the normal comparison group. The effects of age and sex were controlled for by using a covariance procedure. The results did not change significantly. The present results confirm that the SPAN task is sensitive to schizophrenia. First-episode adolescents with schizophrenia showed the same kind of impairment on the SPAN task that has been reported in studies with schizophrenic children as well as with older, more chronic patients. However, the existence of a diagnostic specificity for the SPAN measure was not confirmed.
The SPAN performance in the ADHD group was not significantly poorer than among normal controls. This finding supports the results of McIntire et al. (1978) and indicates that performance deficits decrease when ADHD children grow older. Rund et al. (1992) found that the SAT measure had a certain degree of sensitivity for psychotic disturbances. In the present study, neither the SAT hit measure nor the SAT commission measure was specifically impaired in the schizophrenic patients. However, the SAT commission score as well as the accuracy score proved to be sensitive to the ADHD subjects. The poor performance of ADHD subjects on the commission error score indicates that they are not able to withhold responses in a relatively unstructured situation.
Acknowledgements This study was supported by grants from the Norwegian Research Council (377.94/013), the Nansen Fund, and from Haldis and Josef Andresen’s Foundation.
References Addington, J., Addington, D., 1997. Attentional vulnerability indicators in schizophrenia and bipolar disorder. Schizophr. Res. 23, 197–204. American Psychiatric Association, 1987. Diagnostic and Statis-
Letters to the Editors / Schizophrenia Research 40 (1999) 255–261 tical Manual of Mental Disorders. 3rd rev. ed. American Psychiatric Association, Washington, DC. Asarnow, R.F., Granholm, E., Sherman, T., 1991. Span of apprehension in schizophrenia. Handbook of Schizophrenia. Steinhauer, S.R., Gruzelier, J.H., Zubin, J. ( Eds.), Neuropsychology, Psychophysiology and Information Processing. Vol. 5. Elsevier, Amsterdam, pp. 335–370. Asarnow, R.F., Asamen, J., Granholm, E., Sherman, T., Watkins, J.M., Williams, M.E., 1994. Cognitive/neuropsychological studies of children with a schizophrenic disorder. Schizophr. Bull. 20, 647–669. Buchanan, R.W., Strauss, M.E., Breier, A., Kirpatric, B., Carpenter, W.T., 1997. Attentional impairments in deficit and non-deficit forms of schizophrenia. Am. J. Psychiatry 154, 363–389. Denton, L.C., McIntire, C.W., 1978. Span of apprehension in hyperactive boys. J. Abnorm. Child Psychol. 6, 19–24. McIntire, C.W., Blackwell, S.L., Denton, C.L., 1978. The effect of noise distractibility on the spans of apprehension of hyperactive boys. J. Abnorm. Child Psychol. 6, 483–492. Rund, B.R., Orbeck, A.L., Landro, N.I., 1992. Vigilance deficits in schizophrenics and affectively disturbed patients. Acta Psychiatr. Scand. 86, 207–212. Spaulding, W., Hargrove, S., Crinean, W., Martin, T., 1981. The microcomputer based laboratory for psychopathology research in rural settings. Behav. Res. Meth. Instrum. 13, 616–623.
Bjørn Rishovd Rund Institute of Psychology, University of Oslo, P.O. Box 1094, Blindern N-0317 Oslo, Norway E-mail address: [email protected] (B.R. Rund) Merete Øie Pa˚l Zeiner Centre for Child and Adolescent Psychiatry, P.O. Box 26, Vinderen, N-0319 Oslo, Norway Kjetil Sundet Department of Psychosomatic and Behavioral Medicine, The National Hospital, N-0027 Oslo, Norway * Corresponding author. Tel.: +47-22-85-53-39; fax: +47-22-85-44-19. 0920-9964/99/$ – see front matter © 1999 Elsevier Science B.V. All rights reserved. PII: S0 9 2 0 -9 9 6 4 ( 9 9 ) 0 0 06 0 - 2
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What’s it like to be mentally ill? Dear Editors It took about six months, from the time of a very stressful event in my life until I couldn’t function any more. During this time I began to think that something strange was going on around me. This was just a thought at first. My husband and I have a family business. We have regular customers in our shop and of course I had got to know these customers. My thoughts about the customers began to change. I started to wonder why they said things in the ways that they did and what they ‘really’ meant. I became more and more frightened of the customers I thought that the things that they said meant either that they were attracted to me or wanted to hurt me, and then finally I thought that they were going to rape me. I began to think that they had better watch out in case my husband catches them (the customers were really only being friendly but my thoughts were becoming more bizarre). I began to believe that someone was playing a game with me on a computer and he was sending messages via these customers. I did not know who ‘he’ was — I thought he was playing chess, with the customers as chess pieces. I don’t play chess so you can imagine how difficult it was for me to try to keep one step ahead of him. At the same time, at home I became obsessed with Freddie Mercury (from the rock group Queen). I played his tapes all the time, I joined the fan club, I was on a high and played a video recording of him over and over again. I loved the artistic flair, the costumes, the dancing and the singing. I was telling everyone what a wonderful person he was. This was my escape from the dreaded game of chess, which you must understand was by now becoming very frightening and a life or death situation in my mind. I started speaking in French to my husband about what ‘they’ were doing — I don’t speak French normally — I haven’t spoken it since I was at school, but I thought that ‘they’ would not be able to understand me. Then at home I started sleeping on the floor at the bottom of the bed — things were really getting
260
Letters to the Editors / Schizophrenia Research 40 (1999) 255–261
bad — I could not escape from the shop. I had a lot of responsibility there. I had to suffer the game every day. I finally confronted one of the customers about it, but of course he didn’t have a clue what I was talking about. I wanted to get the persecution out into the open. I had been suffering all by myself. Of course my husband didn’t understand either and ushered me into the office and tried to calm me down. I cried all night. My husband said that I didn’t have to go to the shop anymore. My mind was now working at a thousand miles an hour. He had won — the person with the computer — I shut down. I didn’t say anything. It was too incriminating. I called my friend — I was sitting there with all the curtains closed, as I was frightened that ‘they’ would come to get me. I was crying. My friend came. I told her everything. She said to me ‘‘God knows Diana you don’t deserve it but I think you have depression. You had better go to see the doctor’’. When she had gone I phoned the doctor’s office and arranged to see him in a couple of days time. Unknown to me, my friend went to see my husband and they came back together to my home and told me that they had arranged an emergency appointment with the doctor for me. I went in to see the doctor by myself. I trusted him, and I knew that as a doctor he could not be involved in what was going on. I wanted to tell him everything but my mind was racing and I just couldn’t collect my thoughts enough to put my experiences into words. I was sobbing without really being able to cry. The Doctor obviously realised that something was wrong but had no real idea of what was going through my mind. He said to me ‘‘What would you say if I said you were having a nervous breakdown?’’. I said ‘‘I think you are probably right’’. He was very sympathetic. He told me that I should rest for the next month and that he would arrange for me to see a specialist, looking back, I obviously hadn’t managed to show him how desperate I had become. He also prescribed some sleeping pills for me ( Temazepam). The pills knocked me out. I remained at home for the next couple of weeks and I spent most of the time in bed. A consultant family doctor (from the local medical school ) came to see me a week or two later. I wanted to talk to him in the car because
I was so frightened that people would overhear what I was saying. He insisted on seeing me in my bedroom so that he could give me a physical examination. I shut all the doors and windows so that ‘they’ would not be able to hear what I said, and I was even misinterpreting some of his comments. He told me that my heart was racing like I was in the middle of a race. He prescribed some Propanolol to slow my heart down and he arranged an appointment for me to see a psychiatrist who held clinics at my local health centre. It took another two weeks before the psychiatrist could see me for a routine appointment — so again I had not managed to convey to this doctor how frightened and distressed I felt inside or he would have arranged an emergency appointment for me. Through this period, my family and friends were very worried — they had never seen me like this. I remember that my mother and my sister came to see me. I was rolling on the floor in agony. I felt a terrible tension in my back and in my body and I talked to my dog as if she was my grandmother. By this time I had become paranoid about my family too. I came believe that they were also involved in what was going on. After some days which I spent largely in bed, knocked out by the sleeping pills, my family began to tell me to do things again like take a shower or do the laundry. One day when I was in the shower I looked at a green ring on my finger and discovered that I was an African princess. I began hallucinating. It was like having a dream, in full colour, with all the fear of a nightmare, whilst wide-awake. You see I might have been an African Princess sitting by a beautiful lake, but there were some men in the bushes behind me who were trying to steal me away into slavery, and so it went on. It was summer, I remember sitting by a pond and the bees were talking about me in the flowering fuschia bushes. The magpies with their chattering calls and young chicks were laughing at me, the pond was polluted, it was a time of fear, fear and more fear. I heard dogs howling at the musical chimes from an ice-cream seller’s van and I thought they had changed into the hounds of hell, and were coming to get me. I was misconstruing the newspaper headlines taking them to be personal messages for me, even
Letters to the Editors / Schizophrenia Research 40 (1999) 255–261
the coffee canister in my kitchen wasn’t safe to look at — it too had a message. Car registration plates had messages, it was just unbearable. Please understand that these things were occurring all day, everyday. I did mystical things too. I wore crystals and collected feathers that birds had left in the garden because I thought that they were things that would make me better. At about this time I saw a psychiatrist for the first time. The psychiatrist prescribed Trifluoperazine for me, and slowly these experiences began to subside; however, I continued to feel that I could do very little except simply look after myself. My only support through this dreadful time was my family doctor. I felt that I just could not trust anyone else, but even so, I never really managed
261
to convey the depth of my distress to my doctor. It was a long time before I became stable, then I went to a day hospital where I had a counsellor who talked to me for many hours. He had an empathy with me and helped me to talk things through. I started to do occupational therapy, art, pottery, etc., and then I began to feel I was finding myself again. Today I am happy but I must stress that it is because I take my medication and I would like to thank my family doctor for his support. Diana Gregory Manchester 0920-9964/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved. PII: S0 9 20 - 9 96 4 ( 9 9 ) 00 0 4 9 -3
Letters to the Editors The effects of typical antipsychotics, clozapine, and risperidone on neuropsychological test performance in schizophrenia Dear Editors, Evidence has begun to emerge that atypical antipsychotic medications differ from typical antipsychotics in their effects on memory and executive function in schizophrenia. Specifically, administration of typical antipsychotics has generally been found to produce no significant change in memory or executive functioning (see Goldberg and Weinberger, 1996 for a review). In contrast, clozapine, the prototype of atypical antipsychotics, has been shown to have positive effects on schizophrenic patients’ verbal recall and verbal fluency, and possible adverse effects on visuospatial memory (Goldberg et al., 1993; Hagger et al., 1993; Buchanan et al., 1994; Hoff et al., 1996). More recently, the effects of a new antipsychotic medication, risperidone, on schizophrenic patients’ cognitive functioning have been examined, and risperidone has been found to have beneficial effects on verbal memory, visuospatial memory, and executive function (Daniel, 1994; Green et al., 1997; McGurk et al., 1997). We compared schizophrenic inpatients (N=30) who were non-randomly, naturalistically assigned to treatment with typical antipsychotics, clozapine, or risperidone, on neuropsychological measures of memory and executive function. Verbal memory was assessed using the Selective Reminding Test and the Verbal Paired Associates subtest of the Wechsler Memory Scale ( WMS), and visuospatial memory was measured using the Visuospatial Reproduction subtest of the WMS. Executive function was assessed using the Controlled Oral Word Association Test (COWAT ), Trails B, and the
Wisconsin Card Sorting Test ( WCST ). The typical antipsychotic, clozapine, and risperidone groups were compared on each of these tests using a Kruskal–Wallis ( K–W ) one-way analysis of variance (ANOVA). Neuropsychological test scores for each of the three groups are shown in Table 1. The group main effect was significant for the Long-Term Storage (LTS) score from the Selective Reminding Test, K– W=6.99, p=0.03. Follow-up analyses revealed that risperidone patients had significantly higher scores on LTS than clozapine patients, p<0.02. The differences between risperidone and typical patients and between clozapine and typical patients were not statistically significant. Also, the group main effect for the Continuous Long-Term Retrieval (CLTR) score from the Selective Reminding Test was significant, K–W=6.11, p<0.05. Follow-up analyses revealed no statistically significant differences between groups, although the mean for the risperidone group was the highest. In addition, the group main effect for the WMS Verbal Paired Associates subtest approached significance, K–W=5.15, p<0.08, with the mean for the risperidone group being higher than the means for the typical and clozapine groups. There were no significant differences among the groups on the WMS Visual Reproduction subtest, COWAT, Trails B, number of categories achieved on the WCST, or the number of perseverative errors made on the WCST. These preliminary findings suggest that patients taking risperidone exhibit better verbal memory function than patients on clozapine. Future studies are needed to replicate these findings in a larger sample, to examine functional correlates of improved verbal memory, and to assess the longterm effects of different medications on verbal memory.
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Letters to the Editors / Schizophrenia Research 40 (1999) 255–261
Table 1 Performance on neuropsychological testsa Typical
Verbal memory LTS CLTR WMS Paired Assoc. Visuospatial memory WMS Visual Executive function COWAT WCST categories WCST pers. Errors Trails B
Clozapine
Risperidone
K–W
( p)
n
Score
n
Score
n
Score
6 6 7
65.67±12.50 56.33±3.27 62.29±11.27
8 8 7
55.13±0.35 57.00±4.90 69.14±13.89
12 12 12
73.92±16.46 67.58±16.63 82.42±20.26
6.99 6.11 5.15
(0.03) (0.047) (0.076)
7
85.14±23.02
7
81.71±15.04
12
83.08±19.82
0.02
(0.989)
6 5 5 7
99.33±27.62 82.00±24.65 86.20±25.23 89.71±24.35
9 7 7 8
93.67±23.45 70.43±16.74 68.57±11.69 65.75±19.25
10 10 10 11
77.50±17.59 84.30±18.55 75.40±18.00 74.09±19.79
4.28 2.39 1.63 3.34
(0.118) (0.302) (0.442) (0.188)
a Neuropsychological test scores are standardized scores. See text for abbreviations.
References Buchanan, R.W., Holstein, C., Breier, A., 1994. The comparative efficacy and long-term effect of clozapine treatment on neuropsychological test performance. Biol. Psychiatry 36, 717–725. Daniel, D.G., 1994. Comparison of risperidone and clozapine on clinical and cognitive functions in psychotic disorders. Biol. Psychiatry 35, 667 Goldberg, T.E., Greenberg, R.D., Griffin, S.J., Gold, J.M., Kleinman, J.E., Pickar, D., Schulz, S.C., Weinberger, D.R., 1993. The effect of clozapine on cognition and psychiatric symptoms in patients with schizophrenia. Br. J. Psychiatry 162, 43–48. Goldberg, T.E., Weinberger, D.R., 1996. Effects of neuroleptic medications on the cognition of patients with schizophrenia: a review of recent studies. J. Clin. Psychiatry 57, 62–65. Green, M.F., Marshall, B.D., Wirshing, W.C., Ames, D., Marder, S.R., McGurk, S., Kern, R.S., Mintz, J., 1997. Does risperidone improve verbal working memory in treatmentresistant schizophrenia? Am. J. Psychiatry 154, 799–804. Hagger, C., Buckley, P., Kenny, J.T., Friedman, L., Ubogy, D., Meltzer, H.Y., 1993. Improvement in cognitive functions and psychiatric symptoms in treatment-refractory schizophrenic patients receiving clozapine. Biol. Psychiatry 34, 702–712. Hoff, A.L., Faustman, W.O., Wieneke, M., Espinoza, S., Costa, M., Wolkowitz, O., Csernansky, J.G., 1996. The effects of clozapine on symptom reduction, neurocognitive function, and clinical management in treatment-refractory state hospital schizophrenic inpatients. Neuropsychopharmacology 15, 361–369. McGurk, S.R., Green, M.F., Wirshing, W.C., Ames, D., Marshall, B.D., Marder, S.R., Mintz, J., 1997. The effects of risperidone vs haloperidol on cognitive functioning in treatment-resistant schizophrenia: The Trail Making test. CNS Spectrums 2, 60–64.
Kelly S. Earnst * Psychology Service, Ann Arbor Veterans Administration Medical Center, Ann Arbor, MI, USA E-mail address: [email protected] ( K.S. Earnst) Stephan F. Taylor Irma C. Smet Department of Psychiatry, University of Michigan Medical Center, Ann Arbor, MI, USA Robert S. Goldman Long Island Jewish Medical Center/ Hillside Hospital, New York, NY, USA Rajiv Tandon Stanley Berent Department of Psychiatry, University of Michigan Medical Center, Ann Arbor, MI, USA * Corresponding author. Present address: University of Alabama at Birmingham, Department of Neurology, 1216 Jefferson Tower, 625 19th Street South, Birmingham, AL 35233-7340, USA. 0920-9964/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved. PII: S0 9 20 - 9 96 4 ( 9 9 ) 00 0 6 4 -X
Letters to the Editors / Schizophrenia Research 40 (1999) 255–261
Span of apprehension in adolescents with schizophrenia or ADHD Dear Editors, Despite increasing evidence of attentional deficits in patients with schizophrenia and patients with ADHD, few studies have directly compared the two groups. Several studies have shown that performance on the partial-report version of span tasks is sensitive to schizophrenia (Asarnow et al., 1991). Regarding the specificity of span of apprehension to schizophrenia, research data are still inconclusive (Rund et al., 1992; Addington and Addington, 1997; Buchanan, 1997). Span tasks have been used only to a limited degree in research on subjects with ADHD. Denton and McIntire (1978) demonstrated a decreased accuracy on a span task in hyperactive boys compared to normal boys. McIntire et al. (1978) showed that the span performance of hyperactive and normal boys was affected equally by variations in signal-noise similarity and noise redundancy. Only Asarnow et al. (1994) have compared the span performance of subjects with schizophrenia and ADHD. They compared children with schizophrenia, children with ADHD, and mental agematched normal children. The schizophrenia patients detected significantly fewer targets than the ADHD children on some conditions, but did not differ from them on others. Adults or adolescents with schizophrenia have never been compared to ADHD patients. The aim of the present study was to assess the specificity and sensitivity of two span of apprehension tasks in relation to schizophrenia. This was done by comparing the performance of firstepisode schizophrenic patients with that of both age-matched healthy controls, and another neuropsychiatric group characterized by attentional dysfunctions, namely ADHD. Nineteen subjects with a DSM-III-R (American Psychiatric Association, 1987) diagnosis of a schizophrenic disorder were included: 14 males, five females. The mean age was 16.2 years (s.d.= 1.1). Twenty subjects fulfilled the DSM-III-R cri-
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teria for ADHD. All were males, with a mean age of 14.1 years (s.d.=1.5). Fourteen schizophrenia patients were drug-free. Twelve ADHD subjects used stimulant medication. The medication was discontinued at least 24 h before testing. The ADHD group was significantly younger than the two other groups. This group also consisted of more males than females, as did the group of patients with schizophrenia. The comparison group consisted of 30 healthy adolescents. Sixteen subjects were males, and 14 were females. The mean age was 15.7 years (s.d.=1.6). Two span of apprehension tasks were applied. One of them (SPAN; Asarnow and Nuechterlein, unpublished test) is a forced-choice version in which sets of three or 12 letters are flashed for a period of 83 ms on the screen. The other task, SAT (Spaulding et al., 1981), consists of three different conditions. The subject is instructed to watch the screen for a specified digit and to press a button when it appears. The second and third condition scores were summarized and are those reported here. In these two conditions, an array of eight digits are presented which may or may not contain the target. Responses are scored for the number of hits and commission errors. In addition, an accuracy score was computed, consisting of the number of hits plus correct rejections. SPAN results. The means and standard deviations of the correct identification of target letters are shown in Table 1. Data were analyzed by a 3 (groups)×2 (array size) analysis of variance with repeated measures. There were significant effects of groups on correct responses, F(2,66)=3.63, p= 0.03. Post-hoc comparisons (Duncan) between groups revealed that the schizophrenia patients performed significantly worse than the normal comparison group ( p<0.05). A hit sum score provided a significant distinction between schizophrenic subjects and normal controls: x2 (1)=6.41, p=0.01. Twelve of the 19 schizophrenic subjects scored 107 or below, and 22 of the 30 normal controls scored above 107. The two patient groups did not differ in hit rate, with 11 out of 20 ADHD subjects scoring 107 or less. SAT results. The mean number of SAT hit scores, errors of commission scores, and accuracy
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Letters to the Editors / Schizophrenia Research 40 (1999) 255–261
Table 1 Group means and standard deviations for SPAN and SAT performance SPAN Score
Normal control (n=30) Schizophrenia (n=19) ADHD (n=20)
SAT
Three-letter hit
Three-letter hit RT (ms)
12-letter hit
12-letter hit RT (ms)
Hit (cond. 2+cond. 3)
Commision error (cond. 2+cond. 3)
Accuracy score
Mean
s.d.
Mean
s.d.
Mean
s.d.
Mean
s.d.
Mean
s.d.
Mean
s.d.
Mean
s.d.
61.46
2.08
705.30
131.11
49.53
6.16
1000.17
239.63
16.20
2.30
2.97
2.95
73.23
3.96
58.36
5.89
773.31
109.13
46.47
5.57
1064.84
216.61
15.74
2.83
5.11
5.27
70.63
5.79
59.70
3.06
794.15
168.76
45.90
6.63
1085.70
210.50
15.50
2.86
6.95
7.68
68.55
9.42
scores are shown in Table 1. An overall analysis of variance with the three groups was performed for the hit scores and the commission score. On the correct hits condition, the groups did not differ significantly from each other. No single cut-off score resulted in a significant distinction of subjects. Regarding errors of commission, there was a significant difference between groups, F(2,66)= 3.43, p=0.04. The ADHD group was significantly ( p<0.05) more impaired than the normal comparison group. When comparing the schizophrenia group to the normal comparison group, a difference at trend level was found: t(1,47)=1.82, p= 0.075, with the schizophrenia group having more commission errors. No single cut-off score of commission resulted in a significant distinction of subjects. An ANOVA with the three groups was performed for the accuracy score. A significant group effect was found: F(2,66)=3.25, p=0.045. Posthoc comparisons between groups showed that the ADHD group performed significantly worse than the normal comparison group. The effects of age and sex were controlled for by using a covariance procedure. The results did not change significantly. The present results confirm that the SPAN task is sensitive to schizophrenia. First-episode adolescents with schizophrenia showed the same kind of impairment on the SPAN task that has been reported in studies with schizophrenic children as well as with older, more chronic patients. However, the existence of a diagnostic specificity for the SPAN measure was not confirmed.
The SPAN performance in the ADHD group was not significantly poorer than among normal controls. This finding supports the results of McIntire et al. (1978) and indicates that performance deficits decrease when ADHD children grow older. Rund et al. (1992) found that the SAT measure had a certain degree of sensitivity for psychotic disturbances. In the present study, neither the SAT hit measure nor the SAT commission measure was specifically impaired in the schizophrenic patients. However, the SAT commission score as well as the accuracy score proved to be sensitive to the ADHD subjects. The poor performance of ADHD subjects on the commission error score indicates that they are not able to withhold responses in a relatively unstructured situation.
Acknowledgements This study was supported by grants from the Norwegian Research Council (377.94/013), the Nansen Fund, and from Haldis and Josef Andresen’s Foundation.
References Addington, J., Addington, D., 1997. Attentional vulnerability indicators in schizophrenia and bipolar disorder. Schizophr. Res. 23, 197–204. American Psychiatric Association, 1987. Diagnostic and Statis-
Letters to the Editors / Schizophrenia Research 40 (1999) 255–261 tical Manual of Mental Disorders. 3rd rev. ed. American Psychiatric Association, Washington, DC. Asarnow, R.F., Granholm, E., Sherman, T., 1991. Span of apprehension in schizophrenia. Handbook of Schizophrenia. Steinhauer, S.R., Gruzelier, J.H., Zubin, J. ( Eds.), Neuropsychology, Psychophysiology and Information Processing. Vol. 5. Elsevier, Amsterdam, pp. 335–370. Asarnow, R.F., Asamen, J., Granholm, E., Sherman, T., Watkins, J.M., Williams, M.E., 1994. Cognitive/neuropsychological studies of children with a schizophrenic disorder. Schizophr. Bull. 20, 647–669. Buchanan, R.W., Strauss, M.E., Breier, A., Kirpatric, B., Carpenter, W.T., 1997. Attentional impairments in deficit and non-deficit forms of schizophrenia. Am. J. Psychiatry 154, 363–389. Denton, L.C., McIntire, C.W., 1978. Span of apprehension in hyperactive boys. J. Abnorm. Child Psychol. 6, 19–24. McIntire, C.W., Blackwell, S.L., Denton, C.L., 1978. The effect of noise distractibility on the spans of apprehension of hyperactive boys. J. Abnorm. Child Psychol. 6, 483–492. Rund, B.R., Orbeck, A.L., Landro, N.I., 1992. Vigilance deficits in schizophrenics and affectively disturbed patients. Acta Psychiatr. Scand. 86, 207–212. Spaulding, W., Hargrove, S., Crinean, W., Martin, T., 1981. The microcomputer based laboratory for psychopathology research in rural settings. Behav. Res. Meth. Instrum. 13, 616–623.
Bjørn Rishovd Rund Institute of Psychology, University of Oslo, P.O. Box 1094, Blindern N-0317 Oslo, Norway E-mail address: [email protected] (B.R. Rund) Merete Øie Pa˚l Zeiner Centre for Child and Adolescent Psychiatry, P.O. Box 26, Vinderen, N-0319 Oslo, Norway Kjetil Sundet Department of Psychosomatic and Behavioral Medicine, The National Hospital, N-0027 Oslo, Norway * Corresponding author. Tel.: +47-22-85-53-39; fax: +47-22-85-44-19. 0920-9964/99/$ – see front matter © 1999 Elsevier Science B.V. All rights reserved. PII: S0 9 2 0 -9 9 6 4 ( 9 9 ) 0 0 06 0 - 2
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What’s it like to be mentally ill? Dear Editors It took about six months, from the time of a very stressful event in my life until I couldn’t function any more. During this time I began to think that something strange was going on around me. This was just a thought at first. My husband and I have a family business. We have regular customers in our shop and of course I had got to know these customers. My thoughts about the customers began to change. I started to wonder why they said things in the ways that they did and what they ‘really’ meant. I became more and more frightened of the customers I thought that the things that they said meant either that they were attracted to me or wanted to hurt me, and then finally I thought that they were going to rape me. I began to think that they had better watch out in case my husband catches them (the customers were really only being friendly but my thoughts were becoming more bizarre). I began to believe that someone was playing a game with me on a computer and he was sending messages via these customers. I did not know who ‘he’ was — I thought he was playing chess, with the customers as chess pieces. I don’t play chess so you can imagine how difficult it was for me to try to keep one step ahead of him. At the same time, at home I became obsessed with Freddie Mercury (from the rock group Queen). I played his tapes all the time, I joined the fan club, I was on a high and played a video recording of him over and over again. I loved the artistic flair, the costumes, the dancing and the singing. I was telling everyone what a wonderful person he was. This was my escape from the dreaded game of chess, which you must understand was by now becoming very frightening and a life or death situation in my mind. I started speaking in French to my husband about what ‘they’ were doing — I don’t speak French normally — I haven’t spoken it since I was at school, but I thought that ‘they’ would not be able to understand me. Then at home I started sleeping on the floor at the bottom of the bed — things were really getting
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Letters to the Editors / Schizophrenia Research 40 (1999) 255–261
bad — I could not escape from the shop. I had a lot of responsibility there. I had to suffer the game every day. I finally confronted one of the customers about it, but of course he didn’t have a clue what I was talking about. I wanted to get the persecution out into the open. I had been suffering all by myself. Of course my husband didn’t understand either and ushered me into the office and tried to calm me down. I cried all night. My husband said that I didn’t have to go to the shop anymore. My mind was now working at a thousand miles an hour. He had won — the person with the computer — I shut down. I didn’t say anything. It was too incriminating. I called my friend — I was sitting there with all the curtains closed, as I was frightened that ‘they’ would come to get me. I was crying. My friend came. I told her everything. She said to me ‘‘God knows Diana you don’t deserve it but I think you have depression. You had better go to see the doctor’’. When she had gone I phoned the doctor’s office and arranged to see him in a couple of days time. Unknown to me, my friend went to see my husband and they came back together to my home and told me that they had arranged an emergency appointment with the doctor for me. I went in to see the doctor by myself. I trusted him, and I knew that as a doctor he could not be involved in what was going on. I wanted to tell him everything but my mind was racing and I just couldn’t collect my thoughts enough to put my experiences into words. I was sobbing without really being able to cry. The Doctor obviously realised that something was wrong but had no real idea of what was going through my mind. He said to me ‘‘What would you say if I said you were having a nervous breakdown?’’. I said ‘‘I think you are probably right’’. He was very sympathetic. He told me that I should rest for the next month and that he would arrange for me to see a specialist, looking back, I obviously hadn’t managed to show him how desperate I had become. He also prescribed some sleeping pills for me ( Temazepam). The pills knocked me out. I remained at home for the next couple of weeks and I spent most of the time in bed. A consultant family doctor (from the local medical school ) came to see me a week or two later. I wanted to talk to him in the car because
I was so frightened that people would overhear what I was saying. He insisted on seeing me in my bedroom so that he could give me a physical examination. I shut all the doors and windows so that ‘they’ would not be able to hear what I said, and I was even misinterpreting some of his comments. He told me that my heart was racing like I was in the middle of a race. He prescribed some Propanolol to slow my heart down and he arranged an appointment for me to see a psychiatrist who held clinics at my local health centre. It took another two weeks before the psychiatrist could see me for a routine appointment — so again I had not managed to convey to this doctor how frightened and distressed I felt inside or he would have arranged an emergency appointment for me. Through this period, my family and friends were very worried — they had never seen me like this. I remember that my mother and my sister came to see me. I was rolling on the floor in agony. I felt a terrible tension in my back and in my body and I talked to my dog as if she was my grandmother. By this time I had become paranoid about my family too. I came believe that they were also involved in what was going on. After some days which I spent largely in bed, knocked out by the sleeping pills, my family began to tell me to do things again like take a shower or do the laundry. One day when I was in the shower I looked at a green ring on my finger and discovered that I was an African princess. I began hallucinating. It was like having a dream, in full colour, with all the fear of a nightmare, whilst wide-awake. You see I might have been an African Princess sitting by a beautiful lake, but there were some men in the bushes behind me who were trying to steal me away into slavery, and so it went on. It was summer, I remember sitting by a pond and the bees were talking about me in the flowering fuschia bushes. The magpies with their chattering calls and young chicks were laughing at me, the pond was polluted, it was a time of fear, fear and more fear. I heard dogs howling at the musical chimes from an ice-cream seller’s van and I thought they had changed into the hounds of hell, and were coming to get me. I was misconstruing the newspaper headlines taking them to be personal messages for me, even
Letters to the Editors / Schizophrenia Research 40 (1999) 255–261
the coffee canister in my kitchen wasn’t safe to look at — it too had a message. Car registration plates had messages, it was just unbearable. Please understand that these things were occurring all day, everyday. I did mystical things too. I wore crystals and collected feathers that birds had left in the garden because I thought that they were things that would make me better. At about this time I saw a psychiatrist for the first time. The psychiatrist prescribed Trifluoperazine for me, and slowly these experiences began to subside; however, I continued to feel that I could do very little except simply look after myself. My only support through this dreadful time was my family doctor. I felt that I just could not trust anyone else, but even so, I never really managed
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to convey the depth of my distress to my doctor. It was a long time before I became stable, then I went to a day hospital where I had a counsellor who talked to me for many hours. He had an empathy with me and helped me to talk things through. I started to do occupational therapy, art, pottery, etc., and then I began to feel I was finding myself again. Today I am happy but I must stress that it is because I take my medication and I would like to thank my family doctor for his support. Diana Gregory Manchester 0920-9964/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved. PII: S0 9 20 - 9 96 4 ( 9 9 ) 00 0 4 9 -3