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Deficit syndrome in older schizophrenic patients
Psychiatry
285
Research, 39:285-292
Elsevier
Deficit
Syndrome
in Older
M. Jackuelyn Harris, Dilip V. Jeste, Robert K. Heaton Received
June 21, 1991; revised
version
Schizophrenic Alice
received
Krull,
October
John
Patients Montague,
7, 1991; accepted
and
November
9, 1991.
Abstract. Previous studies have reported that a proportion of younger schizophrenic patients have the “deficit syndrome,” with persistent “negative” symptoms not secondary to factors other than the disease process (e.g., depression). Yet, there is scant information on the deficit syndrome in older schizophrenic patients. We studied 46 schizophrenic patients over age 45. Seventeen met the criteria for the deficit syndrome as described by Carpenter et al. (1988), 20 were considered definite nondeficit patients, and 9 could not be classified. The deficit schizophrenic patients had a significantly higher total score on the Scale for the Assessment of Negative Symptoms but similar scores on scales for positive symptoms, depressive symptoms, and overall psychopathology as compared with nondeficit patients. The deficit patients also had a nonsignificantly Halstead-Reitan Battery. One notable difference
greater impairment on the between our results and those of
Carpenter et al. was in the prevalence of deficit syndrome. We found the prevalence (37%) to be significantly higher than that reported in younger patients (15%). Pending confirmation using larger sample sizes, the increased frequency of the deficit syndrome in our study could possibly be attributed to aging or a longer duration of illness in our subjects. Key Words. Geriatric pathology, aging.
psychiatry,
negative symptoms,
neuropsychology,
psycho-
little is known about the clinical characteristics of older schizophrenic patients. While a great deal of work has documented clinical heterogeneity among young schizophrenic adults, there remains a paucity of data on what happens to these early-onset schizophrenic patients when they grow old, and what clinical patterns characterize late-onset schizophrenic patients (Harris and Jeste, 1988). Since Kraepelin (19 19) and Bleuler (1950), investigators have attempted to define somewhat homogeneous subgroups on the basis of clinical symptoms, but the validity of these subgroups remains unclear (Jeste et al., 1982; Kendler et al., 1984; Carpenter and Kirkpatrick, 1988). One strategy for developing more homogeneous clinical
Surprisingly
M. Jackuelyn Harris, M.D., is Assistant Professor of Psychiatry, University of California, San Diego, and Co-Director, Geriatric Psychiatry Services, San Diego Veterans Affairs Medical Center. Dilip V. Jeste, M.D., is Professor of Psychiatry and Neurosciences, University of California. San Diego, and Chief, Psychiatry Service, San Diego Veterans Affairs Medical Center. Alice Krull. M.D., isclinical Instructor of Psychiatry, University of Califorma, San Diego, and Geriatric Psychiatry Fellow, Psychiatry Service. San Ph.D.. is Clinical Instructor of Psychiatry. Diego Veterans Affairs Medical Center. John Montague, University of California, San Diego, and Physical Rehabilitation Staff Psychologist, Grossmont Hospital. La Mesa, CA. Robert K. Heaton, Ph.D.. is Professor of Psychiatry, University of California. San Diego. (Reprint requests to Dr. M.J. Harris, Psychiatry Service, V-l 16A, Veterans Affairs Medical Center. 3350 La Jolla Village Dr., San Diego, CA 92161, USA.) 0165-1781/91/$03.50
@ 1991 Elsevier Scientific
Publishers
Ireland
Ltd.
286 subtypes is based on prominent symptom patterns. Symptoms in schizophrenia have been divided into two categories: “positive” and “negative.” Crow (1985) has used this distinction to postulate two types of schizophrenia: type I, which is characterized by acute or subacute onset, normal intellectual function, normal brain structure, good response to neuroleptic medication, and absence of negative symptoms; and type II, which is characterized by insidious onset, intellectual deterioration, enlarged cerebral ventricles, poor response to neuroleptic medication, and prominent negative symptoms. Recently, Carpenter et al. (1988) have recommended further delineation of the terminology and recommended that the term “deficit symptoms” be used to refer specifically to those negative symptoms that are present as enduring traits and not considered secondary to factors such as drug effects, dysphoric mood, self-protective reduction of stimulation in the face of psychotic decompensation, or absence of social stimulation. These investigators have published a series of articles on the “deficit syndrome” in younger schizophrenic patients (Wagman et al., 1987; Carpenter et al.. 1988; Buchanan et al., 1990; Kirkpatrick and Buchanan, 1990). The researchers suggested that a large majority of schizophrenic outpatients could be confidently characterized as having the deficit or nondeficit subtype by the physicians providing their care. The prevalence of the deficit syndrome was higher (approximately 30y0) in men than in women (approximately 6%), but the two groups did not differ in their mean current age, age of onset, duration of illness, level of education, number of hospitalizations, age at first hospitalization, and positive symptom and total scores on the Brief Psychiatric Rating Scale. Patients with the deficit syndrome had greater neuropsychological impairment compared with patients without the deficit syndrome (Wagman et al., 1987; Buchanan et al., 1990). The main objective of our article is to present a study of the deficit syndrome in 46 middle-aged and elderly chronic schizophrenic patients with respect to relevant demographic, clinical, and neuropsychological variables. We asked the following questions: (1) Can operational criteria for the deficit syndrome be reliably applied to older schizophrenic patients? If so, what is the prevalence of the deficit syndrome in schizophrenic patients over age 45? (2) How do older deficit syndrome patients compare with older nondeficit patients on the variables studied? Methods Subjects were schizophrenic patients of age 46 and older who met DSM-III-R (American Psychiatric Association, 1987) criteria for chronic schizophrenia. Patients with organic disorders such as dementia and substance abuse (both according to DSM-Ill-R criteria) were excluded. All the patients were clinically stable and living in the community. Subjects were outpatients being followed at the San Diego Veterans Affairs Medical Center mental health clinic or were referred from the University of California-San Diego Outpatient Psychiatry Services or from physicians in the community. We collected all the relevant demographic data and obtained extensive medical history to record information about pertinent medical illnesses (e.g., stroke) and substance abuse. Age of onset of schizophrenia was determined by interviewing the patient and a significant other, and by a comprehensive review of all records. We defined onset as the beginning of schizophrenic symptoms, including prodromal ones. as described in DSM-III- R. We did not use age at first psychiatric hospitalization as the criterion because of wide variations in the policies for hospitalization. If the age of onset of the illness could not be determined with reasonable
287 reliability in a given patient, that patient was excluded from the study. The current daily neuroleptic dose was converted to mg in chlorpromazine equivalents for purposes of comparison (Jeste and Wyatt, 1982). The patients were assessed on the Structured Clinical Interview for DSM-Ill-R-Patient Version (SCID-P; Spitzer and Williams, 1986). All subtypes of schizophrenia were included. In addition, the following rating scales were used: Brief Psychiatric Rating Scale (BPRS; Overall and Gorham, 1962) for judging overall level of psychopathology, Scale for the Assessment of Positive Symptoms (SAPS; Andreasen and Olsen, 1982) Scale for the Assessment of Negative Rating Scale for Depression Symptoms (SANS; Andreasen and Olsen, 1982) Hamilton (HRSD; Hamilton, 1967), and the Mini-Mental State Examination (MMSE; Folstein et al., 1975) to assess the degree of cognitive impairment. The classification of subjects into the deficit or nondeficit groups was made independently by the clinicians who had cared for the patients. All the available information was used for this purpose, as suggested by Carpenter and colleagues (Carpenter et al., 1988; Kirkpatrick et al., 1989). Diagnosis of the deficit syndrome was based on the Schedule for the Deficit Syndrome (SDS; Kirkpatrick et al., 1989) and required that the patient meet DSM-III-R criteria for schizophrenia and have at least two of the following six negative symptoms: restricted affect, diminished emotional range, poverty of speech, curbing of interests, diminished sense of purpose, and diminished social drive. These negative symptoms had to be primary-that is, not secondary to other factors such as anxiety, drug effect, suspiciousness (and other psychotic symptoms), mental retardation, and depression. The patient had to meet the criteria for the deficit syndrome for at least 12 months. To assess the test-retest reliability of our classification of patients into the deficit, nondeficit, or uncertain groups, we reclassified the patients a month after the original grouping in a “blind” fashion. All but two patients retained their original categorization; those two patients were placed in the “uncertain” category. All the patients were also given a comprehensive neuropsychological test battery. This consisted of the Wechsler Adult Intelligence Scale-Revised (WAIS-R; Wechsler, 198 I) and the Halstead-Reitan Neuropsychological Test Battery (HRNB; Reitan, 1955). The neuropsychological battery was administered to the patients after they had been psychiatrically and pharmacologically stable for at least a month. Statistical comparisons between the deficit and nondeficit groups were made using Kolmogorov-Smirnov nonparametric tests, with two exceptions. The data on gender were compared with the x2 test, while the data on age, neuroleptic dose, and the Halstead Impairment Index, which had nonhomogeneous variances, were square-root-transformed and then compared with two-tailed I tests. The prevalence of the deficit syndrome in our sample was compared with that in the Carpenter et al. (1988) study by ~2 tests.
Results Of the 46 middle-aged and elderly schizophrenic patients we studied, 17 (37%) met the for the deficit syndrome as described by Kirkpatrick et al. (1989) 20 (43%) were considered definite nondeficit patients, and 9 (20%) could not be classified. The nonclassification was the result of ambiguity of the clinical presentation. We performed a 3 x 2 x2 analysis comparing the frequencies of deficit, nondeficit, and “uncertain” categories among the Carpenter group’s younger patients and our older patients. The difference was significant at p < 0.01 (x2 = 9.59). Next we did an orthogonal set of two 2 x 2 x2 analyses. Only the comparison of the frequencies of deficit versus nondeficit categories was highly significant (~2 = 9.17, p < 0.005) suggesting a greater prevalence of the deficit syndrome in older schizophrenic patients. Table 1 summarizes the demographic comparison of the deficit and nondeficit schizophrenic patients. The mean current age and the level of education were similar in
criteria
288 Table 1. Demographic patients
comparison
of deficit and nondeficit Deficit (n=17) Mean
Current
age
Gender
, % men
Age
61.4
,yr’
Education
Duration
of illness
of illness
Neuroleptic
dose
Note.CPZE
6.6
Nondeficit (n=20) Mean
(
yr
(yr’ mg CPZE!
mg dose of neuroleptlc
medlcatlon
SD
63.0
77%
yr
at onset
SD
schizophrenic
11.2 65%
11.6
2.5
12.6
3.0
41.7
13.0
48.0
19.5
19.5
13.6
15.0
13.6
213.6
173.4
558.5
754.8
I” chlorpromazine
equivalents
the two groups. The deficit schizophrenic patients differed from the nondeficit patients in having a somewhat greater proportion of men. Thirteen (50%) of the 26 men and four (36yc) of the I I women in the study had the deficit syndrome. The deficit patients had a somewhat earlier age of onset of illness and were being maintained on lower doses of neuroleptics, although these differences failed to reach significance. (The maintenance dose of a neuroleptic had been determined individually for each patient by the respective clinician on the basis of therapeutic needs.) Clinically. there was no evidence of a difference in neuroleptic side effects between the deficit and nondeficit groups. Table 2 compares the deficit and nondeficit schizophrenic patients on clinical rating scales and neuropsychological tests. The two groups differed significantly @= 0.03) on the global summary score (a summary of the five global scores) on the SANS (Andreasen and Olsen, 1982) but had similar scores on the global summary score (a summary of the four global scores) on the SAPS (Andreasen and Olsen, 1982), the Table 2. Comparison of the deficit and nondeficit schizophrenic patients on clinical rating scales and neuropsychological tests Deficit (n=17) Nondeficit (n=20) SAPS
global
SANS
global
Mean
SD
score
6.1
4.0
5.5
score
7.4
5.4
2.5’
45.9
14.6
Mean
SD 3.4 2.6
42.4
10.9 5.8
BPRS
total
score
HRSD
total
score
8.5
7.2
7.1
MMSE
total
score
26.9
2.6
27.8
1.6
85.7
7.2
95.4
12.1
WAIS-R
Full-Scale
Halstead-Reitan Impairment Halstead
IQ Average
Rating impairment
Scale index
2.7
0.8
2.1
0.6
0.88
0.14
0.732
0.26
Note. SAPS : Scale for the Assessment of Positwe Symptoms. SANS = Scale for the Assessment of Negatwe Symptoms. BPRS : Brief Psychiatric Rating Scale. HRSD HamIlton Rating Scale for DepressIon. MMSE = Mln-Mental State Examination WAIS-R = Wechsler Adult lntelllgence Scale-Revised 1 p : 0.03 I Kolmogorov-Smlrnov test 2 p 0.08 12.tailed t test using square root transformations.
because
of nonhomogeneous
variances’
289 total BPRS score (Overall and Gorham, 1962) the total HRSD score (Hamilton, 1967), and the total MMSE score (Folstein et al., 1975). The deficit patients had nonsignificantly poorer performance on the Halstead Impairment Index (p = 0.08). Discussion The questions posed in undertaking this study may be answered, in a somewhat preliminary fashion, as follows: (1) Operational criteria for the deficit syndrome could be reliably applied in our study group of older schizophrenic patients, 37% of whom met these criteria. (2) The deficit syndrome patients had a nonsignificantly greater cognitive impairment, but similar severity of psychosis, especially positive symptoms, compared with the nondeficit group. Our results are similar to those reported in younger schizophrenic patients by Carpenter et al. (1988) except for a higher prevalence of the deficit syndrome. Our study is limited by a relatively small number of subjects, and the risks of type I and type II errors are correspondingly high. Therefore, the results should be considered preliminary. Nevertheless, these patients were well diagnosed and characterized with pertinent clinical rating scales and neuropsychological tests. The higher SANS (Andreasen and Olsen, 1982) scores but similar SAPS (Andreasen and Olsen, 1982) and total BPRS (Overall and Gorham, 1962) scores are consistent with the view held by Carpenter et al. (1988) Strauss et al. (1974), and Crow (1985) that positive symptoms are independent of negative or deficit symptoms. The similar HRSD scores (Hamilton, 1967) in the deficit and nondeficit schizophrenic patients may be viewed as validating the diagnosis of the deficit syndrome-that is, the deficit syndrome was not associated with more depressive symptoms. Also, the roughly equal severity of psychosis in the two groups supports the validity of the deficit syndrome. The deficit symptoms were unlikely to be due to neuroleptic side effects since the two groups did not differ clinically in this respect. Carpenter et al. (1988) have also reported a higher negative symptom score but similar positive symptom score and total score on the BPRS in the deficit syndrome group. (Most of the patients in that study, as in ours, were being treated with neuroleptic drugs.) One notable difference between our results and those of Carpenter et al. was in the prevalence of the deficit syndrome. We found the prevalence (37%) to be significantly higher than that reported in younger patients (15%).Similarly, in an ongoing collaborative study of younger schizophrenic outpatients at the University of California-San Diego, of 34 patients evaluated, seven (20.5%) were found to meet criteria for the deficit syndrome (D.L. Braff et al., unpublished data). This number is similar to that reported by Carpenter et al. (1988). The higher frequency of the disorder in our older population may possibly be due to aging or a longer duration of illness in comparison with a younger schizophrenic population. No conclusions can be drawn until a larger group of schizophrenic patients has been studied. Yet, we found no difference in mean age and duration of illness between the deficit and nondeficit patients in our population. This situation is analogous to the findings in tardive dyskinesia in that advanced age and long-term use of neuroleptics are well-known risk factors for the development of tardive dyskinesia, but in a given study, tardive
290 dyskinesia patients may not differ from those in the nondyskinesia group in mean age or duration of treatment (Jeste and Wyatt, 1987). Crow (1985) has suggested that a predominantly positive symptom syndrome often develops, over a period of years, into a predominantly negative symptom syndrome. Crow maintains that patients who lack negative symptoms early in their illness may develop them during the course of the illness. Once severe negative symptoms develop, they persist, and therefore the type II designation is considered irreversible. The higher prevalence of the deficit syndrome in our older patient population, compared with that reported in younger schizophrenic populations, is consistent with the assumption that negative symptoms, once they develop, tend to be enduring features of the schizophrenic illness, whereas positive symptoms may fluctuate over time. Obviously, only a long-term prospective study can test this hypothesis with certainty. In the study of Carpenter et al. (1988) 24 out of 103 patients could not be categorized as being either deficit or nondeficit. In our group, 9 of 46 patients could not be assigned to either category. The fact that approximately 20% of patients were not classifiable as deficit or nondeficit subtypes of schizophrenia is not surprising. Schizophrenia is a heterogeneous disorder with considerable variation in symptoms and course. A patient with the deficit syndrome has to meet the criteria for at least 12 continuous months. When diagnosticians are in doubt, it seems preferable to be conservative and use the category “uncertain” rather than the deficit or nondeficit category. Although the gender differences in our study did not reach significance, our results are consistent with the literature on gender differences in schizophrenia. A twosyndrome model of schizophrenia has been postulated. In this model, a type with an earlier age of onset, more chronic course, and predominantly negative or deficit symptoms primarily affects men, whereas a type with a later age of onset, more favorable outcome, and affective and positive symptoms more often characterizes women (Lewine, 1981, 1985; Seeman, 1982; Flor-Henry, 1985; Goldstein and Link. 1988; Yassa et al., 1991). On the other hand, the gender difference in our study (50% men and 36% women having the deficit syndrome) was much less dramatic than that in the study by Carpenter et al. (1988) (30% prevalence in men and 60/c in women). This may be a function of a small sample size or may be consistent with the suggestion that gender differences in the prognosis of schizophrenia narrow with increased chronicity (Yassa et al., 1991). With regard to neuroleptic dose, we are unaware of any study of the deficit syndrome looking at this question. The mean dose of neuroleptic drugs used tended to be nonsignificantly lower in the deficit compared with the nondeficit patients. This suggests that the treating physicians perceived the deficit syndrome patients as requiring somewhat lower doses of neuroleptic medication than the nondeficit patients. Negative symptoms have been noted to be associated with poor response to neuroleptic drugs (Johnstone et al., 1978; Crow, 1985). By contrast, in a cluster analysis of schizophrenic symptoms by Morrison et al. (1990) there was no significant correlation between neuroleptic dose and the SANS score. Lindenmayer et al. (1984) found that neuroleptic dose was unrelated to the positive-negative distinction in acute schizophrenic patients, whereas Opler et al. (1984) reported that the maintenance dose
291 of neuroleptics was only half as high in a chronic sample with a preponderance of negative symptoms. Obviously, controlled studies are required to establish therapeutic responsiveness of the deficit compared with the nondeficit patients. Younger schizophrenic patients with the deficit syndrome have been reported to have greater neuropsychological impairment (Wagman et al., 1987). We found nonsignificantly greater global cognitive impairment as judged by the Halstead impairment index in our deficit patients. The failure of this difference to reach statistical significance may be due to relatively small sample size or to greater heterogeneity among older patients. Another possible explanation is that cognitive impairment increases with aging in all the patients (deficit as well as nondeficit), thereby reducing the magnitude of differences between the deficit and nondeficit groups. Further studies of the deficit syndrome in older schizophrenic patients are needed. It will be useful to confirm and extend our results in a larger sample, especially with patients who are free of medication and followed longitudinally. Also, investigations of structural and functional brain imaging that compare schizophrenic patients with and without the deficit syndrome will help shed some light on the brain pathology associated with the deficit syndrome. The research reported was supported in part by the Department of Veterans Affairs and by National Institute of Mental Health grants MH-43693 and MH-45 131.
Acknowledgment.
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Carpenter, W.T., Jr.; Heinrichs, D.W.; and Wagman, A.M.I. Deficit and nondeficit forms of schizophrenia: The concept. American Journal of P.y_vchiatry, 145:578-583, 1988. Carpenter, W.T., Jr., and Kirkpatrick, B. The heterogeneity of the long-term course of schizophrenia. Schizophrenia Bulletin, 14:645-652, 1988. Crow, T.J. The two-syndrome concept: Origins and current status. Schizophrenia Bulletin, 11:471-486,
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292 Jeste, D.V., and Wyatt. R.J. Understanding and Treating Tardive D_vskinesia. New York: Guilford Press, Inc., 19X2. Jeste, D.V.,and Wyatt, R.J. Agingand tardivedyskinesia. In: Miller, N.E.,andCohen, Ci.11.. eds. Schizophrenia and Aging: Schizophrenia, Paranoid and Schizophreniform Disorder.~ in Later Life. New York: Guilford Press. 1987. pp. 275-2X6. Johnstone, E.C.; Crow, T.J.; Frith, C.D.; et al. Mechanism of the antipsychotic effect in the treatment of acute schizophrenia. Lancer, 1:X48-851, 1978. Kendler, KS.; Gruenberg. A.M.; and Tsuang, M.7. Outcome of schizophrenic subtypes defined by four diagnostic systems. Archives of General P.s_ychiatr.v. 4 I : 149- 154, 1984. Kirkpatrick, B., and Buchanan, R. W. Anhedonia and the deficit syndrome of schizophrenia. P.yychiarr_v
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Kirkpatrick, B.; Buchanan, R.W.; McKenney. P.D.; Alphs, L.D.; and Carpenter. W.-I ., Jr. The Schedule for the Deficit Syndrome: An instrument for research in schitophrenia. P.y,,,c,hiarrr’ Research, 30: 119-123, 1989. Kraepelin E. On paranoid diseases. [In German]. Zei/.vchr(f/ .frir Xe.yatnre Nrurologie uncl P.s_vchiatrie, I I:6 17-638. 19 19. I.ewine, R.R.J. Sex differences in schizophrenia: Timing or subtypes? P.~.,~c~ho/ogical Bu//rrin, 90:432-444. I98 I Lewine, R.R.J. SchiT.ophrenia: An amotivational syndrome in men. Canadian Journal o/’ P.s~~c~hiatr,~. 30:3 16-3 IX. 19X5. Lindenmayer. J.P.; Kay, S.R.; and Opler, [..A. Positive and negative subtypes in acute schirophrenia. C‘omprrhrnvive Ps.vc,hiarry, 241455-464. 1984. Morrison. R.L.; Bellack. A.S.; Wixted. J.T.; and Mueser, K.7 Posittve and negative symptoms in schizophrenia: A cluster analytic approach. Journal of Nrr\~ou.~ and Menral lIi.tru.\r. 17X377-384, 1990. Opler. L.A.; Kay. S.R.; Rosado. V.: and I.indenmaycr. J.P. f’ositive and negative syndromes in chronic schirophrenic inpatients. Journuf(~!‘Nervousond Menrul Disea.cr. I72:3 17-325. 19X4. Overall. J.E.. and Gorham, D.R. The Brtel Psychiatric Rating Scale, P.\~rc~hologic~a/R~~torrs, 10:799-X 12. 1962. Reitan, R.M. An investtgation of the validity of Halstead’s measures of biological intelligence. Arc,hivr.s of’ Neurologl~ und P.sJ,c,hiarrr,, 73:2X-35. 1955. Seeman. M.V. Gender differences in schirophrenia. C‘unudiun Journalof P,yl*chialr_~~,27: lO7Ill. 19X2. Spitter. R.I_., and Williams, J.B.W. Strucrured C‘linicul /nrervir~~,/br DSM-III-R~Pu/i(~t7/ Vrr.rion. (SCID-P, 5; 1, X6) New York: New York State Psychiatric Institute, 1986. Strauss. J.S.; C‘arpenter. W. I ., Jr.; and Bartko, J.J. Speculations on the processes that underlie schizophrenic symptoms and signs. Schizophrenia Bulletin, 1l:6f-75, 1974. Wagman, A.M.I.; Heinrichs, D.W.; and Carpenter, W.T.,.lr, Deficit and nondeficit forms of schizophrenia: Neuropsychological evaluation. P.ychiarr~~ Re.tearch. 22:3 19-330, 19X7. Wechsler, D. Wec,hskr Adult Inteiiigenc,i> ScuIe~~Revised: Munuul. Cleveland. OH: .I’he Psychological Corporation, 19XI. Yassa, R.; Uhr, S.: and Jeste, D.V. Gender dnferences in chronic schizophrenia: Need for further research. In: Light, E., and Liebowit/. B.. eds. The Elder!,~ Wirh C‘hronic, Men/a////nrss. New York: Springer, 1991. pp. 16-31.
285
Research, 39:285-292
Elsevier
Deficit
Syndrome
in Older
M. Jackuelyn Harris, Dilip V. Jeste, Robert K. Heaton Received
June 21, 1991; revised
version
Schizophrenic Alice
received
Krull,
October
John
Patients Montague,
7, 1991; accepted
and
November
9, 1991.
Abstract. Previous studies have reported that a proportion of younger schizophrenic patients have the “deficit syndrome,” with persistent “negative” symptoms not secondary to factors other than the disease process (e.g., depression). Yet, there is scant information on the deficit syndrome in older schizophrenic patients. We studied 46 schizophrenic patients over age 45. Seventeen met the criteria for the deficit syndrome as described by Carpenter et al. (1988), 20 were considered definite nondeficit patients, and 9 could not be classified. The deficit schizophrenic patients had a significantly higher total score on the Scale for the Assessment of Negative Symptoms but similar scores on scales for positive symptoms, depressive symptoms, and overall psychopathology as compared with nondeficit patients. The deficit patients also had a nonsignificantly Halstead-Reitan Battery. One notable difference
greater impairment on the between our results and those of
Carpenter et al. was in the prevalence of deficit syndrome. We found the prevalence (37%) to be significantly higher than that reported in younger patients (15%). Pending confirmation using larger sample sizes, the increased frequency of the deficit syndrome in our study could possibly be attributed to aging or a longer duration of illness in our subjects. Key Words. Geriatric pathology, aging.
psychiatry,
negative symptoms,
neuropsychology,
psycho-
little is known about the clinical characteristics of older schizophrenic patients. While a great deal of work has documented clinical heterogeneity among young schizophrenic adults, there remains a paucity of data on what happens to these early-onset schizophrenic patients when they grow old, and what clinical patterns characterize late-onset schizophrenic patients (Harris and Jeste, 1988). Since Kraepelin (19 19) and Bleuler (1950), investigators have attempted to define somewhat homogeneous subgroups on the basis of clinical symptoms, but the validity of these subgroups remains unclear (Jeste et al., 1982; Kendler et al., 1984; Carpenter and Kirkpatrick, 1988). One strategy for developing more homogeneous clinical
Surprisingly
M. Jackuelyn Harris, M.D., is Assistant Professor of Psychiatry, University of California, San Diego, and Co-Director, Geriatric Psychiatry Services, San Diego Veterans Affairs Medical Center. Dilip V. Jeste, M.D., is Professor of Psychiatry and Neurosciences, University of California. San Diego, and Chief, Psychiatry Service, San Diego Veterans Affairs Medical Center. Alice Krull. M.D., isclinical Instructor of Psychiatry, University of Califorma, San Diego, and Geriatric Psychiatry Fellow, Psychiatry Service. San Ph.D.. is Clinical Instructor of Psychiatry. Diego Veterans Affairs Medical Center. John Montague, University of California, San Diego, and Physical Rehabilitation Staff Psychologist, Grossmont Hospital. La Mesa, CA. Robert K. Heaton, Ph.D.. is Professor of Psychiatry, University of California. San Diego. (Reprint requests to Dr. M.J. Harris, Psychiatry Service, V-l 16A, Veterans Affairs Medical Center. 3350 La Jolla Village Dr., San Diego, CA 92161, USA.) 0165-1781/91/$03.50
@ 1991 Elsevier Scientific
Publishers
Ireland
Ltd.
286 subtypes is based on prominent symptom patterns. Symptoms in schizophrenia have been divided into two categories: “positive” and “negative.” Crow (1985) has used this distinction to postulate two types of schizophrenia: type I, which is characterized by acute or subacute onset, normal intellectual function, normal brain structure, good response to neuroleptic medication, and absence of negative symptoms; and type II, which is characterized by insidious onset, intellectual deterioration, enlarged cerebral ventricles, poor response to neuroleptic medication, and prominent negative symptoms. Recently, Carpenter et al. (1988) have recommended further delineation of the terminology and recommended that the term “deficit symptoms” be used to refer specifically to those negative symptoms that are present as enduring traits and not considered secondary to factors such as drug effects, dysphoric mood, self-protective reduction of stimulation in the face of psychotic decompensation, or absence of social stimulation. These investigators have published a series of articles on the “deficit syndrome” in younger schizophrenic patients (Wagman et al., 1987; Carpenter et al.. 1988; Buchanan et al., 1990; Kirkpatrick and Buchanan, 1990). The researchers suggested that a large majority of schizophrenic outpatients could be confidently characterized as having the deficit or nondeficit subtype by the physicians providing their care. The prevalence of the deficit syndrome was higher (approximately 30y0) in men than in women (approximately 6%), but the two groups did not differ in their mean current age, age of onset, duration of illness, level of education, number of hospitalizations, age at first hospitalization, and positive symptom and total scores on the Brief Psychiatric Rating Scale. Patients with the deficit syndrome had greater neuropsychological impairment compared with patients without the deficit syndrome (Wagman et al., 1987; Buchanan et al., 1990). The main objective of our article is to present a study of the deficit syndrome in 46 middle-aged and elderly chronic schizophrenic patients with respect to relevant demographic, clinical, and neuropsychological variables. We asked the following questions: (1) Can operational criteria for the deficit syndrome be reliably applied to older schizophrenic patients? If so, what is the prevalence of the deficit syndrome in schizophrenic patients over age 45? (2) How do older deficit syndrome patients compare with older nondeficit patients on the variables studied? Methods Subjects were schizophrenic patients of age 46 and older who met DSM-III-R (American Psychiatric Association, 1987) criteria for chronic schizophrenia. Patients with organic disorders such as dementia and substance abuse (both according to DSM-Ill-R criteria) were excluded. All the patients were clinically stable and living in the community. Subjects were outpatients being followed at the San Diego Veterans Affairs Medical Center mental health clinic or were referred from the University of California-San Diego Outpatient Psychiatry Services or from physicians in the community. We collected all the relevant demographic data and obtained extensive medical history to record information about pertinent medical illnesses (e.g., stroke) and substance abuse. Age of onset of schizophrenia was determined by interviewing the patient and a significant other, and by a comprehensive review of all records. We defined onset as the beginning of schizophrenic symptoms, including prodromal ones. as described in DSM-III- R. We did not use age at first psychiatric hospitalization as the criterion because of wide variations in the policies for hospitalization. If the age of onset of the illness could not be determined with reasonable
287 reliability in a given patient, that patient was excluded from the study. The current daily neuroleptic dose was converted to mg in chlorpromazine equivalents for purposes of comparison (Jeste and Wyatt, 1982). The patients were assessed on the Structured Clinical Interview for DSM-Ill-R-Patient Version (SCID-P; Spitzer and Williams, 1986). All subtypes of schizophrenia were included. In addition, the following rating scales were used: Brief Psychiatric Rating Scale (BPRS; Overall and Gorham, 1962) for judging overall level of psychopathology, Scale for the Assessment of Positive Symptoms (SAPS; Andreasen and Olsen, 1982) Scale for the Assessment of Negative Rating Scale for Depression Symptoms (SANS; Andreasen and Olsen, 1982) Hamilton (HRSD; Hamilton, 1967), and the Mini-Mental State Examination (MMSE; Folstein et al., 1975) to assess the degree of cognitive impairment. The classification of subjects into the deficit or nondeficit groups was made independently by the clinicians who had cared for the patients. All the available information was used for this purpose, as suggested by Carpenter and colleagues (Carpenter et al., 1988; Kirkpatrick et al., 1989). Diagnosis of the deficit syndrome was based on the Schedule for the Deficit Syndrome (SDS; Kirkpatrick et al., 1989) and required that the patient meet DSM-III-R criteria for schizophrenia and have at least two of the following six negative symptoms: restricted affect, diminished emotional range, poverty of speech, curbing of interests, diminished sense of purpose, and diminished social drive. These negative symptoms had to be primary-that is, not secondary to other factors such as anxiety, drug effect, suspiciousness (and other psychotic symptoms), mental retardation, and depression. The patient had to meet the criteria for the deficit syndrome for at least 12 months. To assess the test-retest reliability of our classification of patients into the deficit, nondeficit, or uncertain groups, we reclassified the patients a month after the original grouping in a “blind” fashion. All but two patients retained their original categorization; those two patients were placed in the “uncertain” category. All the patients were also given a comprehensive neuropsychological test battery. This consisted of the Wechsler Adult Intelligence Scale-Revised (WAIS-R; Wechsler, 198 I) and the Halstead-Reitan Neuropsychological Test Battery (HRNB; Reitan, 1955). The neuropsychological battery was administered to the patients after they had been psychiatrically and pharmacologically stable for at least a month. Statistical comparisons between the deficit and nondeficit groups were made using Kolmogorov-Smirnov nonparametric tests, with two exceptions. The data on gender were compared with the x2 test, while the data on age, neuroleptic dose, and the Halstead Impairment Index, which had nonhomogeneous variances, were square-root-transformed and then compared with two-tailed I tests. The prevalence of the deficit syndrome in our sample was compared with that in the Carpenter et al. (1988) study by ~2 tests.
Results Of the 46 middle-aged and elderly schizophrenic patients we studied, 17 (37%) met the for the deficit syndrome as described by Kirkpatrick et al. (1989) 20 (43%) were considered definite nondeficit patients, and 9 (20%) could not be classified. The nonclassification was the result of ambiguity of the clinical presentation. We performed a 3 x 2 x2 analysis comparing the frequencies of deficit, nondeficit, and “uncertain” categories among the Carpenter group’s younger patients and our older patients. The difference was significant at p < 0.01 (x2 = 9.59). Next we did an orthogonal set of two 2 x 2 x2 analyses. Only the comparison of the frequencies of deficit versus nondeficit categories was highly significant (~2 = 9.17, p < 0.005) suggesting a greater prevalence of the deficit syndrome in older schizophrenic patients. Table 1 summarizes the demographic comparison of the deficit and nondeficit schizophrenic patients. The mean current age and the level of education were similar in
criteria
288 Table 1. Demographic patients
comparison
of deficit and nondeficit Deficit (n=17) Mean
Current
age
Gender
, % men
Age
61.4
,yr’
Education
Duration
of illness
of illness
Neuroleptic
dose
Note.CPZE
6.6
Nondeficit (n=20) Mean
(
yr
(yr’ mg CPZE!
mg dose of neuroleptlc
medlcatlon
SD
63.0
77%
yr
at onset
SD
schizophrenic
11.2 65%
11.6
2.5
12.6
3.0
41.7
13.0
48.0
19.5
19.5
13.6
15.0
13.6
213.6
173.4
558.5
754.8
I” chlorpromazine
equivalents
the two groups. The deficit schizophrenic patients differed from the nondeficit patients in having a somewhat greater proportion of men. Thirteen (50%) of the 26 men and four (36yc) of the I I women in the study had the deficit syndrome. The deficit patients had a somewhat earlier age of onset of illness and were being maintained on lower doses of neuroleptics, although these differences failed to reach significance. (The maintenance dose of a neuroleptic had been determined individually for each patient by the respective clinician on the basis of therapeutic needs.) Clinically. there was no evidence of a difference in neuroleptic side effects between the deficit and nondeficit groups. Table 2 compares the deficit and nondeficit schizophrenic patients on clinical rating scales and neuropsychological tests. The two groups differed significantly @= 0.03) on the global summary score (a summary of the five global scores) on the SANS (Andreasen and Olsen, 1982) but had similar scores on the global summary score (a summary of the four global scores) on the SAPS (Andreasen and Olsen, 1982), the Table 2. Comparison of the deficit and nondeficit schizophrenic patients on clinical rating scales and neuropsychological tests Deficit (n=17) Nondeficit (n=20) SAPS
global
SANS
global
Mean
SD
score
6.1
4.0
5.5
score
7.4
5.4
2.5’
45.9
14.6
Mean
SD 3.4 2.6
42.4
10.9 5.8
BPRS
total
score
HRSD
total
score
8.5
7.2
7.1
MMSE
total
score
26.9
2.6
27.8
1.6
85.7
7.2
95.4
12.1
WAIS-R
Full-Scale
Halstead-Reitan Impairment Halstead
IQ Average
Rating impairment
Scale index
2.7
0.8
2.1
0.6
0.88
0.14
0.732
0.26
Note. SAPS : Scale for the Assessment of Positwe Symptoms. SANS = Scale for the Assessment of Negatwe Symptoms. BPRS : Brief Psychiatric Rating Scale. HRSD HamIlton Rating Scale for DepressIon. MMSE = Mln-Mental State Examination WAIS-R = Wechsler Adult lntelllgence Scale-Revised 1 p : 0.03 I Kolmogorov-Smlrnov test 2 p 0.08 12.tailed t test using square root transformations.
because
of nonhomogeneous
variances’
289 total BPRS score (Overall and Gorham, 1962) the total HRSD score (Hamilton, 1967), and the total MMSE score (Folstein et al., 1975). The deficit patients had nonsignificantly poorer performance on the Halstead Impairment Index (p = 0.08). Discussion The questions posed in undertaking this study may be answered, in a somewhat preliminary fashion, as follows: (1) Operational criteria for the deficit syndrome could be reliably applied in our study group of older schizophrenic patients, 37% of whom met these criteria. (2) The deficit syndrome patients had a nonsignificantly greater cognitive impairment, but similar severity of psychosis, especially positive symptoms, compared with the nondeficit group. Our results are similar to those reported in younger schizophrenic patients by Carpenter et al. (1988) except for a higher prevalence of the deficit syndrome. Our study is limited by a relatively small number of subjects, and the risks of type I and type II errors are correspondingly high. Therefore, the results should be considered preliminary. Nevertheless, these patients were well diagnosed and characterized with pertinent clinical rating scales and neuropsychological tests. The higher SANS (Andreasen and Olsen, 1982) scores but similar SAPS (Andreasen and Olsen, 1982) and total BPRS (Overall and Gorham, 1962) scores are consistent with the view held by Carpenter et al. (1988) Strauss et al. (1974), and Crow (1985) that positive symptoms are independent of negative or deficit symptoms. The similar HRSD scores (Hamilton, 1967) in the deficit and nondeficit schizophrenic patients may be viewed as validating the diagnosis of the deficit syndrome-that is, the deficit syndrome was not associated with more depressive symptoms. Also, the roughly equal severity of psychosis in the two groups supports the validity of the deficit syndrome. The deficit symptoms were unlikely to be due to neuroleptic side effects since the two groups did not differ clinically in this respect. Carpenter et al. (1988) have also reported a higher negative symptom score but similar positive symptom score and total score on the BPRS in the deficit syndrome group. (Most of the patients in that study, as in ours, were being treated with neuroleptic drugs.) One notable difference between our results and those of Carpenter et al. was in the prevalence of the deficit syndrome. We found the prevalence (37%) to be significantly higher than that reported in younger patients (15%).Similarly, in an ongoing collaborative study of younger schizophrenic outpatients at the University of California-San Diego, of 34 patients evaluated, seven (20.5%) were found to meet criteria for the deficit syndrome (D.L. Braff et al., unpublished data). This number is similar to that reported by Carpenter et al. (1988). The higher frequency of the disorder in our older population may possibly be due to aging or a longer duration of illness in comparison with a younger schizophrenic population. No conclusions can be drawn until a larger group of schizophrenic patients has been studied. Yet, we found no difference in mean age and duration of illness between the deficit and nondeficit patients in our population. This situation is analogous to the findings in tardive dyskinesia in that advanced age and long-term use of neuroleptics are well-known risk factors for the development of tardive dyskinesia, but in a given study, tardive
290 dyskinesia patients may not differ from those in the nondyskinesia group in mean age or duration of treatment (Jeste and Wyatt, 1987). Crow (1985) has suggested that a predominantly positive symptom syndrome often develops, over a period of years, into a predominantly negative symptom syndrome. Crow maintains that patients who lack negative symptoms early in their illness may develop them during the course of the illness. Once severe negative symptoms develop, they persist, and therefore the type II designation is considered irreversible. The higher prevalence of the deficit syndrome in our older patient population, compared with that reported in younger schizophrenic populations, is consistent with the assumption that negative symptoms, once they develop, tend to be enduring features of the schizophrenic illness, whereas positive symptoms may fluctuate over time. Obviously, only a long-term prospective study can test this hypothesis with certainty. In the study of Carpenter et al. (1988) 24 out of 103 patients could not be categorized as being either deficit or nondeficit. In our group, 9 of 46 patients could not be assigned to either category. The fact that approximately 20% of patients were not classifiable as deficit or nondeficit subtypes of schizophrenia is not surprising. Schizophrenia is a heterogeneous disorder with considerable variation in symptoms and course. A patient with the deficit syndrome has to meet the criteria for at least 12 continuous months. When diagnosticians are in doubt, it seems preferable to be conservative and use the category “uncertain” rather than the deficit or nondeficit category. Although the gender differences in our study did not reach significance, our results are consistent with the literature on gender differences in schizophrenia. A twosyndrome model of schizophrenia has been postulated. In this model, a type with an earlier age of onset, more chronic course, and predominantly negative or deficit symptoms primarily affects men, whereas a type with a later age of onset, more favorable outcome, and affective and positive symptoms more often characterizes women (Lewine, 1981, 1985; Seeman, 1982; Flor-Henry, 1985; Goldstein and Link. 1988; Yassa et al., 1991). On the other hand, the gender difference in our study (50% men and 36% women having the deficit syndrome) was much less dramatic than that in the study by Carpenter et al. (1988) (30% prevalence in men and 60/c in women). This may be a function of a small sample size or may be consistent with the suggestion that gender differences in the prognosis of schizophrenia narrow with increased chronicity (Yassa et al., 1991). With regard to neuroleptic dose, we are unaware of any study of the deficit syndrome looking at this question. The mean dose of neuroleptic drugs used tended to be nonsignificantly lower in the deficit compared with the nondeficit patients. This suggests that the treating physicians perceived the deficit syndrome patients as requiring somewhat lower doses of neuroleptic medication than the nondeficit patients. Negative symptoms have been noted to be associated with poor response to neuroleptic drugs (Johnstone et al., 1978; Crow, 1985). By contrast, in a cluster analysis of schizophrenic symptoms by Morrison et al. (1990) there was no significant correlation between neuroleptic dose and the SANS score. Lindenmayer et al. (1984) found that neuroleptic dose was unrelated to the positive-negative distinction in acute schizophrenic patients, whereas Opler et al. (1984) reported that the maintenance dose
291 of neuroleptics was only half as high in a chronic sample with a preponderance of negative symptoms. Obviously, controlled studies are required to establish therapeutic responsiveness of the deficit compared with the nondeficit patients. Younger schizophrenic patients with the deficit syndrome have been reported to have greater neuropsychological impairment (Wagman et al., 1987). We found nonsignificantly greater global cognitive impairment as judged by the Halstead impairment index in our deficit patients. The failure of this difference to reach statistical significance may be due to relatively small sample size or to greater heterogeneity among older patients. Another possible explanation is that cognitive impairment increases with aging in all the patients (deficit as well as nondeficit), thereby reducing the magnitude of differences between the deficit and nondeficit groups. Further studies of the deficit syndrome in older schizophrenic patients are needed. It will be useful to confirm and extend our results in a larger sample, especially with patients who are free of medication and followed longitudinally. Also, investigations of structural and functional brain imaging that compare schizophrenic patients with and without the deficit syndrome will help shed some light on the brain pathology associated with the deficit syndrome. The research reported was supported in part by the Department of Veterans Affairs and by National Institute of Mental Health grants MH-43693 and MH-45 131.
Acknowledgment.
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