Psychiatry

Research,

215

43:2 15-222

Elsevier

Negative Symptoms Schizophrenia Janice Rweived

A. Husted, Fehruar,,

and the Early Course

Morton

10. 1992;

Beiser,

revised

and William

version

rec,eived

Ma),

of

G. lacono 20.

1992;

acceptedJu/j,

25, 1992.

Abstract. To determine the usefulness of including a duration criterion in the definition of “negative”symptoms, the prognostic significance of a longitudinally obtained measure of negative symptoms was compared with a cross-sectionally obtained measure. As predicted, the presence of negative symptoms based on longitudinal observation was associated with most aspects of 18-month course in a group of “first-episode” schizophrenic individuals, whereas cross-sectional levels of negative symptoms were not. The findings suggest that negative symptoms, when operationalized as a trait-like phenomenon, help to portend a poor course of illness. Key Words.

Prognosis,

outcome,

onset of illness, psychosis.

A subgroup of persons with schizophrenia create a risk that the illness will become

may suffer

from

brain

abnormalities

that

chronic. Some investigators have suggested that “negative” symptoms such as blunted affect, diminished social drive, and poverty of speech, long considered fundamental manifestations of schizophrenia (Bleuler, 1950; Kraepelin, 1971), are behavioral manifestations of the underlying brain pathology that leads to chronicity (Andreasen, 1985; Crow. 1985). Despite the heuristic appeal of this proposition, attempts to relate the negative symptom dimension to the early course of illness have proved inconclusive to date. Among the five studies that have appeared in the English literature, two reported a modest statistical association between negative symptoms and poor short-term outcome (Pogue-Geile and Harrow, 1985; Biehl et al.. 1986); two demonstrated no association (Johnstone et al., 1979; Prudo and Munroe-Blum, 1987); and one found that negative symptoms were associated with favorable outcome ratings (Kay and Lindenmayer. 1987). Differences in sample characteristics across the various studies may account for these inconsistent findings ( Pogue-Geile, 1989). The two studies that showed a direct relationship between negative symptoms and poor outcome selected a preponderance of clinically stable or remitted schizophrenic outpatients, whereas the two that indicated no association selected hospitalized patients who were

Janice Husted, Ph.D., is Assistant Waterloo, Ontario. Morton Be&r.

Professor. Department of Health Studies. University 01 Waterloo. M.D.. is Professor of Psychiatry, University of Toronto. Toronto,

Ontario. William Iacono, Ph.D., is Professor of Psychology, University of Minnesota. Minneapolis. MN, (Reprint requests to Dr. J. Husted, Dept. of Health Studies. University of Waterloo, Waterloo. Ont.. Canada

N2L 3G I .)

Ol65-17X1/92

‘$05.00 @ 1992 Elsevier Scientific

Publishers Ireland Ltd

216

experiencing an acute episode of illness, as did the study that showed a negative association. The latter three studies may have failed to capture an essential feature of the construct-the presence of the behaviors over time. As Carpenter et al. (1988) have suggested, measures of negative symptoms during episodes of acute psychotic disorganization risk confusing transient and treatable secondary negative symptoms with enduring or core traits. The current study investigates the relationship between negative symptoms and 18-month course of illness in a representative sample of first-episode schizophrenic individuals. Specifically, it examines the hypothesis that while a cross-sectional measure of negative symptoms during an acute phase of illness will bear no association to course, ratings of negative symptoms based on longitudinal observation will identify a subgroup of individuals with an increased likelihood of developing a chronic illness.

Methods Sample Characteristics. Participants in the current study were subjects of the University of British Columbia Markers and Predictors of Schizophrenia Study (MAP), an investigation of the role of biological and psychosocial factors in the 18-month course of first-episode schizophrenia and affective psychosis (Beiser et al., 1988; Iacono and Beiser, 1989). Using an elaborate network of community referral agencies, including hospital-based services, community mental health centers, community social agencies, and private psychiatric and family practice settings, we worked for 2% years to recruit a representative sample of individuals who were experiencing a first lifetime episode of psychosis. To avoid missing potential cases, we requested that the agencies in our network refer all persons who met very broad inclusion criteria-namely, either one or more psychotic symptoms (hallucinations, delusions, thought disorder, or grossly disorganized behavior) or two or more of the following symptoms: social withdrawal, reduction or loss of interest, persistent self-neglect, reduced initiative and drive, and deterioration in performance. Additional inclusion and exclusion criteria required: (1) that all cases be between the ages of 15 and 54; (2) that they had lived in the Vancouver Metropolitan area for at least 6 months; (3) that they had experienced psychotic symptoms within the past 12 months that could not be attributed to drugs, alcohol, or other organic factors; and (4) that there had been no previous psychotic episode or any prior treatment with neuroleptics, antidepressants, or lithium. While trained master’s level research assistants collected psychosocial and symptomatic information from the participants, their significant others, and hospital records, psychiatrists or Ph.D. level clinical psychologists administered the Present State Examination (PSE; Wing et al., 1974). Case conferences attended by at least two clinicians plus a research assistant produced “best estimate” consensus DSM-III (American Psychiatric Association, 1980) diagnoses, a procedure that optimizes reliability when complex and multifaceted data are considered (Leckman et al., 1982). Of the 175 psychotic patients who consented to participate in the study, 91 received a DSM-HIintake spectrum”: schizophrenia, schizophreniform diagnosis that fell within the “schizophrenia disorder, and schizoaffective disorder. Major depression and bipolar affective disorders made up the majority of the other intake diagnoses. To establish short-term outcome, we conducted a followup assessment 18 months after intake. In this assessment, a research clinician readministrated the PSE and the research assistants collected extensive data from the participants about treatment, occupational or school performance, living situation, and social activity during the followup period. In addition, collateral information was obtained from significant others and clinical or hospital records. For the purpose of this report, we selected only those schizophrenia spectrum subjects who were successfully reinterviewed with the PSE and with the battery of clinical and psychosocial

217

measures 18 months after their intake assessments (n = 66). Most of these subjects were white (90%) and young (mean age at intake = 21.9 years, SD = 5.4, range = 15-44). Men outnumbered women by a ratio of three to one; 43 subjects (65.0%) had completed high school. At the followup assessment, only one participant was hospitalized. There were no differences in gender, ethnicity, socioeconomic background, marital status, educational level, premorbid functioning, and negative symptoms at intake between the successfully reinterviewed subjects (n = 66) and those lost to followup (n = 25). Dropouts were, however, slightly older than those remaining in the study (mean f SD ages at intake = 24.8 + 6.3 vs. 21.9 f 5.4 years, respectively; t = 2.35, d’= 89, p < 0.05). Negative Symptoms. For an earlier investigation (Husted, unpublished), we devised a scale for measuring negative symptoms. Although it might have been desirable to use an already existing instrument, most current negative symptoms scales appeared in the literature after the MAP study had already begun (for a review of the major scales, see Pogue-Geile and Zubin, 1988; Fenton and McGlashan, 1992). The 10 items included the following: (1) self-neglect, (2) slowness and underactivity, (3) blunted affect, (4) incongruity of affect, (5) slow speech, (6) restricted quantity of speech, (7) incoherence of speech, (8) poverty of content of speech, (9) diminished adequacy of interview owing to communication problems (e.g., lack of response and delayed response to questions), and (10) poor rapport. These items were selected on the basis of both theoretical and psychometric considerations. According to many theoreticians (Pogue-Geile and Zubin, 1988; Fenton and McGlashan, 1992), several of these items such as blunted affect, psychomotor retardation (slowness and underactivity), and speech impairments (poor rapport and restricted quantity of speech) represent the primary or core negative symptoms. The inclusion of others like incongruity of affect and incoherence of speech is controversial owing to the lack of consensus about the formal definition of the negative symptom construct. Trained clinicians rated each item as either absent (0) or present (1) on the basis of the respondent’s behavior, affect, and speech during the PSE intake interview, as well as on collateral medical record information. Further details about rating and diagnostic procedures can be found elsewhere (Beiser et al., 1988; Iacono and Beiser, 1989). A global rating, arrived at by summing the 10 items, yielded a scale with a potential score ranging from 0 to 10. To estimate the prevalence of the negative symptom syndrome in a group of individuals experiencing their first episode of schizophrenia, we also developed a categorical negative symptom index. In keeping with past research (Carpenter et al., 1988) two or more symptoms qualified to indicate the presence of the negative symptom syndrome. While this categorical index constituted our cross-sectional measure of negative symptoms during the acute phase of illness, our longitudinal definition incorporated an additional criterion. To qualify for the longitudinal category, some combination of two or more negative symptoms had to be present at intake and at 18-month followup (Carpenter et al., 1988). In other words, negative symptoms had to be present in the post-acute phase, as well as during the acute phase. Followup Variables of Interest. Dimensions of illness course, rated approximately 18 months after the initial assessments, included the following: social adjustment, measured by items from the Social Adjustment Scale (SAS; Weissman and Bothwell, 1976); residual psychopathology measured by the Symptom Checklist-90-Revised (SCL-90-R; Derogatis, 1977); occupational functioning assessed by the Occupational Functioning Assessment Scale (OFAS; Katsanis et al., 1991); duration of hospitalization during the followup period; and global functioning as measured by the Global Assessment Schedule (GAS; Endicott et al., 1976). From the 42 questions that appeared in the SAS, we selected one about the number of friends seen and another about the frequency of social contacts over the 2 weeks before reinterview to construct a measure of social functioning. The overall score on this variable was obtained by summing the subscores of the two individual items or questions. It ranged from 0 to 8, with a low score reflecting social isolation. The reliability of the social functioning measure was satisfactory (Cronbach (I coefficient = 0.72).

218 The Global Severity Index (GSI) of the SCL-90-R, used to capture many of the symptomatic impairments typically associated with chronic schizophrenia (American Psychiatric Association, 1980). is a self-report inventory that measures levels of distress across nine symptom dimensions (somatization. obsessive-compulsive, interpersonal sensitivity. depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism) over the week before reinterview. GSI scores range from 30 to 8 1, with high scores indicating greater psychopathology. In this sample. the reliability of the GSI, as measured by the Cronbach a coefficient, was 0.84. We assessed occupational functioning with the OFAS. This scale was developed to assess the percentage of time in gainful employment or an equivalent such as school during the followup period. The format of the OFAS is similar to that of the GAS (see Katsanis et al. [ 19911 for a detailed descripton of the OFAS). Project clinicians assigned scores on the basis of information collected in the I&month structured interview with the schizophrenic participants and from collateral sources. Potential scores ranged from I to 8 I. with a high score indicating good occupational functioning. The interrater reliability of the scale was 0.95. We collected information on the duration of hospitalizations (number of days hospitalized, up to a maximum of 200) through systematic record searches of all hospitals and community mental health centers in the Greater Vancouver Region, In addition, to determine if some participants had been hospitalized outside the catchment area, we asked significant others for treatment information during the followup period. During the case conference held after the l8-month followup, clinicians arrived at a consensus GAS rating on the basis of the data collected from the participant, treatment records, and significant others. Interrater reliability of the GAS was 0.96.

Results Reliability of Negative Symptoms Measure. lnterrater reliability of the negative symptom ratings proved satisfactory. Sixteen PSEs were administered jointly, and the degree of agreement across the items ranged from 82Ye to 100%. The intraclass correlation for the global rating was 0.94. Prevalence of Negative Symptoms. At study intake, the mean level of negative symptoms for the 66 schizophrenia spectrum participants who were interviewed at two time points was I .85 (SD = I .48, range O-6). This was very similar to that found in the original sample of 91 schizophrenia spectrum patients (mean = 1.80, SD = 1.47, range O-6). The prevalence of the cross-sectional negative symptom syndrome in the 66 schizophrenia spectrum subjects at intake was 53.0%. The mean level of negative symptoms at followup was 0.44 (SD = 0.95, range = O-4), which was significantly lower than at intake (paired t = 8. IO, #= 65, y < 0.001). The correlation between negative symptoms at intake and followup was 0.39 (p < 0.001) reflecting a moderate degree of stability over the followup period. The prevalence of the longitudinally obtained negative symptom syndrome was also low. Eight (12%) of the schizophrenic patients had two or more negative symptoms at both the intake and 18-month followup assessments. This prevalence estimate is consistent with the single published estimate of the frequency of primary negative symptoms. Carpenter et al. (1988) reported that of 103 schizophrenic outpatients, 15 (14.5%) had two or more negative symptoms over a 12-month period. Together, these findings suggest that a cross-sectionally obtained measure of negative symptoms during a first psychotic episode probably provides an inflated estimate of the prevalence of primary negative symptoms.

219

Relationship Between Different Definitions of Negative Symptoms and 1 Bmonth Course of illness. Table 1 presents the mean scores and standard deviations on the selected followup variables for both the cross-sectionally and longitudinally defined negative symptom syndrome groups. To test whether the multivariate analysis of variance observed group differences were significant, (MANOVA) followed by univariate tests was calculated for the cross-sectional and the longitudinal data (SPSS, Inc., 1988). Given our hypothesis, one-tailed tests of significance were used for the univariate tests. Before the MANOVAs were calculated, Bartlett tests for the homogeneity of variance were carried out for each of the tabled variables. None of these tests proved significant, indicating that the variables had similar variances for the negative and nonnegative syndrome groups.

Table 1. Scores on selected followup variables for both cross-sectionally and longitudinally defined negative symptom syndrome groups Cross-sectionalmeasure Negative symptom syndrome group (n = 35) Followup dimensions Social functioning’ Residual

psychopathology2

Non-negative symptom syndrome group (n = 31)

Mean

SD

Mean

4.03

2.6

5.3

2.3

13.6

54.2

12.0 26.2

58.5

SD

34.0

30.4

36.5

Duration of hospitalization

81.9

55.5

61.2

42.7

Global functioning’

45.3

21.3

51.9

19.1

Occupational

functioning’

Longitudinal measure Negative symptom syndrome group (n = 8) FOIIOWUDdimensions Social functioning’ Residual

psychopathology2

Occupational Duration

functioning’

of hospitalization

Global functioning’

Non-negative symptom syndrome group (n = 58)

Mean

SD

Mean

2.64

2.5

4.8

2.4

65.53

14.2

55.2

12.4

SD

23.2

29.3

36.8

28.1

101.0

76.0

69.7

48.0

12.3

50.1

20.8

35.63

1. High scores reflect high or good functioning. 2. High scores reflect greater levels of psychopathology. 3. One-tailed t test, cff= 64, p < 0.05. 4. One-tailed t test, df = 64, p < 0.01.

As hypothesized, the cross-sectional definition of the negative symptom syndrome (two or more negative symptoms present at intake or during the first psychotic episode) was not significantly associated with 18-month adaptive functioning (Hotelling’s T* = 1.45; df= 5,60; p > 0.lo), whereas the longitudinal definition was (Hotelling’s T2 = 2.34; df = 5, 60; p < 0.05). Further, the univariate analyses indicated that the presence of two or more symptoms at both the index and followup assessments was significantly associated with poor social functioning (t = 2.42,

220

0.IO). These findings are in agreement with those of others (Buchanan et al., 1990; Pogue-Geile, 1989) and suggest that the prognostic power of negative symptoms may essentially arise from their occurrence in a portion of schizophrenic individuals who were functioning poorly before their onset of illness. Discussion Consistent with arguments advanced by others (Crow, 1985; Sommers, 1985; 1989), our findings suggest that negative Carpenter et al., 1988; Pogue-Geile, symptoms, when measured to include a dimension of stability over time, are associated with a poor course of schizophrenia. This may occur because negative symptoms that are present both during and following an acute psychotic episode are likely to reflect primary deficits, not transient and treatable secondary symptoms (Carpenter et al., 1988; Pogue-Geile, 1989). This may be especially true in samples of early phase schizophrenic patients as symptoms are unconfounded by the long-term effects of illness and medication. Although our findings strongly suggest the importance of including a measure of persistence as part of the definition of negative symptoms, our measure has an inherent limitation. Since we have data at only two points, widely separated in time, we cannot be sure whether the symptoms rated as present at both times were really

221 persistent or whether they tended to occur and recur with sufficient frequency to give the appearance of stability. Further longitudinal studies that assess negative symptoms over short intervals (see Carpenter et al., 1988) are needed to address this issue. In a future study, we shall examine the association between the longitudinally obtained measure of negative symptoms and 5-year outcome. Recall that our sample consisted of individuals experiencing their first episode of a schizophrenia-spectrum disorder. According to some reports, while negative symptoms fluctuate considerably in the early stages of the illness, the frequency of primary negative symptoms may increase with the progression of the illness (Kraepelin, 1971; Andreasen, 1987; Pogue-Geile and Zubin, 1988; McGlashan and Fenton, 1992). These findings suggest that some of the schizophrenic participants who do not have negative symptoms at an early stage of followup may develop these behaviors in the studies of intermediate and later stages of their illness. Hence, longitudinal representative samples of first episode schizophrenic individuals are required to determine the “true” prevalence of these symptoms as well as their relative role in predicting schizophrenic deterioration. Acknowledgments. The research reported was supported by grant 6610-1691-44 and a National Health Ph.D. fellowship, both from Canada Health and Welfare National Health Research and Development Program; B.C. Health Research Foundation grant 11(88-2); grant MH-44643 from the National Institute of Mental Health; and a Young Investigator Award from the National Alliance for Research in Schizophrenia and Depression. The authors thank Dave Erickson, Kathy Keetley, Neil Kyle, Diane Lambrou, Margaret Moreau, and Geoffrey Smith for their significant contributions to data collection and management.

References American Psychiatric Association, DSM-III: Diagnostic and Statistical Manual of Mental Disorders. 3rd ed. Washington, DC: American Psychiatric Press, 1980. Andreasen, N.C. Positive versus negative schizophrenia: A critical evaluation. Schizophrenia Bulletin, 11:380-389, 1985. Andreasen, N.C. The diagnosis of schizophrenia. Schizophrenia Bulletin, 13:9-22, 1987. Beiser, M.; Fleming, J.A.; Iacono, W.G.; and Lin, T. Refining the diagnosis of schizophreniform disorders. American Journal of Psychiatry, 145695-700, 1988. Biehl, H.; Maurer, K.; Schubart. C.; Krumm, B.; and Jung, E. Prediction of outcome and utilization of medical services in a prospective study of first onset schizophrenics. European Archives of Psychiatry and Neurological Sciences, 236:139-147, 1986. Bleuler, E. Dementia Praecox, or the Group of Schizophrenias. Translated by J. Zinkin. New York: International Universities Press, 1950. Buchanan, R.; Kirkpatrick, B.; Heinrichs, W.; and Carpenter, W.T. Clinical correlates of the deficit syndrome of schizophrenia. American Journal of Psychiatry, 147:290-294, 1990. Carpenter, W.T.; Heinrichs, D.W.; and Wagman, A.M. Deficit and nondeficit forms of schizophrenia: The concept. American Journal of Psychiatry, 145578-583, 1988. Crow, T.J. The two-syndrome concept: Origins and current status. Schizophrenia Bulletin, 11:471-485, 1985. Derogatis, L. SCL-90-R Manual. Baltimore, MD: Clinical Psychometric Research, 1977. Endicott, J.; Spitzer, R.L.; Fleiss, J.; and Cohen, J. The Global Assessment Scale: A procedure for measuring overall severity of psychiatric disturbance. Archives of General Psychiatry, 33:766-770, 1976. Fenton, W.S., and McGlashan, T.H. Testing symptoms for assessment of negative symptoms in schizophrenia. Archives of General Psychiatry, 49:179-184, 1992.

222 Harris, J. An abbreviated form of the Phillips Rating Scale of Premorbid Adjustment in Schizophrenia. Journal of Abnormal Psychology, 84:129-137, 1975. Iacono, W.G., and Beiser, M. Age of onset and temporal stability of first-episode psychosis in adults. In: Cicchetti, D., ed. Rochester Symposium on Development in Psychopathology. Hillsdale, NJ: L. Erlbaum, 1989. pp. 221-260. Johnstone, E.C.; Frith, C.D.; Gold, A.; and Stevens, M. The outcome of severe acute schizophrenic illnesses after one year. British Journal of Psychiatry, 134:28-33, 1979. Katsanis, J.; Iacono, W.; and Beiser, M. Relationships of lateral ventricular size to psychophysiological measures and short-term outcome. Psychiatry Research, 37: 115-129, 1991. Kay, S.R., and Lindenmayer, J.P. Outcome predictors in acute schizophrenia: Prospective significance of background and clinical dimensions. Journal of Nervous and Mental Disease, 174:152-160, 1987. Kraepelin, E. Dementia Praecox and Paraphrenia. Translated by R.M. Barclay. New York: R. Krieger Publishing Co., Inc., 1971. Leckman, J.F.; Sholomskas, D.; Thompson, W.D.; Belanger, A.; and Weissman, M. Best estimate of lifetime psychiatric diagnosis: A methodological study. Archives of General Psychiatry, 39:879-883, 1982. McGlashan, T.H., and Fenton, W.S. The positive-negative distinction in schizophrenia: Review of natural history validators. Archives of General Psychiatry, 49:63-72, 1992. Pogue-Geile, M.F. The prognostic significance of negative symptoms in schizophrenia. British Journal of Psychiatry, 155(Suppl. 7):123-127, 1989. M. Negative symptoms in schizophrenia: Their Pogue-Geile, M.F., and Harrow, longitudinal course and prognostic importance. Schizophrenia Bulletin, 11:427-439, 1985. Pogue-Geile, M.F., and Zubin, J. Negative symptomatology and schizophrenia: A conceptual and empirical review. International Journal of Mental Health, 1613-45, 1988. Prudo, R., and Munroe-Blum, H. Five-year outcome and prognoses in schizophrenia. British Journal of Psychintrv, 150:345-354, 1987. symptoms”: Conceptual and methodological problems. Sommers, A. “Negative Schizophrenia Bulletin, 11:364-379, 1985. SPSS, Inc. SPSS/PC+ V2.0 Base Manual. Chicago: SPSS, Inc., 1988. Weissman, M., and Bothwell, S. Assessment of social adjustment by patient self-report. Archives of General Psychiatry, 33: 11I I-1115, 1976. Wing, J.; Cooper, J.; and Sartorius, N. The Measurement and Classification of Psychiatric Symptoms. London: Cambridge University Press, 1974.

Negative symptoms and the early course of schizophrenia.

To determine the usefulness of including a duration criterion in the definition of "negative" symptoms, the prognostic significance of a longitudinall...
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