Course and Outcome for Schizophrenia Versus Other Psychotic Patients: A Longitudinal Study

Transcription

1 Course and Outcome for Schizophrenia Versus Other Psychotic Patients: A Longitudinal Study Abstract by Martin Harrow, James R. Sands, Marshall L. Silverstein, and Joseph F. Qoldberg We studied 276 patients longitudinally, beginning at the acute phase and continuing at three successive followups over 7.5 years, comparing 74 schizophrenia patients with 74 other psychotic patients and 128 nonpsychotic patients on early course and outcome. Schizophrenia patients showed significantly poorer functioning than patients with other psychotic disorders at each of the three followups (p < 0.05). More schizophrenia patients than other psychotic patients showed consistent psychopathology and a course in which there was not complete remission at any of the three followups (p < 0.05). Most schizophrenia patients did not show severe decrements hi social activity level. Poor outcome schizophrenia patients showed significantly slower recovery at each followup than did other psychotic patients with initial poor outcomes (p < 0.01). The results indicate that, during the early course, schizophrenia patients still show relatively poor outcomes, although a small number of schizophrenia patients enter into complete remission. Over time, many schizophrenia patients fluctuate between severe disability and moderate disability rather than always showing severe disability. Schizophrenia patients tend to recover more slowly then other psychotic patients. Differences between schizophrenia patients and other psychotic patients in clinical course over time may be larger than differences at any single followup. Schizophrenia Bulletin, 23(2): ,1997. The current research was designed to investigate early course and outcome in modem-day schizophrenia and to compare it with early course and outcome in other psychotic disorders. Outcome in schizophrenia has long been a central issue in theoretical views of the nature of this disorder (Vaillant 1978; Tsuang et al. 1979; Angst 1988; Carpenter and Kirkpatrick 1988; McGlashan 1988; Sampson et al. 1988; Johnstone 1990; Breier et al. 1991; Carpenter and Strauss 1991). Earlier observations by Kraepelin and others at first suggested that schizophrenia patients show very poor outcomes (Kraepelin 1919/1921). The modern neuroleptic era has altered this once almost totally negative view of outcome in schizophrenia (Hogarty et al. 1974; May et al. 1981). Neuroleptic treatment, other modern treatment modalities, and modern trends toward shorter hospitalizations have resulted in considerably fewer schizophrenia patients with many years of hospitalization in chronic treatment services. Supporting a generally optimistic view of outcome for schizophrenia patients, some recent research with a select sample of neuroleptic-responsive schizophrenia patients has suggested that a large percentage of these patients show relatively favorable outcomes (Harding et al. 1987). This investigation also did not find large differences in outcome between schizophrenia patients and other psychotic patients, which is studied in the present research. Studies finding relatively favorable outcomes in schizophrenia have been questioned by other recent research, however. Large scale followup research has been conducted by Tsuang and colleagues (1979, 1981) with the Iowa 500 sample; by McGlashan (1984a, 1984Z>) with a sample of patients treated at the Chestnut Lodge; and by Breier and colleagues (1991). These followup studies have reported a large percentage of schizophrenia patients showing considerable difficulties in outcome. In addition, our own followup studies have found a large percentage of schizophrenia patients with poor outcomes (Harrow et al. 1978; Carone et al. 1991; Grossman et al. 1991; Marengo etal. 1991). Our own research program studying schizophrenia patients at successive followups has found evidence suggesting that one of the distinguishing characteristics of Reprint requests should be sent to Dr. M. Harrow, Dept. of Psychiatry (M/C913), The University of Illinois at Chicago, 912 South Wood St., Chicago, IL

2 Schizophrenia Bulletin, Vol. 23, No. 2, 1997 M. Harrow et al. schizophrenia, compared with other psychotic disorders, may be course over time. Consistent psychopathology may distinguish schizophrenia patients from other types of psychotic patients more than psychopathology does at any single point in time (Harrow et al. 1995; Marengo and Harrow 1997, this issue). In general, despite many theoretical views about the consistency of disorder over time in schizophrenia, the issue of persistent schizophrenic psychopathology and persistent impairment has not been focused on fully in prospective empirical studies with multiple assessments over time. Concerning a closely related issue, it is not clear from the current literature whether some or many schizophrenia patients enter into periods of complete remission (including both the absence of major symptoms and adequate psychosocial functioning) at any point during their early clinical course. It is also unclear whether schizophrenia patients differ from other psychotic patients on this dimension of course over time. This potential type of clinical course is studied in the current research. In addition, we have proposed that a major feature of schizophrenia course and outcome is slower recoverability from major psychopathology (Harrow et al. 1995). Thus, we have suggested that both schizophrenia patients and other psychotic patients eventually show at least a partial recovery from major psychopathology after the more acute phases, but that schizophrenia patients recover more slowly and less completely and are subject to more frequent relapses than other psychotic patients. The importance of more precise knowledge about schizophrenia course and outcome for theory about the nature of this disorder and the need for guidelines for the practicing clinician suggest the need for a series of outcome studies in this area that (1) are prospectively designed, (2) use modem-day schizophrenia patients, (3) compare schizophrenia patients on course and outcome with other psychotic patients, and (4) employ a multifollowup research design to allow assessment of course over time. The present research prospectively studies outcomes of a large sample of relatively early-phase, young schizophrenia patients and a sample of other psychotic patients, within a multifollowup research design to answer the following specific questions: 1. Do modern-day schizophrenia patients show poor outcomes when studied prospectively at the acute phase and then assessed at three successive followups over 7.5 years? 2. Do schizophrenia patients show poorer outcomes than other psychotic patients? 3. Are there important differences in clinical course over time between schizophrenia patients and other types of psychotic patients? Is schizophrenia a more continuous disorder than other psychoses? 4. Does complete remission (including both the absence of major symptoms and adequate psychosocial functioning) occur in many schizophrenia patients? Methods Sample of Patients. The current investigation is based on data from the Chicago Followup Study, a prospective, multidimensional research program studying schizophrenia longitudinally. The investigation was planned (1) to study prognostic factors and functioning and adjustment over time in schizophrenia and other psychotic disorders (Harrow et al. 1978; Westermeyer and Harrow 1984; Grinker and Harrow 1987; Carone et al. 1991; Marengo et al. 1991), (2) to investigate thought disorders and positive and negative symptoms in schizophrenia on a longitudinal basis (Harrow et al. 1985, 1995; Pogue-Geile and Harrow 1985; Harrow and Marengo 1986; Sands and Harrow 1994), and (3) to explore mechanisms that may be involved in schizophrenic thought disorders and psychosis (Harrow et al. 1983, 1989; Harrow and Quinlan 1985; Port et al., in press). The current sample of 276 patients, diagnosed by Research Diagnostic Criteria (RDC; Spitzer et al. 1978), includes 74 schizophrenia patients, 74 nonschizophrenia psychotic patients (35 bipolar patients, 23 psychotic depressive, and 16 other psychotic patients), and 128 nonpsychotic patients. The nonpsychotic patients included 67 nonpsychotic unipolar depressive patients, 10 nonpsychotic bipolar depressives, 12 patients with minor depression or other depression-related disorders, 6 borderline patients, 7 substance-abuse patients, 6 patients with eating disorders, and 20 other patients with nonpsychotic disorders (i.e., various types of personality disorders, anxiety disorders, antisocial personality disorders). The current report focuses on clinical course and outcome for the 74 RDC schizophrenia patients. However, 64 of these 74 patients also met DSM-III (American Psychiatric Association 1980) diagnostic criteria for schizophrenia. Data are also reported for the DSM-III group. The subjects were assessed at index hospitalization and reassessed in three successive followup interviews conducted at a mean of 2 years, 4.5 years, and 7.5 years after index hospitalization. The study sample includes the 276 patients who were alive and studied at the 7.5-year followup; 267 patients were studied at all three followups, and 9 were studied at either the 2- and 7.5-year followups or the 4.5- and 7.5-year followups. Table 1 presents more detailed information on the number of patients from each group who completed the followup schedule. Data on 288

3 Course and Outcome for Schizophrenia Schizophrenia Bulletin, Vol. 23, No. 2, 1997 posthospital status at the 7-8-year followup were available for slightly more than 80 percent of the original sample. These patients did not differ significantly on major demographic variables from a small subsample of patients studied at the 2-year followup but not available for assessment at the 7.5-year followup. The diagnosis for each patient was based on at least one of two structured interviews that have been used successfully in previous research: (1) the Schizophrenic State Inventory, with each interview tape-recorded (Grinker and Harrow 1987), and (2) the Schedule for Affective Disorders and Schizophrenia (SADS; Endicott and Spitzer 1978). Satisfactory interrater reliability for diagnosis was obtained with these instruments. At index hospitalization, the inpatients were given a series of structured interviews, questionnaires, and tests. Later followups were conducted by trained interviewers who were blind to diagnosis and, at the second and third followups, blind to the results of the previous followup. Informed written consent was obtained at index hospitalization and at each followup. In the current prospective research, we studied young nonchronic inpatients to reduce the effects of long-term treatment, which can sometimes be a factor when chronically ill patients with years of previous treatment are studied. The mean age of the patient sample was 23.1 years at index hospitalization; 271 of the 276 patients (98%) were between the ages of 17 and 30 years when entering the research program. Fifty-one percent of the patients were male, 49 percent were female. Racially, 76 percent of the sample were white, and 24 percent were black. Based on the Hollingshead-Redlich Scale for Socioeconomic Status (SES; Hollingshead and Redlich 1958) with parental SES as the criterion, 59 percent of the sample were from households with SES of 1-3, 41 percent from households with SES of 4 or 5. More than 75 percent of this sample had either one or no previous hospitalizations before the index hospitalization. The mean educational level was Table 1. Number of patients assessed in each group at each followup Diagnostic group Schizophrenia patients Other psychotic patients Nonpsychotic patients No. of patients assessed at followup 2.5-year followup year followup year All 3 followup followups years. There were no significant between-group differences in age, but there were significant sex differences between the diagnostic groups. A higher percentage of the schizophrenia patients were male (64%), and a higher percentage of the nonpsychotic patients were female (59%). To control for the sex differences between these two groups, we conducted separate analyses (1) comparing the male schizophrenia patients with the other psychotic and the nonpsychotic male patients, and (2) comparing the female schizophrenia patients with the other psychotic and the nonpsychotic female patients. The results of these analyses on differences in outcome according to diagnosis were similar to those found when the entire sample of schizophrenia patients was compared with the entire sample of other psychotic and nonpsychotic patients. The patient population is rare in the research literature because it includes both young, early-phase schizophrenia patients studied prospectively at hospital admission and other psychotic patient controls studied prospectively at index, and both groups were assessed over time at three different followups over a 7-8 year period. Medication. As is typical in the natural course of schizophrenia and other psychotic disorders over many years, no single uniform treatment plan emerged for all the patients in this naturalistic multiyear study. At the third (7.5-year) followup, 69 percent of the schizophrenia patients were receiving medications; 58 percent of the schizophrenia sample were receiving neuroleptics. At the 2-year followup, 62 percent of the schizophrenia patients were being treated with neuroleptics, and at the 4.5-year followup 64 percent of the schizophrenia patients were in neuroleptic treatment. Although the majority of the schizophrenia patients were in medication treatment, not all were being medicated, partly because a subgroup of patients choose to leave the mental health caretaking system. Some members of this subgroup are schizophrenia patients who have become discouraged with their treatment; others are former patients who have entered into remission and no longer want treatment (Fenton and McGlashan 1987; Carone et al. 1991). These findings suggest that a subgroup of schizophrenia patients who recover may choose to sustain this recovery without maintenance antipsychotic medications. This thesis is supported by data outlined later on the functioning of patients in neuroleptic treatment compared with those not on neuroleptics. Fifty-one percent of the patients who were diagnosed at index as other (nonschizophrenic) psychoses were being treated with medications at the 7.5-year followup; 30 percent of them were being treated with neuroleptics 289

4 Schizophrenia Bulletin, Vol. 23, No. 2, 1997 M. Harrow et al. during the followup year. At both the 2- and 4.5-year followups, a similar percentage of other initially psychotic patients were being medicated; 28 percent of the initially nonpsychotic patients were in medication treatment at the 7.5-year followup. Schizophrenia patients who were on neuroleptics at the third followup showed significantly poorer overall functioning than those who were not (t = 2.50; df-l\\ p < 0.02). There were also significant differences in overall outcome functioning at the third followup between the other psychotic patients who were on neuroleptics at followup and those who were not (t = 4.79; df - 72; p < 0.001). Since the current research involves followup of a naturalistic sample, the data on differences between treated and untreated schizophrenia patients and psychotic patients were influenced by the tendency for the patients with greater psychopathology to be kept in medication treatment. Followup Assessments. The detailed followup evaluations involved assessments of overall functioning and adjustment, as well as of psychotic symptoms, anxiety symptoms, and affective symptoms. They also included detailed assessments of work and social functioning, potential rehospitalization, and medications and other treatment variables. Symptoms, functioning, and adjustment were assessed at each of the three followups by using the Harrow Functioning Interview (Harrow et al. 1978) to assess work, social activity level, family functioning, and rehospitalization; a modified version of SADS to assess psychotic symptoms, affective symptoms, and other symptoms; performance tasks, including the Proverbs Test (Gorham 1956), the Object-Sorting Test (Rapaport et al. 1968), the Digit Symbol Test (Wechsler 1955) to assess cognitive functioning, thought disorder, and deficit symptoms; and the Katz Adjustment Scale (Katz and Lyerly 1963), Anhedonia Scale (Chapman et al. 1976), and other questionnaires to assess anxiety symptoms, depressive symptoms, personality variables, and other variables. The scale used to assess overall functioning and adjustment was the LKP Scale, developed by Levenstein, Klein, and Pollack (1966). This scale has been used successfully by our research team and others (Grinker and Harrow 1987). Ratings on this scale, obtained at each followup, are based on work and social adjustment, level of self-support, life disruptions, potential symptoms, relapse, potential suicide, and rehospitalization. In a recent assessment of interrater reliability, we obtained an intraclass correlation coefficient of On the 8-point LKP scale, ratings for global outcome in the year before followup range from 1 (adequate functioning or complete remission during the followup year) to 8 (very poor psychosocial functioning, considerable symptoms, and lengthy rehospitalization). The analyses of variance (ANOVAs) of overall adjustment that were used in the present research are based on data from this 8-point scale. In addition, in previous research, this scale has been divided into three broad outcome categories: the first category (scores of 1 or 2) reflecting adequate or good outcome in each area (no major symptoms and adequate psychosocial adjustment, which could be viewed as complete remission during the followup year); the second category (scores of 3 to 6) representing moderate impairment (impairment in some, but not all, areas of functioning); and the third category (scores of 7 or 8) representing uniformly poor overall functioning in each major area of adjustment (major symptoms and poor psychosocial adjustment). Specific areas of functioning were also rated by separate outcome scales developed by Strauss and Carpenter (1972), which assess rehospitalization, social adjustment, work adjustment, and psychiatric symptoms. Adequate interrater reliability has been established for the Strauss- Carpenter scales assessing specific areas of outcome, and these scales have been used in previously reported research. Scores on psychosis were based on data from SADS, and determined by a system of assessment used in previously reported research (Harrow and Silverstein 1977; Harrow etal. 1985, 1995). Results Schizophrenia Patients' Outcome at Three Successive Followups Over 8 Years. Table 2 shows results on overall adjustment and outcome for the schizophrenia patients in terms of the percentage with good outcome (or complete remission during the followup year), moderate impairment, and poor outcome at each of the three followups. 1. At each of the followups the schizophrenia patients showed very poor overall outcomes when considered as a group. 2. In particular, at the 2-year followup, only a small percentage of the schizophrenia patients were in complete remission throughout the followup year. About half of them showed a uniformly poor outcome (poor functioning in multiple areas of adjustment). 3. At the second (4.5-year) followup and at the third (7.5-year) followup, the schizophrenia patients still had relatively poor outcomes; only slightly more than 20 percent showed good outcomes, or complete remission, at each of these followup years, and a much larger percentage showed uniformly poor outcomes. 290

5 Course and Outcome for Schizophrenia Schizophrenia Bulletin, Vol. 23, No. 2, 1997 Table 2. Overall outcome at three successive followups over 7-8 years Followup (n patients) RDC schizophrenia patients 2-year (n = 71) 4.5-year (n = 74) 7-8-year (n» 74) DSM-fll schizophrenia patients 2-year (n = 61) 4.5-year (n = 64) 7-8-year (n = 64) Good Outcome % Moderate Impairment Poor Note. HOC - Research Diagnostic Criteria (Spitzef et al. 1978); DSM-W - Diagnostic and Statistical Manual of Mental Disorders. 3rd ed. (American Psychiatric Association 1980). 4. Viewing the data in terms of those schizophrenia patients experiencing both complete remission of major symptoms and adequate psychosocial functioning showed the following: Twenty-three (32%) of the 71 schizophrenia patients for whom we had complete data at all three followups showed this type of complete remission for at least one of the followup years assessed. However, although 23 schizophrenia patients showed complete remission at one or more of the followups, only 2 of these 23 (less than 5% of the total sample) showed complete remission consistently over time at all three followups. Thus, a number of the schizophrenia patients who showed good functioning at one followup tended to show major problems at the succeeding followups. Despite this, there was at least some general consistency over time in adjustment (see "Correlations: Outcome Over Time" section and tables 5 and 6). Schizophrenia Patients' Outcome Compared With Those of Other Psychotic and Nonpsychotic Patients. Figure 1, which outlines the clinical course for all three groups, also reports the mean scores on overall adjustment and outcome for the schizophrenia patients, the other psychotic patients, and the nonpsychotic patients at 2-, 4.5-, and 7.5-year followups. The data on overall outcome for the three diagnostic groups at the three followups were analyzed by using a 3 X 3 (mixed design) repeated-measures ANOVA in which the two main factors were the three diagnostic groups and the three followup periods assessed (a within-subjects analysis). Figure 1. Overall outcome course among three diagnostic groups for three followups over 7-8 years Outcome Scale (UCP) Good l A Poor e. First Foflowup (2 Years) [ (f D<.001 Second FoBomip (4.5 Ytin) E-18.71, d IXOOl 1. The main effect for diagnosis in the 3X3 repeated measures ANOVA showed significant differences (F = 38.68; df= 2,264; p < 0.001). 2. One-way F tests (reported in figure 1) were signifn»2.58 (1 89) Other Non- Pjychotc Patients Other Psychon: PatJtntj Third Foflowup (7.5 Years) E-40.S0. (f D<.0Ol LKP. Levenstein, Klein, and Polack scale (Levenstein et al. 1996); m, mean. icant in comparisons of the overall adjustment and outcome of the diagnostic groups at each of the three followups; comparisons were based on the raw data for the three groups (scores on the 8-point LKP scale). Individual post hoc comparisons of the diagnostic groups by the Newman- Keuls test for post hoc comparisons showed significant diagnostic differences at each of the three followups between the schizophrenia patients and both the other psychotic patients and the nonpsychotic patients (p < 0.05). 3. The more detailed data from figures 1 and 2 and tables 3 and 7 indicate that, at each of the three followups, a number of the nonschizophrenia psychotic patients also showed functioning difficulties. However, in comparison with the schizophrenia patients, a much smaller percentage of the other psychotic patients showed uniformly poor outcome at each followup. 4. Similarly, more of the other psychotic patients showed complete remission. 5. At each followup after the first, more of the other psychotic patients showed complete remission than showed uniformly poor outcome. This pattern was different from that shown by the schizophrenia patients. 6. The trend toward more favorable outcome and 291

6 Schizophrenia Bulletin, Vol. 23, No. 2, 1997 M. Harrow ct al. toward more patients showing complete remission than showed uniformly poor outcome was even more striking at each of the three followups for the initially nonpsychotic patients. 7. In contrast to the schizophrenia patients, the nonpsychotic sample rarely experienced uniformly poor outcome, although some of the initially nonpsychotic patients showed problems with symptoms, and some showed difficulty in psychosocial functioning. Outcome in RDC Versus DSM-III Schizophrenia. The current research studied clinical course and outcome among a sample of RDC-diagnosed patients. RDC employs a modern, narrow concept of schizophrenia. However, it does not require as long a duration of illness as DSM-III, DSM-III-R (American Psychiatric Association 1987), and DSM-IV (American Psychiatric Association 1994). DSM-III, DSM-III-R, and DSM-IV require a 6-month duration of illness for a diagnosis of schizophrenia. The current sample of 74 RDC-diagnosed schizophrenia patients was separated into those who also met DSM-III criteria for schizophrenia (n = 64) and those who did not (n - 10). Of the 10 patients who did not meet DSM-IH criteria for schizophrenia, 8 were DSM-III schizophreniform patients. The outcome results for the DSM-III schizophrenia patients (see table 2) were similar in principle to those found for the RDC sample, except that the DSM-IH schizophrenia patients showed somewhat poorer outcomes and somewhat poorer clinical courses than the full RDC sample. At each of the three followups, more DSM-III schizophrenia patients showed uniformly poor outcome (42%-57%) when each followup was considered separately. The 64 DSM-III schizophrenia patients had poorer outcomes than did the 10 RDC schizophrenia patients who did not meet DSM-III criteria for schizophrenia. These differences were significant according to a 3 X 2 (mixed design) repeated measures ANOVA of scores from the 8-point LKP outcome scale (F = 9.76; df= 1,69; p < 0.01), using individual tests at each of the three followups (p < 0.05). We also analyzed the data for DSM-III schizophrenia patients and for the full RDC schizophrenia sample by using an index of consistent psychopathology and consistent impairment based on clinical course over three successive followups. (Findings for the RDC-diagnosed patients are presented in greater detail below and figure 2.) Significantly more of the DSM-III schizophrenia patients (X 2 = 8.02; df = 1; p < 0.01) showed persistent psychopathology over time (67%). Outcome in Major Individual Areas of Functioning. Table 3 shows the average Strauss-Carpenter scales Table 3. Work functioning, social functioning, symptom level, and rehospitallzatlon for schizophrenia patients and other psychotic and nonpsychotic patients Outcome area Work functioning, 1 mean (SD) Schizophrenia patients Other psychotic patients Nonpsychotic patients Social functioning, 1 mean (SD) Schizophrenia patients Other psychotic patients Nonpsychotic patients Psychotic symptoms, % Schizophrenia patients Other psychotic patients Nonpsychotic patients Rehospitalized, % Schizophrenia patients Other psychotic patients Nonpsychotic patients Note. SO» standard deviation. First followup 2 years 1.75 (1.65) (1.65) (1.39) 2.73 (1.54) (1.27) (1.03) Second followup 4.5 years (1.71) (1.53) (1.32) (1.44) (1-25) (1.20) Third followup 7-8 years (1-59) (1.61) (1.35) (1.33) (1.28) (1.17) 'Based on scores from the Strauss-Carpenter scales (1972). Higher scores on this 0-4-point scale reflect more favorable functioning. 'indicates that the other psychotic patients and the nonpsychotic patients differ slgnfficantty (p < 0.05) from the schizophrenia patients using the Newman- Keuts post hoc tests, derived from the analyses of variance

7 Course and Outcome for Schizophrenia Schizophrenia Bulletin, Vol. 23, No. 2, 1997 scores on work and social functioning for RDC-diagnosed patients at each followup, along with the percentages of patients who showed definite psychotic symptoms and patients who were rehospitalized. One-way ANOVAs, followed by Newman-Keuls post hoc tests comparing the three diagnostic groups, were conducted on data from the 5-point Strauss-Carpenter scales and the quantitative scale for severity of psychosis. In addition, individual analyses were done to compare the diagnostic groups at key cutoff points (e.g., percentage of patients working half of the time versus percentage working less than half of the time; percentage of patients with any rehospitalizations versus percentage not rehospitalized). Instrumental work functioning. 1. Analysis of the data on work functioning by oneway ANOVAs showed significant group differences at each followup (p < 0.001). 2. There were significant differences in work functioning at each followup between the schizophrenia patients and both the other psychotic patients (Newman- Keuls test, p < 0.05) and the nonpsychotic patients (Newman-Keuls test, p < 0.05). 3. On the basis of the detailed data on the percentage of patients working, we found that, at each of the three followups, less than 50 percent of the schizophrenia patients were employed or engaged in any type of instrumental work functioning (e.g., homemaking) half of the time or more during the followup year. 4. In contrast, at all three followups more than 60 percent of the other psychotic patients were working at least half of the time during the followup year. 5. In addition, by the 7.5-year followup, less than 20 percent of the schizophrenia patients who were not homemakers or students were working full time. Social functioning. 1. The data on the social activity of the schizophrenia patients was relatively positive; many of these patients had at least some moderate level of social contacts (table 3). 2. A small subgroup of 14 percent to 25 percent of the schizophrenia patients showed very poor social functioning, and the schizophrenia patients tended to have less social activity than the other two diagnostic groups at the first two followups. 3. However, use of one-way ANOVAs on the data from the Strauss-Carpenter scale for social contact level, and subsequent Newman-Keuls post hoc tests, showed the differences between the schizophrenia patients and the other two diagnostic groups to be significant only at the first followup (F = 8.09; df'= 2,266; p < 0.001). By the third followup, there were almost no differences in this area between the schizophrenia patients and the other psychotic patients. Psychosis. 1. More than one-third of the schizophrenia patients were determined to be psychotic (score of 3 on the 3-point scale) at each of the three followups, based on the presence of full delusions or hallucinations at some point during the followup year (table 3). Some other studies have found lower rates of psychosis in posthospital schizophrenia patients. However, these other studies usually used data from observations rather than direct interviews covering a broad range of potential psychotic phenomena. 2. At each followup, some of the other psychotic patients, and even some nonpsychotic patients, showed definite psychosis (full delusions or hallucinations). 3. However, significant differences at all three followups (shown by ANOVAs of the psychosis scores [p < 0.001] followed by Newman-Keuls post hoc tests) indicated that the schizophrenia patients showed significantly more psychotic activity than both the other psychotic and the nonpsychotic patients at each followup (p < 0.05). Rehospitalization. Individual ANOVAs using the broader 5-point Strauss-Carpenter scale for rehospitalization showed significant diagnostic differences at each followup (p = 0.02). 1. At each of the three followups, the schizophrenia patients were rehospitalized significantly more frequently than the nonpsychotic patients (Newman-Keuls test, p = 0.05). 2. Although at some point during each of the three followup years more than one-third of the schizophrenia patients were rehospitalized, the differences between the schizophrenia patients and the other psychotic patients were much narrower. The schizophrenia patients were rehospitalized significantly more than the other psychotic patients at the third followup (Newman-Keuls test, p < 0.05). However, although more schizophrenia patients were rehospitalized, there were no significant differences in extent of rehospitalization between the schizophrenia patients and the other psychotic patients at the 2- and 4.5- year followup. 3. The highest rate of rehospitalization for each diagnostic group was at the first followup. After the first few posthospitalization years, patients from the other psychotic and from the initially nonpsychotic patient groups were less likely to be rehospitalized (p < 0.05). Relationship Between Major Dimensions of Outcome. The within-group correlations between the four major dimensions of outcome (work and social functioning, 293

8 Schizophrenia Bulletin, Vol. 23, No. 2, 1997 M. Harrow et al. rehospitalization, and psychosis) at each of the three followups were analyzed. The results of this analysis at the 7.5-year followup are presented in table 4. In general, the intercorrelations between the four dimensions of outcome were moderate. In the majority of comparisons, the relationships were statistically significant, but these relationships only account for a modest percentage of the variance. The results on the interrelationships between these four dimensions of outcome are in general agreement with the views on open-linked systems of outcome proposed by Strauss and Carpenter in their analysis of their data on different dimensions of outcome. The view that these dimensions represent loosely linked dimensions of functioning and adjustment could fit the current data. Correlations: Outcome Over Time. Table S presents the correlations over time on overall outcome. In general, the schizophrenia patients and the other psychotic patients showed consistency in functioning over time. There were product moment correlations of more than r = 0.50 on overall adjustment between the first and second followups, and between the second and third followups. Hence, despite some general improvement after the first Table 4. Relationship between major dimensions of outcome at the 7.5-year followup Schizophrenia patients Work functioning 1 Social activity 1 Rehospitalization 1 Other psychotic patients Work functioning 1 Social activity 1 Rehospitalization Nonpsychotic patients Work functioning 1 Social activity 1 Rehospitalization 1 Intercorrelations between outcome areas for each diagnostic group Social Rehospiactlvlty 1 tallzatlon 1! Psychosis Note. Signs for all correlations adjusted so that positive correlations indicate that scores reflecting greater psychopathology on each of the two variables go with each other. 'Based on scores from the Strauss-Carpenter scales (1972). J Based on scores for psychosis derived from the Schedule for Affective Disorders and Schizophrenia (Endicott and Spttzer 1978). *p< p < *p<0.01. Table 5. Correlations for overall outcome over time for schizophrenia patients, other psychotic patients, and nonpsychotic patients Diagnostic group and followup Schizophrenia patients First followup (2 years) Second followup (4.5 years) Other psychotic patients First followup (2 years) Second followup (4.5 years) Nonpsychotic patients First followup (2 years) Second followup (4.5 years) 'p< Second followup (4.5 years) r Third followup (7-8 years) r followup, especially for the other psychotic patients, there was a clear tendency (p < 0.001), within both of these initially psychotic groups, for patients with good functioning (or those in complete remission) at one followup to show good functioning at the next followup, 2.5 to 3 years later. There was a similar tendency for poorer functioning patients to continue to experience functioning difficulty at the next followup. The high correlations over time, and the tendency for many patients with poor outcome to show subsequent outcome difficulties years later are consistent with other data reported in table 6. However, there were patients in each diagnostic group, at each followup, who showed changes in outcome level at the next followup. Changes in Overall Outcome Over Time. Potential changes in overall functioning and adjustment as the three diagnostic groups moved from the 2-year followup to the 4.5-year followup to the 7.5-year followup were assessed by using the 3 X 3 repeated-measures ANOVA of the data on overall outcome for the three diagnostic groups. The main effect for the followup period assessed was significant (F = 11.16; df= 2,528; p < 0.001), indicating improvement in overall outcome for the patient sample as the length of time since index hospitalization increased. Table 6 displays the percentages of schizophrenia patients who showed changes in overall outcome over time (i.e., improved functioning or decline in functioning). As shown in tables 2, 3, and 6, the mean scores for the schizophrenia patients at the second followup were significantly more favorable than the scores at the first followup (' = 2.65; df= 70; p < 0.01). However, the schizophrenia patients did not continue to improve and were not 294

9 Course and Outcome for Schizophrenia Schizophrenia Bulletin, Vol. 23, No. 2, 1997 Table 6. Percentage of schizophrenia patients showing changes in outcome at 4.5-year and 7-8-year followups Outcome status at first (2 years) followup Good outcome (n = 9) Moderate impairment (n = 26) Poor functioning (n = 36) Outcome status at second (4.5 years) followup Good outcome (n = 16) Moderate impairment (n = 31) Poor functioning (n = 27) functioning significantly better at the 7.5-year followup than they had been at the 2- or 4.5-year followups. In addition, at all followups there continued to be a relatively large number of schizophrenia patients with uniformly poor outcome. The above data indicate that for individual schizophrenia patients the pattern of psychopathology and level of functioning over time are related to previous psychopathology and functioning and can be seen in the relatively high correlations of outcome at successive followups. Also, consistent with the relatively high correlations and indicating a link for many schizophrenia patients between earlier and later functioning and psychopathology are the within-subjects data on potential changes (table 6) and potential improvement (table 7) over time. Unlike the schizophrenia patients, the combined sample of nonschizophrenia patients tended to show improvement in overall outcome since the index hospitalization (see figure 1). Thus, outcome for the nonschizophrenia patients was better at the 7.5-year followup than at the 2- year followup (/ = 4.37; df= \97,p< 0.001) and the 4.5- year followup (f = 2.18; df= 199; p < 0.05). Poor Outcome Patients: Rate of Improvement for Schizophrenia Patients and Nonschizophrenia Patients. In previous research we proposed that one of the factors associated with the poorer outcome of some or many schizophrenia patients is their slower recovery from psychopathology and psychosocial difficulties (Harrow et al. 1995). To assess this, we compared poor outcome schizophrenia patients with poor outcome nonschizophrenia patients on rate of recovery over time (table 7). Table 7 shows the separate analysis of the extent of Same status Same status Second followup (4.5 years) status, % Change in outcome status Improved functioning Third followup (7-8 years) status, % Decline in functioning Change In outcome status Improved functioning Decline In functioning recovery among schizophrenia patients with uniformly poor outcome at each followup in comparison with the recovery among the parallel sample of other psychotic and nonpsychotic patients with poor outcome at the same followup. At the first followup, 36 of the 71 schizophrenia patients for whom we had data at this followup showed uniformly poor outcome. At the second followup, 2.5 years later, 36 percent of these poor outcome schizophrenia patients had improved and were showing either moderate impairment or complete remission. Thirty-nine of the 198 (19.7%) nonschizophrenia patients (both psychotic and nonpsychotic patients) showed uniformly poor outcome at the 2-year followup. Fifty-six percent of the poor outcome nonschizophrenia patients (22 patients) showed at least some improvement 2.5 years later, at the second followup. Within the larger group of poor outcome nonschizophrenia patients, a significantly larger percentage of nonpsychotic patients (63%) than of schizophrenia patients (13%) showed improvement as they moved to the 4.5-year followup (X 2 = 3.67; df=\;p< 0.05). At the 4.5-year followup, 27 of the poor outcome schizophrenia patients showed uniformly poor outcome. At the third followup, 3 years later, 5 of these 27 schizophrenia patients (19%) had improved. None of these schizophrenia patients were in complete remission at the third followup, but all five had improved from uniformly poor outcome to moderate impairment. The rate of improvement at the 7-8 year year followup for patients who had poor outcomes at the 4.5-year followup was significantly better for both the other psychotic patients (X 2 = 7.54; df= 1; p < 0.01) and the nonpsychotic patients (X 2 = 9.74; df= 1; p < 0.01) than it was for the schizophrenia 295

10 Schizophrenia Bulletin, Vol. 23, No. 2, 1997 M. Harrow et al. Table 7. Poor outcome schizophrenia and nonschizophrenia patients: Rate of improvement Poor outcome patients at 2-year followup Schizophrenia patients Nonschizophrenia patients Other psychotic patients Nonpsychotic patients Poor outcome patients at 4.5-year followup Schizophrenia patients Nonschizophrenia patients Other psychotic patients Nonpsychotic patients patients. However, a minority of the poor outcome schizophrenia patients did show improvement at both the second and third followups. Some diagnostic stability can be seen for the schizophrenia patients (tables 5 and 6), indicating that over half of the schizophrenia patients showed the same followup status from one followup to the next. Similarly, the data in figure 1 and table 3 indicate that at each of the three followups over the 7-8 year period the overall schizophrenia sample tended to show poorer outcome, poorer work functioning, and more psychosis than the other patient groups. Does Initial Avoidance of Poor Outcome Make Subsequent Poor Outcome Unlikely? We also analyzed data for the subsample of schizophrenia patients who did not show very poor outcome at either the 2- or 4.5-year followup, to determine whether this rendered future poor outcome at the 7.5-year followup less likely. The data indicated that fewer of this subsample of schizophrenia patients showed very poor outcome at the 7.5-year followup, although some (8 schizophrenia patients) from this subsample still showed very poor outcome at the 7.5-year followup. We also analyzed separately the subsample of schizophrenia patients who had complete remission (a rating of "good" outcome, which also includes adequate work functioning) at either the 2- or 4.5-year followup. Even fewer schizophrenia patients from this subsample showed very poor outcome at the 7.5-year followup. Consistent Psychopathology and Consistent Functioning Problems. The issue of consistent psychopathology and consistent impairment over time also was Improvement at 4.5-year followup n % Improvement at 7.5-year followup Still poor outcome at 4.5-year followup n % Still poor outcome at 7.5-year followup studied. This dimension of clinical course and outcome was analyzed by using an index that takes the combined data from all three followups into account. This index, using the scores for overall outcome from all three followups, was based on the number and percentage of patients in each group who were not in complete remission at any of the three followups (i.e., who showed either moderate impairment or uniformly poor outcome at all followups) and who also showed uniformly poor outcome during at least one followup. Figure 2 presents the data on such consistent psychopathology and impairment for each diagnostic group. The data from figure 2 indicate that more than 60 percent of the schizophrenia patients showed consistent psychopathology or impairment, as defined above. In contrast, 34 percent of the other psychotic patients showed persistent functioning difficulties, and only 14 percent of the nonpsychotic patients showed persistent functioning difficulties. Thus, on this measure, which takes the results from all three followups into account, significantly more of the schizophrenia patients than of the other psychotic patients (X 2 = 9.76; df= \\p< 0.01) and the nonpsychotic patients (X 2 = 45.50; df - 1; p < 0.001) experienced this type of persistent impairment. The results on persistent difficulties seem somewhat more hopeful when one looks at the percentage of patients with uniformly poor outcome at every followup over the 7.5-year period. A much smaller percentage of patients from each group showed uniformly poor outcome at all three followups (28% of the schizophrenia patients and only 9 percent of the other psychotic patients, X 2 = 9.00; df = 1; p < 0.01). Similarly, significantly fewer nonpsychotic patients (1.6%) than schizophrenia patients showed 296

11 Course and Outcome for Schizophrenia Schizophrenia Bulletin, Vol. 23, No. 2, 1997 Figure 2. Percent patients with some or consistent poor outcome and never in complete remission: Three followups over 7-8 years SZ=Schfcophrenia Patients OP=Other Psychotic Patients NP=Nonpsycriotic Patients this type of persistent poor outcome (X 2 = 32.34; df= 1; The results suggest that many schizophrenia patients have persistent problems and over the years do not enter into complete remission, but that many fluctuate between severe disability and moderate disability rather than always showing severe disability. Discussion Overall, in a sample of early-phase, young schizophrenia patients and other psychotic patients who entered the hospital in an acute psychotic state, all diagnostic groups showed some reduction of symptoms as they moved past the acute phase (Harrow et al. 1985; Carone et al. 1991). However, the current data comparing the schizophrenia patients with the nonschizophrenia psychotic patients over a 7.5-year posthospital period indicate the following: 1. Schizophrenia patients had poorer outcomes than other psychotic patients at all three followups. 2. A major factor in the poorer outcome of the schizophrenia patients, compared with the bipolar and unipolar psychotic patients, was that a larger percentage of the schizophrenia patients showed uniformly poor outcome or poor outcome in multiple areas of functioning. 3. The longitudinal data from three successive followups indicate that the greater persistence of psychopathology and psychosocial impairment over time among the schizophrenia patients represents a major difference between these patients and other initially psychotic patients. 4. The data also show that a small number of the schizophrenia patients had complete remission during the year before each of the three followups. However, a relatively small number of schizophrenia patients showed complete remission throughout the year before any one of the followups (fewer than 25% at any followup). Other major investigations also have found relatively low rates of complete recovery or complete remission in schizophrenia. For instance, fewer than 30 percent of schizophrenia patients showed full and sustained remission in the followup studies of Bleuler (1978), Tsuang et al. (1979), Ciompi (1980), Huber et al. (1980), Gardos et al. (1982), McGlashan (1984a, 19846), and Breier et al. (1991). 5. The data suggest improvements in outcome for the schizophrenia patients from the 2- to 4.5-year followup but do not indicate further improvement at the 7- to 8-year followups. 6. The data begin to suggest that the gap between outcome in schizophrenia and outcome in bipolar and unipolar psychotic affective disorders may widen rather than narrow as the patients move further in time from their index hospitalization. Schizophrenia Outcome and Consistent Psychopathology: Comparison With Other Psychoses. The data comparing course and outcome in schizophrenia patients with those nonschizophrenia patients who were psychotic at the acute phase are of particular interest. Many psychotic patients seem to show at least some outcome difficulties. In this respect, the presence of psychosis at the acute phase is often a negative prognostic factor (Coryell and Tsuang 1982; Sands and Harrow 1994; Harrow et al. 1995). However, the pattern of uniformly poor outcome and persistent outcome difficulties is found more often among schizophrenia patients. A number of the nonschizophrenia psychotic patients also showed vulnerability to psychopathology and to functioning difficulties (Harrow et al. 1994, 1995; Sands and Harrow 1994; Marengo and Harrow 1997, this issue). However, fewer nonschizophrenia psychotic patients showed as widespread or as persistent psychopathology as the schizophrenia patients. The results from the current report suggesting more persistent psychopathology in schizophrenia patients fit in with other data on the persistence of thought disorder (Marengo and Harrow 1997, this issue) and of delusional activity (Harrow et al. 1995) in schizophrenia patients. The data indicating a trend toward greater diagnostic differences at the 7.5-year followup than at the 2-year followup deserve further consideration. This trend is due, in part, to greater improvement over time by the bipolar and 297

12 Schizophrenia Bulletin, Vol. 23, No. 2, 1997 M. Harrow et al. unipolar affectively disordered patients and the nonpsychotic depressives, and to the lack of a parallel improvement by the schizophrenia patients. Some theorists have taken the view that diagnosis does not matter much. The current data could indicate that, whatever vulnerabilities or susceptibilities to current and future psychopathology are tapped by a diagnosis of schizophrenia, they manifest themselves in the consistency of psychopathology over time and may manifest themselves to a greater extent over time. Diagnostic Differences in Outcome: Relevance of a Statistical Model Involving Regression to the Mean. Looking at the data on changes over time from one perspective, it might be thought that, since the schizophrenia patients had the poorest functioning at the first (2 year) and second (4.5 year) followups, it should have been easier for them to show subsequent improvement (since they had more room to improve). For most of the schizophrenia patients, even functioning at the moderately impaired level at the 4.5- and 7.5-year followups would mark an improvement. However, the schizophrenia patients as a group showed the least improvement. In regard to the lack of large changes over time, many have discussed results showing regression to the mean using models of biometric data in groups showing extreme scores. Using the model of regression to the mean, one might expect that schizophrenia patients, who showed the poorest functioning at the first followup, would show the greatest improvement at subsequent followups. However, despite their poor functioning at the first followup, schizophrenia patients did not show a dramatic regression to the mean, and instead showed the least improvement. In human data, regression to the mean is usually a statistical expression of biological or psychological factors rather than an entity in itself. It is often influenced by scores collected at the height of pathology, or at the extreme end of a spectrum, followed by a return to more typical or routine scores. In the present case, where the schizophrenia patients did not show regression to the mean, or greater improvement, in comparison with the other psychotic patients, this would appear to be related to biologically, psychologically, and societally induced factors associated with schizophrenia. Functioning of Schizophrenia Patients in Major Areas. In modern society, instrumental work functioning is one of the features that some people use to define their own adequacy; therefore, poor work functioning can be a source of considerable distress. The present data on instrumental functioning reflect the consistent difficulty in work adjustment experienced by most schizophrenia patients. The poor work performance of the schizophrenia patients can be contrasted with the significantly higher percent of other psychotic and nonpsychotic patients with adequate work functioning and points to one of the major areas of dysfunction in schizophrenia patients. Although, during both the 4.5- and 7.5-year followup years, only about 40 percent of the schizophrenia patients were rehospitalized and many were able to maintain some social contacts, a large number of the schizophrenia patients showed considerable difficulty in the area of instrumental work functioning, and a relatively small percentage engaged in full-time employment. The data on level of social activity for the schizophrenia patients were more encouraging. Although these patients did experience some social difficulty as a group, the great majority did not show the type of progressive decline in social functioning or the total social isolation that was described before the modem era. In addition, after the 2-year followup, the differences in extent of social activity between the schizophrenia patients and the other psychotic patients were relatively small. The results on social functioning could have been influenced by treatment factors, including a tendency for many day-treatment programs to emphasize and encourage social interaction. The current data on psychosis, in conjunction with other recent data on delusions (Harrow et al. 1995), suggest that some other types of patients in addition to patients with schizophrenia, are vulnerable to psychosis at followup. Accordingly, the present data and other results (Sands and Harrow 1994) indicate that nonschizophrenia patients who experience psychosis at the acute phase are vulnerable to subsequent psychotic activity. However, despite this vulnerability, the subsequent reality distortions found in other psychotic patients are often less flagrant and less persistent than those found in many schizophrenia patients (Harrow et al. 1995). The consistent trend toward more rehospitalizations at the 2-year followup (i.e., in the year leading up to the followup), followed by a reduction in rehospitalizations at the 4.5- and 7.5-year followups, corresponds to a trend we observed previously when analyzing schizophrenia patients over a shorter followup period (Carone et al. 1991) and without a comparison group of other psychotic patients. The reduction in rehospitalizations after the 2- year followup is consistent with a view that, for patients who were rehospitalized during the first few posthospital years, the expectations that hospital treatment will lead to a permanent cure begins to diminish. Thus, after the first few posthospital years, some patients' relatives are not as eager to see them rehospitalized and sometimes will not seek rehospitalization even when there is an increase in symptoms. 298

13 Course and Outcome for Schizophrenia Schizophrenia Bulletin, Vol. 23, No. 2, 1997 We have called this factor a rising "threshold of hospitalization" (Carone et al. 1991) after years of psychopathology. Once this factor takes effect, hospitals are less likely to be seen as able to provide a sustained cure, and when psychosis becomes more severe, the schizophrenia patients are less likely to be hospitalized, unless they are totally unmanageable or other factors necessitate it. In addition, over the years some psychotic symptoms, although just as frequently present, may diminish in intensity and become less flagrant; this also could be a factor in reduced hospitalizations. For some patients, residual symptoms from their original index illness may persist for several years and create adjustment difficulties or even provide the basis for an acute exacerbation of disorder. However, after the first few posthospital years, the residual symptoms from the acute episode may remit. A fourth possible factor is a "period effect." Thus, in relation to the period effect there has been a tendency toward less use of hospitals in more recent times (or at the later followups) with this possibly influencing the results in this area. It is likely that some combination of the above factors and others may account for the data indicating fewer rehospitalizations over time for schizophrenia patients and a lower correlation over time between psychosis and rehospitalization. The current article has focused on the differences between schizophrenia patients and other psychotic patients in overall outcome, in specific areas of outcome, and in clinical course over time at multiple assessments. However, there are other important aspects of course and outcome not explored in detail in the current report that deserve further consideration. Of particular interest is research that analyzes course and outcome based on a conceptual framework involving three clinical syndromes as proposed by Liddle (Liddle and Barnes 1990; Liddle et al. 1994) and others (Bilder et al. 1985; Lenzenweger et al. 1989;Peraltaetal. 1992; Amdtet al. 1995). Slower Recoverability Over Time as a Factor In Course and Outcome for Schizophrenia Patients. We have suggested that an important characteristic of overall course and outcome in schizophrenia is schizophrenia patients' slower recovery (Harrow et al. 1995). Both schizophrenia patients and other psychotic patients appear to be vulnerable to psychopathology and especially to psychotic activity. Both types of patients show some recoverability after the acute phase. However, schizophrenia patients recover from psychopathology and from psychosis at a slower rate and are more vulnerable to subsequent psychosis, although other types of initially psychotic patients also show vulnerability to subsequent psychosis. Consistent with this view of slower recovery are the data indicating that schizophrenia patients with uniformly poor outcomes at the 2-year followup were less likely than other psychotic patients with uniformly poor outcomes to show improvement at the next followup (see table 7). Parallel data (table 7) indicated that schizophrenia patients with uniformly poor outcomes at the 4.5-year followup were less likely than similar other psychotic patients to show subsequent improvement. Diagnostic Differences in Outcome: A Product of Multiple Factors. What factors are responsible for the differences in outcome between (1) the schizophrenia patients and (2) the bipolar and psychotic unipolar patients and other psychotic patients? One could use the current data on outcome, and data showing increasing diagnostic differences over time, to support a view that some factors that are found in most schizophrenia patients are also associated with consistently poor outcome and contribute to the relatively unfavorable outcome found in a large percentage of schizophrenia patients. Among these might be factors innate to schizophrenia patients that make it harder for them to use environmental experiences to acquire greater personal competency over time. Another factor is the societal impact of having a severe disorder such as schizophrenia, which improves slowly and disrupts functioning drastically and, as a result, sets up societal prejudice against those with the disorder. As an example, it is harder in our competitive society to obtain a job after a sustained period of unemployment. Failure in the employment area and memory of previous work failure can then lead to demoralization and an increased likelihood of avoiding future frustrations and disappointments associated with trying to succeed in this area. Adequate work functioning can become even more problematic in patients who, because of their disorder or premorbid personality, have problems undertaking new initiatives and who may be experiencing negative symptoms (Andreasen and Olsen 1982; Pogue-Geile and Harrow 1985; Andreasen et al. 1990), or depression (Siris 1991; Harrow et al. 1994). Comorbid psychopathology and substance abuse may further contribute to pervasive demoralization and unemployment in a number of schizophrenia patients over time. The data indicate that poor functioning at any given followup assessment tends to predict later poor functioning, and that persistent poor functioning, with its psychological and social impact on the patient, may further increase the chance of poor functioning and disability in the future. It is possible that greater investment in early treatment and early rehabilitative aid for patients with schizophrenia could help lower the rates of long-term disability. Among the other factors that could contribute to 299

14 Schizophrenia Bulletin, Vol. 23, No. 2, 1997 M. Harrow et al. course and outcome differences among the three diagnostic groups are severity of illness and level of functioning at index hospitalization or at the acute phase of illness. In separate studies of delusions over time, thought disorder over time, and the relationship between poor premorbid work functioning and later prognosis, we have found evidence that the presence of these three types of psychopathology at the acute phase has a relationship to later psychopathology in the same area, and sometimes to later overall functioning. However, at best these three factors account only for part of the variance in later course and outcome (Westermeyer and Harrow 1984; Harrow et al. 1986, 1995). A key factor is the greater vulnerability of schizophrenia patients to severe psychopathology after the acute phase, including ongoing susceptibility in the posthospital phase to positive symptoms (Harrow and Silverstein 1977; Harrow et al. 1985, 1995), to lethargy-dullness, and to akinesia (Bermanzohn and Siris 1992) (some of which may be influenced by treatment with neuroleptics), and to depression and negative symptoms, which arc experienced by a number of schizophrenia patients (Siris et al. 1984; Pogue-Geile and Harrow 1985; Andreasen et al. 1990; Siris 1991; Harrow et al. 1994). These psychopathological factors also contribute to the increasing distance of schizophrenia patients from the other major groups in terms of poorer overall functioning. As data become available on the long-term use of newer, atypical neuroleptics such as clozapine and risperidone, it will be interesting to see whether use of these medications is associated with improvements in clinical features such as depression, negative symptoms, lethargy-dullness, and akinesia. A major question is whether these overall differences in outcome between diagnostic groups continue to increase over time. This question is still to be resolved. Recent Evidence on Outcome in Schizophrenia. The current data on course and outcome indicating that many schizophrenia patients experience considerable posthospital problems with both symptoms and instrumental work adjustment are consistent with results reported by Tsuang et al. (1979, 1981), McGlashan (1984a, 1984&, 1988), Johnstone (1990), and Breier et al. (1991). Our data do not completely support a report by Harding and colleagues (1987) that suggests that outcome in schizophrenia has become optimistic. Rather, our data suggest that outcome in schizophrenia is relatively unfavorable. However, the data presented by Harding et al. are based on a sample that differs from our sample in that most of the patients were selected on the basis of neuroleptic responsivity and ability to work with some degree of success in an inpatient vocational program (Chittick et al. 1961; McGlashan 1988). In addition, the data presented by Harding et al. (1987) involve an older sample of patients. These results could indicate that many schizophrenia patients experience fewer symptomatic problems as they age, although not all studies have verified this (e.g., the studies by Tsuang and colleagues). In addition, when one looks at an older sample, with many studied after retirement, one is focusing on a period when adequate work performance is no longer an important aspect of adjustment. At any rate, the issue of whether schizophrenia patients experience fewer symptomatic problems as they age, raised by the data of Harding and colleagues, must be regarded seriously and should be resolved with a sample followed up longitudinally and assessed at multiple time points. The current data, using early-phase, young patients, using other psychotic patients as controls, and looking at clinical course over time (reassessing patients every few years), indicate that schizophrenia patients show less favorable outcomes than other psychotic patients. From this perspective, outcome and clinical course in schizophrenia, at least during the first 7 to 8 years, is relatively unfavorable. However, as we have noted in other reports (Carone et al. 1991; Harrow et al. 1992), the issue of how optimistic one can be depends on which expectations one adopts in considering course and outcome. If one adopts the older outlook, originally proposed for dementia praecox as a disorder in which many patients show progressive deterioration or continually show very poor outcome, our data, based on a multifollowup research design, indicate that, as a group, schizophrenia patients do not deteriorate over time. One can be optimistic since, with modern-day treatment, many schizophrenia patients fluctuate over time between severe disability and moderate disability, with some entering into periodic remissions. Currently, one finds only a moderate decline in social activity, and most schizophrenia patients are not continually hospitalized. In this respect, the modern outlook, based in part on modern pharmacological and psychosocial treatments and on discouragement of multiyear hospitalizations and the type of regression once found in the back wards of large State hospitals, has produced an improved picture from that reported earlier in this century. On the other hand, if one adopts the layman's expectation that success with major disorders occurs when one is able to treat them successfully and patients can be returned to normality or to normal functioning, then outcome for the majority of schizophrenia patients would be seen as poor. Schizophrenia patients show poorer clinical courses and outcomes than other types of initially psychotic patients; many show very poor work adjustment, 300

15 Course and Outcome for Schizophrenia Schizophrenia Bulletin, Vol. 23, No. 2, 1997 and the majority are vulnerable to recurrent psychotic symptoms and other positive symptoms and to both negative symptoms and depressive symptoms, with more persistent impairment over time. The data on both schizophrenia patients and on other psychotic patients would indicate that the presence of psychotic symptoms at the acute phase often is associated with vulnerability to subsequent symptom and outcome difficulties. However, the impairments for schizophrenia patients are often more severe than those of other psychotic patients. Thus, despite optimistic reports by some, the current data collected at four points over a 7- to 8-year period (at the acute phase and three successive followups) suggest that the majority of schizophrenia patients do not show complete and consistent remission over the long term. Rather, they experience symptomatic impairment and difficulty over the years in instrumental work functioning and show more persistent psychopathology and problems in functioning than other psychotic patients. References American Psychiatric Association. DSM-llI: Diagnostic and Statistical Manual of Mental Disorders. 3rd ed. Washington, DC: The Association, American Psychiatric Association. DSM-H1-R: Diagnostic and Statistical Manual of Mental Disorders. 3rd ed., revised. Washington, DC: The Association, American Psychiatric Association. DSM-IV: Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: The Association, Andreasen, N.C.; Flaum, M.; Swayze, V.W. II; Tyrrell, G.; and Arndt, S. Positive and negative symptoms in schizophrenia. Archives of General Psychiatry, 47: , Andreasen, N.C.; Olsen, S.A.; Dennert, J.W.; and Smith, M.R. Ventricular enlargement in schizophrenia: Relationships to positive and negative schizophrenia. American Journal of Psychiatry, 139: , Angst, J. European long-term followup studies of schizophrenia. Schizophrenia Bulletin. 14(4): , Arndt, S.; Andreasen, N.C.; Flaum, M.; Miller, D.; and Nopoulos, P. A longitudinal study of symptom dimensions in schizophrenia. Archives of General Psychiatry, 52: , Bermanzohn, PC, and Sins, S.G. Akinesia: A syndrome common to Parkinsonian, retarded depression, and negative symptoms of schizophrenia. Comprehensive Psychiatry, 33: , Bilder, R.M.; Mukherjee, S.; Rieder, R.O.; and Pandurangi, A.K. Symptomatic and neuropsychological components of defect states. Schizophrenia Bulletin, ll(3): , Bleuler, M.N. The Schizophrenic Disorders: Long-Term Patient and Family Studies. New Haven, CT: Yale University Press, Breier, A.; Schreiber, J.D.; Dyer, J.; and Pickar, D. National Institute of Mental Health longitudinal study of chronic schizophrenia. Archives of General Psychiatry, 48: , Carone, B.J.; Harrow, M.; and Westermeyer, J.F. Posthospital course and outcome in schizophrenia. Archives of General Psychiatry, 48: , Carpenter, W.T., Jr., and Kirkpatrick, B. The heterogeneity of the long-term course of schizophrenia. Schizophrenia Bulletin, 14(4): , Carpenter, W.T., Jr., and Strauss, J. The prediction of outcome in schizophrenia: IV. Eleven-year follow-up of the Washington IPSS cohort. Journal of Nervous and Mental Disease, 179: , Chapman, L.J.; Chapman, J.P.; and Raulin, M.L. Scales for physical and social anhedonia. Journal of Abnormal Psychology, 85: , Chittick, R.A.; Brooks, G.W.; Irons, F.S.; and Deane, W.N. The Vermont Story: Rehabilitation of Chronic Schizophrenic Patients. Burlington, VT: Queen City Printers, Ciompi, L. Catamnestic long-term study on the course of life and aging of schizophrenics. Schizophrenia Bulletin, 6(4): , Coryell, W., and Tsuang, M.T. Primary unipolar depression and the prognostic importance of delusions. Archives of General Psychiatry, 39: , Endicott, J., and Spitzer, R. A diagnostic interview: The Schedule for Affective Disorders and Schizophrenia. Archives of General Psychiatry, 35: , Fenton, W.S., and McGlashan, T.H. Sustained remission in drug-free schizophrenic patients. American Journal of Psychiatry, 144: , Gardos, G.; Cole, J.O.; and LaBrie, R.A. A twelve-year follow-up study of chronic schizophrenics. Hospital and Community Psychiatry, 33: , Gorham, D.R. Proverbs tests for clinical and experimental use. Psychological Reports, l(suppl-): 1-12, Grinker, R.R., and Harrow, M., eds. A Multidimensional Approach to Clinical Research in Schizophrenia. Springfield, IL: Charles C Thomas,

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