Distress Attributed to Negative Symptoms in Schizophrenia

Distress Attributed to Negative Symptoms in Schizophrenia by Jeari'Paul Selten, Durk Wiersma, and Robert J. van den Bosch Abstract The purpose of the study was to examine (1) to which negative symptoms schizophrenia patients attribute distress and (2) whether clinical variables can predict the levels of reported distress. With the help of a research assistant, 86 hospitalized patients completed a self-rating scale for negative symptoms. The 21 items of the self-rating scale were taken from the Scale for the Assessment of Negative Symptoms (SANS). A psychiatrist rated the patients on a number of scales, including the SANS. When patients reported particular symptoms, they were asked whether those symptoms bothered or distressed them. Answers to this question were highly dependent on the type of symptom involved. Distress was most often attributed to symptoms in the subscale avolition-apathy. Patients were also asked how much they were bothered or distressed. Again, high levels of distress were most often attributed to items in the subscale avolition-apathy. A summary score was developed for the level of reported distress: the distress score. Regression analysis showed that distress scores were not associated with the observed severity of negative symptoms or with the level of psychiatric disability. High distress scores were best predicted by the combination of high scores for depression and high scores for insight into positive symptomatology. However, this model explained only a quarter of the variance in distress scores. Keywords: Schizophrenia, negative symptoms, awareness, phenomenology, neuropsychology, rehabilitation. Schizophrenia Bulletin, 26(3):737-744, 2000. Several reports have indicated that schizophrenia patients may be aware of some, but not all, signs of the disorder (e.g., McEvoy et al. 1993; Amador et al. 1994). To examine the awareness of negative symptoms, we developed a selfrating scale for negative symptoms, the Subjective Experience of Negative Symptoms (SENS; Selten et al. 1993). Since the 21 SENS items were taken from the Scale for the Assessment of Negative Symptoms (SANS; Andreasen 1989), the patient's rating can be compared to the psychiatrist's rating for the corresponding SANS item, and discrepancies may provide a measure of the awareness of negative symptoms. The SENS also attempts to collect information on attributions for negative symptoms and to measure the level of distress ascribed to such symptoms. A previous study using the SENS compared schizophrenia patients to patients with a depressive disorder and to normal subjects. The schizophrenia patients reported more impairments than normal subjects and attributed higher levels of distress to these impairments. However, they reported fewer negative symptoms than did the patients with a depressive disorder, attributed these impairments less often to mental illness, and attributed lower levels of distress to such impairments. Since the schizophrenia patients did not assess themselves as the normal subjects did, it was inferred that they were at least "somewhat" aware of their negative symptoms. On the other hand, as their self-assessments were less realistic than those of patients with a depressive disorder, the results suggested that schizophrenia patients are less aware of and concerned about their impairments than are patients with a depressive disorder (Selten et al. 1998). The aim of this study was (1) to assess the prevalence and severity of distress that schizophrenia patients attribute to negative symptoms and (2) to examine whether the levels of reported distress are predictable. The predictive performance of a large number of clinical variables was studied. How some variables that hold an important place in the symptomatology and treatment of schizophrenia (positive and negative symptoms, psychiatric disability, depression, anxiety, legal status of stay, type and dosage of medication) Send reprint requests to Dr. J.-P. Selten, Dept. of Psychiatry, University Hospital, Reference nr B01.206, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands; e-mail: j.p.selten@psych.azu.nl. 737

Schizophrenia Bulletin, Vol. 26, No. 3, 2000 J.-P. Selten et al. were selected is, we believe, self-explanatory. The reason for the selection of other variables (length of illness, severity of illness, age at first admission, length of admission) may need some clarification. Kraepelin (1971) regarded schizophrenia as an illness with a deteriorating course. It was of interest, therefore, to assess to what extent the level of reported distress was influenced by length of illness or severity of illness ("Kraepelinian type" or not; see below). Johnstone et al. (1989) reported that age at onset was an important predictor of cognitive impairments in schizophrenia. Since in many cases reliable information about illness onset was no longer available, age at first admission was chosen as a measure of age at onset. Since it has been suggested that long-term hospitalization may lead to emotional indifference, the variable length of admission was included. Methods Patients. Schizophrenia patients (DSM-Ill-R criteria; American Psychiatric Association 1987) were recruited from the medium- and long-stay wards of the Rosenburg Psychiatric Hospital in The Hague and the Joris Psychiatric Hospital in Delft, The Netherlands. We excluded patients who had a physical handicap that explained their impaired functioning. Other reasons for exclusion were the presence of mental subnormality (defined as having failed to complete primary education or having repeated more than one grade in primary school), an organic mental disorder (DSM-III R), recent or current substance abuse (DSM-IH-R), a current manic or major depressive episode (DSM-III-R), having a first language other than Dutch, and incomprehensible speech. Thirty-one patients refused to take part. They were patients who had been committed more often than those who agreed to participate (32.3% versus 13.8%; x 2 = 10.6; df= 1; p < ) but did not differ significantly from participants with regard to age, sex, level of education, length of illness, or length of current admission (two-tailed chi-square tests or t tests). The final sample included 60 men and 26 women. Their mean age was 44.4 years (standard deviation [SD] = 10.3; range 20-65). The mean age at first admission was 25.7 years for men (SD = 8.7) and 28.0 years (SD = 9.4) for women. Length of illness was defined as the number of years since first admission. The length of the current admission was not normally distributed and varied greatly: less than 1 year in 26 patients and more than 5 years in 35 patients (median: 44.5 months; 25th percentile: 9.8 months; 75th percentile: 132.0 months; range 1 495 months). Five patients were on clozapine. The mean dosage of classic neuroleptics for the remaining 81 patients, converted into equivalents of haloperidol, was 21.9 mg (SD = 27.3; range 0-171; van Wielink 1987). Forty patients were on anticholinergics. Forty-nine patients had at least a tenth-grade education; the remainder did not. According to the physician responsible, 54 patients fulfilled criteria for Kraepelinian schizophrenia. This designation was introduced by Keefe et al. (1987) for severely deteriorated patients who had been either continuously hospitalized for the previous 5 years or who had been unable to provide themselves with necessities such as food, shelter, and clothing. The admission was involuntary in 12 patients. After complete description of the study to the subjects, written informed consent was obtained. The SENS. Self-ratings were elicited in a semistructured interview. The interviewer gave a standardized explanation of each item in everyday language and asked a first question (e.g., "How much energy do you have?"). Next, the interviewer handed the patient a card that listed five alternative answers: "very little" (1), "little" (2), "average" (3), "a lot" (4), and "very much" (5). It is important to bear in mind that impairments are reported by low scores, not by high scores. Questions about frequency (e.g., "How often do you succeed in making friends?") were answered with the help of a second card displaying the response categories "rarely" (1), "not often" (2), "average" (3), "often" (4), and "very often" (5). Symptoms were thus reported with a rating of 1 or 2. The patients had to choose one answer. They were instructed to compare themselves to people of their age who had not been admitted to a psychiatric hospital, and they were reminded of this instruction at four points in the SENS interview. Having asked the first question for all 21 SENS items, the interviewer asked two more questions about items that had elicited a rating of 1 or 2 (i.e., the patient had indicated the presence of the symptom). The aim of the second question was to collect information regarding the patient's attributions. Finally, the interviewer asked the patients whether they were bothered or distressed by the symptom (question 3a). If the answer was affirmative, the patients were asked how much they were bothered or distressed (question 3b) and were given a third card listing five alternative answers: "very little" (1), "little" (2), "quite a lot" (3), "much" (4), and "very much" (5). The SENS rating procedure has two important advantages over one in which the interviewer decides to what extent the patient is aware of the symptom. First, there is no risk of interpretation bias. Second, SENS ratings are independent of the amount of the patient's spontaneous speech. The three questions constitute the three parts of the SENS (awareness, attribution, and distress). The items "blocking" and "poverty of content of speech" and the items measuring attention are not included in the SENS and in the analysis of the SANS because they do not appear to belong to the negative syndrome (Miller et al. 1993). 738

Distress Attributed to Negative Symptoms Schizophrenia Bulletin, Vol. 26, No. 3,2000 Procedure. Nurses completed the REHAB (Rehabilitation Evaluation Hall and Baker), a scale for the assessment of psychiatric disability (Baker and Hall 1988). They had followed the standard REHAB training program. The aim of this procedure was to provide the psychiatrist (J.-P.S.) with detailed information on the patient's daily activities. In addition, the REHAB total general behavior score (REHAB score) provides a measure of psychiatric disability. Nurses also provided written information about the patient's "relationships with friends and peers," "abihty to feel intimacy and closeness," and "sexual interest and activity." Patients were interviewed twice. In one session they completed the SENS with the help of a research assistant. In the other session the psychiatrist assessed all patients using the SANS, the Montgomery-Asberg Depression Rating Scale (MADRS; Montgomery and Asberg 1979), the Manchester scale (Hyde 1989), and a slightly modified version of item 104 ("insight into psychotic condition") of the Present State Examination (PSE; Wing et al. 1974). The order of the sessions was random, and the interval was limited to a maximum of a week. The Manchester scale includes nine key items of chronic schizophrenia (delusions, hallucinations, incoherence, incongruous affect, depression, anxiety, poverty of speech, psychomotor retardation, flattened affect). Four items relate to positive symptoms (delusions, hallucinations, incoherence, and incongruous affect). The PSE item, which has been defined as "the subject's ability to recognize that the psychotic symptoms are anomalies of his own mental processes" (Wing et al. 1974, p. 177), served as a measure for insight into positive symptoms. The psychiatrist assessed this item in patients with psychosis and patients without psychosis and examined their ability to recognize that their current or previous psychotic symptoms were anomalies of their own mental processes. After 2 months, the assessments were repeated in 80 patients. The times of the first and second measurement will be indicated as time I and time PL The interrater reliability of the psychiatrist's ratings was largely sufficient for all instruments (ICC [intraclass correlation coefficient] for SANS summary score = 0.81). Analysis. To calculate the prevalence of negative symptoms according to patients, self-ratings in reply to the first SENS question were dichotomized. Ratings of 1 or 2 were taken as scores indicating the presence of the symptom. Sometimes patients failed to give a "valid" reply to the first SENS question (i.e., a rating of 1 through 5): They said that they did not know the answer or refused to answer questions about sexuality. The prevalence of symptoms, therefore, was expressed in percentages of the number of valid replies to the first SENS question. The prevalence of reports of disruption or distress (as evidenced by a positive reply to question 3a) was expressed in percentages of the number of valid replies to the first SENS question. A total score for disruption and distress was obtained by adding all scores for question 3b: This provided the distress score. SANS summary scores were arrived at by adding the scores for four SANS subscales (affective flattening, alogia, avolition-apathy, and asociality-anhedonia). Bivariate and multiple regression analyses were used to examine the predictability of distress scores. We studied the predictive qualities of 20 variables, divided into four sets (table 1). To avoid collinearity, four Manchester scale items (depression, flat affect, psychomotor retardation, and poverty of speech) were excluded from the fourth set. Scores for the depression item correlated strongly with Table 1. Predictors of distress score (bivariate regression analysis) Predictor variable Demographic Age Sex 2 Education 3 Clinical Age on first admission Length of illness Length of current admission Kraepelinian type 4 Forced admission 4 Pharmacological Equivalents of haloperidol Use of anticholinergics 4 Use of clozapine 4 Psychopathological Anxiety 5 Delusions 5 Hallucinations 5 Incoherence 5 Incongruous affect 5 SANS summary score MADRS score REHAB score Insight (item 104 PSE) Timel beta 1-0.10 0.12 0.04-0.10-0.20 0.07 0.13 0.05 0.05-0.22* 0.25* 0.14 0.17 0.05-0.07 0.04 0.44** 0.28** Time II beta 1-0.07 0.21-0.20 0.17-0.21-0.24* 0.05-0.03-0.04-0.08 0.19 0.13 0.07 0.13-0.11 0.45** 0.33** Note. SANS = Scale for the Assessment of Negative Symptoms; MADRS score = Montgomery-Asberg Depression Rating Scale, total score; REHAB score = Rehabilitation Evaluation Hall and Baker total general behavior score; PSE = Present State Examination. 1 Standardized regression coefficient. 2 Male = 1, female = 2. 3 At least a tenth-grade education: yes = 1, no = 0. 4 Yes = 1,no = 0. 5 Items of Manchester scale. 'p < 0.05; "p < 739

Schizophrenia Bulletin, Vol. 26, No. 3, 2000 J.-P. Selten et al. MADRS scores and those for the remaining items with SANS summary scores. All scores were transformed into z scores. Use was made of a backward elimination strategy that starts with all variables in the equation and sequentially removes them (Kleinbaum et al. 1988). The first step was to examine the performance of all the variables individually (bivariate regression analysis). Next, multiple regression analysis was used to control for covariance among these variables. First, all variables pertaining to one set were entered into the regression equation, and then the variables meeting the criterion for removal (p > 0.15) were eliminated one by one. Next, all variables selected in one of the foregoing sets of regression were entered into the final regression analysis (criterion for removal: p > 0.05). All quoted p values are two-sided. Results The results obtained with the various instruments are given in table 2. The prevalence of negative symptoms according to the patients is given in table 3. In a previous study it was shown that patients underestimate the prevalence of these symptoms (Selten et al. 2000). Prevalence and Severity of Reported Distress. It is important to note that the question about disruption or distress (the third SENS question) is asked only about those symptoms that are present according to the patient (as evidenced by a rating of 1 or 2 in reply to the first SENS question). Replies to the question about whether they were bothered or distressed by the symptom (question 3a) Table 2. Results of assessment at time I Variable Anxiety 1 Incongruous affect 1 Incoherence 1 Delusions 1 Hallucinations 1 Poor insight 2 SANS summary score MADRS score REHAB score % 26 22 16 58 41 51 Mean 10.1 10.5 47.0 Prevalence n (22/86) (19/86) (14/86) (50/86) ' (35/86) (44/86) SD 4.4 9.4 23.7 Note. SD = standard deviation; SANS = Scale for the Assessment of Negative Symptoms; MADRS score = Montgomery-Asberg Depression Rating Scale, total score; REHAB score = Rehabilitation Evaluation Hall and Baker total general behavior score. 1 1tem of Manchester scale, rating of at least 2 (moderate). 2 Item 104 of Present State Examination, rating of 2 or 3 (pathological). were more often negative (341 times) than positive (264 times; table 3). Occasionally (11 times) patients said they did not know the answer to this question. Remarkably few patients attributed distress to inability to feel or affective nonresponsivity. In addition, relatively few patients seemed to be distressed about the experience of decreased sexual interest and activity. Distress was attributed most frequently to items in the SANS avolition-apathy subscale: lack of energy and impersistence. The same applies to high ratings for the severity of distress (question 3b). The results obtained at time II were similar (data not shown). The stability of distress scores across a 2-month interval was moderate (table 4). Bivariate Regression Analysis. At both assessments distress scores were found to be associated with MADRS scores and the PSE item. Distress scores were not associated with SANS summary scores or REHAB scores (table 1). Multiple Regression Analysis. First, all variables pertaining to each set were entered into the regression equation (table 5). Next, the selected variables were entered into the final regression equation. The final model for the efficient prediction of distress scores at time I included two variables: the MADRS score and the score for the PSE item (Multiple R = 0.49). When this procedure was followed to predict distress scores at time II, the same variables were selected (Multiple R = 0.52). Thus, the combination of depression and insight into positive symptoms predicted high distress scores. Discussion Prevalence of Distress. The patients' reports varied greatly. Some patients made it clear that they suffered a lot from a particular symptom, but others denied the experience of disruption or distress. A discussion about the validity of these findings should take into account the concepts of primary and secondary negative symptoms. According to Carpenter et al. (1988), primary negative symptoms should be viewed as the expression of a schizophrenia-specific pathological process, whereas secondary negative symptoms can be traced back to known causes of diminished functioning (e.g., long-term hospitalization, depression, side effects of neuroleptics). Neither the SANS nor the SENS excludes secondary negative symptoms, and some patients may have complained (or may have failed to complain) about secondary negative symptoms. It is unlikely, however, that the SENS measures mainly the experience of impairments that are due to a long admission. Staff in both hospitals made every effort to activate the patients and to prepare them for living in the community or in a sheltered home. A long period of 740

Table 3. Prevalence of negative symptoms according to patient and psychiatrist and prevalence of reported distress (assessment at time I) Negative symptoms 1. Unchanging facial expression 35 (29/84) 2. Decreased spontaneous movements 31 (26/83) 3. Paucity of expressive gestures 57 (48/85) 4. Lack of vocal inflections 35 (29/82) 5. Affective nonresponsivity 33 (27/82) 6. Poor eye contact 20 (17/85) 7. Inability to feel 18(15/84) 8. Poverty of speech 45 (38/85) 9. Increased latency of response 13(11/85) 10. Absence of thoughts 26(22/85) 11. Poor grooming and hygiene 12(10/86) 12. Impersistence 48(40/84) 13. Physical anergia 45 (38/85) 14. Lack of motivation 37 (31 /84) 15. Lack of energy 40(34/84) 16a. Decreased recreational interest 41(35/86) 16b. Decreased recreational activity 55 (47/86) 17a. Decreased sexual interest 59 (47/80) 17b. Decreased sexual activity 81(65/80) 18. Inability to feel intimacy 44 (37/85) 19. Few relationships with friends 38(32/84) 20. Asociality 26 (22/86) 21. Anhedonia 28 (23/86) Prevalence of Symptoms Prevalence of According to patient 1 According to psychiatrist 2 reported distress 3 54 (45/84) 40 (33/83) 58 (49/85) 50 (41/82) 63 (52/82) 38 (32/85) 64 (54/84) 45 (38/85) 19(16/85) 44 (37/85) 63 (54/86) 93 (78/84) 88 (75/85) 92 (77/84) 91 (77/85) 78 (67/86) 78 (67/86) 71 (57/80) 71 (57/80) 85 (72/85) 92 (77/84) 91 (78/86) % (n) 5 (4/84) 6 (5/83) 11 (9/85) 13(11/82) 10(8/82) 9 (8/85) 6 (5/84) 15(13/85) 8 (7/85) 11 (9/85) 7 (6/86) 35 (29/84) 21 (18/85) 18(15/84) 32 (27/85) 26 (22/86) 23(18/80) Prevalence of high ratings for severity of distress 4 % (n) 0 (0/84) 1 (1/83) 5 (4/85) 4 (3/82) 5 (4/82) 4 (3/85) 2 (2/84) 7 (6/85) 6 (5/85) 7 (6/85) 5 (4/86) 20(17/84) 13(11/85) 11 (9/84) 22(19/85) 13(11/86) 9(7/80) 73 (63/86) 18(15/85) 18(15/84) 7 (6/86) 16(14/86) 6 (5/85) 8 (7/84) 4 (3/86) 9 (8/86) On g en' 9 en en I cr I o B. < a I 1 As evidenced by rating of 1 or 2 in reply to first Subjective Experience of Negative Symptoms question. 2 As evidenced by Scale for the Assessment of Negative Symptoms rating of at least 2. 3 As evidenced by positive reply to Subjective Experience of Negative Symptoms question 3a. 4 As evidenced by rating of 4 or 5 in reply to Subjective Experience of Negative Symptoms question 3b. to 'f

Schizophrenia Bulletin, Vol. 26, No. 3, 2000 J.-P. Selten et al. Table 4. Stability of distress scores (2-month interval) Variable Mean Timel SD Mean Time II SD Correlation, r 1 Distress score 11.3 12.8 10.8 11.3 0.53 Note. SD = standard deviation. 1 Pearson's correlation; p < 0.001. Table 5. Predictors of distress scores (significant contributors to final regression equation in multiple regression analysis) Variable MADRS score Insight (item 104 PSE) Timel Beta 1 0.41*" 0.22* Time II Beta 1 0.41*** 0.26** Note. MADRS score = Montgomery-Asberg Depression Rating Scale, total score; PSE = Present State Examination. 1 Standardized regression coefficient. *p < 0.05; "p < ; ***p < 0.001 stay was therefore more likely the consequence, not the cause, of negative symptoms. One might suggest that information on what constitutes "normal behavior" is no longer available to patients who have been hospitalized for a long time, but all patients had ample occasion to observe the behavior of nurses and therapists, to watch television, and to read newspapers. Even the few patients who lived in locked wards were frequently permitted to leave the hospital. There is also no evidence that the SENS measures primarily the experience of impairments that are caused by depression. First, the sum of self-ratings in response to the first SENS question, which measures the level of awareness of negative symptoms, correlated only weakly with MADRS scores (at time I: r = -0.23; p > 0.05). Second, patients who suffered from a major depressive episode were excluded from the study. It follows that the third SENS question (about distress) was asked to patients with normal mood as well as to (mildly) depressed patients. In sum, some self-assessments may have been of secondary negative symptoms, but it is unlikely that such self-assessments were more frequent than self-assessments of primary negative symptoms. The finding of a relative indifference toward negative symptoms agrees with clinical experience. The problem here may be that mental health professionals have gotten so used to the low frequency and intensity of schizophrenia patients' complaints about negative symptoms that the professionals have come to consider this state normal. Our results confirm and extend the findings of a study in which the interviewer decided to what extent the patient suffered from negative symptoms: complaints about affective flattening, alogia, avolitionapathy, and asociality-anhedonia were found to be much less severe in a group of patients with schizophrenia than in a group of patients with a major depressive disorder (Kulhara and Chadda 1987). A lack of emotional reaction to a given lesion or impairment has been described in a variety of neuropsychiatric conditions, including tardive dyskinesia (Alexopoulos 1979; Rosen et al. 1982; Myslobodsky et al. 1985). Babinski (1914) coined the term "anosodiaphoria" to describe a lack of emotional reaction to left hemiplegia. According to Babinski, anosodiaphoria, as a rule, followed the stage of "anosognosia," during which the patient was unaware of the paralysis. In view of the evidence for organic causes of negative symptoms, anosodiaphoria can be regarded as a proper designation for the lack of concern that some schizophrenia patients display toward negative symptoms. Perhaps the mechanisms underlying anosognosia and anosodiaphoria are the same, in that they prevent the patient from appreciating the full extent of the severity of the impairments. The nature of these mechanisms remains unknown. Predictability of Distress. The lack of association between levels of reported distress and measures of negative symptoms and psychiatric disability was a striking finding. The final model for the prediction of distress scores, which included MADRS scores and scores for the PSE item, suggests that the combination of depression and insight into positive symptoms determines to some degree the level of suffering from negative symptoms. Since patients with greater insight may be expected to have greater levels of dysphoria, this finding makes good sense and provides some evidence for the construct validity of the third part of the SENS. Limitations. Several limitations have already been mentioned. We should point out that the sample was not repre- 742

Distress Attributed to Negative Symptoms Schizophrenia Bulletin, Vol. 26, No. 3, 2000 sentative of the population of schizophrenia patients as a whole, in that the patients were more severely impaired than patients in the community. Conclusion We found that a large number of clinical variables were relatively weak predictors of the degree to which the patients suffered from the clinical variables. Perhaps one negative result was the most interesting finding: the level of distress attributed to negative symptoms was not related to their observed severity. A clinical implication of our findings is that mental health professionals should be aware of a broad spectrum of possible attitudes toward negative symptoms: from indifference at one end of the spectrum to deep suffering at the other end. Future studies could try to distinguish between primary and secondary negative symptoms and examine the experience of each type of symptom. References Alexopoulos, G.S. Lack of complaints in patients with tardive dyskinesia. Journal of Nervous and Mental Disease, 167:125-127, 1979. Amador, X.F.; Flaum, N.; Andreasen, N.C.; Strauss, D.H.; Yale, S.A.; and Gorman, J.M. Awareness of illness in schizophrenia and schizoaffective and mood disorders. Archives of General Psychiatry, 51:826-836, 1994. American Psychiatric Association. DSM-III-R: Diagnostic and Statistical Manual of Mental Disorders. 3rd ed., revised. Washington, DC: APA, 1987. Andreasen, N.C. Scale for the Assessment of Negative Symptoms (SANS). British Journal of Psychiatry, 155 (Suppl 7):53-58, 1989. Babinski, M.J. Contribution a l'^tude des troubles mentaux dans l'hemiplegie organique ce're'brale (anosognosie). Revue Neurologique, 12:845-848, 1914. Baker, R., and Hall, J.N. REHAB: A new assessment instrument for chronic psychiatric patients. Schizophrenia Bulletin, 14(1):97-111, 1988. Carpenter, W.T.; Heinrichs, R.W.; and Wagman, A.M.I. Deficit and non-deficit forms of schizophrenia: The concept. American Journal of Psychiatry, 145:578-583,1988. Hyde, C. The Manchester Scale. British Journal of Psychiatry, 155(Suppl 7):45-48, 1989. Johnstone, E.C.; Owens, D.G.C.; Bydder, G.M.; and Crow, T.J. The spectrum of structural changes in the brain: Age at onset as a predictor of cognitive and clinical impairments and their cerebral correlates. Psychological Medicine, 19:91-103,1989. Keefe, R.S.E.; Mohs, R.C.; Losonczy, M.F.; Davidson, M.A.; Silverman, J.; Kendler, K.S.; Horvath, T.B.; Nora, R.; and Davis, K.L. Characteristics of very poor outcome schizophrenia. American Journal of Psychiatry, 147:889-895,1987. Kleinbaum, D.G.; Kupper, L.L.; and Muller, K.E. Applied Regression Analysis and Other Multivariable Methods. Boston, MA: PWS-Kent, 1988. Kraepelin, E. Dementia Praecox and Paraphrenia. New York, NY: Krieger, 1971. Kulhara, P., and Chadda, R. A study of negative symptoms in schizophrenia and depression. Comprehensive Psychiatry, 28:229-235, 1987. McEvoy, J.P.; Schooler, N.R.; Friedman, E.; Steingard, S.; and Allen, M. Use of psychopathology vignettes by patients with schizophrenia or schizoaffective disorder and by mental health professionals to judge patients' insight. American Journal of Psychiatry, 150:1649-1653,1993. Miller, D.; Arndt, S.; and Andreasen, N.C. Alogia, attentional impairment and inappropriate affect: Their status in the dimensions of schizophrenia. Comprehensive Psychiatry, 34:221-226, 1993. Montgomery, S.A., and Asberg, M. A new depression scale designed to be sensitive to change. British Journal of Psychiatry, 134:382-389, 1979. Myslobodsky, M.S.; Tomer, R.; Holden, N.T.; Kempler, S.; and Sigal, M. Cognitive impairment in patients with tardive dyskinesia. Journal of Nervous and Mental Disease, 173:156-160, 1985. Rosen, A.M.; Mukherjee, S.; Olarte, S.; Varia, V.; and Cardenas, C. Perception of tardive dyskinesia in outpatients receiving maintenance neuroleptics. American Journal of Psychiatry, 139:372-373, 1982. Selten, J.-P; Gernaat, H.B.; Nolen, W.A.; Wiersma, D.; and van den Bosch, R.J. The experience of negative symptoms: Comparison of schizophrenic patients to patients with a depressive disorder and to normal subjects. American Journal of Psychiatry, 155:350-354,1998. Selten, J.-P.; Sijben, A.; van den Bosch, R.J.; Omloo- Visser, H.; and Warmerdam, H. The subjective experience of negative symptoms: A self-rating scale. Comprehensive Psychiatry, 34:192-197,1993. Selten, J.-P.; Wiersma, D.; and van den Bosch, R.J. Discrepancy between subjective and objective ratings for negative symptoms in schizophrenia. Journal of Psychiatric Research, 34:11-13, 2000. van Wielink, P. Comparative Doses of Haloperidol. Tilburg, the Netherlands: Janssen Pharmaceutica, 1987. Wing, J.K.; Cooper, J.E.; and Sartorius, N. The Measurement and Classification of Psychiatric Symptoms. Cambridge, UK: Cambridge University Press, 1974. 743

Schizophrenia Bulletin, Vol. 26, No. 3, 2000 J.-P. Selten et al. Acknowledgments The authors thank Margaret Jones and Hugo Duivenvoorden for advice. The Authors Jean-Paul Selten, M.D., Ph.D., is Associate Professor, Department of Psychiatry, University of Utrecht, Utrecht, The Netherlands. Durk Wiersma, Ph.D., is a sociologist and Associate Professor, Department of Social Psychiatry; and Robert J. van den Bosch, M.D., Ph.D., is Professor of Psychiatry, University of Groningen, Groningen, The Netherlands. 744