Mortality in DSM-IIIR schizophrenia

Schizophrenia Research, I (1992) 109- 1 I6 80 1992 Elsevier Science Publishers B.V. All rights

SCHIZO

109 reserved

0920-9964/92/$05.00

00235

Mortality in DSM-IIIR Donald Department (Received

qf Psychiatry, 3 December

W. Black

University 1991; revision

and

schizophrenia Ron

Fisher

of Iowu College of Medicine, received

24 February

Iowa City, IA 52242, USA

1992; accepted

1 March

1992)

Mortality was investigated in 356 DSM-IIIR schizophrenics admitted to a university psychiatric hospital over a 12-year period. Determination of death was made through a record-linkage process and observed death was compared with the mortality experience of the general population of the State of Iowa. Schizophrenics had nearly a three-fold increase in overall mortality. Mortality was primarily attributable to unnatural causes of death, particularly suicide, which was more than twenty-three times greater than expected. Mortality was greater in schizophrenic patients younger than 40 years and during the early portion of follow-up. Studies of mortality in psychiatric patients continue to be important, particularly as diagnostic criteria become better refined. Key word.s: Mortality;

Suicide;

Death

rate; (Schizophrenia)

INTRODUCTION

Mortality studies of psychiatric populations have proliferated over the past decade (Tsuang and Simpson, 1985). In general, they demonstrate excess mortality for most psychiatric diagnostic groups (Black et al., 1985a; Martin et al., 1985). More important, studies have demonstrated that risk of mortality is, to some extent, diagnosis specific. For example, the risk of premature death associated with depression differs from that associated with Briquet’s syndrome (Coryell, 1983). Moreover, within diagnostic groups mortality risk may be associated with a specific age group, gender distribution, clinical symptoms, phase of followup, and death cause. It is important to recognize that as we become more sophisticated in developing diagnostic criteria and refining psychiatric diagnosis, we need to periodically reassess mortality using contemporary definitions. Mortality risk associated with schizophrenia is Correspondence to: D.W. Black, University of Iowa College of Medicine, Department of Psychiatry, 500 Newton Road, Iowa City, IA 52242, USA.

well documented. Excess mortality has been shown in both inpatients and outpatients, in different parts of the United States, and in different countries around the world (Tsuang et al., 1980; Allebeck and Wistedt, 1986; Black, 1988; Buda et al., 1988). Schizophrenia unquestionably leads to early death. However, the changing definition of schizophrenia places in doubt the relevance of the findings from older studies, or recent studies not using current diagnostic criteria. Early investigators of mortality in schizophrenia based their diagnosis on then current definitions of schizophrenia, often deriving from the work of Kraepelin or Bleuler. In the United States, concepts of schizophrenia gradually became very broad so that by the 19.50s and 1960s patients with conditions that would not now be considered schizophrenic, were often included in the definition (e.g., patients with atypical psychoses, mood disorders, anxiety disorders, and personality disorders). The concept of schizophrenia was finally narrowed when research criteria were introduced in the early 1970s prompted by the United States/United Kingdom diagnostic project (Cooper et al., 1972) and were incorporated into official nosology with the publication of DSMIII (American Psychiatric Association, 1980).

I IO

However. several recent reports, mostly from Europe, have used the ICD-8 or ICD-9 (Herrman et al., 1983; Allebeck and Wistedt, 1986; Lesage et al.. 1991). According to this classification system, traditional subtypes of schizophrenia (i.e., hebephrenic, catatonic, paranoid, undifferentiated) are included along with simple, acute and latent subtypes* schizoaffectives, residual schizophrenics and others. For example, Allebeck and Wistedt (1986) reported on mortality in 1,190 ICD-9 schizophrenic patients, less than 50% of whom would be likely to satisfy DSM-IIIR criteria for schizophrenia. In addition to changing diagnostic criteria, there are other reasons to continue to study mortality in schizophrenia (Tsuang and Simpson, 1985). It is important to monitor the effect of secular trends that may affect rates of death: death rates may be influenced by age, period, or cohort effects. In addition, death rates may be influenced by new developments in therapy and methods of aftercare, whose contribution to altering death rates needs to be periodically re-assessed. Additionally, many mortality studies rely on chart diagnoses which may be inaccurate, have used relatively small samples that are inappropriate for multivariate analyses. or provide few clinical risk factors that can be looked at for possible associations with death. The current project to study mortality in schizophrenics began in 1987. This article reports increased mortality risk in DSM-IIJR schizophrenic patients hospitalized during a recent I2 year period and who were followed-up through a record-linkage process. The results of the study indicate not only excessive mortality. but also show that increased risk of death is associated with gender, specific age groups, certain diagnostic subtypes, phase of follow-up, and specific death causes.

SUBJECTS

AND

METHODS

The charts of each patient with a clinical diagnosis of schizophrenia admitted to the University of Iowa Psychiatric Hospital between 1970 and 1981 were retrieved and reviewed by a trained research assistant (R.F.). Using an instrument developed by the project director (D.W.B.), information was abstracted from the charts for each patient. The information included the subject’s age, gender,

marital status, and educational background; occupation and social history; clinical features and personality; and treatment and aftercare. Using the chart material, the projecL director made a DSM-IIIR (American Psychiatric Association. 1987) diagnosis on each subject and evaluated premorbid personality; he then subtyped each schizophrenic patient as catatonic. disorganized, paranoid, undifferentiated, or residual. Schizophrenic patients were also subtyped according to the classifications developed by Tsuang and Winokur (1974) (i.e.. paranoid, non-paranoid, indeterminate) and Andreasen and Olsen (1982) (i.e., positive. negative, mixed). The first admission was defined as the index admission for subjects hospitalized more than one time.

Death ascertainment was made using a recordlinkage process in which the patient list was electronically matched with Iowa death certificates issued between 1970 and 1988. Copies of these certificates arc kept on file in the University of Iowa Department of Preventive Medicine and Environmental Health. Multiple identifiers (c.g.. name, social security number. date of birth. etc.) were used in the process to insure that patients who had died were properly identified. When a match was confirmed, we obtained the death certificate. Although our study sample was restricted to Iowans, some of our subjects may have moved out of state; likewise, Iowans who had assumed a different surname (e.g., female patients who had married) would have been difficult to trace and follow-up information may not have been available for them. We have no estimate oti how large this group might be, but our earlier studies indicate that the number is probably insignificant. In any event. the effect of nonascertainment of death would be to underestimate the true number of deaths. and thus overall excess mortality. The death certificates were reviewed by the project director. Deaths were first broadly categorized as either ‘natural’ or ‘unnatural‘. Natural deaths included those in which no ‘external’ cause was identified and correspond to those referred to in vital statistics as due to ‘diseases’. Unnatural deaths referred to those due to external causes including suicides. accidents, and ‘undetermined’ or ‘open’ verdicts. Death causes were further cate-

III

gorized using classifications derived from the International Classification of Diseases, 9th Edition (1980) and consolidated into five groups, including cancer (ICD-9 group 14OG209). heart disease (ICD-9 group 390-429) other natural causes (all other natural death codes), accidents (ICD-9 group E800 to 949, 960-999). and suicide (ICD-9 group E950-959).

Age, mean, years (SD) Men Women Gender

by age group.

< 29 Years 30-39 Years Statistical

analysis

To compare the mortahty experience of the schizophrenic sample with a relevant base population, we computed mortality tables that had been adjusted for age, gender, and follow-up time. The latter adjustment is important since not all subjects were followed the same amount of time; for instance, a person followed 10 years would have a greater probability of death during the followup than a person followed one year. We used vital statistics and census data for Iowa to compute expected rates of death. This method is described in the ‘Iowa Record Linkage Study’ (Black et al., 1985a). Standardized mortality ratios (SMRs) were calculated and represent the ratio of observed to expected mortality. An SMR greater than 1.0 means that the number of observed (or true) deaths exceeds the expected number of deaths. The SMRs were tested for significance using the chi square statistic modified by the Freeman-Tukey method (Freeman and Tukey, 1950). The Freeman-Tukey transformation was used since it is more conservative than the regular chi square. A p value of < 0.05 was considered to be statistically significant.

RESULTS

Of the 529 patients with a clinical diagnosis of schizophrenia, 356 (67%) met DSM-IITR criteria for schizophrenia. Their age, gender distribution, age at first hospitalization, duration of follow-up and schizophrenic subtypes are presented in Table 1. Of these patients, 42 (18 men and 24 women) (11.8%) died during the follow-up perio,d. Table 2 shows the relationship between age at death and gender in schizophrenic patients dying from all causes. The SMR is greatest among men

40-69 > 69 Total

Years

n(%)

Women

30.1

(10.7)

33.6

(12.0)

27.7

(10.7)

Men

75 32

(51.0) (21.X)

153 37

(73.2) (17.7)

40 0 147

(27.2) (0) ( 100.0)

17 2 209

(8.1) (0.6) ( 100.0)

Age at first hospitalization, mean. years (SD) Men Women Duration of follow-up, mean. years (SD) Men Women DSM-IIIR schizophrenic subtype, n(%) Catatonic Paranoid Dlsorganised Undifferentiated Residual Tsuang-Winokur subtype n(%) paranoid non-paranoid indeterminate Anderson-Olsen subtype n(%) positive negative mixed

24.7 22.3 26.6 12.9 12.8 13.1

(8.3) (7.4) (9.2) (3.1) (3.0) (3.2)

20 III 81 125 I9

(5.6) (31.2) (22.8) (35.1)

108

102 146

(30.3) (28.7) (41.1)

149 54 I53

(41.9) (15.2) (43.0)

(5.3)

and women younger than 40 years, and continues to be significantly excessive for women 40 years and over. Table 3 shows the association between cause of death and age. Among 20 deaths due to natural causes, 14 (70%) occurred in patients over 49 years. Twenty of 22 (9 1Oh) deaths from unnatural causes occurred in patients under 49 years, particularly those between ages 20 and 39 years. The table also shows that death from both unnatural causes and natural causes is significantly greater than expectation. Table 4 shows that 14 of 16 (87.5%) suicides were confined to persons under 40 years of age, and that suicides were significantly excessive in both men and women. Among men, the suicides clustered in the 20s and 30s age range. In women, the four suicides were distributed more equally

112 TABLE

2

AN deaths during ~jiillow-up among 356 DSM-IIIR

schi-_ophrenics Women

Age (I! Dearh

i 40 Years 240 Years Total

Totul

E.xpected deaths

SMR

Observed druths

Expected deuths

SMR

Observed deaths

Especred deaths

SMR

3.85 4.58 8.43

4.16 0.44 2.14’

8 16 24

1.00 4.76 5.76

8.00” 3.36” 4.17”

24 I8 42

4.85 9.34 14.19

4.95” l.93h 2.96”

“Pi 0.005 bP
TABLE

3

Dislrihution Cause of death

ofall

deaths by age md cuu.w in 356 DSM-IIIR

.schizophrenics

Age (years)

Deaths

<2v

20-29

Natural Men Women Combined

0 0 0

0 I I

Unnatural Men Women Combined Total

0 I I I

6 I 7 8

30-39

40-49

>49

TO101 observed

TOllI/ e.xpec/ed

2 2 4

0 I

I

2 I2 14

4 I6 20

5.74 5.14 10.78

0.43 3.llb I .84”

8 3 II I5

0 I I 2

0 2 2 I6

I4 8 22 42

2.69 0.62 3.31 14.19

5.20b 12.90b 6.65b 2.96b

SMR

“PiO.01 bP<0.005

across the age groups. No suicide occurred among men or women younger than 20 years. Suicides occurred in patients with all but the DSM-IIIR catatonic subtype. According to Table 5, most deaths occurred more than two years after hospital discharge for both men and women. Seven (43.7%) suicides occurred during the first two years after hospital discharge. In Table 6, the association between mortality and schizophrenic subtypes is explored. The death rate for the DSM-IIIR paranoid, disorganized, and undifferentiated subtypes is excessive (Table 6). Only one patient with residual schizophrenia died. No catatonic patients died during the follow-up. All Tsuang-Winokur subtypes, but only the positive and mixed Andreasen-Olsen subtypes were associated with risk for death.

DISCUSSION

In a follow-up of 356 DSM-IIIR schizophrenic patients hospitalized between 1970 and 1981, we were able to demonstrate higher than expected death rates with findings specific for gender, age at admission, schizophrenic subtype, cause of death, and phase of follow-up. Briefly, SMRs were highest among women, patients younger than 40 years, and during the early portion of follow-up. Death rates were significantly elevated among patients with the paranoid, disorganized, and undifferentiated DSM-IIIR subtypes. Natural causes of death were greater than expected, but this finding was confined to women. Suicide was the most common cause of death in this cohort.

113 TABLE

4

Distribution

of suicidesby

Age (years) 120 20-29 30-39 40-49 > 49 Deaths Total observed Total expected SMR DSM-IIIR subtype Catatonic Paranoid Disorganised Undifferentiated Residual

age, subtype

Men

Women

Total

0 5

0

0

1

6 8

0 0

1

12 0.53 22.64”

4

0 4 2 5

0

I

prematurely (Black, 1988). However, studies have also shown that the causes of death in schizophrenic patients have gradually changed. In the past, when patients were hospitalized for long periods of time, natural causes of death were common, whereas suicide and other unnatural death causes now predominate. This trend may be the result of changing patterns of aftercare (e.g., deinstitutionalization), improvements in diet and living conditions in mental hospitals, as well as advances in the treatment of physical and mental disorders (e.g., the development of antipsychotic medication). As we have argued in the case of mood disorders (Black et al., 1989) a schizophrenic patient is unlikely to die from physical causes (e.g., dehydration, electrolyte imbalance) or infectious diseases while hospitalized, since these conditions are easily diagnosed and treated. However, according to our data, natural causes of death in schizophrenic patients continue to be excessive in women, in contrast to some earlier studies, including our

and gender

0.16 25.00h

16 0.69 23.19”

0

3 0

“P
TABLE

5

Distribution

of deaths by time interval,follon~ing

dischurge

i 2 Yews

Men Women Combined

B 2 Yeurs

Observed

Expected

SMR

5 6 II

I.0 0.51 1.51

II .16”

5.0b 7.28”

Ob.yerved

E.xpected

SMR

13 18 31

7.43 5.25 12.68

1.15 3.43” 2.44”

“PiO.005 “Pi0.025

In the past decade, mortality studies of psychiatric populations have proliferated, leading investigators to question the need for additional studies. Tsuang and Simpson (1985) argued eloquently that additional studies are needed in order to monitor the effect of changing criteria and the effects of secular trends on mortality rates. They further argued that new studies with larger sample sizes are needed to take advantage of multivariate analytic techniques, to resolve differences in existing data, and to assess the effect of new treatments on mortality as well as the effects of new developments in aftercare. The finding that death rates are elevated comes as no surprise, since evidence has accumulated over the past century that schizophrenic patients (both broadly and narrowly defined) tend to die

own (Black et al., 1985) which suggested that deaths from natural causes were not increased. It is likely that schizophrenic patients dying from natural causes have accompanying physical disorders that may account for the excess rates of death, since there is a tendency for patients with two or more disorders to seek hospitalization more readily than those with only one disorder (Berkson, 1946). Referral patterns at tertiary care centers, such as ours, lead to this situation. Herrman et al. (1983) using data from the Oxford record-linkage study, showed that schizophrenic patients were, in fact, more likely to have general hospital admissions than expected. It is probably not possible with this data set to resolve the issue of whether schizophrenic patients possess an inherent ‘biological disadvantage’ (Kendell, 1975) that would lead to an

114 TABLE

6

Disrrihurion

qf deaths

DSM-III-R Catatonic Disorganized Paranoid Undifferentiated Residual Twang-Winokur Paranoid Non-paranoid Indeterminate Andreasen-Olsen Positive Negative Mixed

bJ3 diagnostic

subtype

0 3 8 6 I

0

0

0.85

1

8 9 0

IO I6 I5 I

3.07 5.36 3.92 0.99

3.26” 2.99” 3.83” I.01

6 5 I

12 5 7

I8 IO I4

5.42 3.60 5.17

3.32 2.78” 2.71’

7 2 9

II 3 IO

I8 5 I9

6.43 2.67 5.09

2.80 1.87 3.73”

“P~O.005 bf’<0.029 ‘P
increased risk of death, since the answer to such questions requires a less biased sample. We can conclude, however, that schizophrenic patients hospitalized in tertiary care centers still exhibit high rates of death, including death from natural causes. Our finding of excess mortality between 2 and 3 times expected, and that the largest excess occurs in persons younger than 40 years, is in agreement with earlier work by our group and others. Another consistent finding is that of a relatively greater excess mortality in women, compared to the general population. The fact that early death occurs in younger schizophrenic patients leads to several possible explanations, particularly as the excess is nearly confined to death from unnatural causes. Schizophrenia is usually associated with an onset in the late teens and early 20s and may be more pernicious early in its course; suicide may be the end result of a severe illness. Hallucinations, delusions, and disturbances of thought are more pronounced, and mood symptoms more prevalent in younger schizophrenic patients (Pfohl and 1983). Some young schizophrenic Winokur, patients may be motivated to kill themselves by feelings of hopelessness and an awareness of their chronic illness (Warnes, 1964; Drake et al., 1984). Other possible explanations for the finding that

younger schizophrenic patients are at high risk for early death include improvement or remission with age making suicide less likely later on (Harding et al., 1987); increasing negative (or defect) symptoms with advancing age, leaving patients too inert or unmotivated to commit suicide (Pfohl and Winokur, 1983); increasing cognitive impairment with age, which may leave a patient too confused or disoriented to contemplate suicide. Younger schizophrenic patients may also be more likely to live alone, and less likely to live with relatives, in a nursing home, or in a custodial care setting that can protect against the psychological effect of living alone, as well as reducing the opportunity to harm oneself (i.e., due to constant supervision). Lastly, older schizophrenics may have a late onset illness that differs constitutionally from the younger onset illness, and may be less prone to suicide (Pearlson et al., 1989). The high relative risk of death for females for both natural and unnatural deaths requires some explanation. For example, although the risk for suicide is higher (as indicated by the SMR), the actual percentage of deaths by suicide is less for females than among males. In fact, some investigators have suggested that suicide is a rare outcome in women with schizophrenics (Tsuang et al.,

115

1980). While mortality rates for women are very high, most deaths are due to natural causes. This may reflect the greater tendency of women to seek medical attention than men. Other factors may explain the gender differences. Women tend to have a later onset of illness (Loranger, 1984) and so complications of schizophrenia, including suicide may occur later. Women tend to have a milder course of illness than men, a better response to neuroleptics, and are less likely to live alone (Seeman, 1986). All of these factors may help lower the absolute risk for suicide. The following data help to put these risks into perspective. While 2.7% of women and 5.7% of men in the study committed suicide, the percentage of suicides among all deaths was 16.7% for women and 66.7% for men. None of the systems used for subtyping patients had a robust association with death rates. All but the DSM-IIIR catatonic and the Andreasen-Olsen negative subtypes were associated with increased risk. Fenton and McGlashan (1991) recently reported from a 6 to 32 year follow up of schizophrenic patients that 10% of paranoid patients, 4% of undifferentiated patients, but no hebephrenit patient committed suicide. Our DSM-IIIR catatonic patients and Andreasen-Olsen negative patients would probably have been categorized as hebephrenic using their system. These findings seem consistent with clinical intuition and observation. Catatonic patients are probably too ill to organize a suicide, in contrast to the paranoid and undifferentiated, while schizophrenic patients with prominent negative symptoms are probably too inert to attempt suicide. Many paranoid and undifferentiated schizophrenics, in fact, may be motivated to commit suicide by their delusions and hallucinations. Our study also finds that the early posthospitalization period is a time of greatest risk for premature death, including suicide, although risk continues throughout follow-up. This finding has also been noted in several, but not all studies of schizophrenic patients. Tsuang et al. (1980) found that during a 30 to 40 year follow-up of schizophrenic patients, the first decade was the period of greater risk for suicide, and in our own work (Black, 1988), schizophrenic suicides were found to cluster within the first two years after hospital discharge. Others have concluded that the risk of suicide is spread out over the entire course of the

illness (Allebeck and Wistedt, 1986). However, our finding that suicide tends to occur primarily in young persons lends support to the belief that the early post-hospitalization period is the time of greater risk. These findings should be of importance to those clinicians who evaluate and treat schizophrenic patients, since knowledge of risk factors for premature death is the first step to prevention. However, suicide is not easily predicted in psychiatric patients, even in groups at high risk (Goldstein et al., 1991), since suicide is a relatively rare event. Schizophrenic patients may present a particular problem, since studies have found that their suicides are often inexplicable and may occur without warning (Breier and Astrachan, 1984) in contrast to suicide in depressive disorders, which generally occurs during episodes of clinical depression (Black et al., 1985b). Furthermore, most depressed patients give warnings about their suicidal intentions, unlike the schizophrenic suicide completer (Breier and Astrachan, 1984). There are several potential criticisms of our data collection and analysis. The data analyses included age and gender standardization, but standardization for other factors (i.e., marital status, age of onset) were not attempted. We are presently planning multivariate analyses, where these factors can be taken into account. Other potential criticisms of our study include the retrospectively collected data base and diagnostic assessments, which are less desirable than prospective assessment and follow-up. Further the death ascertainment may not have been complete, as some deaths may have been missed. On the other hand, this study offers a recent cohort of well diagnosed schizophrenic patients, a careful chart review with multiple variables which allow for multivariate analytic approaches. This, and additional studies, will be instrumental in leading to a greater understanding of mortality in schizophrenia. We have only considered a few important variables here, including gender, age at admission, cause of death, phase of follow-up, and schizophrenic subtype. Other variables, such as depressed mood, treatments used, or aftercare instructions, are also important and will be the subject of subsequent reports, where we will attempt a full multivariate study of correlations between risk factors and mortality.

116

ACKNOWLEDGEMENTS This research was supported by grants MH 43652 and MH 43271 from the National Institute of Mental Health, Bethesda, MD.

REFERENCES Allebeck, P.. Varla. A.. Kristjansson, E. and Wistedt. B. (I 987) Risk factors for suicide among patients with schizophrenia. Acta Psychiatr. Stand. 76. 414-419. Allebeck, P. and Wistedt. B. (I 986) Mortality in schizophrenia. A IO year followup based on the Stockholm County inpatient registrar. Arch. Gen. Psychiatry 43, 650-653. American Psychiatric Association. (1980) Diagnosttc and Statistical Manual of Mental Disorders. 3rd Edn. Washington. DC: American Psychiatric Press. American Psychiatric Association, (1987) Diagnostic and Statistical Manual of Mental Disorders, 3rd edn.-revised Washington, DC: American Psychiatric Press. Andreasen, N.C. and Olsen, S. (1982) Negative v. positive schizophrenia: definition and validation. Arch. Gcn. Psychiatry 39. 7899794. Black, D.W.. Warrack. G. and Winokur, G. (1985a) Excess mortality among psychiatric patients. The Iowa recordlinkage study. J. Am. Med. Assoc. 253, 58-61. Black. D.W.. Winokur. G. and Warrack. G. (1985b) Suicide in schizophrenia. The lowa record-linkage study. J. Clin. Psychiatry 46. 14-17. Black. D.W., Winokur. G. and Nasrallah. A. (1987) Suicide in subtypes of affective disorder. Arch. Gen. Psychiatry 44. X78%380. Black. D.W.. Winokur, G.. Mohondoss, E.. Woolson, R.F. and Nasrallah. A. (1989) Does treatment influence mortality in depressives? A follow-up of 1076 patients with major affective disorder. Ann. Clin. Psychiatry I, 1655173. Black, D.W. and Winokur, G. (1988) Age. mortality and chronic schizophrenia. Schizophr. Res. I ~267-272. Black, D.W. (1988) Mortality in schizophrenia. The Iowa Record-linkage study: a comparison with general population mortality. Psychosomatics 29, 55-60. Breier, A. and Astrachan. B.M. (1984) Characterization of schizophrenic patients who commit suicide. Am. J. Psychiatry 141. 206-209. Buda. M., Tsuang. M.T. and Fleming. J.A. (1988) Causes of death in DSM-III schizophrenics and other psychotics (atypical group): a comparison with the general population. Arch. Gen. Psychiatry 45. 283-285. Cooper, J.E., Kendall, R.E.. Gurland, B.J. et al. (1972) Psychiatric diagnosis in New York and London: a comparative study of mental hospital admissions. Institute of Psychiatry. Maudsley Monograph No. 20. London Oxford U.P. Coryell, W. (1981) Diagnosis-specific mortality. primary unipolar depression and Briquet’s syndrome (somattzation disorder). Arch. Gen. Psychiatry 38, 9399942.

Drake. R.E., Gates, C.. Cotton. P.G. and Whitakcr. A. (19X4) Suicide among schizophrenics-who is at risk’! J. Ncrv. Ment. Dis. 172, 613-617. Eastwood, M.R.. Stiasny. S.. Mcicr. H.M.R. and Woogh. C.M. (1982) Mental illness and mortality. Comp. Psychiatry 23, 377-385. Fenton. W.S. and McGlashan. (1991) Natural history ofschizophrenic subtypes. I. Longitudinal study of paranoid. hehcphrenic. and undifferentiated schizophrenia. Arch. Gcn. Psychiatry 48, 9699977. Freeman. M.F. and Tukey. J.W. (1950) Transformations related to the angular end of the square root. Am. Math. Statist. 21. 607761 I. Goldstein, R.B.. Black. D.W., Winokur. G. and Nasrallah, A. (1991) The prediction of suicide: sensitivity. specificity. and predictive value of a multivariate model apphcd to suicide among 1,906 patients with affective disorder. Arch Gen. Psychiatry 48. 418-422. Harding. C.M.. Brooks. G.W.. Ashikaga. T., Strauss. J.S. and Breier, A. (1987) The Vermont longitudinal study of persons with seven mental illnesses. I. Methodology. study sample and overall status 32 years later. Am. J. Psychiatry 144. 71% 726. Hcrrman. H.E.. Baldwin. J.A. and Christie, D. (1983) A recordlinkage study of mortality in general hospital discharged inpatients diagnosed as schizophrenics. Psychol. Med. 13. 581-593. International Classification of Diseases (Vol. I). (19X1) Ninth Revision. Second edn. Washington, DC. U.S. Department of Health and Human Services, 1980. Kendell, R.E. (I 975) The concept of disease and its implications for psychiatry. Br. J. Psychiatry 127. 3055315. Lesagc. A.D.. Trapani. V. and Tansella. M. (1990) Excess mortality by natural causes of Italian schizophrenic patients. Arch. Eur. Psych. Neurosci. 239. 361-365. Loranger. A.W. (1984) Sex difference in age of onset 01 schizophrenia. Arch. Gen Psychiatry. 41_ 157- 161. Martin, R.L.. Cloninger. C.R., Guze. S.B. and Clayton. P.J. (1985) Mortality in a follow-up of 500 psychiatric outpatients. II. Cause-specific mortality. Arch. Gcn. Psychiatry 42. 58-66. Pearlson. G.D.. Kreger. L., Rabins. D.V.. Chase. G.A.. Cohen. B.. Wirth, J.B.. Schlaepfer. T.B. and Tune. L.E. (1989) A chart review study of late-onset and early-onset schizophrenia. Am. J. Psychiatry. 146. 156% 1574. Pfohl. B. and Winokur, G. (1983) The micropsychopathology of hchephrenic:catatonic schizophrenia. J. Nerv. Ment. Dis. 171, 296-300. M.V. (1986) Current outcome in schizophrenia: Seeman, women versus men. Acta Psychiatr. Stand. 13. 609 617 Tsuang, M.T. and Simpson. J.C. (1985)Mortaltty studies in psychiatry-should they stop or proceed? Arch. Gcn. Psychiatry 42. 98 103. Tsuang, M.T. and Winokur, G. (1974) Criteria for subtyping schizophrenia. clinical differentiation of hebephrenic and paranoid schizophrenia. Arch. Gen. Psychiatry 31. 43347. Tsuang, M.T.. Woolson, R.F. and Fleming. J.A (1980) Causes of death in schizophrenia and mamc dcpresston. Br. J. Psychiatry 136. 239~-242. Warnes. H. (1968) Suicide in schizophrenics. Dis Nerv. Sys. 29. 35-40.