Prodromal symptoms of schizophrenia in first-episode psychosis: Prevalence and specificity

Comprehensive Psychiatry (Official Journal of the American Psychopathological Association)

JULY/AUGUST 1995

V O L . 36, N O . 4

Prodromal Symptoms of Schizophrenia in First-Episode Psychosis: Prevalence and Specificity Henry J. Jackson, Patrick D, McGorry, and Paul Dudgeon Three hundred thirteen patients with first-episode psychosis were assessed using the Royal Park Multidiagnostic Instrument for Psychosis (RPMIP) to determine differences among seven DSM-III-R diagnoses in the comparative frequencies and diagnostic efficiencies of DSM-III-R schizophrenia prodromal symptoms. Patients w i t h a diagnosis of schizophrenia and schizophreniform disorder were significantly more likely to evince prodromal symptoms. A multinomial Iogit model

suggested that individual prodromal symptoms were relatively poor at distinguishing between diagnoses. This was confirmed when sensitivity, specificity, and positive (PPP) and negative (NPP) predictive power of individual prodromal symptoms were examined. Alt h o u g h DSM-III.R schizophrenia prodromal symptoms do occur more commonly in schizophrenia, they are by no means pathognomonic of that disorder. Copyright © 1995by W.B. Saunders Company

O D R O M A L SYMPTOMS are premonip Rtory symptoms that precede the develop-

sense, knowledge of their predictive power and specificity for psychosis, particularly schizophrenia, is needed. However, to date, there are many questions that can be raised concerning the validity and reliability of DSM-III/DSM-III-R 6,7 prodromal symptoms. Indeed, punished data pertain solely to interrater reliability; to the best of our knowledge, there are four such studies. Two of these are problematic in that they involved populations who all had more than one admission. 8,9 Hence, rather than examining prodromal symptoms preceding the initial episode, they were focusing on symptoms that preceded a second or subsequent admissions and would have included an amalgam of residual and

ment of more florid illness. In the case of schizophrenia, it has been argued that both so-called neurotic symptoms, most usually associated with depression and anxiety, and symptoms typically indicative of schizotypy or emerging florid psychosis are harbingers of full-blown schizophrenia, as well as residua of an episode. 1 Two recent issues of Schizophrenia Bulletin (no. 2 and 3, 1992) were devoted to issues pertaining to first-episode psychosis. As asserted by Keshavan and Schooler, 2 it is important to study this group to ascertain the effects of illness chronicity and institutionalization, and to allow prospective follow-up evaluation. Additionally, it would be important to ascertain the effect of long-term neuroleptic medication and its sequelae. Although a number of articles in those two issues of Schizophrenia Bulletin were concerned with premorbid functioning and onset of psychosis variables, 3,4 not one focused on prodromal symptoms. This is an oversight, since one would argue that identification of prodromal symptoms would permit early intervention, thus attenuating the severity and length of illness, not to mention reducing the length of hospital stay or even obviating the need for hospital admission. 5 Clearly, to estimate the value of prodromal symptoms in this clinical

From the Early Psychosis Research Centre, National Health and Medical Research Council Schizophrenia Unit, and Departments of Psychology and Psychiatry, University of Melbourne, Parkville, Victoria, Australia. Supported by a grant from the Psychopathology Section of the National Health and Medical Research Council Schizophrenia Research Unit Program, a National Health and Medical Research Council Project Grant to P.D.M., and an Early Psychosis" Research Grant from the Victorian Health Promotion Foundation to P.D.M. and HJJ. Address reprint requests to Henry J. Jackson, Ph.D., Associate Professor, Department of Psychology, University of Melbourne, Private Bag 3. P. 0., Parkville 3052, Victoria, Australia. Copyright © 1995 by W.B. Saunders Company 0010-440)(/95/3604-0002503.00/0

ComprehensivePsychiatry, Vol. 36, No. 4 (July/August), 1995: pp 241-250

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242

reemerging prodromal symptoms. It is only in the first-episode group that the specificity of prodromal symptoms for schizophrenia versus other psychoses can really be examined because chronicity renders such issues cloudy and difficult to clarify or examine. The third study derives from the multicenter DSM-IV Field Trial for Schizophrenia and Related Psychotic Disorders 1° in which our unit participated. The trials involved a sample of multiple-admission and a much smaller subsample of first-admission psychotic patients. The essential conclusions were that interrater reliability data were consistently higher for the measurement of both prodromal and residual symptoms in multiple-admission patients and lower for first-admission patients in both phases, particularly for the initial prodromal period. The fourth study reported by Jackson et a111 focused on first-admission psychotic patients and reported stronger interrater reliability data for prodromal symptoms than the previous three studies. The design of the study made it impossible to assess test-retest reliability, but serial semistructured interviews and the use of multiple data sources appeared to produce more valid ratings of the prodromal features. Because of the putative difficulty in making reliable ratings of DSM-III-R prodromal symptoms, DSM-IV x2 criteria retain the concept of a prodrome but omit a specific list of items, apparently because of concerns in particular about test-retest reliability. The International Classification of Diseases, 10th Revision, 13 eschews the prodromal concept as a contributor to diagnosis, due to concerns about specificity and reliability of prodromal symptoms. To date, no study has examined the comparative frequency of particular DSM-III-R schizophrenia prodromal symptoms in the various functional psychoses, nor has any study investigated whether these psychoses can be discriminated on the basis of DSM-III-R prodromal symptoms. Similarly, no data exist regarding the diagnostic efficiency14 (i.e., sensitivity, specificity, and positive [PPP] and negative [NPP] predictive power) of individual DSM-III-R prodromal symptoms. It is important both (1) to assess the validity and utility of prodromal symptoms and (2) to make that assessment in an appropriate sample

JACKSON, MeGORRY, AND DUDGEON

of patients. To this end, we examined three relevant questions: (1) To what extent do the frequencies of prodromal symptoms vary according to diagnosis?; (2) What is the diagnostic efficiency of prodromal symptoms for the various diagnostic groups?; and (3) To what extent do prodromal symptoms differentiate among these diagnostic groups? In the current study, we sought to investigate these issues in a large sample of first-admission psychotic patients who were carefully diagnosed using a semistructured instrument that maximizes clinical validity. 15,16We believe this sample to be the largest prospective cohort of firstepisode psychotic patients yet reported in the literature. METHOD

Patients At admission, 313 first-episode psychosis patients (196 males, 117 females) were aged 14 to 46 years (mean - SD, 25.5 -+ 6.6), and all were admitted between 1986 and 1992 to the Aubrey Lewis Unit, an inpatient unit linked with the National Health and Medical Research Council Schizophrenia Research Unit, and now part of the Early Psychosis Prevention and Intervention Centre based at Royal Park Hospital. All patients were experiencing their first psychotic episode, and organic factors had been excluded. Other inclusion criteria for the study were that patients had to be of normal intelligence, be able to speak adequate English, and be no older than 45 years at the onset of the disorder (mean, 24.9; range, 13 to 45). Sociodemographic characteristics did not differ significantly in other respects from those reported previously for the sample. 11,16

Frequency counts or the mean - SD for three demographic variables across the seven DSM-III-R diagnostic groups are listed in Table 1. There was no sex difference among the seven diagnostic groups (X2 = 6.02, df= 6, P = .42), nor was there any difference in the age at first onset of psychosis (F = 0.95, dr= 6, 306, P = .45). Although there was a significantdifference overall for age at hospitalization (F = 2.38, df = 6, 306, P = .02), post hoc testing using a modifiedleast-significantdifferencecontrast showed no significant differences at the .05 level between any of the groups. However, there was a significantdifference for years of education (X2 = 13.0, df = 6, P = .02), with the adjusted residual values]7 showing significantly fewer schizophreniform patients and significantly more major depressive patients with postsecondaryeducation as compared with those who had completed _<12 years of schoolingonly.

Procedure During inpatient admission, patients were assessed with the Royal Park Multidiagnostic Instrument for Psychosis

PRODROMAL SYMPTOMS IN FIRST-EPISODE PSYCHOSIS

243

Table 1. Descriptive Statistics for Sociodemographic Characteristics of Seven DSM-III-R Diagnostic Groups Sociodemographic Characteristic Age at onset of psychosis, years Mean SD Age at hospitalization, years Mean SD Sex Male No. % Female No. % Educational level < 12 years of secondary schooling No. % At least some tertiary education No. %

Sz (n = 94)

Sf (n = 62)

Sa (n = 43)

Del (n = 16)

Bp (n = 49)

Dp (n = 28)

NOS (n = 21)

Total (N = 313)

25.9 7.9

24.3 6.0

24.9 6.2

26.7 7.2

23.8 4.9

24.1 5.2

25.4 6.2

24.9 6.5

27.2 8.0

24.3 6.0

25.2 6.2

27.4 7.1

23.9 4.9

24.1 5.2

25.6 6.1

25.5 6.6

64 68.1

37 59.7

23 53.5

10 62.5

33 67.3

14 50.0

15 71.4

196 62.6

30 31.9

25 40.3

20 46.5

6 37.5

16 32.7

14 50.0

6 28.6

117 37.4

74 78.7

57* 91.9

34 79.1

14 87.5

37 75.5

18 64.3

14 66.7

248 79.2

20 21.3

5 8.1

9 20.9

2 12.5

12 24.5

10" 35.7

7 33.3

65 20.8

Abbreviations: Sz, schizophrenia; Sf, schizophreniform; Sa, schizoaffective; Del, delusional disorder; Bp, bipolar disorder; Dp, major depressive disorder; NOS, psychotic disorder NOS. *Adjusted residuals value suggests significantly greater number than expected.

(RPMIP), 15A6 which permits diagnosis of psychotic disorders according to a wide range of nosological concepts including DSM-III-R. It aims to achieve maximum clinical validity, is with multiple interviews and information sources used to reconstruct comprehensively the current episode. Interrater reliabilities for the various psychotic diagnoses are high. 16 In the current study, the following numbers of patients received the following DSM-III-R diagnoses: schizophrenia, n = 94; schizophreniform, n = 62; schizoaffective, n = 43; delusional disorder, n = 16; bipolar disorder, n = 49; major depression, n = 28; and psychotic disorder NOS, n = 21. (Two patients in the intake sample were excluded from all analyses reported herein; one had a brief reactive psychosis and the other was diagnosed with an induced psychosis.) Patients were interviewed by one or two trained raters with the RPMIP on two occasions: as soon as possible after admission and then late in the episode close to discharge. (Interrater reliability data for a portion of the sample are reported elsewhere. 16) An informant, typically a close relative, was interviewed shortly after the first patient interview by the same rater. A special informant interview, the Illness Duration Interview, was developed as part of a wider study of onset and duration in first-episode psychosis 19 and provided a particularly detailed reconstruction of the period of illness preceding hospitalization. In the case of prodromal symptoms, raters made two sets of ratings based on these separate sources and then proceeded to blend independently the responses of the patient and informant, in accordance with clear-cut rules set out in the RPMIP Glossary. 16 This procedure was intended to maximize clinical validity of the prodromal ratings. Because approximately one third of the sample was originally diag-

nosed under DSM-III criteria, 6 information was not available for this subgroup on the ninth prodromal symptom (marked lack of initiative, interests, or energy) introduced under DSM-III-R. 7 Analyses on this ninth item were performed on only 198 patients. It should be noted that all prodromal ratings were rigorously focused on the period between the first evidence of change from premorbid status and the first evidence of frank psychotic features, that is, delusions, hallucinations, or marked formal thought disorder. Care was therefore taken to exclude the positive rating of prodromal symptomatology that might have arisen from the effect of any chronic personality disorder rather than from a deterioration in functioning from a premorbid level. It is equally important to emphasize that prodromal symptoms were rated in ignorance of the final diagnosis for the episode. The RPMIP procedure requires symptom and criteria ratings to be completed first. To arrive at a diagnosis requires a computerdriven algorithm to be applied to symptom and criteria ratings, which is then checked against the clinical judgment of a senior psychiatrist or clinical psychologist. This minimizes rater bias and can be contrasted with the approach used by the Structured Clinical Interview for DSM-III-R (SCID-P), 2° wherein the rater makes the symptom ratings and makes the diagnosis. To summarize, with the SCID-P, the pathway through the symptoms is linked to the diagnosis and the rater is conscious of the likely diagnosis during the course of the interview.

Overview o f Data Analysis We adopted a strategy of increasing delineation in the analysis of the data that mirrored the definition of pro-

244

JACKSON, McGORRY, AND DUDGEON

drome in DSM-III-R7--"a clear deterioration of functioning before the active phase of the illness not due to a disturbance in mood or to a Psychoactive Substance Use Disorder and involving at least two . . . symptoms" (p. 194)--and its applicability to a diagnosis of schizophrenia. Accordingly, we first examined differences between the seven diagnostic groupings in terms of the nine individual prodromal symptoms. Then we examined differences in terms of any two prodromal symptoms being present, which enabled possible confounding from affective disturbances or substance abuse to be still present. The third level of the hierarchy was in terms of the DSM-III-R definition of prodrome itself. Finally, we included a 6-month duration component in the DSM-III-R definition so that the differential impact of the length of the prodrome on a diagnosis of schizophrenia could become apparent. We used an identical strategy of increasing delineation when we examined the indices of diagnostic efficiency (i.e., sensitivity, specificity, PPP, and NPP). The hierarchical approach allowed us to determine whether and how the addition of more specific criteria to individual prodromal symptoms improved discrimination between diagnostic groups and diagnostic efficiency.

RESULTS

Differences in Prodromal Symptoms for Patient Diagnosis Individual symptoms. Frequencies of the nine prodromal symptoms for the seven diagnostic groups are listed in Table 2. The most frequently reported symptom was socialisolation or withdrawal (52% of cases), followed by marked impairment in role functioning (44%) and odd or bizarre ideation (38%). The least prevalent symptoms were marked impairment in hygiene (14%) and markedly peculiar behavior (16 %). Six of nine prodromal symptoms varied significantly between diagnostic groups. These were social isolation or withdrawal, marked impairment in role functioning, marked impairment in personal hygiene, odd or bizarre ideation, unusual perceptual experiences, and marked lack of initia-

Table 2. Frequencies (and percentages) of Patients With Prodromal Symptoms for Seven DSM-III-R Diagnostic Groups (N = 313) Symptom Social isolation or withdrawal No. % Marked impairment in role functioning No. % Markedly peculiar behavior No. % Marked impairment in personal hygiene No. % Blunted, flat, or inappropriate affect No. % Digressive, vague, or metaphoric speech No. % Odd or bizarre ideation No. % Unusual perceptual experiences No. % Marked lack of initiative, interests, or energy No. %

Sz (n = 94)

Sf (n = 62)

Sa (n = 43)

Del (n = 16)

Bp (n = 49)

Dp (n = 28)

71" 75.5

26 41.9

26 60.5

41" 25.0

71 14.6

21" 75,0

59* 62.8

22 35.5

20 46.5

31 18.8

91 18.8

24 25.5

10 16.1

3 7.0

0 0.0

21" 22.3

6 9.7

6 14.0

31 33.3

11 17.7

27 29.0

NOS (n = 21)

×2

p

7 33.3

65.1

< .001

17" 60.7

7 33.3

36.1

< .001

3 6.3

5 17.9

5 23.8

16.4

.012

1 6.3

It 2.1

8* 28.6

2 9.5

17.6

.007

14 32,6

O O.O

9 18.8

9 32.1

3 14.3

15.0

.021

14 22.6

8 18.6

0 0.0

13 27.1

6 21.4

8 38.1

9.6

.143

49* 53.3

21 33.9

19 45.2

4 25.0

81" 16.7

7 25.0

7 33.3

23.2

.001

22* 23.7

6 9,7

13" 30.2

0 O.0

31" 6.3

6 21.4

2 9.8

19.3

.004

32* 23.7

14 29,2

13" 65.0

3 23.1

11" 3.8

12" 70.6

4 30.8

34.3

<.001

NOTE. df = 6. Abbreviations are as in Table 1. There were only 198 patients measured on the ninth prodromal item dealing with a marked lack of initiative. *Adjusted residuals value suggests significantly greater number than expected. tAdjusted residuals value suggests significantly lower number than expected.

PRODROMAL SYMPTOMS IN FIRST-EPISODE PSYCHOSIS

245

five (all Pearson X2 values significant beyond the overall .01 level set for the nine symptoms). Adjusted residual values for the six significant results were inspected to assess where the predominant relationships between each prodroreal symptom and the diagnostic categories were occurring. The most noticeable feature was that a greater proportion of schizophrenic patients showed each of the six significant symptoms, whereas significantly fewer bipolar patients reported the same six symptoms. In addition, a greater proportion of depressive patients showed social isolation or withdrawal, marked impairment in role functioning, marked impairment in hygiene, and marked lack of initiative, and a greater number of schizoaffective patients evidenced unusual perceptual experiences and marked lack of initiative. In contrast, fewer delusional patients showed social isolation or withdrawal and marked impairment in role functioning. Any two symptoms. Frequencies of patients exhibiting any two prodromal symptoms are listed in Table 3, and there was significant variation in occurrence across the seven diagnostic groups (×2 = 66.61, df = 6, P < .001). Adjusted residual values suggested that there were significantly more schizophrenic and depressive patients and significantly fewer delusional and bipolar patients. The result for the bipolar group is surprising, given that this delineation still allowed for an affective component to be operating in the defined prodrome. DSM-III-R-definedprodrome. Although significantly fewer bipolar and depressive patients were found to have a strict DSM-III-R pro-

drome, as would be expected given its definition, there were still nearly 20% of depressive patients diagnosed in this phase. A significantly higher proportion of schizophrenic patients continued to be found. It is of interest that greater than one third of all schizophreniform, schizoaffective, and psychotic disorder NOS patients plus one fourth of all delusional patients meet criteria for a DSM-III-R prodrome. DSM-III-R prodrome for at least 6 months. Although DSM-III-R does not define a duration for the prodromal symptoms, it does permit a diagnosis of schizophrenia to be made when a patient exhibits 5.75 months of prodromal symptoms and only 1 week of florid psychotic features. Adjusted residuals again demonstrated that there were significantly more schizophrenic patients and (not surprisingly) significantly fewer schizophreniform, bipolar, and depressed patients meeting this more stringent definition. Although the duration criterion led to a much greater separation of the schizophrenic patients from the other six diagnostic groupings, there were still 20% of patients in the schizoaffective and psychotic disorder NOS groups plus some delusional, bipolar, and depressive patients who had a DSM-III-R prodrome for at least 6 months.

Diagnostic Efficiency of Prodromal Symptoms Individual symptoms. Table 4 lists the sensitivity, specificity, PPP, and NPP of each prodromal symptom for the schizophrenia group. This group obtained the strongest PPP and sensitivity on every prodromal symptom. Also listed are the same values for the schizophreniform group,

Table 3. Frequencies [and percentages) of Patients in Prodromal Hierarchy for Seven DSM-III-R Diagnostic Groups (N = 313) Prodromat Characteristic

Sz (n = 94)

Sf (n = 62)

Sa (n = 43)

Del (n = 16)

Bp (n = 49)

Dp (n = 28)

NOS (n = 21)

79* 84.0

31 50.0

27 62.8

41" 25.0

141" 28.6

23* 82.1

78* 83.0

24 38.7

17 39.5

4 25.0

31" 6.1

59* 62.8

01" 0.0

9 20.9

2 12.5

11" 2.0

X2

P

10 47.6

60.8

< .001

5t 17.9

7 33.3

98.6

< .001

21" 7.1

4 19.0

114.0

<.001

Any 2 prodromal symptoms No. % DSM-III-R prodrome No. % DSM-III-R prodrome for >_6 months No. %

NOTE. df = 6. Abbreviations are as in Table 1. *Adjusted residuals value suggests significantly greater number than expected. "l'Adjusted residuals value suggests significantly lower number than expected.

246

JACKSON, McGORRY, AND DUDGEON

Table 4. Sensitivity, Specificity, PPP, and NPP for Each Prodromal Symptom for Schizophrenia and Schizophreniform Diagnostic Groups ProdromalSymptom Social isolation or withdrawal Schizophrenia Schizophreniform Marked impairment in role functioning Schizophrenia Schizophreniform Markedly peculiar behavior Schizophrenia Schizophreniforrn Marked impairment in personal hygiene Schizophrenia Schizophreniform Blunted, flat, or inappropriate affect Schizophrenia Schizophreniform Digressive, vague, or metaphoric speech Schizophrenia Schizophreniform Odd or bizarre ideation Schizophrenia Schizophreniform Unusual perceptual experiences Schizophrenia Schizophreniforrn Marked lack of initiative, interests, or energy Schizophrenia Schizophreniform

SensitivitySpecificity PPP NPP .76 .42

.58 .46

.44 .16

.85 .76

.63 .36

.64 .54

.43 .16

.80 .77

.26 .16

.88 .84

.48 .20

.73 .80

.22 .10

.89 .84

.47 .13

.73 .79

.33 .18

.78 .74

.40 .14

.74 .78

.29 .23

.78 .75

.36 .18

.72 .80

.53 .34

.70 .62

.43 .18

.78 .79

.24 .10

.86 .82

.42 .12

.73 .78

.53 .29

.68 .57

.41 .18

.76 .72

NOTE. There were only 198 patients measured on the ninth prodromal item dealing with a marked lack of initiative.

which obtained the second strongest PPP for every prodromal symptom. (Details of values for the remaining five diagnostic groups can be obtained by request from H.J.J.) The presence of every prodromal symptom consistently identified (i.e., sensitivity) a higher proportion of schizophrenic patients than schizophreniform patients, although this was only marginal for approximately half the prodromal symptoms (Table 4). Again, the absence of the symptom (i.e., specificity) was consistently better in schizophrenic patients than in schizophreniform patients. When considering only these two indices, most symptoms were clearly better at excluding rather than identifying schizophrenia, with the exceptions being social isola-

tion or withdrawal and marked impairment in role functioning. Examining the efficacy of the symptom in predicting the presence of a disorder (i.e., PPP) showed that prodromal symptoms predicted between 36% and 48% of schizophrenic cases, but only 12% to 20% of schizophreniform cases. On the other hand, for both diagnostic groupings the absence of symptoms (NPP) accurately predicted the absence of either diagnosis for between 72% and 85% of the cases. Any two symptoms. Table 5 lists the indices of diagnostic efficiencywhen any two prodromal symptoms were present for the schizophrenia and schizophreniform groups. (Again, details of values for the remaining five diagnostic groups can be obtained by request from H.J.J,) The schizophrenia group obtained the highest PPP and sensitivity for this variable as compared with the remaining six diagnostic groups. One should note in comparing Tables 4 and 5 that the use of any two symptoms does not produce marked improvement over single prodromal symptoms. This variable identified 82% of the cases of schizophrenia and predicted 42% of the cases of schizophrenia. For schizophreniform disorder, the variable identified 50%, but predicted only 17% of the patients. Specificity and NPP were moderate to high (50% and 88%, respectively) for schizophrenia and poor to moderately high for schizophreniform (38% and 75%, respectively), suggesting that the presence of at least two prodromal symptoms was better at including rather than excluding schizophrenia and schizophreniform disorders. DSM-III-R-defined prodrome. Table 5 also lists diagnostic efficiency indices for a strict DSM-III-R prodrome, which resulted in a noTable 5. Sensitivity, Specificity, PPP, and NPP for Prodromal Hierarchy for Schizophrenia and Schizophreniform Diagnostic Groups Prodromal S y m p t o m Any 2 prodromal symptoms Schizo )hrenia Schizo }hreniform DSM-III-R )rodrome Schizo )hrenia Schizo )hreniform DSM-III-R )rodrome >6 months Schizo )hrenia Schizo )hreniform

SensitivitySpecificity PPP NPP .84 .50

.50 .38

.42 .88 .17 .75

.83 .39

.73 .55

.57 .85 .17 .74

.63 .00

.92 .69

.77 .85 .00 .74

PRODROMAL SYMPTOMS IN FIRST-EPISODE PSYCHOSIS

ticeable improvement over each individual and any two prodromal symptoms for predicting the diagnosis of schizophrenia. There was a slight reduction in sensitivity (73%) and NPP (85%) and a greater improvement in specificity (92%), as would be expected given its definition being linked to schizophrenia. For schizophreniform disorder, there was a decrease in sensitivity, a slight improvement in PPP and NPP, and a notable improvement in specificity (sensitivities and PPPs were inferior for the remaining five diagnostic groupings). However, the variable defined as the DSM-III-R prodrome clearly results in better diagnostic efficiency for the schizophrenia group versus the schizophreniform group. DSM-III-R prodrome for at least 6 months. Finally, diagnostic efficiency was dramatically improved for the prediction of schizophrenia for a DSM-III-R prodrome lasting at least 6 months versus a DSM-III-R prodrome with unspecified duration, with a slight reduction in NPP, a more noticeable improvement in specificity, and a reduction in sensitivity (Table 5).

247

Table 6. Number and Percentage of Patients Within Each of the Three Diagnostic Groups Correctly Classified by Multinomial Logit Models P(edictedGroup Observed Group 8 prodrome items only Schizophrenia (n = 92) No. % Schizophreniform (n = 62) No. % Other psychoses (n = 155) No. % 8 items + DSM-III-R prodrome Schizophrenia (n = 92) No. % Schizophreniform (n = 62) No. % Other psychoses (n = 155) No. %

Schizo- SchizoOther phrenia phreniform Psychoses

33 35.9

0 0.0

59 64.1

11 17.7

0 0.0

61 82.4

35 22.6

2 1.3

118 76.1

69 75.0

1 1.1

22 23.9

20 32.3

1 1.6

41 66.1

34 21.9

6 3.9

115 74.0

NOTE. Two cases with schizophrenia and two with other

psychoses were deleted because of missing responses to some prodromal symptom items.

Classification of Cases From Prodromal Symptoms Given the number of prodromal items, the small number of cases in both the depressive and psychotic disorder NOS diagnostic groups, and especially in the delusional group, preclude any meaningful attempt to classify patients over the seven diagnostic groups on the basis of responses to prodromal symptoms. The number of diagnostic entities was therefore reduced to three groups, schizophrenia, schizophreniform, and other psychoses (i.e., delusional, schizoaffective, bipolar, depressed, and psychotic disorder NOS), for this analysis (Table 6). A multinomial logit model el was used to examine the classificatory power of prodromal symptoms rather than a discriminant function analysis, because the required assumptions of normality underlying the latter may not be robust for dichotomously scored items such as prodromal symptoms. To guard against a liberal classification rate, jackknifing was used. This involved fitting the model individually for each of the 313 patients, with one case being left out in turn and then classified from the parameter estimates obtained from the remaining 312

cases. Furthermore, because the multinomial logit model requires complete responses to all data, only the first eight prodromal symptoms were included in the analysis. Fitting the model to the 198 cases with complete data on all nine items showed little difference to the findings reported here. The results are listed in Table 6. The correct classification rate overall was 48%, but this was by no means uniform across the three groups. Less than half of the schizophrenia group were correctly classified, versus two thirds of the other-psychoses groups, whereas few cases of the schizophreniform group were predicted at all, with over two thirds being assigned incorrectly and enigmatically to the other-psychoses group rather than to schizophrenia. Only one symptom of the eight, social isolation or withdrawal, proved to be a significant predictor of group membership beyond the .05 level. Adding the presence or absence of a strict DSM-III-R prodrome to the multinomial logit model for the eight items resulted in a significant improvement in correct classification to 60%, with three fourths of schizophrenia cases

248

JACKSON, McGORRY, AND DUDGEON

now being accurately predicted but schizophreniform patients still being poorly classified. Once this variable was added to the multinomial logit model, all individual prodromal symptoms, including social isolation or withdrawal, ceased to be significant, leaving only the presence of a DSM-III-R prodrome as a significant predictor of group membership. DISCUSSION

To the best of our knowledge, this is the largest cohort of prospectively assessed firstepisode psychotic patients. Each patient has been carefully and rigorously diagnosed by the RPMIP, with particular focus on the definition of the prodromal phase. This study is also the first to focus exclusively on prodromal symptoms in this group of patients and to determine specifically both the differential frequency of schizophrenic prodromal symptoms across various psychotic groupings and the diagnostic efficiency of individual prodromal symptoms. When individual prodromal symptoms, which include examples of both negative and positive phenomena, 22,23 are examined, the schizophrenia group was more likely to have a significantly higher proportion of prodromal symptoms than the other diagnostic groups. However, these symptoms were by no means exclusive to schizophrenia; rather, there was a higher valence for schizophrenia. Understandably, some negative prodromal symptoms were not uncommon in the (psychotic) depressed group (marked impairment in role functioning and personal hygiene). This suggests that negative symptoms are relatively nonspecific and can simulate other forms of psychosis such as psychotic depression. 24-27 The ability to predict cases of schizophrenia from prodromal symptoms alone in the multinomial logit model was virtually no better than chance. In addition, few cases were correctly assigned to the schizophreniform group, but were allocated instead either to schizophrenia or more likely to the other psychotic diagnoses group. These symptoms therefore do not appear to be useful in discriminating schizophreniform from schizophrenia, nor are they successful in discriminating schizophreniform from other psychotic disorders. However, inclusion of patients having a strict DSM-III-R prodrome in

the model doubled the correct classification of schizophrenic patients. Although diagnostic efficiency indices are highest for schizophrenia, in general individual symptoms only predict approximately half the cases of schizophrenia and one fourth of the cases of schizophreniform disorder. (We used the same indices for the other five psychotic diagnostic categories and found them to be uniformly worse than for schizophreniform disorder.) The presence of any two prodromal symptoms did not produce improved diagnostic efficiency for schizophrenia or schizophreniform disorders. However, the DSM-III-Rdefined prodrome, which involves > two symptoms, functional deterioration, and exclusion of affective or substance use factors, differentiates the two disorders. Moreover, the 6-month duration criterion in combination with >_ two symptoms and excluding drug and affective features (both of which may mask or mimic prodromal schizophrenic symptoms) results in the best diagnostic efficiency indices for both schizophrenia and schizophreniform. Although this final level is in a sense tautological because it is implicit in the definition of schizophrenia and excludes a diagnosis of schizophreniform, it was included to show the extent to which the duration component of the criteria for schizophrenia can be met by prodromal characteristics alone, and also to demonstrate that a 6-month DSMIII-R prodrome is not sensitive solely to schizophrenia. Prodromal symptoms are specified in DSMIII-R for schizophrenia, but are not specified for other psychotic diagnoses. Therefore, although we determined that DSM-III-R schizophrenia prodromal symptoms are not specific to schizophrenia since they are found in other psychotic diagnostic categories, we do not know whether prodromal criteria may be different in type and kind for other psychotic disorders, although none are specified in DSM-III-R. Yet in the literature prodromal symptoms are reported as occurring in other psychotic disorders.24-27 On the basis of these results, the decision of the DSM-IV Planning Committee 12 to omit specific prodromal criteria for schizophrenia finds empirical support. The presence of prodromal symptoms adds to the likelihood of patients

PRODROMAL SYMPTOMS IN FIRST-EPISODE PSYCHOSIS

being given a diagnosis of schizophrenia, and the absence of affective symptoms and substance abuse plus the addition of a 6-month duration of prodromal symptoms further increases the diagnostic efficiency of the prodrome. Yet it is overly optimistic to expect a prodrome (even as defined earlier) to predict a diagnosis of schizophrenia (or any other psychotic diagnosis, for that matter) when florid psychotic symptoms are an essential defining characteristic of psychotic illness. 1.6,7,9 This analysis raises two important considerations for future research. First, if DSM-III-R prodromal symptoms are to be studied, then ultimately it is important to study patients prospectively, not retrospectively as we have. Moreover, it must be recognized that we have only studied a group of true positive patients in the sense that all patients were psychotic. A prospective study would allow patients with prodromal symptoms to be investigated, only a portion of whom may go on to develop schizo-

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phrenia in particular and psychotic illness in general, or to develop other psychopathological conditions (e.g., depression) or not to develop any psychological condition at all. Second, it is important to determine whether alternative conceptualizations of prodromal symptomatology (e.g., Chapman, 28 Birchwood et al, 29 and Herz and Melville 3°) might prove to possess better discriminant and predictive validity than the ones linked to DSM-III-R schizophrenia. Possible ways of proceeding might include undertaking a naturalistic, descriptive investigation free from preexisting conceptualizations of prodromal symptoms (e.g., Brier and Strauss31). ACKNOWLEDGMENT

We thank Cathy Mihalopoulos, Lisa Henry, Colleen McFarlane, Cathy Dossetor, Rita Bourke, Ann Linsten, and Peter Henderson for assistance in data collection, Andrew Mackinnon for a number of useful suggestions to improve an earlier draft of the report, and Kay Flynn for efficient preparation of the manuscript.

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