Childhood and Adolescent Schizophrenic, Bipolar, and Schizoaffective Disorders: A Clinical and Outcome Study JOHN SCOTT WERRY, M .D. , JO N M. Mc CLELLAt"i , M .D. ,
AND
LL"IDA CHARD, M.Sc.
Abstract. Fifty-n ine child and adolescent psychotic patients (mean onset age 13.9, range 7-17 , 83% 13 + years) had. history and outcome studied using diagnoses .confirmed.at follow-up afrer I to 16 years (mean, 5 years). There were no differences in sex ratio, socioeconomic status, age of onset , and symptoms, but bipolar patients (N = 23) were often misdiagnosed as schizophreni c, had a better outcome, and a 50% homo typic family history. Schizophrenic subjects (N = 30) were more abnormal premorbidly, and only 17% were well at follow-up. Schizoaffective disorder was unreliable. infrequent. and more severe. Prernorbid adjustment and IQ were the best predictors of outcome. Differences from the adult disorders were only quantitative. Careful follow-up of psychotic patients is needed to detect diagnostic errors. 1 . Am. Acad. Child Adolesc, Psychiatry, 1991,30,3:457-465 . Key Words: psychosis, schizophrenia, mood disorder, mania, depression with psychosis.
Schizophrenia Clinical Features Schizophrenia (SZ) was reponed to occur in children by Kraepelin (Eisenberg, 1957) . Child schizophrenia is often known as "prepubertal," although it is defined by age (12 or under), not physical development. Similarl y , the term • " adolescent" schizophrenia bas no clear definition . For reasons of clarity then , the term early onset (EO), embracing both childhood and adolescence , will be used here to mean beginning before age 18; very early onset (YEO), before 13; and adolescent, 13 through 17. Studies of EO sch izophrenia that meet DSM-III criteri a for SZ or their equivalent are infrequent (Beitchman , 1985; Kolvin and Berney, 1990; Werry, in press). This infrequency may be caused by low incidence before early adulthood and because, from 1960 to 1980, the term "childhood schizophrenia" was used in official taxonomies to include all psychoses of infancy and childhood, making interpretation of some studies difficult (Beitchman, 1985; Kydd and Werry, 1982). In theface of accumulating evidence well summarized by Beitchman (1985) , DSM-III abolished childhood schizophrenia as a category separate from the adult disorder and again made the distinction from autism and other psychotic disorders clear. Recent reviews (Asamow et al., in press; Beitchman, 1985; Kolvin and Berney , 1990; Werry, in press) affirm the Accepted November 15, 1990. Dr. Werry is Professor of Psych iatry at the University ofAuckland . Dr. McClellan is with the Department of Psychiatry , University of Washington, Seattle. Mrs. Chard is at the Child and Famil y Unit, Auckland Children's Hospital. Dr. Werry's research was supported by the Medical Research Coun cil of New Zealand and Dr . McClellan's research was supp orted by the American Academy of Child and Adolescent Psychiatry. The assistance of Drs. M . Aimer . G. Finucane, M. Gudex, H. Clarkson , M . Taikato, R. Wvness in the collection of data and of Sarah Turbott in data analysis is gratefully acknowledged. Reprint requests to Prof. 1 .S . Werry , School ofMedicine . University of Auckland . P.B., Auckland, New Zealand. 0890-8567/91/3003-0457S03 .00/0 © 1991by the American Academy of Child and Adolescent Psychiatry . J .Am .Acad. Child Adolesc. Psychiatry, 30:3, May 1991
DSM-III position that EO (child and adolescent) schizophrenia is a variant, differing only quantitatively from the adult disorder in probably having the following: (1) male predominance, (2) higher rate of insidious onset, (3) more neurodevelopmental abnormalities, (4) more maladaptively " odd" premorbid personalities , (5) greater resistance to antipsychotic drug treatment, (6) poorer outcome, (7) less differentiated symptomatology , such as well-formed delusions , and (8) increased family history of SZ. These features are said to be particularly characteristic of YEO (prepubertal) schizophrenia. However, most, except male predominance, require confirmation. Outcome This is an area fraught with methodological problems discussed in detail by Westermeyer and Harrow (1988 ). Prospective studies that are the ideal are difficult to execute because of the long-term investment of time required. There are also difficulties of. varying diagnostic criteria (Andreasen, 1987), of the reliability of initial diagnosis, and of defining outcome criteria. Westermeyer and Harrow (1988) thought that outcome criteria should be multiple to include level of symptoms, occupation, and so on , not just vague terms like "improved." In fact, DSM-III-R's general adaptive function scale (GAF) is such a multifaceted measure. Using these multiple criteria, Westermeyer and Harrow (1988) concluded that only about 25% of patients with SZ will make a complete recovery-the rest will have varying degrees of persisting or in termitte n t symptoms and/or show
major deficits in interpersonal and occupational function. There are few studies of long-term outcome in EO schizophrenia (Kydd and Werry , 1982) and while the convention is that the prognosis is worse than in adults, this remains firmly to be established. In fact, in the largest study of any , that by Eggers (1978) , 20'70 of cases showed complete recovery, which is close to the adult 25%. The other major follow-up study (Kydd and Werry, 1982) which had a rather better prognosis (40%) , is now invalid because, at longer term follow-up described here, a number of their cases proved to have bipolar mood (affective) disorder (BPAD). 457
"VERRY ET AL.
The variables that predict outcome are drawn mostly from adult schizophrenia (Kaplan and Sadock, 1988, p. 262) but are partially supported in EO studies. The se variables (adverse) are the following : early or insidious onset, poor premorbid function, disorganized or undifferentiated subtype, negati ve symptoms , no precipita ting events , family history of SZ, neurological symptoms/history , and nonfluctuating course. Paranoid delusions, affective symptoms, and family history of mood disorder auger a better outcome. As Kydd and Werry (1982) point out, many of the adverse indicators are'said-to cluster together-in EO schizophrenia and on those grounds alone, a worse prognosis would be expected.
Bipolar Mood (Affective) Disorder C finical Features
As with SZ there were similar efforts in the 1970s to define distinctive childhood mood disorders (Kazdin , 1990; Pataki and Carlson, 1990; Strober et aI., 1989); but again on the basis of accumulating data, mood disorders were made the same in DSM-IlI for children, adolescents , and adults (Carlson. J 990; Kazdin, 1990; Pataki and Carlson, 1990; Strober et al., 1989). Nevertheless, suspicion that this assumption may not always be correct lingers (e.g., atypical manic attacks, antidepressant resistance-see Carlson, 1990; Conners, 1990). By definition, BPAD requires at least one manic attack, though two-thirds of adults present first with depression . Most (80--90%) will experience both manic and depressive episodes (Kaplan and Sadock, 1988 , p. 296). BPAD in children and adol escents was once thought rare, but retrospective studies have shown that one-third of adults with BPAD have their first episode before age 20 (Carlson, 1990; Carlson et al., 1977; Strober et al., 1989). There is also now a small but convincing cross-sectional literature to show that BPAD does exist in EO form (Carlson 1990; Strober et al., 1988, 1989). However, this form has been studied much less frequently than EO unipolar depression and dys thymic disorder (Carlson, 1990; Pataki and Carlson, 1990), and its true prevalence is unknown (Strober et al., 1989). This may be because, like SZ, it is probably quite infrequent especially before adolescence, though atypical forms of mania may be preventing some early detection (Carlson, 1990) . ' .: As a result, there is less data than for SZ on how EO BPAD resembles or differs from the adult disorder. In areas such as prognosis (see below) and drug response, it may be more serious, although this is disputed (Carlson, 1990; Strober et al., 1989). In one of the few formal studies, Carlson et al. (1977) found no difference in outcome although most of the "early onset" group were late adolescent/early adults , which may have muted any differences . In symptomatology , there may be a slightly higher frequency of first presentations with mania rather than depression (Carlson and Strober, 1978; Hassanyeh and Davison, 1980) and greater frequency of florid , bizarre psychosis (Bashir et al., 1987; Carlson, 1990 ; Rosen et al., 1983 ; Strober et al., 1989), making the differential diasnosis more di~ficult. The frequency of;; positive family his~ory may be raised (Strober et al ., 1988 , 1989). When the EO mood
458
disorder presents with florid psychotic depression , a family history of BPAD, and/or pharmacologically-induced hypomania, BPAD is almost inevitable (Strober and Carlson, 1982). Carlson (1990) argues that a characteristic of BPAD is a tendency to be first misdiagnosed as SZ and that this may be wor se in earl y onset cases . Some error is cau sed by the similarity in symptomatology-c-even in adults, there are real problems in distinguishing psychotic mood and schizophrenic symptoms, including mood-congruent delusions (Kendall, 1985). As Levitt and Tsuang (1988) point out, Kraepelin emphasized that the differentiation between SZ and manic depressive disorder. could only be made reliably on the basis of course. Thus, the clinician who is forced to make a diagnosis during the first episode runs a real risk of misdiagnosis. While lack of access to longitudinal data may explain the error in some cases, it cannot explain wh y it seems to wo rk only in one direction-that is to misdiagnose BPAD as -SZ and not vice versa. Carlson (1990) thinks there is a false belief that SZ is much commoner than mania in adolescence, Not only would this explain the favoring of SZ in genuinely difficult cases, but it might cause an avoidable misdiagnosis through biased diagnostic set. Mood symptoms, such as euphoria, depression, or irritability, can be minimized or overlooked , as the study by Carlson and Strober (1978) shows.
Outcome
In adults, 93% of patients have more than one episode (mean around nine) with intervals decreasing to stabilize at around 1 year after having about five episodes (Kaplan and Sadock, 1988 , p. 296). As noted, in less than 20% will these episodes be manic only. At long-term follow-up, 60 % of patients are well, mostly despite multiple episodes , while 20 to 40% have varying levels of chronic disability (Kaplan and Sadock, 1988; Strober et al. , 1989). The prognosis is thus considerably better than in SZ, although howmuch of this is due to the impact of a specific and highly effective prophylactic is unclear (Strober et al., 1989). In EO disorder, poor outcome and lithium resistance may be predicted by the same variable-long-standing poor premorbid adjustment (Strober et al., 1988). , " ' .. . _ .__ In their review, Pataki and Carlson (1990) claim that the outcome in EO BPAD is similar to that in adults; but they cite only two studies, and one is actually contradictory, suggesting a much poorer prognosis, especially in YEO cases. There are other reports by Carlson and Strober (1979) and Bashir et al., (1987), but although both suggest a good
outcome in over half, the reports are informal, and details such as length of follow-up are not stated . The issue mu st. therefore, be left in abeyance (Strober et al. , 1989) . Schizoaffective Disorder In some cases , it is impossible to make a firm distinction between SZ and psychotic mood disorder because features of both are present especially during different episodes. Then , the diagnosis of schizoaffective disorder may be made. Typical mo od disorder criteria must be present and so rnus ' l.Am.A cad. Child Adolesc . Psychiatry, 30:3, May 199J
SCHIZOPHRE:-.lJC AND BIPOLAR DISORDERS
schizophrenic criteria without mood disturbance for at least 2 weeks . This diagnosis is controversial and probably heterogen ous (Andreasen, 1987; Lev itt and Tsuang , 1988). Although it may be a distinct disorder, family history and outcome studies suggest some cases are variants of SZ and, where the disorder is marked by clear manic- type episode s (bipolar type) , of mood diso rder. Put another wa y, schizoaffective disorders seem to be the point at which the difficult separation of SZ and mood disorder becomes impo ssible . Outcome in Schizophrenia and Mood Disorder Because of the lack of firm conclusions about most aspects of EO schizophrenia and BPAD, careful studies of each are required. This is especially so of compara tive studies that may assist in reducing misdiagnosis of BPAD. Such studies from the same center and at the same point in time will be more truly comparable since they will share more of the same inevitable methodological problems , such as sampling bias . There are very few such studies, and they address only selected issues, such as- family history (Strober et al., 1988). The present study reports a comparative stud y of SZ , bipolar, and schizoaffective disorder that also includes data relating ~?_ 10ng-teI1Il o~tcome. Method
and bizarre-at least, in its active ph ases-it is likely that most cases would be referred to this unit, although referral of bipolar disorder, wh ich may not be psychotic: would be less complete. Case Finding The case reco rds of all patients who had a diagnosis of schizophrenic, schizophreniform, schizoaffective, BPAD, or any psychosis (except organic or pervasive developmental disorder) were-examined . It is unlikely any subjects were missed since a similar major review had been performed in 1980 (Kydd and Werry, 1982) , and since then, too , the log of the unit and the hospital computer admission and discharge register both carried the discharge diagnosis. All case records were then carefully reviewed and the index (first admission) diagnosis matched to DSM-III-R criteria. 'A ny cases not meeting one o f the thre e criterion diagnoses were then discarded with the exception of those with psychotic depression (N = 3), because psychotic depression was known commonly to presage BPAD (Pataki and Carlson, 1"990). As many subjects as possible were contacted and permission sought to interview the patient and/or family , and/or review medical records , and/or contact current mental health professionals. Few refused , but some declined direct contact on the grounds that they did not want to be reminded of their illness. Almost all did agree to the access of other sources of information. Diagnostic Methods
;;~; . ,
Representatives of the Sample .. .
The Child and Family Unit is the only child and adolescent psychiatric inpatient unit in the region (population , 1 million) . The base rate of SZ and bipolar mood disorder under 18 years of age is unknown . Inqu iries suggest that most psychotic children and nonemancipated adolescents brought to any psychiatric service in the region in the last 10 years (during which time 80% of subjects were seen) would be referred to the unit. This is because it is generally believed locally that such a serious illness requires a thorough psychiatric and pediatric asse ssment best done as an inpatient procedure. Since SZ is nearly always psychotic l,Am.Acad. Child Adolesc, Psychiatry. 30 :3. May 1991
1. Sources of info rmation. As many sources as possible were used-subject, parent, medical records, professionals, reports to the coroner, etc. ,-and as many time points. Conflict between sources proved surprisingly infrequent, and data were usually confirmatory or complementary. When differences remained, preference was given to data that seemed more reliable. In eight cases (four dead) , there were no current data , so that information available at the patient's last contact with the unit or any of its staff was used. Only two cases had to be discarded because of insufficient data. 2. Diagnostic criteria. DSM-/ll-R criteria were used with the exception of chang es in adaptive functioning because one of the main objectives was to compare long-term outcome among the three diagnoses . Although this may violate Kraeplin's dictum of the necessity of taking course into consideration, to admit other than key symptoms and past psychiatric episodes would have had the danger of contaminating diagnosis by outcome, for example, diagnosing recovered patients as BPAD in unclear cases. biasing the . . . . '. . . outcome in SZ. · - 3. Diagnostic techniques. The Structured Clinical Interview (SCID) for DSl.. / -III-R (Spitzer et al., 1988) was administered (in a few interviews indirectly using parents) . The Schedules of Negative (SANS) and Positive (SAPS) Symptoms (Andreason. 1983) and the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham, 1962) were also used to assist in the eliciting and defining of symptomatology .
4. Diagnosticians. In 68% of subjects, two diagnosers could be used . One would conduct the examination with
459
WERRY ET AL. T ABLE
1. Estab lishment of Criterion (Follow-up; Dia gnosis
Item Criteria Primary method Interview
Parent/Relative Chart/physician Number of sources Two plus Confidence in diagnosis Good Last seen (l989-X) Mean yrsISD Follow-up interval Mean yrsfSD
Schizophrenia (N = 30)
Mood Disorder (N = 23)
DSM-IIl-R
DSM-lIJ-R
T ABLE
Schizophrenia (N = 30)
P Item
40% 13% 47%
70% 0% 26%
0.10
83%
74 %
NS
83%
87%
NS
1.8/2 .82
1.111.82
NS
4 .3/3.24
6.214.5
NS
the second asking only clarifying questions and recording item ratings independently. Because time and resources were Iimited; consensus diagnosis arrived at after the interview seemed most appropriate . Robustness of Diagnosis A reliability study (Werry et al., 1983) had shown in the past that the unit was achieving a satisfactory interdiagnoser reliability for most DSM-1II disorders. lnterdiagnoser reliability on the SOD was found to be satisfactory in pretrials in psychotic subjects not in the study . Except in a minority (32%) of cases, most not living locally or consenting to be reviewed only by their current psychiatrist , two diagnosers were used. Diagnosers were kept blind to the initial diagnosis as much as possible. However, even when the subject was known to one diagnoser, the other diagnoser was blind, and an element of uncertainty prevailed since it was known from the literature and some ' previous cases that the index diagnosis could be wrong. Diagnosers were asked to estimate their confidence in the diagnosis taking account of the amount and quality of data available. As seen in Table 1, the diagnosis was regarded as robust in over 80% of cases. First, and Index Episode Measures ' These had to be extracted from the chart, which thus limited the scope and accuracy of some data. The general standard of records was high, and, since patients were inpatients for some weeks, there was a wealth of descriptive material, including detailed nursing notes . After comparing several extractions and clarifying issues, 10 completed charts were pulled at random and independently checked by a senior psychiatric resident. She found only a few trivial errors, if discrepancies of one point on quantitative scales are allowed. Most patients were admitted during their first episode, but in 20% (N = 13), there was a clear history of a previous episode that was described in the notes or amplified at follow-up . In these cases, except where it would be clearly inaccurate (such as detailed symptomatology, length of psychosis), first episode data were used in preference to admission (index) episode data. 46()
2. Ba ckground and Family Variab les
Sex Male Socioeconomic status Upper /middle Skilled Lower Ethnic Maori White Other Family Intact Broken before 5 years Broken after 5 years Family history (primary and grand parents) Neither Schizophrenia Mood Either (? ) Adopted
%
Mood Disorder (N = 23) %
p
50
61
NS
43 37 20
34 52 13
NS
7 67 . 27
30 57 13
0 .06
57 23 20
61 22 17
NS
66 0 17
43 0 52 5
3
9
n
0.03 NS
J. Background and family variables (Table 2). Most of these are self-explanatory. Family intactness refers to the biological or first parents. Family history of psychiatric illness was felt to be too inaccurate and too incomplete for any except first-degree relatives and grandparents. In some cases, it was known only that a major psychotic illness had occurred. This item was sometimes clarifiable at follow-up. 2. Premorbid variables (Table 3). These included personality, neurological, intellectual, and adaptive function. Estimates of premorbid personality abnormality were made globally on a four-point scale of severity, using DSM-IIJ-R major divisions of personality disorder (odd, anxious, disruptive). Finer grained categorizations were felt to lack accllracy. Neurological status was rated abnormal only for major disorders, such as epilepsy or cerebral palsy. IQ was dichotomized at 80 since this marks the borderline of mental retardation, and, mostly, only children with a history of school failure had been tested . Those without such a history were presumed to have an IQ greater than 79. The premorbid DSM-JIl-R GAF was the highest level of function achieved in the last 12 months or, if the illness had started before that, the highest level of premorbid function ever achieved, using such data as school reports to confirm parent and chart reports. 3. Clinical features offirst or index episode (Table 4) . Again, most of these are self-explanatory. Prodrome was defined as the first appearance of deteriorating function without any psychotic symptoms or, if onset was insidious. rated as grea ter than 1 year. In a few cases of SZ , it was not easy to separate prodrome from onset of the psychosis. although in the majority, the latter had two conspicuous hallmarks: appearance of psychotic symptoms and a severe l .Am.Acad. Child Ado/esc. Psychiatry. 30:3, May 199/
SCHIZOPHRE.'.
;",
Schizophrenia (N = 30)
Item
Moderate/severe With psychosis In remission 0.05 0.05] NS]
6. Outcome--Diagnostic Data
indicator. Adaptive function (OAF) before illness was inferior in SZ, on average in the moderately impaired range, although a subgroup had been quite normal. " , .. 3. Background and family factors . There were rio differences in sex 'ratio (equaljv age of onset, age when seen, socioeconomic status, or fami ly breakup. Homotypic disorder was much more frequent (over 50%) in BP AD than in SZ in first-degree relatives and grandparents, although a positive fami ly history for possible SZ or mood disorder was higher in SZ than in comparable studies (Strober et al., 1988). ", . .
4. Clinical features, of index episode . Symptomatology was similar in SZ and BPAD, although there were signs that a larger sam ple might have revealed more delusions, fewer hallucinations, and less flattened affect in the BPAD group . These finding's of similar symptoms consistent with the well-known difficulty of distinguishing schizophrenic and mood symptoms (Kendler, 1985). SZ subjects took longer to lose psychotic symptoms, and return to school, and few recovered completely from the index episode. 5 . Outcome. Th e follow- up interval was longer in the BPAD group because more SZ subjects became lost to follow- up. SZ subjects were also more reluctant to be interviewed personally. SZ subjects showed greater illness (in additional episodes or chronicity), depen dency , occupational inactivity and/or death ; and lower OAF levels. However, assuming linearity in the OAF scale (which is questionable), the degree of deterioration in OAF scores was
are
l.Am .Acad. Child Adolesc. Psychiatry, 30:3. May 1991
SCHIZOPHRENIC AND BIPOLAR DISORDERS
not significantly different in the two groups--SZ subjects were worse at outcome because they had been worse before the psychosis ever developed. At the time of follow-up, nearly all subjects were on diagnosis-appropriate medication, although 17% of BPAD patients were receiving antipsychotic rather than antimanic medication. One-third of patients were judged as receiving inadequate care during their careers, mostly as a result of poor compliance rather than the fault of their clinicians.
Schizo affective Group With only six members, less confidence in the diagnosis (only half "good"), and the uneasy status of this disorder, comments about this group must be read with great caution. The group seemed more floridly psychotic during the index episode and, on some short and long-term outcome measure, were sicker and more disabled. In consideration that most were bipolar type, it is perhaps not too surprising that their families showed increases of both SZ and mood disorders.
Gender and Age Effects Factorial ANOYA failed to reveal any gender effects on diagnosis, duration of index episode, or age of onset either within or across diagnostic groups. No age effects on outcome were observed, although analyzable YEO ("prepubertal") cases were few (N = 10), and those with subjects uml.er age 12 were very few (N = 3).
Prediction of Outcome A multiple regression analysis was performed using the ANOYA technique (Matthews and Farewell, 1988, pp. 134140), with outcome GAF, and global measures of occupation and peer function as criterion variables. These results will be reported elsewhere, but, in general, the best predictors of outcome were premorbid adjustment (SZ, BPAD) and IQ (for BPAD), accounting for 20 to 50% of the variance. The more clinical measures, such as diagnosis, positive and negative symptoms, and family history, were significant but contributed little (less than 5-8%) to the variance.
either disorder, particularly in adolescence and of long-term outcome. Such studies, especially longitudinal ones, are difficult to execute and allowances have to be made, given current limited knowledge. In general, the findings here have few surprises and are consistent with what is known about SZ and BPAD in general and in childhood and adolescence in particular. This suggests that in spite of the methodological shortcomings, the results have face validity. However, residual errors in diagnosis remain a possibility. In 20% of cases .there was some element of doubt, while in a few, follow-up was less than 2 years. Additional followup is in progress and, if history and Kraepelin are any guide, will reveal further misdiagnosis. But, studies that report only cross-sectional data may also have diagnostic error--except it will not be discernable.
Premorbid Features . The findings ofahigh--frequerrcyor-abnomml, odd, or schizotypal personalities and signs of brain and cognitive dysfunction in SZ areconsistent with better studies by others (Kelvin and Berney, 1990; Werry, in press), especially the ones at the University of California, Los Angeles (Asamow et al., in press). The consonance of findings suggests both that the crude measures used here are still valid and that these premorbid factors are highly influential in some way to be detectable by even crude measures. Whether these abnormalities are vulnerabilities or, in a significant number of cases, the beginning of the disease process with psychosis only a later manifestation, is a matter of current debate (Asarnow et al., in press, Kolvin and Berney, 1990) and not answerable here. Family Factors
The high frequency of mood disorder in families of EO BPAD is consistent with the genetic hypothesis of BPAD and with other studies (Carlson, 1990; Strober etal., 1988) so is the probable increased frequency of homotypic disorder in EO schizophrenia (Strober et al., 1988; Werry, in press) although the size of the increase and frequency of heterotypic (mood) disorder is not. These differences may be a Discussion result of the smaller sample and to the less exact methods Methodology of obtaining a family history in the present study, which This study has a number of defects that require comment. made distinguishing SZ and BPAD in the families of SZ First, all initial and some follow-up data were retrospective .- cases difficult. i and thus limited in scope and accuracy. Second, there were Diagnosis signs that a larger sample might have shown differences in symptomatology (e.g., fewer hallucinations and more deThe most significant finding of this study is that over half lusions) and number of previous (and missed) episodes in the bipolar subjects were misdiagnosed as schizophrenic BPAD. Third, measures and methods are not asprecise as when first seen. It is not suggested that others would necin some recent U.S. studies (Asarnow et al., in press; Carlessarily have as high an error rate (although Strober and son, 1990; Werry, in press) in the areas of family history Carlson [1979] and Bashir et al. [1987] report similar figof disorder, premorbid personality, cognitive dysfunction, ures); but the problem is universal in some degree (Carlson, and/or index symptomatology. Fourth, unlike U.S. studies 1990). In addition, at long-term follow-up, there were six (Beitchman 1985; Werry, in press), especially of SZ, the cases (schizoaffective disorder) where the two disorders were majority of subjects (83%) were teen aged (adolescent). still not able to be discriminated. Fortunately, for patients and for this study, the misclasFifth, there must be local peculiarities in detection; since sification error has now been minimized but does emphasize all of the subjects in this study were inpatients, there was the need for careful follow-up of childhood and adolescent some bias toward the more severely affected. There are few psychoses especially in the first few years . comparative studies of SZ and BPAD, and not enough of l.Am.Acad. Child /vlolesc.PsychiaIry,30:3 .May 1991
463
"''ERRY ET AL.
There were many confusing similarities in the two disorders early on, primarily caused by floridly psychotic states in both; but there were also factors that could assist in differential diagnosis. Symptoms suggestive of schizophrenia include the following: an odd personality, poor premorbid adaptive function, a history or evidence of major brain dysfunction, a family history of SZ, insidious onset, psychosis lasting over 3 months, incomplete recovery, and poor outcome. A strong family history of mood disorder argues against SZ, but at a rather low level of specificity here... The best way of not misdiagnosing BPADas SZ is first to be vigilant to the problem, second to search carefully for a depressed or manic mood, and third to assess any delusions for congruence and temporal concurrence with mood symptoms (Carlson, 1990). More use of symptom checklists, such as the SAPS, SANS (Andreasen, 1983) or the BPRS (Overall and Gorham, 1962), and structured interviews might reduce misdiagnosis. However, none of these is absohrte (Kendall, l-985),arrd a change irrdiagnostic set brings its own risk of misdiagnosing SZ as BPAD. Thus, it is not only children and adolescents with SZ who should be followed carefully, but also those with BPAD. Outcome 1. Schizophrenia. The picture of child and adolescent (EO) SZ revealed here is disturbing. It is that of a chronic or relapsing.disorder.accompanied by considerable disability and significant deterioration in adaptive furrctionfrom often already impaired premorbid levels-all more like Kraepelin's dementia praecox than some modem, more benevolent views of SZ (Westermeyer and Harrow, 1988). Only 17% of patients had GAF scores of 60 (i.e., other than serious symptoms or disabilities), were fully employed, or attending school full time. Four patients (three males and one female) were dead, reflecting the 15%. mortality in SZ from suicide that mostly occurs within the first 10 years of the illness (Cohen et al., 1990). It was impossible to be sure how many here had committed suicide and how many suffered delusion-driven accidents, but all had actively put themselves . in the lethal situation. How much of this poor outcome is an artifact of the DSMIII criterion of a 6-month history is unclear (Andreasen, 1987), although no cases diagnosed initially as schizophreniform had to be discarded because they failed this criterion at follow-up. Unfortunately, this study cannot provide much data on treatment response of EO schizophrenia other than that, although 90% of the subjects were receiving appropriate medication at follow-up, disability was common and extensive. 2. Bipolar disorder. On the other hand, those with BPAD began from a strong position and held this throughout their patient careers. Not only did they show less disability, they had fewer episodes, and 83% were in remission at followup. A quarter were entirely symptom free and half in full time in employment or schooling. How much of this better outcome is inherent in the disorder and how much a result of the lithium being taken by two-thirds is debatable. Neverthcless, ~PAD is not entirely benign. Half still had significant active symptoms or impaired function, and, even more
464
important, as a whole, the group had shown the same degree of deterioration with respect to premorbid levels (about 10 points on the GAF)-they looked better because they had started better. If schizophrenic subjects are worse premorbidly because the disorder is often lifelong, then BPAD is definitely less malignant. However, both disorders are serious and potentially disabling. 3. Predictors of outcome. This is a complex topic and analysis will be the subject of a separate report. Premorbid adjustment variables and, for BPAD IQ, were the best predictors oLoutcom.e..and clinical.measures like diagnosis, and symptoms, although significant, were so small in effect as to lack utility in the clinical situation. This may seem only partially to support what is known about SZ, but the "predictors" in the literature seem to be anecdotal or correlationalwith size of any effect unstated.
Adult and Child/Adolescent Disorders Compared This study supports others that suggest that in both 5Z and BPAD, the EO and adult forms are qualitatively similar (Beitchman, 1985; Carlson, 1990, Pataki and Carlson, 1990; Werry, in press). Symptomatology must be similar because the disorders are defmed similarly for both adults and children in DSM-m-R. Outside this, nothing has been found that has not already been described in the adult disorders. Although it is commonly believed that outcome is worse in early onset than in adult onset disorders, the figures here .are.only slightly worse than those in some studies of adults (Westermeyer and Harrow, 1988). Sample size, variations in methodology, and the small number (N = 10) of subjects beginning before 13 do not permit finn conclusions. There is more support for the hypothesis that when these disorders begin early, they may have greater family loadings and be more difficult to discriminate from each other. This study confirms that EO schizophrenia is often insidious and associatedwith odd, abnormal premorbid personalities and with neurodevelopmental abnormalities. How this differs, if at all, from adults is unclear since, as with predictors of outcome, exact figures are not stated in DSM-III-R or standard texts (Kaplan and Sadock, 1988).
Conclusions There is a need for continuing studies in EO schizophrenia and BPAD, especially prospective and comparative ones,
which can remedy the defects in this study. Because these disorders are infrequent, consideration should be given to : collaborative studies. .: Perhaps the most important findings of this study are clinical---each and every child or adolescent with a diagnosis of 5Z should be followed for several years because of the possibility of misdiagnosis of BPAD. Misdiagnosis is not an idle matter since it leads to the unnecessary use of neuroleptic drugs with attendant risks; precludes highly effecrive prophylatic antimanic treatment, thus causing unnecessary suffering and disability; gives the wrong set of prognostic indicators; and could lead to underestimating risks in genetic counseling. Diagnostic fashions however, tend to run in cycles, and if, as seems likely, the set toward diagnosing SZ moves toward bipolar or psychotic mood l.Am.Acad. Child Ado/esc. Psychiatry, 30:3, May 1991
SCHIZOPHRE~:: C
disorder, the consequences will be equally undesirable; so that careful follow-up of bipolar patients is just as necessary. Last, since one-third of patients were getting inadequate care mostly because of poor compliance, active, helperdriven follow-up after failed appointments and lost contact is a necessary part of good clinical care in these two often chronic or recurrent disorders. Pharmacotherapy and psychosocial management can do much to reduce distress and disability and , therefore , poor compliance presentsthe clinician with a worthy challenge.
References Andreason, N. C. (1983). The Scales for Assessment ofNegat ive and Positive Symptoms. Iowa City. IA: University of Iowa . - - (1987). The diagnosis of schizophrenia. Schizophr, Bull .. 13:2538. Asarnow, R. F .• Asarnow, J . R. & Strandburg, R. (in press), Schizophrenia: a developmental perspective . In: Rochester Symposium on Developmental Psychology, ed. D. Chicchetti. New York : Cambridge University Press. Bashir, M. , Russell. J. & Johnson, G. (1987), Bipolar affective disorder in adolescence: a ten year study. Aust. NL J. Psychiatry. 21:3&-43 . . Beitchrnan, J. H. (1985), Childhood schizophrenia: a review and a comparison 'With adult-onset cases. Psychiatr. Clin. NonhAm .,8:793814 . . Carlson, G. A. (1990), Child and adolescent mania: diagnostic considerations. J. Child Psychol, Psychiatry, 31:331-342. - - Strober. M. (1978), Manic depressive illness in early adolescence: a study of clinical and diagnostic characteristics in six cases. J. Am . Acad. Child Psychiatry, 17:138-153. - - Strober. M . (1979). Affective disorder in adolescence. Psychiatr. Clin . North Am., 2:511-526. - - Davenport, Y. B. & Jamison, K. R. (1977), A comparison of outcome in adolescent and late onset bipolar manic depressive illness. Am. J . Psychiatry. 134:919-922 . Cohen, L. J., Test, M. A. & Brown. R. L. (1990), Suicide and schizophrenia: data from a prospective community treatment study . Am . J . Psy chiatry. 147:602-607. Conners , C. K. (1990. June), Methodology of antidepressant drug trials with adolescents . Paper presented to the NIMH Workshop on Tricyclic Drugs in Adolescence. Bethesda, MD. Eggers. C. (1978). Course and prognosis of childhood schizophrenia. J. Autism Child. Schizophr., 8:21-35. Eisenberg. L. (1957), The course of childhood schizophrenia. Arch. Psychiatry Neurol., 78:69-83. Hassanyeh, F. & Davison. K. (1980), Bipolar affective psychosis with onset before age 16: areport of 10 cases. Br . J. Psychiatry, 137:530539. '
J.Am.Acad. Child Adolesc, Psychiatry. 30:3. May 1991
A:-
AND
LL"IDA CHARD, M.Sc.
Abstract. Fifty-n ine child and adolescent psychotic patients (mean onset age 13.9, range 7-17 , 83% 13 + years) had. history and outcome studied using diagnoses .confirmed.at follow-up afrer I to 16 years (mean, 5 years). There were no differences in sex ratio, socioeconomic status, age of onset , and symptoms, but bipolar patients (N = 23) were often misdiagnosed as schizophreni c, had a better outcome, and a 50% homo typic family history. Schizophrenic subjects (N = 30) were more abnormal premorbidly, and only 17% were well at follow-up. Schizoaffective disorder was unreliable. infrequent. and more severe. Prernorbid adjustment and IQ were the best predictors of outcome. Differences from the adult disorders were only quantitative. Careful follow-up of psychotic patients is needed to detect diagnostic errors. 1 . Am. Acad. Child Adolesc, Psychiatry, 1991,30,3:457-465 . Key Words: psychosis, schizophrenia, mood disorder, mania, depression with psychosis.
Schizophrenia Clinical Features Schizophrenia (SZ) was reponed to occur in children by Kraepelin (Eisenberg, 1957) . Child schizophrenia is often known as "prepubertal," although it is defined by age (12 or under), not physical development. Similarl y , the term • " adolescent" schizophrenia bas no clear definition . For reasons of clarity then , the term early onset (EO), embracing both childhood and adolescence , will be used here to mean beginning before age 18; very early onset (YEO), before 13; and adolescent, 13 through 17. Studies of EO sch izophrenia that meet DSM-III criteri a for SZ or their equivalent are infrequent (Beitchman , 1985; Kolvin and Berney, 1990; Werry, in press). This infrequency may be caused by low incidence before early adulthood and because, from 1960 to 1980, the term "childhood schizophrenia" was used in official taxonomies to include all psychoses of infancy and childhood, making interpretation of some studies difficult (Beitchman, 1985; Kydd and Werry, 1982). In theface of accumulating evidence well summarized by Beitchman (1985) , DSM-III abolished childhood schizophrenia as a category separate from the adult disorder and again made the distinction from autism and other psychotic disorders clear. Recent reviews (Asamow et al., in press; Beitchman, 1985; Kolvin and Berney , 1990; Werry, in press) affirm the Accepted November 15, 1990. Dr. Werry is Professor of Psych iatry at the University ofAuckland . Dr. McClellan is with the Department of Psychiatry , University of Washington, Seattle. Mrs. Chard is at the Child and Famil y Unit, Auckland Children's Hospital. Dr. Werry's research was supported by the Medical Research Coun cil of New Zealand and Dr . McClellan's research was supp orted by the American Academy of Child and Adolescent Psychiatry. The assistance of Drs. M . Aimer . G. Finucane, M. Gudex, H. Clarkson , M . Taikato, R. Wvness in the collection of data and of Sarah Turbott in data analysis is gratefully acknowledged. Reprint requests to Prof. 1 .S . Werry , School ofMedicine . University of Auckland . P.B., Auckland, New Zealand. 0890-8567/91/3003-0457S03 .00/0 © 1991by the American Academy of Child and Adolescent Psychiatry . J .Am .Acad. Child Adolesc. Psychiatry, 30:3, May 1991
DSM-III position that EO (child and adolescent) schizophrenia is a variant, differing only quantitatively from the adult disorder in probably having the following: (1) male predominance, (2) higher rate of insidious onset, (3) more neurodevelopmental abnormalities, (4) more maladaptively " odd" premorbid personalities , (5) greater resistance to antipsychotic drug treatment, (6) poorer outcome, (7) less differentiated symptomatology , such as well-formed delusions , and (8) increased family history of SZ. These features are said to be particularly characteristic of YEO (prepubertal) schizophrenia. However, most, except male predominance, require confirmation. Outcome This is an area fraught with methodological problems discussed in detail by Westermeyer and Harrow (1988 ). Prospective studies that are the ideal are difficult to execute because of the long-term investment of time required. There are also difficulties of. varying diagnostic criteria (Andreasen, 1987), of the reliability of initial diagnosis, and of defining outcome criteria. Westermeyer and Harrow (1988) thought that outcome criteria should be multiple to include level of symptoms, occupation, and so on , not just vague terms like "improved." In fact, DSM-III-R's general adaptive function scale (GAF) is such a multifaceted measure. Using these multiple criteria, Westermeyer and Harrow (1988) concluded that only about 25% of patients with SZ will make a complete recovery-the rest will have varying degrees of persisting or in termitte n t symptoms and/or show
major deficits in interpersonal and occupational function. There are few studies of long-term outcome in EO schizophrenia (Kydd and Werry , 1982) and while the convention is that the prognosis is worse than in adults, this remains firmly to be established. In fact, in the largest study of any , that by Eggers (1978) , 20'70 of cases showed complete recovery, which is close to the adult 25%. The other major follow-up study (Kydd and Werry, 1982) which had a rather better prognosis (40%) , is now invalid because, at longer term follow-up described here, a number of their cases proved to have bipolar mood (affective) disorder (BPAD). 457
"VERRY ET AL.
The variables that predict outcome are drawn mostly from adult schizophrenia (Kaplan and Sadock, 1988, p. 262) but are partially supported in EO studies. The se variables (adverse) are the following : early or insidious onset, poor premorbid function, disorganized or undifferentiated subtype, negati ve symptoms , no precipita ting events , family history of SZ, neurological symptoms/history , and nonfluctuating course. Paranoid delusions, affective symptoms, and family history of mood disorder auger a better outcome. As Kydd and Werry (1982) point out, many of the adverse indicators are'said-to cluster together-in EO schizophrenia and on those grounds alone, a worse prognosis would be expected.
Bipolar Mood (Affective) Disorder C finical Features
As with SZ there were similar efforts in the 1970s to define distinctive childhood mood disorders (Kazdin , 1990; Pataki and Carlson, 1990; Strober et aI., 1989); but again on the basis of accumulating data, mood disorders were made the same in DSM-IlI for children, adolescents , and adults (Carlson. J 990; Kazdin, 1990; Pataki and Carlson, 1990; Strober et al., 1989). Nevertheless, suspicion that this assumption may not always be correct lingers (e.g., atypical manic attacks, antidepressant resistance-see Carlson, 1990; Conners, 1990). By definition, BPAD requires at least one manic attack, though two-thirds of adults present first with depression . Most (80--90%) will experience both manic and depressive episodes (Kaplan and Sadock, 1988 , p. 296). BPAD in children and adol escents was once thought rare, but retrospective studies have shown that one-third of adults with BPAD have their first episode before age 20 (Carlson, 1990; Carlson et al., 1977; Strober et al., 1989). There is also now a small but convincing cross-sectional literature to show that BPAD does exist in EO form (Carlson 1990; Strober et al., 1988, 1989). However, this form has been studied much less frequently than EO unipolar depression and dys thymic disorder (Carlson, 1990; Pataki and Carlson, 1990), and its true prevalence is unknown (Strober et al., 1989). This may be because, like SZ, it is probably quite infrequent especially before adolescence, though atypical forms of mania may be preventing some early detection (Carlson, 1990) . ' .: As a result, there is less data than for SZ on how EO BPAD resembles or differs from the adult disorder. In areas such as prognosis (see below) and drug response, it may be more serious, although this is disputed (Carlson, 1990; Strober et al., 1989). In one of the few formal studies, Carlson et al. (1977) found no difference in outcome although most of the "early onset" group were late adolescent/early adults , which may have muted any differences . In symptomatology , there may be a slightly higher frequency of first presentations with mania rather than depression (Carlson and Strober, 1978; Hassanyeh and Davison, 1980) and greater frequency of florid , bizarre psychosis (Bashir et al., 1987; Carlson, 1990 ; Rosen et al., 1983 ; Strober et al., 1989), making the differential diasnosis more di~ficult. The frequency of;; positive family his~ory may be raised (Strober et al ., 1988 , 1989). When the EO mood
458
disorder presents with florid psychotic depression , a family history of BPAD, and/or pharmacologically-induced hypomania, BPAD is almost inevitable (Strober and Carlson, 1982). Carlson (1990) argues that a characteristic of BPAD is a tendency to be first misdiagnosed as SZ and that this may be wor se in earl y onset cases . Some error is cau sed by the similarity in symptomatology-c-even in adults, there are real problems in distinguishing psychotic mood and schizophrenic symptoms, including mood-congruent delusions (Kendall, 1985). As Levitt and Tsuang (1988) point out, Kraepelin emphasized that the differentiation between SZ and manic depressive disorder. could only be made reliably on the basis of course. Thus, the clinician who is forced to make a diagnosis during the first episode runs a real risk of misdiagnosis. While lack of access to longitudinal data may explain the error in some cases, it cannot explain wh y it seems to wo rk only in one direction-that is to misdiagnose BPAD as -SZ and not vice versa. Carlson (1990) thinks there is a false belief that SZ is much commoner than mania in adolescence, Not only would this explain the favoring of SZ in genuinely difficult cases, but it might cause an avoidable misdiagnosis through biased diagnostic set. Mood symptoms, such as euphoria, depression, or irritability, can be minimized or overlooked , as the study by Carlson and Strober (1978) shows.
Outcome
In adults, 93% of patients have more than one episode (mean around nine) with intervals decreasing to stabilize at around 1 year after having about five episodes (Kaplan and Sadock, 1988 , p. 296). As noted, in less than 20% will these episodes be manic only. At long-term follow-up, 60 % of patients are well, mostly despite multiple episodes , while 20 to 40% have varying levels of chronic disability (Kaplan and Sadock, 1988; Strober et al. , 1989). The prognosis is thus considerably better than in SZ, although howmuch of this is due to the impact of a specific and highly effective prophylactic is unclear (Strober et al., 1989). In EO disorder, poor outcome and lithium resistance may be predicted by the same variable-long-standing poor premorbid adjustment (Strober et al., 1988). , " ' .. . _ .__ In their review, Pataki and Carlson (1990) claim that the outcome in EO BPAD is similar to that in adults; but they cite only two studies, and one is actually contradictory, suggesting a much poorer prognosis, especially in YEO cases. There are other reports by Carlson and Strober (1979) and Bashir et al., (1987), but although both suggest a good
outcome in over half, the reports are informal, and details such as length of follow-up are not stated . The issue mu st. therefore, be left in abeyance (Strober et al. , 1989) . Schizoaffective Disorder In some cases , it is impossible to make a firm distinction between SZ and psychotic mood disorder because features of both are present especially during different episodes. Then , the diagnosis of schizoaffective disorder may be made. Typical mo od disorder criteria must be present and so rnus ' l.Am.A cad. Child Adolesc . Psychiatry, 30:3, May 199J
SCHIZOPHRE:-.lJC AND BIPOLAR DISORDERS
schizophrenic criteria without mood disturbance for at least 2 weeks . This diagnosis is controversial and probably heterogen ous (Andreasen, 1987; Lev itt and Tsuang , 1988). Although it may be a distinct disorder, family history and outcome studies suggest some cases are variants of SZ and, where the disorder is marked by clear manic- type episode s (bipolar type) , of mood diso rder. Put another wa y, schizoaffective disorders seem to be the point at which the difficult separation of SZ and mood disorder becomes impo ssible . Outcome in Schizophrenia and Mood Disorder Because of the lack of firm conclusions about most aspects of EO schizophrenia and BPAD, careful studies of each are required. This is especially so of compara tive studies that may assist in reducing misdiagnosis of BPAD. Such studies from the same center and at the same point in time will be more truly comparable since they will share more of the same inevitable methodological problems , such as sampling bias . There are very few such studies, and they address only selected issues, such as- family history (Strober et al., 1988). The present study reports a comparative stud y of SZ , bipolar, and schizoaffective disorder that also includes data relating ~?_ 10ng-teI1Il o~tcome. Method
and bizarre-at least, in its active ph ases-it is likely that most cases would be referred to this unit, although referral of bipolar disorder, wh ich may not be psychotic: would be less complete. Case Finding The case reco rds of all patients who had a diagnosis of schizophrenic, schizophreniform, schizoaffective, BPAD, or any psychosis (except organic or pervasive developmental disorder) were-examined . It is unlikely any subjects were missed since a similar major review had been performed in 1980 (Kydd and Werry, 1982) , and since then, too , the log of the unit and the hospital computer admission and discharge register both carried the discharge diagnosis. All case records were then carefully reviewed and the index (first admission) diagnosis matched to DSM-III-R criteria. 'A ny cases not meeting one o f the thre e criterion diagnoses were then discarded with the exception of those with psychotic depression (N = 3), because psychotic depression was known commonly to presage BPAD (Pataki and Carlson, 1"990). As many subjects as possible were contacted and permission sought to interview the patient and/or family , and/or review medical records , and/or contact current mental health professionals. Few refused , but some declined direct contact on the grounds that they did not want to be reminded of their illness. Almost all did agree to the access of other sources of information. Diagnostic Methods
;;~; . ,
Representatives of the Sample .. .
The Child and Family Unit is the only child and adolescent psychiatric inpatient unit in the region (population , 1 million) . The base rate of SZ and bipolar mood disorder under 18 years of age is unknown . Inqu iries suggest that most psychotic children and nonemancipated adolescents brought to any psychiatric service in the region in the last 10 years (during which time 80% of subjects were seen) would be referred to the unit. This is because it is generally believed locally that such a serious illness requires a thorough psychiatric and pediatric asse ssment best done as an inpatient procedure. Since SZ is nearly always psychotic l,Am.Acad. Child Adolesc, Psychiatry. 30 :3. May 1991
1. Sources of info rmation. As many sources as possible were used-subject, parent, medical records, professionals, reports to the coroner, etc. ,-and as many time points. Conflict between sources proved surprisingly infrequent, and data were usually confirmatory or complementary. When differences remained, preference was given to data that seemed more reliable. In eight cases (four dead) , there were no current data , so that information available at the patient's last contact with the unit or any of its staff was used. Only two cases had to be discarded because of insufficient data. 2. Diagnostic criteria. DSM-/ll-R criteria were used with the exception of chang es in adaptive functioning because one of the main objectives was to compare long-term outcome among the three diagnoses . Although this may violate Kraeplin's dictum of the necessity of taking course into consideration, to admit other than key symptoms and past psychiatric episodes would have had the danger of contaminating diagnosis by outcome, for example, diagnosing recovered patients as BPAD in unclear cases. biasing the . . . . '. . . outcome in SZ. · - 3. Diagnostic techniques. The Structured Clinical Interview (SCID) for DSl.. / -III-R (Spitzer et al., 1988) was administered (in a few interviews indirectly using parents) . The Schedules of Negative (SANS) and Positive (SAPS) Symptoms (Andreason. 1983) and the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham, 1962) were also used to assist in the eliciting and defining of symptomatology .
4. Diagnosticians. In 68% of subjects, two diagnosers could be used . One would conduct the examination with
459
WERRY ET AL. T ABLE
1. Estab lishment of Criterion (Follow-up; Dia gnosis
Item Criteria Primary method Interview
Parent/Relative Chart/physician Number of sources Two plus Confidence in diagnosis Good Last seen (l989-X) Mean yrsISD Follow-up interval Mean yrsfSD
Schizophrenia (N = 30)
Mood Disorder (N = 23)
DSM-IIl-R
DSM-lIJ-R
T ABLE
Schizophrenia (N = 30)
P Item
40% 13% 47%
70% 0% 26%
0.10
83%
74 %
NS
83%
87%
NS
1.8/2 .82
1.111.82
NS
4 .3/3.24
6.214.5
NS
the second asking only clarifying questions and recording item ratings independently. Because time and resources were Iimited; consensus diagnosis arrived at after the interview seemed most appropriate . Robustness of Diagnosis A reliability study (Werry et al., 1983) had shown in the past that the unit was achieving a satisfactory interdiagnoser reliability for most DSM-1II disorders. lnterdiagnoser reliability on the SOD was found to be satisfactory in pretrials in psychotic subjects not in the study . Except in a minority (32%) of cases, most not living locally or consenting to be reviewed only by their current psychiatrist , two diagnosers were used. Diagnosers were kept blind to the initial diagnosis as much as possible. However, even when the subject was known to one diagnoser, the other diagnoser was blind, and an element of uncertainty prevailed since it was known from the literature and some ' previous cases that the index diagnosis could be wrong. Diagnosers were asked to estimate their confidence in the diagnosis taking account of the amount and quality of data available. As seen in Table 1, the diagnosis was regarded as robust in over 80% of cases. First, and Index Episode Measures ' These had to be extracted from the chart, which thus limited the scope and accuracy of some data. The general standard of records was high, and, since patients were inpatients for some weeks, there was a wealth of descriptive material, including detailed nursing notes . After comparing several extractions and clarifying issues, 10 completed charts were pulled at random and independently checked by a senior psychiatric resident. She found only a few trivial errors, if discrepancies of one point on quantitative scales are allowed. Most patients were admitted during their first episode, but in 20% (N = 13), there was a clear history of a previous episode that was described in the notes or amplified at follow-up . In these cases, except where it would be clearly inaccurate (such as detailed symptomatology, length of psychosis), first episode data were used in preference to admission (index) episode data. 46()
2. Ba ckground and Family Variab les
Sex Male Socioeconomic status Upper /middle Skilled Lower Ethnic Maori White Other Family Intact Broken before 5 years Broken after 5 years Family history (primary and grand parents) Neither Schizophrenia Mood Either (? ) Adopted
%
Mood Disorder (N = 23) %
p
50
61
NS
43 37 20
34 52 13
NS
7 67 . 27
30 57 13
0 .06
57 23 20
61 22 17
NS
66 0 17
43 0 52 5
3
9
n
0.03 NS
J. Background and family variables (Table 2). Most of these are self-explanatory. Family intactness refers to the biological or first parents. Family history of psychiatric illness was felt to be too inaccurate and too incomplete for any except first-degree relatives and grandparents. In some cases, it was known only that a major psychotic illness had occurred. This item was sometimes clarifiable at follow-up. 2. Premorbid variables (Table 3). These included personality, neurological, intellectual, and adaptive function. Estimates of premorbid personality abnormality were made globally on a four-point scale of severity, using DSM-IIJ-R major divisions of personality disorder (odd, anxious, disruptive). Finer grained categorizations were felt to lack accllracy. Neurological status was rated abnormal only for major disorders, such as epilepsy or cerebral palsy. IQ was dichotomized at 80 since this marks the borderline of mental retardation, and, mostly, only children with a history of school failure had been tested . Those without such a history were presumed to have an IQ greater than 79. The premorbid DSM-JIl-R GAF was the highest level of function achieved in the last 12 months or, if the illness had started before that, the highest level of premorbid function ever achieved, using such data as school reports to confirm parent and chart reports. 3. Clinical features offirst or index episode (Table 4) . Again, most of these are self-explanatory. Prodrome was defined as the first appearance of deteriorating function without any psychotic symptoms or, if onset was insidious. rated as grea ter than 1 year. In a few cases of SZ , it was not easy to separate prodrome from onset of the psychosis. although in the majority, the latter had two conspicuous hallmarks: appearance of psychotic symptoms and a severe l .Am.Acad. Child Ado/esc. Psychiatry. 30:3, May 199/
SCHIZOPHRE.'.
;",
Schizophrenia (N = 30)
Item
Moderate/severe With psychosis In remission 0.05 0.05] NS]
6. Outcome--Diagnostic Data
indicator. Adaptive function (OAF) before illness was inferior in SZ, on average in the moderately impaired range, although a subgroup had been quite normal. " , .. 3. Background and family factors . There were rio differences in sex 'ratio (equaljv age of onset, age when seen, socioeconomic status, or fami ly breakup. Homotypic disorder was much more frequent (over 50%) in BP AD than in SZ in first-degree relatives and grandparents, although a positive fami ly history for possible SZ or mood disorder was higher in SZ than in comparable studies (Strober et al., 1988). ", . .
4. Clinical features, of index episode . Symptomatology was similar in SZ and BPAD, although there were signs that a larger sam ple might have revealed more delusions, fewer hallucinations, and less flattened affect in the BPAD group . These finding's of similar symptoms consistent with the well-known difficulty of distinguishing schizophrenic and mood symptoms (Kendler, 1985). SZ subjects took longer to lose psychotic symptoms, and return to school, and few recovered completely from the index episode. 5 . Outcome. Th e follow- up interval was longer in the BPAD group because more SZ subjects became lost to follow- up. SZ subjects were also more reluctant to be interviewed personally. SZ subjects showed greater illness (in additional episodes or chronicity), depen dency , occupational inactivity and/or death ; and lower OAF levels. However, assuming linearity in the OAF scale (which is questionable), the degree of deterioration in OAF scores was
are
l.Am .Acad. Child Adolesc. Psychiatry, 30:3. May 1991
SCHIZOPHRENIC AND BIPOLAR DISORDERS
not significantly different in the two groups--SZ subjects were worse at outcome because they had been worse before the psychosis ever developed. At the time of follow-up, nearly all subjects were on diagnosis-appropriate medication, although 17% of BPAD patients were receiving antipsychotic rather than antimanic medication. One-third of patients were judged as receiving inadequate care during their careers, mostly as a result of poor compliance rather than the fault of their clinicians.
Schizo affective Group With only six members, less confidence in the diagnosis (only half "good"), and the uneasy status of this disorder, comments about this group must be read with great caution. The group seemed more floridly psychotic during the index episode and, on some short and long-term outcome measure, were sicker and more disabled. In consideration that most were bipolar type, it is perhaps not too surprising that their families showed increases of both SZ and mood disorders.
Gender and Age Effects Factorial ANOYA failed to reveal any gender effects on diagnosis, duration of index episode, or age of onset either within or across diagnostic groups. No age effects on outcome were observed, although analyzable YEO ("prepubertal") cases were few (N = 10), and those with subjects uml.er age 12 were very few (N = 3).
Prediction of Outcome A multiple regression analysis was performed using the ANOYA technique (Matthews and Farewell, 1988, pp. 134140), with outcome GAF, and global measures of occupation and peer function as criterion variables. These results will be reported elsewhere, but, in general, the best predictors of outcome were premorbid adjustment (SZ, BPAD) and IQ (for BPAD), accounting for 20 to 50% of the variance. The more clinical measures, such as diagnosis, positive and negative symptoms, and family history, were significant but contributed little (less than 5-8%) to the variance.
either disorder, particularly in adolescence and of long-term outcome. Such studies, especially longitudinal ones, are difficult to execute and allowances have to be made, given current limited knowledge. In general, the findings here have few surprises and are consistent with what is known about SZ and BPAD in general and in childhood and adolescence in particular. This suggests that in spite of the methodological shortcomings, the results have face validity. However, residual errors in diagnosis remain a possibility. In 20% of cases .there was some element of doubt, while in a few, follow-up was less than 2 years. Additional followup is in progress and, if history and Kraepelin are any guide, will reveal further misdiagnosis. But, studies that report only cross-sectional data may also have diagnostic error--except it will not be discernable.
Premorbid Features . The findings ofahigh--frequerrcyor-abnomml, odd, or schizotypal personalities and signs of brain and cognitive dysfunction in SZ areconsistent with better studies by others (Kelvin and Berney, 1990; Werry, in press), especially the ones at the University of California, Los Angeles (Asamow et al., in press). The consonance of findings suggests both that the crude measures used here are still valid and that these premorbid factors are highly influential in some way to be detectable by even crude measures. Whether these abnormalities are vulnerabilities or, in a significant number of cases, the beginning of the disease process with psychosis only a later manifestation, is a matter of current debate (Asarnow et al., in press, Kolvin and Berney, 1990) and not answerable here. Family Factors
The high frequency of mood disorder in families of EO BPAD is consistent with the genetic hypothesis of BPAD and with other studies (Carlson, 1990; Strober etal., 1988) so is the probable increased frequency of homotypic disorder in EO schizophrenia (Strober et al., 1988; Werry, in press) although the size of the increase and frequency of heterotypic (mood) disorder is not. These differences may be a Discussion result of the smaller sample and to the less exact methods Methodology of obtaining a family history in the present study, which This study has a number of defects that require comment. made distinguishing SZ and BPAD in the families of SZ First, all initial and some follow-up data were retrospective .- cases difficult. i and thus limited in scope and accuracy. Second, there were Diagnosis signs that a larger sample might have shown differences in symptomatology (e.g., fewer hallucinations and more deThe most significant finding of this study is that over half lusions) and number of previous (and missed) episodes in the bipolar subjects were misdiagnosed as schizophrenic BPAD. Third, measures and methods are not asprecise as when first seen. It is not suggested that others would necin some recent U.S. studies (Asarnow et al., in press; Carlessarily have as high an error rate (although Strober and son, 1990; Werry, in press) in the areas of family history Carlson [1979] and Bashir et al. [1987] report similar figof disorder, premorbid personality, cognitive dysfunction, ures); but the problem is universal in some degree (Carlson, and/or index symptomatology. Fourth, unlike U.S. studies 1990). In addition, at long-term follow-up, there were six (Beitchman 1985; Werry, in press), especially of SZ, the cases (schizoaffective disorder) where the two disorders were majority of subjects (83%) were teen aged (adolescent). still not able to be discriminated. Fortunately, for patients and for this study, the misclasFifth, there must be local peculiarities in detection; since sification error has now been minimized but does emphasize all of the subjects in this study were inpatients, there was the need for careful follow-up of childhood and adolescent some bias toward the more severely affected. There are few psychoses especially in the first few years . comparative studies of SZ and BPAD, and not enough of l.Am.Acad. Child /vlolesc.PsychiaIry,30:3 .May 1991
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"''ERRY ET AL.
There were many confusing similarities in the two disorders early on, primarily caused by floridly psychotic states in both; but there were also factors that could assist in differential diagnosis. Symptoms suggestive of schizophrenia include the following: an odd personality, poor premorbid adaptive function, a history or evidence of major brain dysfunction, a family history of SZ, insidious onset, psychosis lasting over 3 months, incomplete recovery, and poor outcome. A strong family history of mood disorder argues against SZ, but at a rather low level of specificity here... The best way of not misdiagnosing BPADas SZ is first to be vigilant to the problem, second to search carefully for a depressed or manic mood, and third to assess any delusions for congruence and temporal concurrence with mood symptoms (Carlson, 1990). More use of symptom checklists, such as the SAPS, SANS (Andreasen, 1983) or the BPRS (Overall and Gorham, 1962), and structured interviews might reduce misdiagnosis. However, none of these is absohrte (Kendall, l-985),arrd a change irrdiagnostic set brings its own risk of misdiagnosing SZ as BPAD. Thus, it is not only children and adolescents with SZ who should be followed carefully, but also those with BPAD. Outcome 1. Schizophrenia. The picture of child and adolescent (EO) SZ revealed here is disturbing. It is that of a chronic or relapsing.disorder.accompanied by considerable disability and significant deterioration in adaptive furrctionfrom often already impaired premorbid levels-all more like Kraepelin's dementia praecox than some modem, more benevolent views of SZ (Westermeyer and Harrow, 1988). Only 17% of patients had GAF scores of 60 (i.e., other than serious symptoms or disabilities), were fully employed, or attending school full time. Four patients (three males and one female) were dead, reflecting the 15%. mortality in SZ from suicide that mostly occurs within the first 10 years of the illness (Cohen et al., 1990). It was impossible to be sure how many here had committed suicide and how many suffered delusion-driven accidents, but all had actively put themselves . in the lethal situation. How much of this poor outcome is an artifact of the DSMIII criterion of a 6-month history is unclear (Andreasen, 1987), although no cases diagnosed initially as schizophreniform had to be discarded because they failed this criterion at follow-up. Unfortunately, this study cannot provide much data on treatment response of EO schizophrenia other than that, although 90% of the subjects were receiving appropriate medication at follow-up, disability was common and extensive. 2. Bipolar disorder. On the other hand, those with BPAD began from a strong position and held this throughout their patient careers. Not only did they show less disability, they had fewer episodes, and 83% were in remission at followup. A quarter were entirely symptom free and half in full time in employment or schooling. How much of this better outcome is inherent in the disorder and how much a result of the lithium being taken by two-thirds is debatable. Neverthcless, ~PAD is not entirely benign. Half still had significant active symptoms or impaired function, and, even more
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important, as a whole, the group had shown the same degree of deterioration with respect to premorbid levels (about 10 points on the GAF)-they looked better because they had started better. If schizophrenic subjects are worse premorbidly because the disorder is often lifelong, then BPAD is definitely less malignant. However, both disorders are serious and potentially disabling. 3. Predictors of outcome. This is a complex topic and analysis will be the subject of a separate report. Premorbid adjustment variables and, for BPAD IQ, were the best predictors oLoutcom.e..and clinical.measures like diagnosis, and symptoms, although significant, were so small in effect as to lack utility in the clinical situation. This may seem only partially to support what is known about SZ, but the "predictors" in the literature seem to be anecdotal or correlationalwith size of any effect unstated.
Adult and Child/Adolescent Disorders Compared This study supports others that suggest that in both 5Z and BPAD, the EO and adult forms are qualitatively similar (Beitchman, 1985; Carlson, 1990, Pataki and Carlson, 1990; Werry, in press). Symptomatology must be similar because the disorders are defmed similarly for both adults and children in DSM-m-R. Outside this, nothing has been found that has not already been described in the adult disorders. Although it is commonly believed that outcome is worse in early onset than in adult onset disorders, the figures here .are.only slightly worse than those in some studies of adults (Westermeyer and Harrow, 1988). Sample size, variations in methodology, and the small number (N = 10) of subjects beginning before 13 do not permit finn conclusions. There is more support for the hypothesis that when these disorders begin early, they may have greater family loadings and be more difficult to discriminate from each other. This study confirms that EO schizophrenia is often insidious and associatedwith odd, abnormal premorbid personalities and with neurodevelopmental abnormalities. How this differs, if at all, from adults is unclear since, as with predictors of outcome, exact figures are not stated in DSM-III-R or standard texts (Kaplan and Sadock, 1988).
Conclusions There is a need for continuing studies in EO schizophrenia and BPAD, especially prospective and comparative ones,
which can remedy the defects in this study. Because these disorders are infrequent, consideration should be given to : collaborative studies. .: Perhaps the most important findings of this study are clinical---each and every child or adolescent with a diagnosis of 5Z should be followed for several years because of the possibility of misdiagnosis of BPAD. Misdiagnosis is not an idle matter since it leads to the unnecessary use of neuroleptic drugs with attendant risks; precludes highly effecrive prophylatic antimanic treatment, thus causing unnecessary suffering and disability; gives the wrong set of prognostic indicators; and could lead to underestimating risks in genetic counseling. Diagnostic fashions however, tend to run in cycles, and if, as seems likely, the set toward diagnosing SZ moves toward bipolar or psychotic mood l.Am.Acad. Child Ado/esc. Psychiatry, 30:3, May 1991
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disorder, the consequences will be equally undesirable; so that careful follow-up of bipolar patients is just as necessary. Last, since one-third of patients were getting inadequate care mostly because of poor compliance, active, helperdriven follow-up after failed appointments and lost contact is a necessary part of good clinical care in these two often chronic or recurrent disorders. Pharmacotherapy and psychosocial management can do much to reduce distress and disability and , therefore , poor compliance presentsthe clinician with a worthy challenge.
References Andreason, N. C. (1983). The Scales for Assessment ofNegat ive and Positive Symptoms. Iowa City. IA: University of Iowa . - - (1987). The diagnosis of schizophrenia. Schizophr, Bull .. 13:2538. Asarnow, R. F .• Asarnow, J . R. & Strandburg, R. (in press), Schizophrenia: a developmental perspective . In: Rochester Symposium on Developmental Psychology, ed. D. Chicchetti. New York : Cambridge University Press. Bashir, M. , Russell. J. & Johnson, G. (1987), Bipolar affective disorder in adolescence: a ten year study. Aust. NL J. Psychiatry. 21:3&-43 . . Beitchrnan, J. H. (1985), Childhood schizophrenia: a review and a comparison 'With adult-onset cases. Psychiatr. Clin. NonhAm .,8:793814 . . Carlson, G. A. (1990), Child and adolescent mania: diagnostic considerations. J. Child Psychol, Psychiatry, 31:331-342. - - Strober. M. (1978), Manic depressive illness in early adolescence: a study of clinical and diagnostic characteristics in six cases. J. Am . Acad. Child Psychiatry, 17:138-153. - - Strober. M . (1979). Affective disorder in adolescence. Psychiatr. Clin . North Am., 2:511-526. - - Davenport, Y. B. & Jamison, K. R. (1977), A comparison of outcome in adolescent and late onset bipolar manic depressive illness. Am. J . Psychiatry. 134:919-922 . Cohen, L. J., Test, M. A. & Brown. R. L. (1990), Suicide and schizophrenia: data from a prospective community treatment study . Am . J . Psy chiatry. 147:602-607. Conners , C. K. (1990. June), Methodology of antidepressant drug trials with adolescents . Paper presented to the NIMH Workshop on Tricyclic Drugs in Adolescence. Bethesda, MD. Eggers. C. (1978). Course and prognosis of childhood schizophrenia. J. Autism Child. Schizophr., 8:21-35. Eisenberg. L. (1957), The course of childhood schizophrenia. Arch. Psychiatry Neurol., 78:69-83. Hassanyeh, F. & Davison. K. (1980), Bipolar affective psychosis with onset before age 16: areport of 10 cases. Br . J. Psychiatry, 137:530539. '
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