Adult Outcomes of Child- and Adolescent-Onset Schizophrenia: Diagnostic Stability and Predictive Validity

Article
Adult Outcomes of Child- and Adolescent-Onset
Schizophrenia: Diagnostic Stability
and Predictive Validity
Chris Hollis, Ph.D., M.R.C.Psych.
Objective: The goal of the study was to
establish the predictive validity of a diagnosis of schizophrenia in childhood and
early adolescence by examining diagnostic
continuity into adult life and comparing
social and symptomatic outcomes of childand adolescent-onset schizophrenia with
those of nonschizophrenic psychoses.
Method: A total of 110 consecutive patients with first-episode child- or adolescent-onset psychosis (mean age at onset=
14.2 years) presenting to the Maudsley
Hospital in London between 1973 and
1991 were followed up an average of 11.5
years after first contact. Ninety-three
(84.5%) of 110 patients were successfully
followed-up, 51 with a first-episode diagnosis of DSM-III-R schizophrenia and 42
with nonschizophrenic psychoses. Consensus best-estimate DSM-III-R diagnoses
were made at follow-up, and course and
outcome were assessed blind to first-episode diagnosis.
Results: Diagnostic stability was high for
child- and adolescent-onset DSM-III-R
schizophrenia (positive predictive value=
80%) and affective psychoses (positive
predictive value=83%) but much lower for
schizoaffective and atypical psychoses.
Compared with other psychoses, child- or
adolescent-onset schizophrenia was associated with significantly worse symptomatic and social outcomes, which were
characterized by a chronic illness course
and severe impairments in social relationships and independent living.
Conclusions: The diagnosis of DSM-III-R
schizophrenia in childhood and adolescence has good predictive validity. The
high level of diagnostic stability suggests
etiological continuity with adult schizophrenia, with onset in childhood and adolescence associated with a particularly
malignant course and outcome.
(Am J Psychiatry 2000; 157:1652–1659)
S
ince the publication of DSM-III in 1980, schizophrenia
has been diagnosed in children and adolescents by using
unmodified “adult” criteria. Although compelling evidence
suggests that schizophrenia can be reliably identified in
children as young as age 7 by using adult diagnostic criteria
(1, 2), there remains uncertainty about the diagnostic stability and predictive validity of schizophrenia in childhood
and early adolescence. Misdiagnosis may occur because
the symptoms of other disorders overlap with schizophrenia. Affective psychoses (3–6) and developmental disorders
with psychotic episodes (2, 7) can mimic schizophrenia in
childhood and adolescence leading to false-positive diagnostic errors. Developmental variation could also mean
that phenotypic variants of schizophrenia in childhood and
adolescence may be missed by adult diagnostic criteria
leading to false-negative diagnostic errors (7).
In the absence of specific biological markers, careful longitudinal follow-up remains a crucial method for determining the validity of psychiatric diagnoses. Robins and
Guze (8) included outcome and stability of diagnosis over
time as two of the five criteria for establishing diagnostic
validity. Kraepelin distinguished the poor outcome of de-
1652
mentia praecox from the more benign outcome and episodic course of manic-depressive psychosis. Evidence of
diagnostic stability is also important for validation because
it is likely to reflect a stable underlying psychopathological
process (9). In adults, definitions of schizophrenia that include duration criteria (e.g., DSM-III, DSM-III-R, DSM-IV,
and Feighner criteria) have higher levels of diagnostic stability (10, 11) and better predictive validity (11–14) than
definitions of schizophrenia based on Schneiderian firstrank symptoms.
There is a widely held view that a valid diagnostic distinction cannot be made between schizophrenia and affective psychosis in childhood and adolescence. This view
has been supported by several follow-up studies of childand adolescent-onset psychoses showing a high degree of
diagnostic instability (6, 15). In a study of patients who
presented both as children and adults to the Maudsley
Hospital in London, adolescents with a diagnosis of affective psychosis were just as likely to receive an adult diagnosis of schizophrenia as those who were first described as
having schizophrenia were to follow a bipolar course (15).
Werry et al. (6) examined the stability of DSM-III-R diagAm J Psychiatry 157:10, October 2000
CHRIS HOLLIS
noses in a follow-up study of adolescent-onset psychoses
and found that 25% of first-episode diagnoses of schizophrenia were changed to bipolar disorder after 5 years and
50% of patients with bipolar disorder were initially diagnosed as having schizophrenia. A recent follow-up study
of DSM-IV-defined adolescent-onset schizophrenia and
affective psychoses found a higher degree of diagnostic
stability with 90% diagnostic agreement over a 2-year period, although follow-up assessment was not blind to the
initial diagnosis (16).
To establish predictive validity and diagnostic sensitivity
and specificity, follow-up studies of child- and adolescentonset psychoses must include a nonschizophrenia comparison group. There is a lack of consensus among the few
studies that meet this criterion, with some reporting no differences in outcome between schizophrenia and affective
psychoses (17, 18) and others suggesting a poorer outcome
for schizophrenia compared to other psychoses (19, 20).
These later studies have significant methodological limitations, including a low follow-up rate (19) and outcome
comparisons made on the basis of adult follow-up diagnoses rather than the first-episode diagnoses (20). Hence,
inconsistent findings, together with important methodological limitations, make it very difficult to draw any secure conclusions about the diagnostic stability and predictive validity of child- and adolescent-onset schizophrenia.
The purpose of the study reported here was to test the
predictive validity of DSM-III-R schizophrenia in childhood
and adolescence by examining whether the diagnosis
showed stability into adult life and predicted a worse outcome compared to other psychoses. The design aimed to
avoid the methodological limitations that have beset previous follow-up studies of psychoses in this age group. Although the age at onset of psychosis in the followed-up
sample ranged from 10 to 17 years, the shorthand term “adolescent-onset” will be used here. Fifty-one patients with
DSM-III-R schizophrenia and 42 with nonschizophrenic
psychoses were retrospectively ascertained and followed
up in adult life an average of 11 years after their first psychotic episode. The primary outcomes of the study were indices of diagnostic stability (sensitivity, specificity, likelihood ratio, and positive predictive value) and measures of
social disability and symptomatic functioning in adult life.
Method
Subjects
Initial psychosis screen. A retrospective psychosis screen was
applied to the records of all patients under 18 years of age who
had attended the Maudsley Hospital in South London between
1973 and 1991. At the Maudsley Hospital Children’s Department,
data from clinical assessments are combined through standard
coding of specified symptoms, and the symptom codes are recorded on standardized clinical data summaries (“item sheets”)
and stored on a computer (21). Item sheets were completed on
more than 95% of all patients during the study period, during
which the format of the item sheets remained constant. Patients
who screened positive for psychosis were identified from the item
Am J Psychiatry 157:10, October 2000
sheets if at least one of the following criteria were met: 1) an ICD9 diagnosis of schizophrenia (295.0–295.9), affective psychosis
(296.0–296.9), paranoid state (297.0–297.9), or other nonorganic
psychosis (298.0–298.9) (equivalent ICD-8 codes were used from
1973 to 1977), or 2) one or more of the symptoms of hallucinations, delusions, or ideas of reference was definitely present. Patients attending the Maudsley Hospital Adult Department were
also included in the screened-positive group if they were under
age 18 at the baseline assessment and had an ICD-9 psychotic diagnosis (ICD-8 codes were used from 1973 to 1977). A total of 196
patients screened positive for psychosis.
Baseline study group. At the second stage of the study, a detailed chart review was conducted for the 196 screened-positive
patients. The selection criterion was unequivocal evidence of one
or more of the following Research Diagnostic Criteria (RDC) psychotic symptoms (22) occurring in clear consciousness and lasting
for at least 2 weeks: prominent hallucinations, delusions, or incoherence/loosening of associations. The records of 23 of the initial
196 patients who screened positive had missing case notes or not
enough clinical details to confidently determine the presence or
absence of psychotic symptoms, 58 patients were confirmed as
nonpsychotic after their case records were examined, and five had
a diagnosis of autism in the absence of an RDC psychotic symptom. The remaining 110 patients constituted the baseline adolescent-onset psychosis sample and were eligible for follow-up.
Success of the follow-up. Adequate follow-up data were obtained on 93 (84.5%) of the 110 patients over a 2-year period.
These 93 patients will be referred to as the followed-up sample.
Subjects were located by using a variety of methods, including
searches of the U.K. National Health Service Central Register and
records of local U.K. Family Health Service Authorities. Information recorded in the patients’ medical records at the first admission was also used to contact subjects’ parents, family doctors,
and consultant psychiatrists. After subjects had been traced, they
received a letter introducing the study. Finally, subjects were visited by the author to explain the purposes of the study and to seek
their consent. After complete description of the study to subjects,
written informed consent was obtained.
Seventeen subjects (15.4%) were excluded from the final followed-up sample because of inadequate data. Seven subjects refused to be interviewed, and sufficient clinical information for
these subjects was not available from other sources. Four subjects
could not be traced, and nine had died. However, for three of the
deceased subjects, there were enough detailed clinical data to include them in the followed-up sample. Seventy-four (80%) of the
followed-up sample were assessed in face-to-face interviews. For
a further 19 subjects, high-quality information was available from
relatives, professionals, and case records. There were no significant differences between the followed-up sample (N=93) and
those not followed-up (N=17) in age at onset, gender, ethnicity,
place of residence, and DSM-III-R baseline diagnoses.
Adolescent Baseline Assessment
Procedure. Baseline information was extracted from patients’
medical records by using a structured coding procedure specifically
designed for the study. The quality of case note information recorded by Maudsley Hospital psychiatry trainees was uniformly
high and followed the guidelines on obtaining and recording clinical information produced by the Maudsley Hospital and Institute of
Psychiatry. To minimize potential bias and to avoid inferential impressions, items were rated only if the case notes contained explicit
positive statements concerning the patient’s status. All baseline ratings were made blind to adult outcome status. The mean age of subjects at baseline assessment was 14.9 years (SD=1.5, range=11–17).
The mean duration from onset of psychotic symptoms to baseline
assessment was 5.3 months (SD=7.1, range=0.2–36).
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DIAGNOSTIC STABILITY OF CHILDHOOD SCHIZOPHRENIA
TABLE 1. Characteristics of Patients Who Received a Psychotic Diagnosis in Childhood or Adolescence and Were
Followed Up in Adulthood
Child or Adolescent DSM-III-R Diagnosis
Characteristic
Age at onset of psychosis
(years)
Age at follow-up (years)
Length of follow-up (years)
Male
Female
Referral source
Local areaa
Other greater London
Other U.K./abroad
Social class of parentsb
1 and 2
3 M and NM
4 and 5
Ethnicity
White European
African Caribbean
Asian or other
Schizophrenia
(N=51)
Other Psychosis
(N=42)
Mean
SD
Mean
SD
14.0
27.4
11.8
1.6
5.6
5.5
14.4
26.8
11.1
1.6
4.6
4.8
N
%
N
%
29
22
57
43
20
22
48
52
19
23
9
37
45
18
15
16
11
36
38
26
14
20
17
27
39
33
19
11
11
45
26
26
30
17
4
59
33
8
25
14
3
60
33
7
a
Maudsley Hospital local catchment area, including the London
boroughs of Southwark, Lewisham, and Lambeth.
b U.K. Registar General’s classification of occupations. Levels 1 and 2
include professional occupations, level 3 includes skilled occupations involving manual (M) or nonmanual (NM) work, and levels 4
and 5 include semi- or unskilled occupations.
Measures. Data on psychopathological characteristics at baseline from medical records were rated by using the OPCRIT checklist for psychotic illness, version 3.31 (23). OPCRIT comprises a
checklist of 90 items constructed from operational criteria for the
major psychiatric classifications (ICD, RDC, DSM-III-R, etc.) and
a suite of computer programs that allows psychopathological
data to be entered and edited and diagnoses to be generated according to each set of diagnostic criteria. OPCRIT has been shown
to have good reliability for DSM-III-R diagnoses made by using
the 90-item checklist (kappa=0.73) (24). The concurrent validity
of OPCRIT DSM-III-R diagnoses has been established in analyses
showing good to excellent agreement with consensus best-estimate diagnoses (25).
Of the 93 subjects in the followed-up sample, 51 (55%) had a
DSM-III-R diagnosis (OPCRIT derived) of schizophrenia at baseline, 12 (13%) had a schizoaffective psychosis, 23 (25%) had an affective psychosis (unipolar major depressive and bipolar psychoses), and seven (8%) had an atypical psychosis (unspecified
functional psychosis). Data for all patients with nonschizophrenic psychoses (N=42) were combined for further analysis. Table 1 shows the characteristics of the 51 patients with schizophrenia and the 42 patients with nonschizophrenic psychoses. Both
groups were similar in age at onset, duration of follow-up, gender
ratio, referral source (local area versus elsewhere), socioeconomic
status, and ethnicity.
Adult Follow-Up Assessment
Procedure. All assessments were done by raters who were blind
to baseline diagnosis, as the OPCRIT data were not analyzed until
all follow-up interviews had been completed. Although the main
emphasis in the adult follow-up assessment was on direct interviewing of subjects, where possible multiple sources of information (medical records and interviews with health professionals
1654
and relatives) were used to corroborate or supplement information from subject interviews. A median of two sources of information was obtained per subject. After all available sources of information were combined, adult best-estimate DSM-III-R diagnoses
were made. The mean length of follow-up (time from baseline)
for the 93 subjects in the followed-up sample was 11.5 years (SD=
5.2, range=4–22). The mean age at follow-up assessment for the
sample was 27.2 years (SD=5.2, range=17–39).
Measures. Interviews to determine adult lifetime diagnosis were
conducted with a modified version of the Schedule for Affective
Disorders and Schizophrenia—Lifetime Version (SADS-L) (26).
Coverage was broadened to include diagnoses not covered in the
original schedule (27) and some additional questions specifying
precise DSM-III-R diagnostic criteria for psychoses. The author,
who conducted the SADS-L interviews, obtained training from
experienced interviewers at the Institute of Psychiatry.
Although no “gold standard” exists to measure lifetime psychiatric diagnosis, the currently accepted standard procedure involves consensus best-estimate diagnosis on the basis of all available data by two or more clinicians (28). Diagnostic data were
extracted and rated independently on a random sample of 25 patients by a second experienced psychiatrist who trained at the
Maudsley Hospital. There was a 100% concordance for DSM-III-R
diagnoses for the 25 patients rated by two psychiatrists.
Cross-sectional symptomatic and social outcome were measured with several instruments. Cross-sectional measures of psychopathology were obtained by using the Scale for the Assessment of Positive Symptoms (SAPS) (29), the Scale for the
Assessment of Negative Symptoms (SANS) (30), and the Global
Assessment of Functioning symptom scale (31). The total SAPS
score represented the sum of scores on all 35 items (maximum
score=170). The total SANS score represented the sum of scores
on all 24 items (maximum score=120). The Global Assessment of
Functioning symptom scale rates severity of symptoms in the
past month on an ordinal scale from 1 (most severe) to 90 (no
symptoms). Cross-sectional social outcome/disability was measured with the Global Assessment of Functioning disability scale
(31) and the World Health Organization (WHO) Disability Assessment Schedule (32). The Global Assessment of Functioning disability scale rates severity of disability in the past month on an ordinal scale from 1 (most severe) to 90 (no disability).
Course of illness and disability was assessed by using a slightly
modified version of the Life Chart instrument from the WHO
Multi-Centre Study on the Course and Outcome of Schizophrenia
(31). The Life Chart assesses course of illness according to quality
of remission, course type, and severity of symptoms, each with
clear definitions. Two varieties of remission are distinguished:
1) complete remission, in which the subject is virtually symptomfree and shows his/her usual premorbid personality, and 2) incomplete remission, in which the subject is no longer psychotic
but shows any combination of residual symptoms, nonpsychotic
symptoms, or personality change. Course type characterizes the
entire follow-up period in one of four ways: 1) continuous course,
in which the patient was psychotic over most of the period and
any remissions that occurred were brief (none longer than 6
months), 2) episodic course, in which discrete psychotic episodes
(none longer than 6 months) occurred with clear periods of remission between episodes and at least one period of remission lasting
6 months or more, 3) mixed course, which had characteristics
other than those of an episodic or continuous course (e.g., the
longest psychotic episode lasted 12 months, and longest remission lasted 9 months), and 4) not psychotic, in which the patient
was never actively psychotic during follow-up. Severity of symptoms during the majority of the follow-up period was characterized by four levels: 1) severe, in which the patient could not carry
on a coherent conversation, could not work without close supervision, or required constant care; 2) moderate, in which the patient
Am J Psychiatry 157:10, October 2000
CHRIS HOLLIS
TABLE 2. Stability of Psychotic Diagnosis Made in Childhood or Adolescence for Patients Followed Up in Adulthood
DSM-III-R Follow-Up Diagnosis
Diagnostic Indices
Child or Adolescent DSM-III-R
Affective Schizoaffective Atypical
Sensitivity Specificity Likelihood Predictive
Diagnosis
Schizophrenia Psychosis
Psychosis
Psychosis Nonpsychotic Total
(%)
(%)
Ratio
Value (%)
Schizophrenia
Affective
psychosis
Schizoaffective
psychosis
Atypical
psychosis
Total
41
2
2
4
2
51
83.7
77.3
3.7
80.4
1
19
2
0
1
23
70.4
93.9
11.5
82.6
3
5
4
0
0
12
40.0
90.4
4.2
33.3
4
49
1
27
2
10
0
4
0
3
7
93
0.0
92.1
0.0
0.0
consistently showed signs of health despite marked psychotic
symptoms, e.g., could speak with reasonable clarity on some occasions or could work or care for others to some extent; 3) mild, in
which the patient’s behavior was generally normal and illness was
not immediately obvious in conversation, although definite psychotic symptoms persisted; and 4) recovered, in which the patient
experienced no psychotic symptoms or only residual symptoms.
The Global Assessment of Functioning symptom scale range expressed the variability in levels of symptoms during the follow-up
period and was defined as the difference between the highest and
lowest Global Assessment of Functioning symptom scale score for
each subject. Variables measuring time were expressed as the proportion (percentage) of the individual follow-up period. The definition of employment included any time spent in full-time education or vocational training (or full-time child care). Independent
adult living was defined as living either alone or with friends/partner or with parents and receiving no more support than would be
received by the majority of individuals at a similar age.
Statistical Analysis
The stability of child and adolescent psychotic diagnoses was
assessed by using the following indices: sensitivity, specificity,
likelihood ratio, positive predictive value, and kappa coefficient
of diagnostic agreement. Categorical data were analyzed with the
chi-square test with Yates’s correction for continuity. Categorical
r-by-two tables with ordered categories were analyzed with the
chi-square test for linear trend. Fisher’s exact test was used when
expected cell numbers were less than 5. For continuous variables,
independent t tests were used when assumptions of normality
and homogeneity were met. When appropriate, continuous variables were either transformed so assumptions were better met or
analyzed with nonparametric tests such as the Mann-Whitney U
test (corrected for ties). All reported tests of significance are twotailed. Multiple linear regression was used to determine the extent of confounding by demographic variables (ethnicity, social
class, area of residence, and gender) in the relationship between
adolescent-onset diagnosis and outcome (Global Assessment of
Functioning symptom scale score).
Results
Stability of Adolescent-Onset Diagnoses
Table 2 shows the continuities between adolescent and
adult follow-up DSM-III-R psychotic diagnoses. Among
the 51 patients given a DSM-III-R diagnosis of schizophrenia in adolescence, 41 received the same diagnosis as
adults (positive predictive value=80%). Among the 23 patients given a diagnosis of affective psychosis in adolescence, 19 received the same diagnosis as adults (positive
predictive value=83%). In contrast, schizoaffective psychosis had a positive predictive value of only 33% (only
Am J Psychiatry 157:10, October 2000
four of 12 patients received the same diagnosis as adults),
and none of the seven patients diagnosed with atypical
psychosis in adolescence received the same diagnosis at
adult follow-up.
Although the sensitivity of the adolescent diagnoses for
schizophrenia and affective psychosis were high (84%
and 70%, respectively), sensitivity was low for schizoaffective psychosis (40%) and zero for atypical psychosis.
The low number of false-positive diagnoses of adolescent
affective psychosis contributed to a high specificity (94%)
and the high likelihood ratio (11.5). In contrast, the likelihood ratio for schizophrenia was only 3.7. However, the
higher rate of schizophrenia, relative to affective psychoses, in the sample resulted in very similar positive predictive values for adolescent diagnoses of schizophrenia and
affective psychoses.
The overall diagnostic agreement (kappa) between adolescent-onset and adult DSM-III-R diagnoses were as follows: schizophrenia, kappa=0.61 (95% confidence interval
[CI]=0.45–0.77); affective psychosis, kappa=0.67 (95% CI=
0.50–0.84); schizoaffective psychosis, kappa=0.28 (95%
CI=–0.06–0.62); and atypical psychosis, kappa=–0.10 (95%
CI=–0.40–0.20).
Predictive Validity of Adolescent-Onset Diagnosis
Prediction of clinical course and outcome. Table 3
shows the results of the comparison between the clinical
course of adolescent-onset schizophrenia and other psychoses on measures adapted from the WHO Life Chart
(31). The results indicate that an adolescent diagnosis of
schizophrenia predicted a greater likelihood of a severe,
unremitting illness course. Only 12% (N=6) of patients
given a diagnosis of schizophrenia in adolescence were
in complete remission for most of the follow-up, compared to 52% (N=22) of those with nonschizophrenic
psychoses. Subjects with a diagnosis of adolescent-onset
schizophrenia were psychotic for a greater proportion of
the follow-up (N=46; median 84.0% of follow-up, interquartile range [IQR]=33.7–100) than were those with
other psychoses (N=42; median 15.5%, IQR=8.3–39.0)
(Mann-Whitney U, z=–4.49, p<0.0001).
Table 4 shows that subjects with adolescent-onset
schizophrenia were significantly more impaired at outcome than those with other psychoses. Compared to subjects with adolescent-onset schizophrenia, subjects with
1655
DIAGNOSTIC STABILITY OF CHILDHOOD SCHIZOPHRENIA
TABLE 3. Clinical Course Over Follow-Up Period Among Patients Who Received a Psychotic Diagnosis in Childhood or
Adolescence and Were Followed Up in Adulthood
Child or Adolescent
DSM-III-R Diagnosis
Schizophrenia
(N=51)b
Clinical Coursea
N
%
Child or Adolescent
DSM-III-R Diagnosis
Other
Psychosis
(N=42)
N
%
Analysis
χ2
df
p
First-episode
remission
25.8 2 <0.0001
Complete
6
12
21
50
Incomplete
20
40
19
45
Remained
psychotic
24
48
2
5
Course type
17.7 3 <0.0001
Continuous
25
50
7
17
Mixed
14
28
3
7
Episodic
8
16
30
71
Not psychotic
3
6
2
5
Severity of
symptoms
7.7 3
0.005
Severe
25
50
7
17
Moderate
14
28
3
7
Mild
8
16
30
71
Recovered
3
6
2
5
Follow-up
remissionc
21.8 3 <0.0001
Complete
6
12
22
52
Mixed
4
8
3
7
Incomplete
16
32
13
31
Never in
24
48
4
10
remission
a Categories adapted from WHO Life Chart (31).
b Data missing for some variables, so total number of subjects varies.
c Describes the longest remission during the follow-up period.
“Mixed” type refers to equal periods of complete and incomplete
remission.
nonschizophrenic psychoses had greater symptom variability over the course of follow-up. At outcome, subjects
with adolescent-onset schizophrenia had more negative
symptoms (N=37, median total SANS score=30 of the maximum score of 120, IQR=13–49) than subjects with other
psychoses (N=39, median total SANS score=4 of the 120
maximum score, IQR=0–25) (Mann-Whitney U, z=–4.14,
p<0.0001) and more positive symptoms (median total
SAPS score=14 of the maximum score of 170, IQR=3–21 for
subjects with schizophrenia [N=48] versus median total
SAPS score=0 of the 170 maximum score, IQR=0–12 for
subjects with other psychoses [N=42]) (Mann-Whitney U,
z=–3.12, p=0.002).
Independent adult living. Subjects with adolescentonset schizophrenia spent less time living independently
(N=50, median time independent <1 year, <1% of followup period) than subjects with nonschizophrenic psychoses (N=42, median time independent=5.9 years, 74% of
follow-up period) (Mann-Whitney U, z=–4.5, p<0.0005).
Twenty percent (N=10) of the subjects with adolescentonset schizophrenia were living independently (nine of
these 10 were still living with parents), compared to 50%
(N=21) of subjects with other psychoses (10 of 21 were living with friends or partners). Thirty-two percent (N=16) of
1656
TABLE 4. Scores on Measures of Symptoms and Disability
at Follow-Up Among Patients Who Received a Psychotic Diagnosis in Childhood or Adolescence and Were Followed
Up in Adulthood
Follow-Up
Measure
Schizophrenia
(N=51)
Other
Psychosis
(N=42)a
Mean
SD
Mean
48.1
15.8
17.4
16.0
63.0
35.8
Global Assessment
of Functioning
symptom scale
Scoreb
Rangec,d
Global Assessment
of Functioning
disability scale
scoreb
SD
Analysis
t
df
p
17.6 4.1 91 <0.0001
14.9 6.2 90 <0.0001
42.6
16.0 59.7 18.3 4.8 91 <0.0001
Data on the Global Assessment of Functioning symptom scale score
and range missing for one patient.
b Children or adolescents with schizophrenia were significantly more
impaired at follow-up.
c Difference between the highest and lowest scores over the followup period.
d Adolescents with other psychoses had a significantly greater variability of scores over the follow-up period.
a
TABLE 5. Quality of Social Relationships at Follow-Up Among
Patients Who Received a Psychotic Diagnosis in Childhood or
Adolescence and Were Followed Up in Adulthood
Child or Adolescent DSM-III-R Diagnosis
Highest level of adult
relationship
Married/stable partnerc
Girlfriend or boyfriendd
Friendse
Aquaintancesf
No social contactsg
Schizophrenia
(N=50)a,b
Other Psychosis
(N=42)
N
%
N
%
0
1
7
20
22
0
2
14
40
44
2
9
13
12
6
5
21
31
29
14
a Data missing for one subject.
b Schizophrenia associated with a lack of close social relationships
(χ2=20.2, df=4, p<0.0001).
c Cohabiting or noncohabiting partner of >6 months.
d Duration of relationship <6 months.
e Subject meets friends for social activity at least twice a month.
f Subject regularly talks to neighbors or to other patients.
g Besides those with professionals or close relatives (parents or
siblings).
the subjects with schizophrenia had spent the majority of
the follow-up period in long-stay residential or psychiatric
hospital care, compared to only 17% (N=7) of subjects with
other psychoses. There was a significant linear association
between adolescent-onset schizophrenia and nonindependent adult living (χ2=10.8, df=5, p=0.001).
Education and employment. Sixty percent (N=30 of
50) of the subjects with adolescent-onset schizophrenia
left school with no formal qualifications and undertook no
further postschool training. Despite this overall low level
of educational achievement, it is notable that 22% (N=11)
achieved passes on the “GCSE” (General Certificate of
Standard Education, the U.K. national scholastic examination for 16-year-olds) or the “A level” (U.K. national
Am J Psychiatry 157:10, October 2000
CHRIS HOLLIS
scholastic examination for 18-year-olds) after the onset of
psychosis. Educational achievement was significantly better for those with nonschizophrenic psychoses, with only
33% (N=14) without any formal qualification or training,
while 38% (N=16) achieved GCSE or higher qualifications.
There was a significant linear association between the diagnosis of schizophrenia and low educational achievement (χ2=6.9, df=5, p<0.01).
Subjects with an adolescent diagnosis of schizophrenia spent significantly less time in employment over the
follow-up period (N=50, median=0%, IQR=0%–18.0%)
than subjects with nonschizophrenic psychoses (N=42,
median=32.4%, IQR=5.0%–63.6%) (Mann-Whitney U, z=
–3.73, p=0.0002).
Social relationships in adult life. Table 5 indicates that
adolescent-onset schizophrenia predicts impoverished social relationships in adult life. Almost half of subjects with
adolescent-onset schizophrenia (N=22, 44%) had no social
contacts other than with professionals or close relatives.
Only 14% socialized with a friend or friends, only one subject had had a reciprocal love relationship, and none had
married or had a stable partner. Subjects with an adolescent diagnosis of nonschizophrenic psychoses were much
less socially impaired, with more than half (N=24, 57%)
having either a regular friendship or love relationship.
The effect of demographic confounding on outcome. To estimate the magnitude of confounding in the
association between diagnosis and symptomatic outcome, the Global Assessment of Functioning symptom
scale score was regressed on DSM-III-R adolescent-onset
diagnostic category (schizophrenia versus nonschizophrenic psychosis) and the following variables were then
added to the model: gender, social class, location (area of
residence), and ethnicity. The unadjusted regression coefficient (Beta) for diagnosis was 14.9, and the fully adjusted
regression coefficient (Beta) was 13.4. Overall, adjusting
for demographic confounding had a minor effect (about
10%) on the association between diagnosis and symptomatic outcome.
Discussion
Methods
This study examined the predictive validity of a diagnosis of adolescent-onset DSM-III-R schizophrenia by measuring diagnostic stability and comparing course and outcome with those of other adolescent-onset psychoses. The
study has significant strengths and represents the largest
longitudinal follow-up of adolescent-onset schizophrenia
we are aware of that was free from diagnostic bias and that
included a nonschizophrenic comparison group. A high
follow-up rate (84%) reduced the opportunity for attrition
bias, and a mean duration of follow-up of more than 11
years ensured that the subjects had entered well into adult
life. Furthermore, the complete follow-up group was repAm J Psychiatry 157:10, October 2000
resentative of the local catchment area subgroup, which
reduced the potential for significant referral bias. Hence,
the diagnostic comparisons are likely to be valid and generalizable to other populations of adolescents with psychotic disorders. Observer bias could not have affected
baseline assessments as they were conducted blind to outcome. Outcome assessments were also conducted blind to
baseline diagnosis. A single interviewer at outcome obviated the issue of interrater reliability. The fact that a second experienced psychiatrist achieved 100% concordance
for outcome diagnoses with the initial rater suggests that
there was very little observer error. Demographic confounding (gender, ethnicity, social class, and area of residence) accounted for no more than 10% of the variability
in outcome score (Global Assessment of Functioning
symptom scale) due to diagnosis. It is possible that differences in the quality and approach to treatment may have
affected outcome. However, this seems an unlikely explanation for the outcome differences, as equal proportions
of patients with schizophrenia and with nonschizophrenic
psychoses received their follow-up care at the Maudsley
Hospital.
The main weakness of the design was the retrospective
case ascertainment and the reliance on case note ratings
of psychopathology. However, the OPCRIT rating method
is well suited to rating case notes and has good demonstrated reliability and validity. Although the Maudsley case
records were extremely detailed, the secondary rating of
chart data collected by a large number of different examining psychiatrists is likely to have introduced considerable random error. Given this caveat, the observed continuity and predictive validity of diagnoses was impressive
and may in fact underestimate true effects.
Stability of Diagnoses
Diagnostic stability was high for the adolescent DSMIII-R diagnoses of schizophrenia (positive predictive
value=80%) and affective psychoses (positive predictive
value=83%). In contrast, the positive predictive value was
only 33% for schizoaffective psychosis and 0% for atypical
psychosis. There was moderate diagnostic agreement
between adolescent and adult follow-up diagnoses for
schizophrenia and affective psychosis (kappa statistic),
and agreement for schizoaffective and atypical psychoses
was no better than chance. The results suggest that operationalized DSM-III-R diagnoses of schizophrenia and affective psychoses have substantial predictive validity
when applied to a sample of adolescent-onset psychotic
patients. However, the likelihood ratio for schizophrenia
of 3.7 suggests lower predictive values would occur in
samples with a lower prevalence of schizophrenia (i.e.,
among adolescents from community mental health settings rather than specialist centers).
The results of the study reported here challenge the
widely held belief that diagnoses of adolescent schizophrenia and affective psychoses are unstable and are of
1657
DIAGNOSTIC STABILITY OF CHILDHOOD SCHIZOPHRENIA
doubtful validity (6, 15). The findings confirm the higher
levels of diagnostic stability reported in some previous follow-up studies of adolescent-onset schizophrenia (19, 20,
33) and avoid the methodological limitations of these
studies. Unlike the findings of Werry et al. (6), the results of
the present study did not suggest that bipolar disorder was
commonly preceded by an adolescent diagnosis of schizophrenia. There was also little evidence that schizophrenia
commonly presents in the guise of affective or atypical
psychoses in adolescence. Finally, the level of diagnostic
stability for schizophrenia in this study was broadly similar to the level reported in studies of adult-onset schizophrenia that used DSM-III-R diagnostic criteria (11).
Predictive Validity of Adolescent-Onset
Diagnoses
The psychiatric and social outcomes of adolescent-onset schizophrenia were significantly worse, across a broad
range of clinical and social outcome measures, than the
outcomes of nonschizophrenic psychoses. An adolescent
diagnosis of schizophrenia predicted less independence,
poorer educational achievement, less likelihood of employment or access to further education, and higher global
disability scores. The most striking finding among the subjects with schizophrenia was the poverty of their social relationships in adult life. The chronic illness course and
very poor outcome described here support findings from
previous follow-up studies of child- and adolescent-onset
schizophrenia (6, 19, 20, 33) and suggest that schizophrenia with a very early onset predicts a more severe and unremitting illness course than the adult-onset form of the
disorder (34, 35).
and DSM-IV diagnostic criteria suggests that the results of
this study are likely to apply equally to DSM-IV diagnoses.
Received Dec. 7, 1999; revision received Apr. 24, 2000; accepted
May 3, 2000. From the Division of Psychiatry, University of Nottingham. Address reprint requests to Dr. Hollis at the Section of Developmental Psychiatry, Division of Psychiatry, University of Nottingham,
South Block, E Floor, Queen’s Medical Centre, Nottingham, NG7 2UH,
U.K.; chris.hollis@nottingham.ac.uk (e-mail).
This study was supported by a Research Training Fellowship from
the U.K. Medical Research Council. The author thanks Prof. Eric Taylor, Dr. Karmen Slaveska, Kate Garrett, and Pam Remon for their help
with the study.
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