Division of Psychological Medicine, Institute of Psychiatry, London
Section of Developmental Psychiatry, University of Nottingham, Nottingham
Division of Psychological Medicine, Institute of Psychiatry, London
Department of Child and Adolescent Psychiatry, Institute of Psychiatry, London
Division of Psychological Medicine, Institute of Psychiatry, London
Department of Psychiatry, University of Cambridge.
Correspondence: Dr Mary Cannon, Division of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK. E-mail: m.cannon{at}iop.kcl.ac.uk
Declaration of interest None. Funding detailed in Acknowledgements.
See editorial, pp.
395396, this issue.
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ABSTRACT |
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Aims To compare childhood psychological antecedents of adult schizophrenia and affective psychosis.
Method Childhood item sheets, which give standardised information on signs and symptoms of mental illness in the year preceding assessment are completed for all attendees at the children's department of the Maudsley and Bethlem Royal Hospital. We examined item sheet data on individuals with an adult diagnosis of schizophrenia (n=59) or affective psychosis (n=27) and a comparison group with no adult mental illness (n=86) (all had attended the department).
Results Abnormal suspiciousness or sensitivity and relationship difficulties with peers are associated with later schizophrenia. In contrast, affective psychosis is associated with childhood hysterical symptoms and disturbances in eating.
Conclusions Childhood psychological precursors for schizophrenia and affective psychosis differ and do not simply reflect non-specific psychiatric disturbance in adolescence.
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INTRODUCTION |
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METHOD |
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Each symptom on the item sheet is rated by the clinician as absent (0), minimal or dubious (1) or definitely present (2). The list of symptoms and socio-demographic variables recorded on the item sheets comprises the following.
Cases
All discharge summaries from the Maudsley Hospital Adult Psychiatric
Service up to 1993 were searched for a unique identifying code signifying that
patients had previously attended the Children's and Adolescents' Department of
the Maudsley and Bethlem Royal Hospital between 1968 and 1989. Discharge
summaries with a diagnosis of psychosis were entered into the OPCRIT system
(version 3.2) (McGuffin et al,
1991) to give ICD-10 diagnoses
(World Health Organization,
1992). In total, 56 cases fulfilling ICD-10 criteria for
schizophrenia and 24 fulfilling ICD-10 criteria for affective psychosis
(defined as bipolar affective disorder or severe depression with psychotic
symptoms) were identified.
Comparison group
The next four children, of the same age and gender, who were registered at
the clinic after the index psychosis case were taken as the initial
raw comparison group. We then undertook a follow-up study in
order to identify a final comparison group who had no mental illness in
adulthood, and to identify those individuals who later developed psychosis and
had been treated elsewhere. Tracing was carried out in three stages:
Using these methods, we located general practitioners for 256 subjects. The general practitioners for 203 subjects agreed to participate in the study. From this group we identified 86 individuals who had never suffered any mental illness in adulthood, and these were taken as the final comparison group. Nine individuals were found to have an adult diagnosis of schizophrenia and four had a diagnosis of affective psychosis. In order to increase statistical power, we decided to add these individuals to our original case group. The remainder of the traced comparison group had suffered non-psychotic psychiatric disorders in adulthood.
Final sample
We identified 65 childhood attendees with an adult diagnosis of
schizophrenia and 28 childhood attendees with an adult diagnosis of affective
psychosis, comprising 20 cases with bipolar disorder and 8 cases with
psychotic depression. Our comparison group comprised 86 childhood attendees
who had not suffered mental illness in adulthood. We could not locate
childhood item sheets for six subjects with schizophrenia and one subject with
affective psychosis. The final sample available for analysis thus comprised:
59 subjects with schizophrenia; 27 subjects with affective psychosis; 86
controls.
Statistical analysis
We included only variables rated as definite (score=2) on the
item sheets in our analysis. Odds ratios and confidence intervals were
calculated to measure the association between each variable from the item
sheet separately with later schizophrenia or affective psychosis. Items that
were associated significantly with schizophrenia or affective psychosis at the
5% level on the univariate analysis. Stepwise logistic regression was used to
identify those variables that were independently associated with later
schizophrenia or affective psychosis. Analyses were performed using STATA v.5
(Stata Corporation, 1995).
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RESULTS |
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Univariate analysis
Variables from the item sheets that were associated significantly with
later schizophrenia are presented in Table
2. Fifteen variables (nine symptom variables and six
socio-demographic variables) were associated significantly with later
schizophrenia on univariate analysis. Odds ratios could not be calculated for
four variables (elective mutism, hypoactivity,
in-patient status on referral and twin) because
they did not occur in the comparison group. The strongest univariate
association was between the symptom of abnormal suspiciousness or
sensitivity and later schizophrenia, with an odds ratio of about 10.
Three symptom variables (disturbance of relationship with other
adults, disturbance of relationship with peers and
autism/social withdrawal) that were concerned with aspects of
interpersonal relationships (outside the family) were associated significantly
with later schizophrenia. Because the three variables were felt to be
describing the same underlying phenomenon, they were combined into one
variable called relationship difficulties (extrafamilial) for
the multivariate analysis. Other symptom variables associated with later
schizophrenia were: morbid depression, morbid
irritability/temper tantrums and disturbance of sleeping.
There was no association with speech and language disturbance (apart from
elective mutism), motor disturbance or antisocial behaviour.
Among the sociodemographic variables, family psychiatric
history, previous psychiatric assessment, residing
in a children's home or other type of institution or parent born
in the Caribbean or Africa were associated significantly with later
schizophrenia.
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Symptoms associated with affective psychosis on the univariate analysis are presented in Table 3. The strongest associations were with hysterical symptoms (which, because of low base rates of endorsement, was a combination variable comprising depersonalisation, conversion hysterical symptoms and non-epileptic disturbance of consciousness) and gross overactivity, with odds ratios of about 20. Morbid depression, hypochondriasis and disturbance of eating also were associated significantly with affective psychosis. Among the antisocial behaviours there was a positive association with violent assault, but stealing was significantly less likely to occur than among the comparison group. There were no associations with speech and language disturbance. Among the socio-demographic variables, family psychiatric history and referral by another psychiatrist were associated positively with affective psychosis. Odds ratios could not be calculated for the symptoms of hypomania and hypoactivity or for the socio-demographic variable in-patient on referral because they did not occur in the comparison group.
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Multivariate analysis
All variables that were associated significantly with schizophrenia or
affective psychosis on univariate analysis were entered into multivariate
analyses. Table 4 shows the
variables that were associated independently with schizophrenia and affective
psychosis after logistic regression. The final model for schizophrenia
comprised two symptom variables (abnormal suspiciousness or
sensitivity and relationship difficulties) and two
socio-demographic variables (family psychiatric history and
past psychiatric contact). The positive predictive power of the
model for this sample of child psychiatric clinic attenders was 81.2% (26/32
cases correctly classified) and the model sensitivity was 65%. Adjusting for
gender made no difference to the model. When we examined the
Maudsley cases only, the associations did not change. When the
early-onset cases were excluded, the association with relationship
difficulties became stronger. The associations with past
psychiatric history and family psychiatric history were
no longer statistically significant, although the odds ratios remained above
2. The final model for affective psychosis comprised three variables:
hysterical symptoms, disturbance of eating and
family psychiatric history. The positive predictive power of the
model for this sample was 63.6% (7/11 cases correctly classified) and the
model sensitivity was 43.8%. The likelihood ratio test showed that gender made
a significant difference to the model, so the odds ratios are presented after
adjustment for gender. The wide confidence intervals for hysterical
symptoms reflect the loss of precision due to the 25 missing values in
the comparison group. After excluding the early-onset cases, the association
with family psychiatric history became stronger but the
associations with hysterical symptoms and disturbance of
eating were no longer significant.
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DISCUSSION |
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Limitations
A limitation of this study design is the possible lack of
representativeness of our findings. Our sample represents adults who were
sufficiently disturbed as children to be seen in a child psychiatric clinic
that accepted both local and tertiary referrals. Strictly speaking, therefore,
our results apply only to prediction of later psychosis among children who
attend child psychiatric clinics. However, we will discuss the similarity of
our results to findings from epidemiological general population samples, and
show that there may be a wider application for our findings. In addition, by
choosing as the comparison group children who had not suffered from mental
illness in adulthood we hoped to find a comparison group as close as possible
to a general population control group. Another limitation of this study is
that some of the children were diagnosed with psychosis while still in the
children's department. However, such diagnoses would have been made, in most
cases, after a period of inpatient evaluation and not on the initial
assessment, and the assessing psychiatrist would not have distinguished
between schizophrenia and affective psychosis at that time. In addition, when
we conducted our analysis without these early-onset cases, it made little
difference to the findings. We feel, therefore, that we have identified
precursors for psychosis rather than prodromes.
Comparison with previous work on schizophrenia
The two childhood symptoms independently associated with later
schizophrenia in this study were abnormal suspiciousness or
sensitivity and relationship difficulties
(extrafamilial). Relationship difficulties and social withdrawal in
childhood and adolescence have long been known to be risk factors for
schizophrenia and have been found in previous work on precursors of
schizophrenia among child psychiatric clinic attendees
(Offord & Cross, 1969;
Hartman et al, 1984;
Ambelas, 1992). Indeed, a
review of this literature revealed so much evidence of pervasive social
isolation that Garmezy (1974)
deemed it "the fundamental dimension that is most integral in the
developmental histories of schizophrenics". Our study had the power to
distinguish between different types of relationship and found that familial
relationships in childhood were not disturbed to the same extent as
relationships with peers and other adults (usually teachers). Findings of
relationship difficulties preceding schizophrenia are not confined to child
psychiatric clinic samples. Two large cohort studies of male conscripts have
found that poor social functioning at ages 16-18 years was the strongest
predictor of later schizophrenia (Malmberg
et al, 1998; Davidson
et al, 1999). General population birth cohort studies
have found problems with socialisation at even earlier ages: in the 1946
British birth cohort (National Survey of Health and Development), a preference
for solitary play was apparent by 4 years of age among children who later
developed schizophrenia (Jones et
al, 1994). However, the inability to relate effectively with
peers during childhood is probably a non-specific predictor of psychiatric and
social morbidity, and we cannot determine the degree to which peer rejection
contributes to this morbidity or is merely a marker of risk
(Brown & Dodge, 1997;
Hollis & Taylor,
1997).
The strongest risk factor for schizophrenia in this study was abnormal suspiciousness or sensitivity in childhood and adolescence, and this was independent of relationship difficulties. Few studies have examined this symptom separately, and it may have been incorporated into many of the earlier reports of relationship difficulties. One exception is the Swedish conscript study (Malmberg et al, 1998) mentioned above, which found that reporting oneself as more sensitive than others at age 18 years was a risk factor for schizophrenia, and conscripts who endorsed this symptom, in combination with having fewer than two close friends, preferring to socialise in small groups and not having a steady girlfriend, were 30 times more likely to develop schizophrenia than their peers. Accumulation of exposure to these four variables was associated with a linear increase in the risk of developing schizophrenia: a doseresponse relationship (Malmberg et al, 1998). Reports of childhood experiences by patients with schizophrenia also describe hypersensitivity as a prominent feature (Wagner, 1996). Investigation of the neuro-psychological basis of this symptom in childhood may give insight into the development of psychotic phenomena.
Comparison with previous work on affective psychosis
The literature regarding childhood precursors of affective psychosis is
less clear than for schizophrenia. There is evidence for premorbid social
impairment although to a lesser degree than in schizophrenia
(Cannon et al, 1997).
In the 1958 British birth cohort study (National Child Development Study),
boys who later developed affective psychosis were rated as more hostile to
other children and more restless at age 7 years but these differences had
disappeared by age 11 years and otherwise they were very similar to the
control group (Done et al,
1994; Crow et al,
1995). This is the first study to demonstrate that childhood
hysterical symptoms and eating problems can precede adult affective psychosis,
but these associations have wide confidence intervals, are based on small
numbers of cases and need replication in other samples.
Genetic risk factors
It is well known that both schizophrenia and affective psychosis have
substantial genetic components; having a first-degree relative who suffers
from bipolar disorder or schizophrenia increases the risk for the illness in
probands by 6-10-fold (Sham,
1995). We found that children who developed either schizophrenia
or affective psychosis were more likely to have a family history of
psychiatric illness in a first-degree relative, but we had no information
about the exact nature of the psychiatric illness in the relatives. A previous
study of Maudsley Child Psychiatric Clinic attendees found that the presence
of any psychiatric illness in relatives was a significant predictor of
early-onset affective disorder (Guth
et al, 1993).
Disagreement with previous studies
The schizophrenia group were more likely to have been seen by a
psychologist or psychiatrist previously, emphasising that psychological
difficulties began at a very early age. We were initially surprised to find no
evidence for motor or language developmental impairments in our prepsychosis
sample (apart from elective mutism, which was noted in about 8% of the
schizophrenia group but did not occur in the comparison group). Our
explanation is that the item sheets only rated symptoms or signs occurring
over the past 12 months, and would therefore not detect very early
developmental impairments. Previous studies of child psychiatric clinic
populations that have found such impairments have examined early-onset
patients only or have used maternal interview information recorded in case
notes (Guth et al,
1993; Hollis,
1995; Sigurdsson et
al, 1999).
Implications of our findings
Our findings suggest that the premorbid precursors for schizophrenia and
affective psychosis differ and do not simply reflect non-specific psychiatric
disturbance in adolescence. There appear to be separate tracks
leading from suspiciousness, sensitivity and social difficulties to
schizophrenia, and from eating disorders/hysterical symptoms to affective
psychosis. An interesting question (which we cannot answer from our data) is
whether these childhood problems are markers of the neurocognitive substrate
of schizophrenia or affective psychosis, or are independent risk factors for
the disorder. At a general population level, the predictive power of
individual childhood symptoms is low (social difficulties are common and
schizophrenia is rare) (Malmberg et
al, 1998). However, within the context of a child psychiatric
clinic the predictive power of our model was relatively high. Our study
demonstrates the benefits of moving from a risk factor approach to a
risk model approach to the prediction of adult psychosis,
including not just symptoms but also measures of genetic risk, psychiatric
history and demographic variables.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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Received for publication May 10, 2000. Revision received November 27, 2000. Accepted for publication December 12, 2000.
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