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Evidence for Early-Childhood, Pan-Developmental Impairment Specific to Schizophreniform Disorder
Results From a Longitudinal Birth Cohort
Mary Cannon, MD, PhD;
Avshalom Caspi, PhD;
Terrie E. Moffitt, PhD;
HonaLee Harrington, BS;
Alan Taylor, MSc;
Robin M. Murray, MD, DSc;
Richie Poulton, PhD
Arch Gen Psychiatry. 2002;59:449-456.
ABSTRACT
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Background Childhood developmental abnormalities have been previously described
in schizophrenia. It is not known, however, whether childhood developmental
impairment is specific to schizophrenia or is merely a marker for a range
of psychiatric outcomes.
Methods A 1-year birth cohort (1972-1973) of 1037 children enrolled in the Dunedin
Multidisciplinary Health and Development Study was assessed at biennial intervals
between ages 3 and 11 years on emotional, behavioral, and interpersonal problems,
motor and language development, and intelligence. At age 11 years, children
were asked about psychotic symptoms. At age 26 years, DSM-IV diagnoses were made using the Diagnostic Interview Schedule. Study
members having schizophreniform disorder (n = 36 [3.7%]) were compared with
healthy controls and also with groups diagnosed as having mania (n = 20 [2%])
and nonpsychotic anxiety or depression disorders (n = 278 [28.5%]) on childhood
variables.
Results Emotional problems and interpersonal difficulties were noted in children
who later fulfilled diagnostic criteria for any of the adult psychiatric outcomes
assessed. However, significant impairments in neuromotor, receptive language,
and cognitive development were additionally present only among children later
diagnosed as having schizophreniform disorder. Developmental impairments also
predicted self-reported psychotic symptoms at age 11 years. These impairments
were independent of the effects of socioeconomic, obstetric, and maternal
factors.
Conclusions The results provide evidence for an early-childhood, persistent, pan-developmental
impairment that is specifically associated with schizophreniform disorder
and that predicts psychotic symptoms in childhood and adulthood.
INTRODUCTION
SCHIZOPHRENIA IS a clinical syndrome with peak onset in late adolescence
or early adulthood, whose symptoms are manifest in multiple domains of behavior,
language, thought, and affect, and whose etiology remains obscure.1 A neurodevelopmental etiologic model or hypothesis
of schizophrenia has been influential during the past decade.2-3
It proposes a subtle deviance in early brain development whose full adverse
consequences do not emerge until adolescence or early adulthood. Central to
this hypothesis is the identification of developmental deficits preceding
overt clinical symptoms of adult schizophrenia.4-6
In this study, we apply a life-course approach to the study of schizophrenia
and focus on developmental risk factors in early life
Several different research strategies have been used to examine the
developmental precursors of adult schizophrenia, including the use of archived
information, follow-up studies of existing birth cohorts, and genetic high-risk
studies that follow offspring of an affected parent throughout childhood and
adolescence. Such strategies have uncovered robust evidence for childhood
motor, language, cognitive, and behavioral precursors to schizophrenia7-23
but there are 3 caveats. First, different developmental impairments have been
examined in separate studies using a variety of case ascertainment methods
and developmental scales. As a result, conclusions about the etiologic significance
of developmental impairments may have been confounded by these variations.
One should examine whether different types of developmental impairment predict
the same adult schizophrenic outcome in one longitudinal study. Second, evidence
of specificity for schizophrenia is limited. Childhood developmental problems
associated with schizophrenia may also occur in patients with other psychiatric
disorders24-25 and may thus be
nonspecific markers for a wide range of psychologic disturbances in adulthood.
A third area of debate is the etiology of such developmental precursors. A
genetic cause is suggested by the occurrence of developmental problems in
25% to 40% of children at genetically high risk for schizophrenia7-8,16 but it has been suggested
that maternal and social factors26-29
or obstetric factors7-8,30
may be partly responsible for these associations. Therefore, a comprehensive
investigation of developmental processes involved in the genesis of psychopathology
should also incorporate perinatal and postnatal environmental factors.31-33
The longitudinal Dunedin Study has followed up 1000 children from the
general population from birth to age 26 years and offers several advantages
for investigating childhood risk factors for adult outcomes. First, we can
examine multiple developmental risk factors within one sample using detailed
childhood data that were prospectively collected from age 3 years using well-established
and validated instruments. Second, we can examine the specificity of early
developmental risk factors for schizophreniform outcomes since psychiatric
diagnoses were made for all study members at age 26 years based on structured
diagnostic interviews conducted by trained health professionals. A third unique
strength is that we can study whether the same developmental risk factors
predict psychotic symptoms in childhood and in adulthood. In an earlier report
from the Dunedin cohort, we showed that children's self-reported psychotic
symptoms at age 11 years predicted a schizophreniform diagnosis at age 26
years.34 If the same (or similar) relationships
are found between childhood developmental risk factors and psychotic symptoms
at age 11 years as with schizophreniform disorder at age 26 years, it would
suggest that the psychotic symptoms at age 11 years are part of the disease
process itself rather than an independent risk factor/marker for later schizophreniform
disorder.
PARTICIPANTS AND METHODS
SAMPLE
Participants are members of the Dunedin Multidisciplinary Health and
Development Study, a longitudinal investigation of health and behavior in
a complete birth cohort.35 The study members
were born in Dunedin, New Zealand, between April 1972 and March 1973. Of these,
1037 children (91% of eligible births; 52% males) participated in the first
follow-up assessment at age 3 years, and they constitute the base sample for
the remainder of the study. Cohort families represent the full range of socioeconomic
status (SES) in the general population of New Zealand's South Island and are
primarily white. Assessments have been conducted at ages 3 (n = 1037), 5 (n
= 991), 7 (n = 954), 9 (n = 955), 11 (n = 925), 13 (n = 850), 15 (n = 976),
18 (n = 993), 21 (n = 961), and most recently at age 26 years (n = 980; 96%
of living cohort members). Participants are brought to the research unit within
60 days of their birthday for a full day of individual data collection. Various
research topics are presented as standardized modules, each administered by
a different trained examiner. Informed consent was obtained for all procedures.
CHILDHOOD MEASURES
SES, Obstetric Complications, and Maternal Factors
Family SES measured the average SES level of the study members' families
across the first 15 years of life,36 using
a 6-point scale designed for New Zealand where 1 = unskilled laborer and 6
= professional.37
Each child was examined shortly after birth and prenatal information
was taken from the hospital records.38-39
The obstetric complications assessed in this study were maternal diabetes;
glycosuria; epilepsy; hypertension; eclampsia; antepartum hemorrhage; accidental
hemorrhage; placenta previa; having had a previous small baby; gestational
age younger than 37 weeks or older than 41 weeks; birth weight less than 2500
g or greater than 4 kg; small or large for gestational age; major or minor
neurologic signs; Rh incompatibility; ABO incompatibility; nonhemolytic hyperbilirubinemia;
hypoxia at birth (idiopathic respiratory distress syndrome or apnea), and
low Apgar score at birth. (The infant was defined as having a low Apgar score
if one of the following conditions applied: [1] at 5 minutes of life, the
infant's heart rate was <100 beats/min, respiration was irregular or absent,
and the infant was centrally cyanosed; [2] the infant took more than 10 minutes
to establish normal respiration; or [3] the infant's asphyxia at birth warranted
resuscitation.) Each complication was weighted equally and summed to yield
an obstetric complication index.38
Mothers were rated on their general attitude and behavior in relation
to their child by a psychologist or medical doctor during the course of the
child's assessment at age 3 years. Mothers were rated on 8 features: harshness
toward the child; critical or negative evaluation of the child; rough, awkward
handling of the child; no effort to help the child; unaware or unresponsive
to the child's needs, indifference to the child's performance; demanding of
the child's attention; and soiled, unkempt appearance of the child. This assessment
has been found in previous research to be reliable and valid.40
Scores on these 8 ratings were summed to create a mother-child interaction
variable for each mother, and a score of 1 or more indicated atypical mother-child
interaction for the purposes of this study.
Neuromotor Development
Infant milestones were assessed retrospectively at age 3 years. Mothers
were asked to remember to the nearest month when their child attained various
milestones: smiling, sitting up, walking, dry-by-day, dry-by-night, fed self,
talked (words), and talked (sentences). Responses were recorded only when
the mother was certain that she could recall this information accurately.
Most mothers referred to their "Plunkett books," in which study mothers had
recorded this information as their baby developed.
Neurologic abnormalities were assessed at age 3 years based on procedures
described by Touwen and Prechtl.41 Each child
was examined by a pediatric neurologist for neurologic signs, including assessment
of motility, passive movements, reflexes, facial musculature, strabismus,
nystagmus, foot posture, and gait. Motor development was assessed at age 3
years with the Bayley Motor Scales,42 at age
5 years using the McCarthy Motor Scales,43
and at ages 7 and 9 years using the Basic Motor Ability Test.44
Language and Cognitive Development
Receptive and expressive language development was assessed at ages 3
and 5 years using the Reynell Developmental Language Scales,45
which have separate subtests for receptive (verbal comprehension) and expressive
language. At ages 7 and 9 years, language development was assessed using the
Auditory Reception and Verbal Expression subtests of the Illinois Test of
Psycholinguistic Abilities.46
Intelligence was assessed at age 3 years with the Peabody Picture Vocabulary
Test,47 at age 5 years with the Stanford-Binet
Intelligence Scales,48 and at ages 7, 9, and
11 years with the Weschler Intelligence Scales for Children–Revised.49 All tests were administered by trained psychometrists
according to standard protocol.50
Internalizing and Externalizing Behavior Problems
At ages 5, 7, 9, and 11 years, parents and teachers completed the Rutter
Child Scales,51-52 which inquire
about children's emotional and behavioral functioning during the past year.
The Internalizing Problems scale describes children who worry about many things
or who often appear miserable, unhappy, and tearful. The Externalizing Problems
scale describes children who frequently fight, bully other children, lie,
steal, disobey, truant, destroy property, and have irritable tempers. The
relevant items were summed across the 4 age periods and 2 raters (parents
and teachers) to derive measures indexing children's internalizing and externalizing
problems, respectively.
Interpersonal Adjustment
At ages 5, 7, 9, and 11 years, parents evaluated 2 statements about
their child: "my child is a loner" and "my child is not much liked by other
children." Each statement was rated on a 3-point scale. At ages 7, 9, and
11 years, teachers independently evaluated the same statements. Mean scores
for each statement were calculated separately for parents and teachers and
these ratings were averaged for each child to derive 2 measures indexing social
isolation and peer rejection, respectively.
Psychotic Symptoms at Age 11 Years
At age 11 years, 789 study members were administered the Diagnostic
Interview Schedule for Children53 by a child
psychiatrist.54 The schizophrenia section of
the Diagnostic Interview Schedule for Children was composed of 5 questions
regarding possible psychotic symptoms, which were scored by the psychiatrist
as no (0); yes, likely (1); and yes, definitely (2). The scores for each item
were summed. Most study members (n = 673) obtained a score of 0, 103 (13%)
obtained a score of 1 and were called the weak-symptom group, and the remaining
13 obtained a score of 2 or higher and were called the strong-symptom group.
Individuals in the strong-symptom group at age 11 years were found to have
a very high risk of schizophreniform disorder at age 26 years (odds ratio
[OR], 16.4; 95% confidence interval [CI], 3.9-67.8).34
Individuals in the weak-symptom group also had an increased risk of schizophreniform
disorder at age 26 years but to a lesser degree (OR, 5.1; 95% CI, 1.7-18.3).
Psychiatric Status at Age 26 Years
Psychiatric interviews at age 26 years were available for 976 of the
1019 cohort members still living. The Diagnostic Interview Schedule55 was administered by health professionals with either
a medical or master's degree to yield DSM-IV diagnoses.56 The reporting period was 12 months prior to the interview.
The Axis I disorders diagnosed at age 26 years were grouped into the following
diagnostic outcome groups: (1) schizophreniform disorder (n = 36 [3.7%]),
(2) manic episodes (n = 20 [2.0%]), and (3) anxiety or depressive disorders
(n = 278 [28.5%]). The primary outcome for this study was schizophreniform
disorder. Diagnostic procedures for schizophreniform disorder are explained
in detail by Poulton et al.34 To enhance the
validity of our research diagnosis, we took 2 additional steps: (1) We required
the presence of hallucinations (not substance-related) plus at least 2 other
symptoms from Criterion A of the DSM-IV (this is
more strict than the DSM-IV diagnostic criteria).
and (2) We required objective evidence of impairment from informants to complement
self-reports. Following this protocol, 1% of the sample met criteria for formal
schizophrenia at age 26 years and a further 2.7% met all criteria except 6-month
chronicity. For the purposes of this analysis, study members who were comorbid
for 2 or more disorders were assigned to 1 of 3 diagnostic groups, in the
following order of priority: schizophreniform disorder, mania, and anxiety/depression.
STATISTICAL ANALYSIS
Analyses compare 4 mutually exclusive groups defined according to psychiatric
outcomes at age 26 years: schizophreniform disorder, mania, anxiety/depression,
and a control group composed of the remainder of the cohort, who had none
of the aforementioned disorders.  2 Tests were used to examine
the associations among adult psychiatric disorders, sex, and family SES.
The raw scores for childhood developmental variables were standardized,
within age, on the entire cohort, using the z-score
transformation so that the cohort had a mean of 0 and an SD of 1 on these
variables. The figures show the standardized scores for each outcome group.
Differences between outcome groups can be evaluated by comparing differences
in z scores (SD units), where 0.2 is a small, 0.5
is a moderate, and 0.8 is a large effect size.57
Relationships between childhood developmental impairments and psychiatric
outcomes at age 26 years were examined using a collection of regression techniques
as required by the different types of developmental variables examined in
this study (categorical, continuous, and repeated). Each regression equation
was composed of 3 dummy variables for diagnostic status (schizophreniform,
mania, and anxiety/depression groups), with the control group as the reference
category. All reported regression coefficients and ORs were adjusted for sex
and SES. Logistic regression analysis examined the following categorical variables:
individual obstetric complications, maternal rejection, and presence of 1
or more neurologic signs at age 3 years. Ordinary least squares regression
examined the following continuous variables: peer rejection and social isolation.
Motor and language development, IQ, and internalizing and externalizing problems
were measured on multiple occasions and analyzed using the generalized estimating
equation (GEE) approach—a form of repeated-measures regression analysis
in which any required covariance structure may be assumed and parameters estimated
without specifying the joint distribution of the repeated observations.58 We specified an unstructured correlation matrix and
used robust SEs to protect against model misspecification.59
The GEE approach can accommodate noninformative missing values.60-61
We report regression coefficients adjusted for sex and SES and their 95% CIs.
These coefficients represent the average difference among diagnostic groups.
To test whether relationships between developmental impairments and psychiatric
outcomes at age 26 years were obtained independently of perinatal and postnatal
environmental factors, all GEE analyses were repeated, controlling for obstetric
complications and maternal rejection.
To test whether the developmental impairments that were associated with
a schizophreniform outcome at age 26 years were also associated with psychotic
symptoms at age 11 years, we repeated the GEE analyses using 2 dummy variables
representing the weak- and strong-symptom groups at age 11 years, with the
nonsymptom group as the reference category. All analyses were carried out
using Stata version 6.0 (Stata Corp, College Station, Tex).62
Interactions between sex and diagnosis were not examined owing to power limitations.
All significance tests were 2-tailed.
RESULTS
There were significant overall sex and family SES differences among
the adult diagnostic groups. The adult anxiety/depression group contained
significantly more females than the control group (60.1% vs 45%; 21 = 17.6; P<.01) and a significantly
higher proportion of adults in the schizophreniform group came from low-SES
families (categories 1 and 2) compared with controls (47.2% vs 9.2%; 21= 16.5; P<.01).
OBSTETRIC COMPLICATIONS, MATERNAL FACTORS, AND PSYCHIATRIC OUTCOMES
There was a significant association between the obstetric complications
index and later schizophreniform disorder (ß = .38; 95% CI, 0.25-0.52; P = .02) but no significant association with later mania
(ß = .03; 95% CI, -0.15 to 0.21) or anxiety/depression (ß
= -.03; 95% CI, -0.08 to 0.03). Post hoc analyses revealed that
3 complications were associated with an increased risk of schizophreniform
disorder: low Apgar score at birth (OR, 5.9; 95% CI, 1.1-32.0); hypoxia at
birth (apnea or idiopathic respiratory distress syndrome) (OR, 5.0; 95% CI,
1.5-16.4); and small-for-gestational-age status (OR, 2.8; 95% CI, 1.1-6.9).
The mothers of the schizophreniform group (OR, 2.65; 95% CI, 1.2-5.6) but
not the manic group (OR, 1.7; 95% CI, 0.6-4.9) or the anxiety/depression group
(OR, 1.4; 95% CI, 0.9-2.03) were significantly more likely to have atypical
mother-child interactions when compared with mothers of controls.
NEUROMOTOR DEVELOPMENT AND PSYCHIATRIC OUTCOMES
The schizophreniform group began to walk significantly later than controls
(mean [SE], 14.9 [1.0] months vs 13.6 [0.13] months; F3,661= 5.01
[adjusted for sex and SES]; P = .02) but there were
no differences for any other infant milestones. At age 3 years, the schizophreniform
group was significantly more likely than controls to have one or more neurologic
signs (OR, 4.6; 95% CI, 1.9-10.9). The mania group (OR, 0.8; 95% CI, 0.1-6.4)
and the anxiety/depression group (OR, 1.7; 95% CI, 0.9-2.8) were not significantly
more likely to have neurologic signs than controls. The schizophreniform group
also performed worse than controls (more than 0.3 SDs) on standard tests of
motor skill at ages 3, 5, and 9 years but not at age 7 years (Figure 1). The repeated-measures analysis showed that the schizophreniform
group performed significantly worse than the control group overall, while
the mania group performed significantly better than the control group on motor
performance, even after controlling for sex and SES (Table 1). The anxiety/depression group did not differ significantly
from controls on any of these motor assessments.
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Figure 1. The mean standardized scores for
motor development at ages 3, 5, 7, and 9 years for adults diagnosed as having
schizophreniform disorder (n = 36), mania (n = 20), anxiety/depression (n
= 278), and controls (n = 642).
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Table 1. Results From Regression Analyses Showing the Association Between
Developmental Functioning During the First Decade of Life and Adult Psychiatric
Outcomes at Age 26 Years*
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LANGUAGE DEVELOPMENT, COGNITIVE DEVELOPMENT, AND PSYCHIATRIC OUTCOMES
The schizophreniform group did not exhibit any problems with expressive
language but their receptive language skills were significantly poorer than
those of the controls (between 0.2-0.6 SDs) at each of the 4 biennial testings
during the first decade of life (Figure 2). The schizophreniform group also performed more poorly than controls
(about 0.4 SDs) on standard IQ tests at each of 5 assessments between ages
3 and 11 years (Figure 3). These
significant impairments in receptive language and cognitive development among
the schizophreniform group were independent of sex and SES (Table 1). The mania and the anxiety/depression groups did not differ
significantly from controls on either language measure or on IQ test performance
(Table 1).
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Figure 2. The mean standardized scores for
expressive and receptive language development at ages 3, 5, 7, and 9 years
for adults diagnosed as having schizophreniform disorder (n = 36), mania (n
= 20), anxiety/depression (n = 278), and controls (n = 642).
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Figure 3. The mean standardized scores for
intelligence tests at ages 3, 5, 7, 9, and 11 years for adults diagnosed as
having schizophreniform disorder (n = 36), mania (n = 20), anxiety/depression
(n = 278), and controls (n = 642).
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INTERNALIZING AND EXTERNALIZING PROBLEMS, INTERPERSONAL ADJUSTMENT,
AND PSYCHIATRIC OUTCOMES
The schizophreniform group and the anxiety/depression group exhibited
significantly more childhood internalizing problems as rated by parents and
teachers than the control group (Figure 4). These effects were independent of sex and SES (Table 1). All 3 diagnostic groups exhibited more childhood externalizing
problems than the control group (Figure 4) but, when adjusted for sex and SES, these differences just missed
significance at the 5% level (Table 1).
All 3 diagnostic groups were significantly more likely than the control group
to be rejected by peers, as rated by parents and teachers (Table 1). The mania group and the anxiety/depression group, but
not the schizophreniform group, were significantly more likely than controls
to be rated by parents and teachers as socially isolated (Table 1).
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Figure 4. The mean standardized scores for
internalizing and externalizing problems at ages 5, 7, 9, and 11 years for
adults diagnosed as havingschizophreniform disorder (n = 36), mania (n = 20),
anxiety/depression (n = 278), and controls (n = 642).
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OBSTETRIC AND MATERNAL FACTORS IN RELATION TO DEVELOPMENTAL IMPAIRMENT
We investigated whether the relationships between developmental deficits
and schizophreniform disorder were independent of obstetric complications
and atypical mother-child interaction. Adjusting for the obstetric complications
that were significantly related to schizophreniform outcome and for atypical
mother-child interaction (as well as sex and SES), the associations between
schizophreniform disorder and motor development (ß = -.35; 95%
CI, -0.59 to -0.12; P = .003), receptive
language (ß = -.22; 95% CI, –0.45 to 0.02; P = .07), and IQ (ß = -.26; 95% CI, –0.52 to -0.004; P = .04) did not change significantly.
CHILDHOOD DEVELOPMENTAL IMPAIRMENT AND PSYCHOTIC SYMPTOMS AT AGE 11
YEARS
Self-reported strong psychotic symptoms at age 11 years were associated
with significant developmental impairments in neuromotor development, receptive
language, intelligence, and emotional development (Table 2). The effect sizes were generally even larger than those
noted for schizophreniform disorder at age 26 years. Apart from an association
with receptive language impairment, self-reported weak psychotic symptoms
at age 11 years were not significantly associated with childhood developmental
impairments. However, the direction of the coefficients for the weak-symptom
group was in the same direction as the coefficients for the strong-symptom
group.
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Table 2. Results From Regression Analyses Showing the Association Between
Developmental Functioning During the First Decade of Life and Psychotic Symptoms
at Age 11 Years*
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COMMENT
This longitudinal investigation of an unselected birth cohort examined
several childhood risk factors in relation to 3 adult psychiatric outcomes.
Children who later fulfilled diagnostic criteria for schizophreniform disorder
at age 26 years exhibited significant impairments across a range of developmental
domains (neuromotor, language, cognitive, emotional, and interpersonal development)
from as young as 3 years. In contrast, children who later fulfilled diagnostic
criteria for mania and anxiety/depression exhibited problems only in the areas
of emotional and interpersonal development. Early neuromotor, language, and
cognitive developmental impairments therefore seem to show specificity to
schizophreniform disorder, whereas childhood emotional and interpersonal difficulties
are associated with a range of psychiatric disorders in adulthood. Of special
interest is the finding that similar childhood developmental deficits were
observed in relation to self-reported psychotic symptoms at age 11 years and
in relation to schizophreniform disorder at age 26 years. This suggests that
these developmental deficits are associated with psychotic illness processes
that begin in childhood, and that childhood psychotic symptoms may be part
of a disease process rather than an independent risk factor/marker for later
schizophreniform disorder.
The relationship between neuromotor developmental problems and later
schizophreniform disorder in this study was particularly strong, with evidence
of delay in learning to walk during infancy, an excess of neurologic signs
at age 3 years, and significant impairments on repeated motor testing between
ages 3 and 9 years. We found that the schizophreniform group exhibited deficits
in receptive language development (verbal comprehension) rather than expressive
language development. Previous work on this cohort has shown that receptive
but not expressive language delay at age 3 years was significantly associated
with behavior problems in late childhood,63
and a follow-up study of a group of children with developmental receptive
language disorder has found that 10% of the children later developed schizophrenia.64 Our study also revealed that childhood cognitive
impairments among the schizophreniform group were emerged early and were persistent,
with significant deficits in IQ detectable from age 3 years. In sum, our findings
on motor, language, and cognitive impairments add to a body of work showing
that childhood developmental deficits are found among individuals with schizophrenia
and among those at genetic risk for schizophrenia.7-23
Our study provides new evidence that these impairments may be specific to
schizophrenia. Although 2 previous studies have noted some (albeit weaker)
associations between childhood motor and speech problems and affective disorder,
these abnormalities were mainly confined to childhood-onset cases.24-25
Recent work has found that obstetric complications involving hypoxia
and fetal growth retardation are risk factors for schizophrenia,65-69
and such effects were also noted in this study. In agreement with other cohort
studies,9, 70 we found that aspects
of the mother-child interaction were associated with later schizophreniform
disorder. However, these perinatal and maternal risk factors could not entirely
account for the early developmental impairments found in our schizophreniform
group. We therefore surmise, along with others,20-22
that neurodevelopmental impairments are not merely mediators of the effects
of obstetric complications on risk for schizophrenia. These early developmental
impairments are more likely to reflect the expression of schizophrenia-susceptibility
genes,71-72 and reports of developmental
impairments among offspring at high genetic risk for schizophrenia lend support
to this view.7-8,16, 19
Emotional problems and poor interpersonal functioning in childhood were
associated with a host of different adult psychiatric outcomes at age 26 years,
including schizophreniform disorder, manic episodes, and anxiety/depression
disorders. These predictive associations are of actuarial interest—they
span more than 15 years and do not exhibit specificity to any one outcome.
Lack of specificity is important because it indicates a common pathway to
the development of a range of different disorders. Although this constellation
of childhood behaviors observed in children as young as 5 years is unlikely
to represent a prodrome, it may index, more generally, a vulnerable personality
that is at risk for all adult psychiatric disorders. Although we found no
significant association between childhood social isolation and schizophreniform
disorder, as noted by others,9, 73-75
it is possible that such peer problems become more evident during adolescence.76-77
Limitations of our study should be noted. First, the sample sizes in
the schizophreniform and manic groups are not large. Nevertheless, the developmental
impairments in the schizophreniform group were consistently detected on repeated
testings throughout childhood and were robust to adjustment for sex and social
class effects. Second, the study members have not passed through the entire
period of risk for psychosis. However, the childhood developmental risk factors
found in this study are remarkably similar to those found in a cohort study
that has followed up participants to age 43 years,9
suggesting that our findings can be extrapolated throughout the age-incidence
distribution. Last, throughout this analysis we have reported on findings
for schizophreniform disorder rather than schizophrenia alone, partly because
of sample-size considerations and also because dimensional or continuum models
of psychosis are becoming established as the most likely theoretically78 and the most useful clinically.79
Indeed, it is impressive that the same childhood developmental risk factors
seem to apply to the broader phenotype of schizophreniform disorder as to
the narrower concept of schizophrenia itself.
In conclusion, this study demonstrates that schizophreniform disorder
is associated with childhood developmental deficits across a range of domains.
Motor, language, and cognitive developmental deficits emerge early and are
persistent and specific to schizophreniform disorder. In addition, we have
shown that pan-developmental impairments are associated with psychotic symptoms
both in childhood and in adulthood. Taken as a whole, the evidence from this
study provides support for a neurodevelopmental model of schizophrenia,2-6
echoing the earlier theoretical concept of schizotaxia.80-82
It is increasingly evident that understanding the complex mechanisms governing
brain development will ultimately hold the key to the etiology of schizophrenia.
AUTHOR INFORMATION
Submitted for publication February 5, 2001; final revision received
August 6, 2001; accepted September 4, 2001.
Dr Cannon was supported by an Advanced Fellowship from the Wellcome
Trust, London, England, and an EJLB Scholar Research Award from the EJLB Foundation,
Montreal, Quebec. Additional funding was provided by the Schizophrenia Research
Fund, London, England (Drs Cannon, Caspi and Moffitt). The Dunedin Multidisciplinary
Health and Development Study is supported by the Health Research Council of
New Zealand, Auckland, and grants MH49414 (Dr Caspi), MH45548, and MH45070
(Dr Moffitt) from the National Institute of Mental Health, Bethesda, Md.
We thank Phil Silva, PhD, founding director of the study, Air New Zealand,
the study members and their families for their participation and support,
Matt Smart for secretarial assistance, and Professor Sir Michael Rutter, FRS,
and Professor Peter Jones, PhD, for comments on the manuscript.
Corresponding author and reprints: Terrie E. Moffitt, PhD, Social,
Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry,
Box P080, London SE5 8AF, England (e-mail: t.moffitt{at}iop.kcl.ac.uk).
From the Division of Psychological Medicine (Drs Cannon and Murray),
and the Social, Genetic, and Developmental Psychiatry Research Centre (Drs
Caspi and Moffitt and Mr Taylor), Institute of Psychiatry, London, England;
the University of Wisconsin–Madison, Madison (Drs Caspi and Moffitt
and Ms Harrington); and the Dunedin Multidisciplinary Health and Development
Research Unit, University of Otago, Dunedin, New Zealand (Dr Poulton).
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