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[Original Articles]
GOODWIN, R. D.1; FERGUSSON, D. M.; HORWOOD, L. J.
From Christchurch Health and Development Study, Department of Psychological
Medicine, Christchurch School of Medicine and Health Sciences, Christchurch, New
Zealand; and Department of Epidemiology, Columbia University, New York, NY,
USA
1
Address for correspondence: Dr Renee D. Goodwin, 1051 Riverside Drive, Unit 43,
New York, NY 10032, USA.
This research was funded by grants from the Health Research Council of New
Zealand, the National Child Health Research Foundation, the Canterbury Medical
Research Foundation and the New Zealand Lottery Grants Board. Work on this
project was funded by NIMH MH64736.
ABSTRACT
Background. The aims of this research were to examine the associations between the
personality trait of neuroticism in adolescence and later psychotic symptoms, taking
into account potential confounding factors.
Method. Data were gathered over the course of a longitudinal study of a birth cohort of
New Zealand born young people (N=1265). Over the course of the study, data were
gathered on: (a) neuroticism at age 14; (b) psychotic symptoms predominantly
subclinical, assessed on the Symptom Checklist (SCL-90), at ages 18 and 21; (c) a
range of potential confounding factors including measures of childhood adversity and
co-morbid mental disorders.
Results. Young people in the highest quartile of neuroticism at age 14 had rates of
psychotic symptoms that were two to three times higher than those in the lowest
quartile. After statistical adjustment for confounding factors, including childhood
adversity and co-morbid mental disorders, the association between neuroticism and
later psychotic symptoms reduced but remained statistically significant (P<0.05). After
adjustment for confounding, young people with high levels of neuroticism had rates of
psychotic symptoms that were between 1.5 to 1.8 times higher than those with low
levels of neuroticism.
Conclusions. Early neuroticism may be a precursor to the onset of psychotic
symptoms. The mechanisms underlying this association are unclear, but may relate to
overlapping features between prodromal phases of psychosis and items that measure
neuroticism.
INTRODUCTION
There has been extensive research into the linkages between the personality factor of
neuroticism and subsequent psychiatric disorders. Studies have variously shown that
individuals with high neuroticism have increased risk of a range of disorders including
depression (Fergusson et al. 1989a,b; Rodgers, 1990; Kendler et al. 1993; Roy, 1999;
Bienvenu et al. 2001), anxiety disorders (Gershuny & Sher, 1998; Bienvenu et al.
2001) and substance use disorders (Prescott et al. 1997; McCormick et al. 1998;
Loukas et al. 2000; Mulder, 2002). In general, these findings suggest that rates of
disorder, and particularly internalizing disorders, are elevated among those with high
neuroticism.
In contrast, less research has been conducted into the relationship between neuroticism
and psychotic symptoms and disorders. However, a recent longitudinal study of a large
population-based cohort found that measures of neuroticism obtained at age 16 were
predictive of schizophrenia during adulthood (Van Os & Jones, 2001). Using a national
birth cohort, Van Os & Jones found that neuroticism at age 16 was associated with
increased risk of schizophrenia in adulthood (summary OR=1.9 (1.09, 3.43)), which
persisted after adjusting for symptoms of anxiety and depression measured at ages 36
and 43 (OR=1.73 (1.00, 3.36)). These findings clearly raise the possibility that high
neuroticism may be a precursor of later psychosis or psychotic symptoms. However, a
difficulty with this conclusion concerns the extent to which linkages between
neuroticism and later psychosis reflect the presence of: (a) common factors that are
associated with both early neuroticism and later psychotic symptoms; (b) the presence
of co-morbid disorders that may be related to both neuroticism and psychotic
symptoms.
Against this background, this paper reports on a longitudinal study of the relationships
between neuroticism in adolescence (age 14) and subsequent psychotic symptoms in a
birth cohort of New Zealand children studied to age 21 years. The aims of this study
were: (1) to estimate associations between neuroticism in adolescence and later
psychotic symptoms; and (2) to adjust any such associations for childhood factors
related to neuroticism and co-morbid mental disorders. More generally, the aims of the
research were to validate the report by Van Os & Jones (2001) of linkages between
neuroticism and psychotic symptoms and to examine the extent to which this
relationship persisted after control for antecedent childhood factors and co-morbid
disorder.
METHOD
The data described in this report were gathered during the course of the Christchurch
Health and Development Study (CHDS). The CHDS is a longitudinal study of an
unselected birth cohort of 1265 children (635 males, 630 females) born in the
Christchurch, New Zealand, urban region in mid-1977. This cohort has now been
studied at birth, 4 months, 1 year and at annual intervals to age 16 years, and again at
ages 18 and 21 years, using information obtained from a combination of sources
including: parental interview, teacher report, self-report, psychometric assessment,
medical and Police records. For a detailed overview of the study design and synthesis
of study findings see Fergusson et al. (1989a) and Fergusson & Horwood (2001). The
following measures were used in the present analysis.
Neuroticism
Neuroticism in adolescence was assessed using a short form version of the neuroticism
scale of the Eysenck Personality Inventory (Eysenck & Eysenck, 1964), administered
when sample members were aged 14 years. The reliability of this scale, assessed using
coefficient [alpha], was 0.80.
Psychotic symptoms
At age 18 and 21, DSM-IV symptom criteria for conduct disorder were assessed using
items from the SRDI. At age 21, this information was supplemented by further custom
written survey items to assess DSM-IV criteria for antisocial personality disorder.
Overall, 4.7% of the sample met criteria for conduct disorder at age 16-18 years and
4.0% for conduct or antisocial personality disorder at age 18-21 years.
Alcohol/illicit drug dependence
At each interview sample members were questioned about their use of alcohol,
cannabis and other illicit drugs since the previous assessment. As part of this
questioning, items from the CIDI were used to assess DSM-IV symptom criteria for
alcohol dependence and illicit drug dependence. On the basis of this questioning 8.7%
of the sample were classified as having met criteria for alcohol or illicit drug
dependence during the period 16-18 years and 10.7% from 18-21 years.
Childhood factors
To control the association between child neuroticism and later psychotic symptoms for
possible confounding by childhood and family risk factors, a range of variables were
selected from the database of the study. These variables were selected on the basis that
they were known to be correlated with child neuroticism and were as follows.
Gender
Maternal education
Maternal education levels were assessed at the time of the survey child's birth using a
three level classification reflecting the highest level of educational attainment (no
formal qualifications; high school qualifications tertiary qualifications).
Childhood sexual abuse
At age 18 and 21 years, sample members were questioned about their experience of
childhood sexual abuse prior to the age of 16 years (Fergusson et al. 2000). This
questioning spanned an array of unwanted sexual experiences ranging from episodes of
non-contact abuse (e.g. indecent exposure, lewd comments) to incidents involving
sexual contact (e.g. sexual fondling, genital contact, attempts to undress the
respondent) to incidents involving attempted or completed intercourse. Young people
who reported an episode of abuse were further questioned about the extent and nature
of the abuse. For the purposes of the present analysis, the young person was classified
as having experienced childhood sexual abuse if s/he reported, at either age 18 or 21,
any episode of sexual abuse involving physical contact with the perpetrator.
Changes of parents (0-15 years)
An overall index of family instability during childhood was constructed on the basis of
a count of the number of changes of parents experienced by the child up to age 15
years. All changes resulting from parental separation/divorce, reconciliation,
remarriage, death, fostering and any other changes of custodial parents were included.
Interparental violence (0-16 years)
At age 18, sample members were questioned using items from the Conflict Tactics
Scale (Straus, 1979) to assess the extent to which they had witnessed incidents of
physical violence or serious threats of physical violence between their parents during
childhood (Fergusson & Horwood, 1998). This information was used to construct
separate scale scores representing the extent of father-initiated and mother-initiated
interparental violence witnessed by the child. These scale scores were of moderate to
good internal consistency, with coefficient alpha values ranging from 0.77 to 0.86. For
the purposes of the present analysis the two scales were combined to provide an overall
measure of interparental violence.
Adverse family life events (0-15 years)
At each assessment to age 15 years, parents were questioned about the occurrence of
adverse family life events during the preceding 12 months using a life events checklist
based on the Holmes and Rahe Social Readjustment Rating Scale (Holmes & Rahe,
1967). An overall index of the extent of family adversity during childhood was
constructed from a sum of the life events reported in each year.
Parental history of depression/anxiety
When sample members were aged 15 years, parents were questioned concerning their
history of depression or anxiety disorders. On the basis of this questioning 29.3% of
the sample were classified as having a parental history of depression or anxiety.
Parental attachment (14 years)
The quality of parental attachments was assessed at age 14 years using the parental
attachment scale developed by Armsden & Greenberg (1987). The full scale score was
used in the present analysis, and this scale was found to have excellent reliability
([alpha]=0.91).
Sample size and sample bias
The present analysis is based on the sample of 961 young people for whom
information was available on neuroticism at age 14 and psychotic symptoms at 18 or
21 years. This sample represented 76% of the initial cohort of 1265 children. This level
of sample loss raises the issue of the extent to which the results may have been
influenced by sample selection bias. To address this issue, the techniques described by
Carlin et al. (1999) were used. These methods involved a two stage analysis process. In
the first stage a sample selection model was constructed by using data gathered at birth
to predict inclusion in the sample for analysis. This analysis showed that there were
statistically significant (P<0.05) tendencies for the obtained sample to under-represent
children from more socially disadvantaged backgrounds (low parental education, low
socio-economic status family, single parent family). On the bias of the fitted selection
model the sample was then post-stratified into a series of groups and the probability of
study participation estimated for each group. In the second stage, the data were reanalysed using negative binomial regression with robust estimates of standard errors
and with the observations for each individual weighted by the inverse of the
probability of sample inclusion. This analysis produced essentially identical
conclusions to those reported here, suggesting that the effects of missing data and
possible sample selection bias on the results were likely to be minimal.
RESULTS
Association between neuroticism and psychotic symptoms
Table 1 shows the measure of neuroticism at age 14 divided into quartile groups. For
each group, the mean number of psychotic symptoms reported at ages 18 and 21 is
given. The association between neuroticism and psychotic symptoms is tested for
linearity using one-way analysis of variance for linear trend. This analysis shows
highly significant (P<0.0001) linear associations between neuroticism and the mean
number of psychotic symptom scores. Those in the highest quartile of neuroticism had
rates of psychotic symptoms that were between 2-3 times higher than those in the
lowest quartile.
dichotomized. However, in subsequent analyses (see below) all childhood factors were
scored in their natural metric as described in the Method section.
Examination of Table 3 shows that neuroticism was associated with: (1) gender, with
high levels of neuroticism being more common among females; (2) maternal
education, with higher levels of neuroticism being associated with poorer maternal
educational achievement; (3) exposure to childhood sexual abuse, with those in the
highest quartile of neuroticism reporting more than three times the rate of abuse
compared to those in the lowest quartile; (4) parental change and conflict, with
increasing neuroticism being associated with more frequent exposure to changes of
parents and higher levels of inter-parental violence; (5) adverse family life events, with
those in the highest quartile being exposed to higher levels of family stress and
adversity during childhood; (6) parental depression/anxiety, with those reporting high
levels of neuroticism being more likely to have parents with a history of internalizing
disorders; and (7) the quality of parental attachment in adolescence, with increasing
levels of neuroticism being associated with poorer quality parental attachment.
These results clearly suggest that high neuroticism tended to be associated with female
gender, parental educational disadvantage, exposure to childhood sexual abuse,
parental change and conflict, family stress, a family history of internalizing problems,
and poor quality parental attachments.
Associations between neuroticism and psychotic symptoms, adjusted for childhood
background and co-morbid disorder
The results in Tables 2 and 3 raise the clear possibility that the apparent associations
between neuroticism and psychotic symptoms may reflect the confounding effects of
co-morbid disorders (see Table 2), or exposure to childhood adversity (see Table 3). To
address this issue, the data were analysed using a negative binomial regression model
in which the rate of psychotic symptoms at ages 18 and 21 was the dependent variable
and measures of neuroticism, co-morbid disorder, and childhood adversity were
predictors. The results of these analyses are summarized in Table 4, which shows the
associations between neuroticism and psychotic symptoms after adjusting for: (a)
childhood factors; (b) co-morbid disorders; and (c) all covariates. For each association,
the table shows estimates of the adjusted incidence rate ratios (IRR) and corresponding
95% confidence intervals. The IRR estimates the rate of psychotic symptoms for those
with a given level of neuroticism relative to the rates of symptoms for those in the
lowest quartile. For comparative purposes, Table 4 also gives the estimated IRRs prior
to adjustment for other factors. The Table shows that, even following adjustment, there
were still significant linkages (P<0.05) between neuroticism at age 14 and rates of
psychotic symptoms at ages 18 and 21. Those in the highest quartile of neuroticism had
rates of later psychotic symptoms that were between 1.5 to 1.8 times higher than those
in the lowest quartile. These findings suggest that the association between neuroticism
and later psychotic symptoms cannot be explained as being due to the confounding
effects of early childhood adversity or co-morbid disorders.
Sensitivity analysis
For the purposes of exposition, the above analyses have presented neuroticism in
quartile groups. This approximation has the advantage of making it possible to tabulate
the association between neuroticism with other factors in a readily accessible and
readable way. A potential limitation of this approach is that by classifying neuroticism
into broad groups, statistical precision may be lost. To address this issue, the data were
reanalysed using a model in which neuroticism was treated as a continuous variable.
This reanalysis produced very similar results to those reported above suggesting that
the results were not adversely influenced by the classification of neuroticism into
quartile groups.
DISCUSSION
In this paper, we have used data gathered over the course of a 21-year longitudinal
study to investigate the linkages between neuroticism in mid adolescence and
subsequent psychotic symptoms in early adulthood. The key findings of this analysis
are reviewed below.
The results confirm the findings of Van Os & Jones (2001) and suggest that young
people with high neuroticism are at increased risk of later psychotic symptoms. Those
in the highest quartile of neuroticism had rates of psychotic symptoms that were
between two and three times higher than those in the lowest quartile. There seems to be
little doubt on the basis of this accumulated evidence that young people scoring high
on neuroticism in youth are at increased risk of later psychotic symptoms.
Further analysis suggested that some of the association between neuroticism and
psychotic symptoms was spurious and arose from confounding effects of factors that
were associated with neuroticism and later psychotic symptoms. These factors
included: childhood adversity and co-morbid internalizing disorders. Statistical
adjustment for these potentially confounding factors reduced the association between
neuroticism and psychotic symptoms somewhat. It could be suggested that including
co-morbid disorders as covariates may have led to some 'over control' of the
association. However, even following such control, young people in the highest
quartile of neuroticism had rates of psychotic symptoms that were between 1.5 to 1.8
times higher than those of young people in the lowest quartile of psychotic symptoms.
These results were robust and stable and were replicable at ages 18 and 21.
Collectively, these findings suggest that it is unlikely that the association between early
neuroticism and later psychotic symptoms can be ascribed to the effects of common
confounding factors.
These results suggest a possible causal link in which high neuroticism is a precursor of
later psychotic symptoms. The mechanisms underlying these associations are unclear.
It could be that there is a common genetic or familially inherited factor underlying the
lifetime co-occurrence of neuroticism and psychotic symptoms. It is also possible that
in some persons, high levels of neuroticism are a reflection of a prodromal, or
subclinical, phase of psychosis. Alternatively, it may be that the tendency to experience
the world with a negative perspective, one of the key features of neuroticism, leads to
the development of more severe perceptual disturbances - with the same theme but that
are not based on reality - as a later development of severe early perceptual styles
characterized by neuroticism. It may be that there is a continuum of negative
perceptual disturbances, with the milder end being characterized by neuroticism which
extends to the more severe extreme characterized by psychosis. High levels of
neuroticism at age 14 may reveal a vulnerability to psychotic symptoms later in life
among some proportion of individuals. It is also of interest that neuroticism was
consistently associated with increased rates of depression, panic disorder, social phobia
and specific phobia, which are considered internalizing disorders and have also shown
strong co-morbidity with psychotic disorders in clinical and community samples
(Bermanzohn et al. 2000; Goodwin & Davidson, 2002). In contrast, neuroticism was
not statistically significantly associated with conduct disorder at either time point, and
there were less consistent associations between neuroticism and GAD and
alcohol/illicit drug dependence. It is not clear why psychotic symptoms, depression,
panic, and phobic disorders might be predicted by neuroticism but conduct disorder
would not but further exploration of the potential differential strength of these links
may be fruitful in understanding possible shared aetiological links or preventive
interventions.
The present study has a number of strengths including: (a) the use of a well-studied
population sample; (b) the prospective measurement of personality thus reducing the
potential for psychotic symptoms to contaminate reporting of personality traits; (c)
availability of a wide range of co-morbid mental disorders and childhood factors.
There are, nonetheless, limitations of the study. The most important shortcoming is the
assessment of psychotic symptoms. From a clinical perspective, it is important to know
to what degree neuroticism is predictive of psychotic illness. The results of this study
are not able to address this question directly as the rate of psychotic disorders is too
low for analysis in this cohort. We have used a scale measure of symptoms that are
known to occur in psychotic states, and though not reflective of psychotic illness per
se, have been shown to be associated with significant functional impairment even in
the absence of a full-blown psychotic disorder (Van Os et al. 1999). Still, the extent to
which endorsement of items on the SCL-90 reflects the presence of a psychotic
disorder remains unknown. Therefore, replication of these findings in future studies
with larger samples will be needed.
Notwithstanding the above limitations, the present study suggests that early
neuroticism may be a precursor for later psychotic symptoms. Future studies that are
able to examine these linkages even earlier in life may help illuminate the mechanism
of the observed association, as well as the specific roles played by confounding risk
factors and co-morbid mental disorders.
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