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Hong Kong Jockey Club Centre for Suicide Research and Prevention, University of Hong Kong, China, College of Professional Studies, University of Guam, USA, and Institute of Mental Health, West China Medical School of Sichuan University, Chengdu, China
Hong Kong Jockey Club Centre for Suicide Research and Prevention, Universisty of Hong Kong, China
Department of Psychiatry, University of Rochester Medical Center, Rochester, New York, USA
Hong Kong Jockey Club Centre for Suicide Research and Prevention, University of Hong Kong
Institute of Mental Health, West China Medical School of Sichuan University, Chengdu, China
Department of Psychiatry, University of Rochester Medical Center, Rochester, New York, USA
Correspondence: Dr Mao-Sheng Ran, College of Professional Studies, University of Guam, Mangilao, Guam 96923, USA. Tel: +1 671 735 2655; fax: +1 671 734 1203; email: ranmaosh{at}yahoo.com
Funding detailed in Acknowledgements.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Aims To explore the 10-year mortality and its risk factors among patients with schizophrenia.
Method We used data from a 10-year prospective follow-up study (1994–2004) of mortality among people with schizophrenia, and death registration data for Xinjin County, Chengdu, China.
Results The mortality rate was 2228 per 100 000 person-years during
follow-up. Both all-cause mortality and suicide rates were significantly
greater in male than in female patients. Age at illness onset (>45 years),
duration of illness (
10 years), age greater than 50 years, physical
illness, in ability to work, male gender, and never having received treatment
were identified as independent predictors of increased mortality.
Conclusions Higher mortality rates in male patients may contribute to the higher prevalence of schizophrenia in women compared with men in China. The findings of risk factors for mortality should be taken into account when developing interventions to improve outcomes among people with schizophrenia.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Although there are higher rates of schizophrenia in men than in women worldwide (Murray & Lopez, 1996; Aleman et al, 2003), evidence indicates that there are substantially higher rates of schizophrenia in women than in men in China (Cooper & Sartorius, 1996; Zhang et al, 1998; Liu et al, 2000; Ran et al, 2003; Phillips et al, 2004). The reasons why the pattern of schizophrenia in China differs from that in other parts of the world are unknown and largely unstudied.
Suicide is one of the most common causes of premature death in people with schizophrenia (Mortensen & Juel, 1993; De Hert & Peuskens, 2000). Given the unique pattern of suicide in China – rural rates are three times greater than urban rates, and rates in women are 25% higher than those for men in the general population (Phillips et al, 2002)–it is crucial to explore the characteristics of suicide in people with schizophrenia in rural China (Ran & Chen, 2004). Previous studies have been limited by use of retrospective or cross-sectional designs, small numbers of patients, general problems of diagnostic standardisation, restricting the focus to in-patients only, and the relatively low rates of follow-up. Therefore, long-term prospective follow-up study of mortality in people with schizophrenia living in the community should be worthwhile (Harrison et al, 2001; Ran & Chen, 2004).
Our study objectives were to explore the rates of all-cause mortality and suicide among people with schizophrenia, and to identify major causes of death and factors increasing the risk of death.
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METHOD |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Measurement
The principal assessment tools included the PSE and Social Disability
Screening Schedule (SDSS; Shen et
al, 1986) used in the baseline investigation in 1994 (Ran
et al, 2001,
2003). For cohort members who
were alive when followed up in 2004, at least one informant familiar with the
person's life and circumstances and/or the cohort members themselves were
interviewed. For those who had died, the next of kin or at least one informant
familiar with the dead person was interviewed. All the interviews were
conducted by trained psychiatrists using the Patients Follow-up Schedule (PFS)
for about 30 min; this questionnaire was used to collect information
concerning demographic characteristics, cause and time of death, treatment and
social support. For all cases, medical and psychiatric treatment records were
obtained from hospital, village doctors' clinics and traditional healers.
Information from the death certification and suicide note (where applicable)
was also obtained. The classification of each death as due to suicide,
accident or natural causes represented the consensus opinion of interviewers
and independent researchers after reviewing all information obtained during
the interviews. Participants were defined as homeless and lost to follow-up if
an informant reported that they had wandered and slept in public places and
that their whereabouts were now unknown. Participants' physical illnesses
(e.g. heart disease, respiratory disease, cancer) at baseline and follow-up
were defined according to the baseline data, informants' reports and doctors'
diagnoses. Family economic status was defined according to the family mean
income. Marked symptoms were defined according to the assessment of the
PSE.
Statistical analysis
The follow-up period for every participant started at recruitment and ended
at interview, death or the point when the inidividual was lost to follow-up.
Mortality rates were calculated overall and by subgroups defined according to
various characteristics. Mortality rates were estimated using the
person–time method (number of deaths divided by person-years of
follow-up). The effects of gender on all-cause mortality and suicide rates
were tested using univariate Cox hazard regression analyses. Survival analyses
were also used to explore gender differences in survival rates. Standardised
mortality ratios were calculated by dividing observed deaths by expected
deaths, with the general population of Xinjin County as the standard
population. Death registration records for Xinjin County were used to derive
data for the general population.
Predictors of mortality (crude mortality rates) were identified using
univariate and multivariate Cox hazard regression analyses. Hazard ratios for
potential predictors and the corresponding 95% confidence intervals were
determined using univariate Cox regression. All variables with
P
0.10 in univariate analyses were included in a multivariate Cox
model using a backwards procedure. Those with P0.05 were
retained in the final model. The backwards procedure was used to exclude the
potential confounding effect of variables by adding them, one at a time, in
the final model. In addition, 2 x 2 interactions between independent
predictors were tested.
In the Cox analyses and for estimation of the mortality and suicide rates, all independent variables other than gender were treated as time-dependent. All these variables were based on the measures at baseline or follow-up.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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According to the investigation in 1994 (Ran et al, 2001, 2003) the incidence of schizophrenia was 0.58 per 1000 annually for men, and 0.57 per 1000 annually for women. The incidence risk ratio for men to develop schizophrenia relative to women was 1.01 (95% CI 0.79–1.30, P>0.05). At the follow-up assessment in 2004, informants were available for all cases in the sample (n=500). Information on 305 cases was provided by both participants themselves and informants, and information on 195 cases was provided by informants alone.
Current status and mortality
At the end of the follow-up period 372 (74.4%) of the initial cohort were
known to be alive (Table 2).
The status of 30 people (6.0%) who had been homeless was unknown to their
family and friends. Twenty-one people (4.2%) had died by suicide, 13 (2.6%)
had died due to accident and 64 (12.8%) had died from natural causes during
the follow-up period. Among all the 500 participants, 134 (26.8%) had had
various physical illnesses at baseline or at some time during the follow-up
period, 11 (2.2%) had migrated to cities for temporary work, and 6 women
(1.2%) had married and moved to other counties during the 10 years of
follow-up.
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The 98 deaths observed during follow-up represented a mortality rate of 2228 per 100 000 person-years (95% CI 1792–2664). Among men the mortality rate was 2913 (95% CI 2174–3652) and among women it was 1661 (95% CI 1150–2172). The rate was significantly higher in male than in female cohort members (hazard ratio 2.0, 95% CI 1.3–3.2, P<0.005). The standardised mortality ratio for the whole cohort was 4.0 (95% CI 2.4–5.8); for men it was 4.9 (95% CI 2.8–8.1) and for women it was 3.3 (95% CI 1.9–6.1).
Among those who died in the follow-up period, 21 (21.4%) took their own lives, representing a suicide rate of 477 per 100 000 person-years (95% CI 273–681). Among men, the suicide rate was 753 per 100 000 person-years (95% CI 373–1133) and among women it was 249 per 100 000 person-years (95% CI 50–448). The rate was significantly higher in male than in female cohort members (HR=3.1, 95% CI 1.2–8.0, P<0.05). The standardised mortality ratio for all the cohort members who died by suicide was 32.0 (95% CI 18.5–52.5), for men it was 63.5 (95% CI 43.6–94.5) and for women it was 13.4 (95% CI 6.2–32.8). The 13 people who died as a result of accidents during the follow-up period represented a mortality rate due to accident of 296 per 100 000 person-years (95% CI 135–457). The standardised mortality ratio for the people who died by accidents was 6.6 (95% CI 4.3–10.2). The 64 natural deaths during follow-up period represented a mortality rate due to natural causes of 1455 per 100 000 person-years (95% CI 1101–1809). The standardised mortality ratio for all the cohort members who died from natural causes was 2.6 (95% CI 1.7–4.1). Among these 64 deaths, the specific causes of death in 42 cases (66%) were known (various cancers, n=9; heart disease, n=7; respiratory disease, n=7; other disease, n=19).
The survival probability for the whole cohort in 2004 was 0.80 (95% CI
0.76–0.84). Compared with women, the survival rate of men during the
10-year follow-up was significantly lower (survival probability in 2004 for
women, 0.84, 95% CI 0.80–0.88; survival probability in 2004 for men,
0.74, 95% CI 0.68–0.80; log-rank test 
2=7.85,
P<0.01).
Mortality rates by clinical and demographic characteristics and results of
the univariate and multivariate Cox regression analyses are presented in
Table 3. The independent
predictors of mortality identified in the final model were age at onset of
schizophrenia (>45 years), duration of illness (10 years), age greater
than 50 years, physical illness, inability to work, male gender, and never
having received treatment. None of the variables excluded by the backwards
procedure had a confounding effect.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Mortality and suicide
Compared with previous studies (Harris
& Barraclough, 1997; Osby
et al, 2000; Harrison
et al, 2001), our results showed that mortality and
suicide rates are relatively high among people with schizophrenia, both men
and women, in rural China. The overall mortality rate of 2228 per 100 000
person-years observed in our study is extremely high, exceeding by 4 times the
rate observed among people over 15 years old in the general population. This
result is consistent with other results from low- and middle-income countries
(Mojtabai et al,
2001). The suicide rate that we observed (477 per 100 000
person-years) is close to the estimated rate in a previous study of people
with schizophrenia in China (0.68% per year;
Phillips et al,
2004). Standardised mortality ratios were 32.0 for all suicide and
63.5 for males, which is much higher than in other countries
(Osby et al, 2000).
After excluding homeless individuals whose data were unavailable, we
calculated the risk of suicide during the follow-up period as 4.5%, which is
close to the 4.9% risk found in a meta-analysis by Palmer et al
(2005). Our study also
indicated that the direct use of proportionate mortality rates in previous
studies assuming a constant rate of suicide over a lifetime may overestimate
suicide risk (Caldwell & Gottesman,
1990). The rate of suicide in men with schizophrenia was
significantly higher than that in women, which is consistent with a previous
study (Phillips et al,
2004). Suicide rates among men and women with schizophrenia may be
significantly influenced by the illness (e.g. onset, symptoms and treatment),
which could be one explanation for the variation in suicide rates between
people with schizophrenia and the general population.
Mortality and prognosis
Although some authors have suggested that there is a better prognosis for
individuals with schizophrenia in low- and middle-income countries
(Leff et al, 1992),
our study showed a higher rate of mortality and missing due to homelessness
among people with this disorder. It may be premature to suggest that there is
a better prognosis for schizophrenia in these countries if withdrawals or
attrition due to death and homelessness are not included in follow-up
analyses. If the deceased and homeless cases were included in such analyses,
the picture might change significantly. Deaths and homelessness among people
with schizophrenia should be explored more in future natural history studies
of this illness.
Mortality and prevalence
Different mortality rates in men and women in our study may explain the
unique phenomenon of schizophrenia being more prevalent in women than in men
in China. First, given that men have an earlier age at onset than women
(Ran et al, 2003),
the results of our study indicate that the higher mortality rate in men might
be the major reason for the higher prevalence of schizophrenia in women than
in men in China. Higher survival rates for female patients compared with male
patients also support this opinion. This result may also explain in part why
one finds more women among geriatric and late-onset patients with
schizophrenia (Ran et al,
2004). Second, the results also indicated that women with
schizophrenia were more likely to have married and moved away from the area.
Even though the number is small, it is possible that female patients move to
cities, which may increase the prevalence rates for women in urban areas.
Third, our previous study did not support differences in the full remission
rates between men and women (Ran et
al, 2003).
All the risk factors identified in this study reflect the influence of both the socio-economic characteristics of rural China and the clinical characteristics of the cohort. Gender was an independent predictor of death during the follow-up period. Male gender was associated with an increased risk of death in this group, which is consistent with previous studies (Salokangas et al, 2002); the survival advantage of women held also among these participants. Why did the men have a significantly higher mortality rate than the women? Possible reasons may be that oestrogen has a protective effect in women (Seeman & Lang, 1990), or that men with schizophrenia may accept less support and treatment than female patients in rural China (Ran et al, 2003). These possibilities warrant further study.
Mortality and age
Age (>50 years) was an independent predictor of mortality during
follow-up, as one would expect – older people with schizophrenia are
much more likely to die (Palmer et
al, 2005). Although young patients, early in the course of
the illness, are more likely to attempt suicide than older patients, more
patients may die from other causes with increasing age; the proportion who
died by suicide is relatively small among all age groups. Our study showed
that the mortality rate was significantly higher among people with later onset
of schizophrenia (>45 years) than among those with onset before 45 years of
age. Although evidence indicates that individuals with a later onset may have
a more benign illness course, symptom severity and cognitive deficits may be
similar in both early-onset and late-onset cases
(Jeste et al, 1995).
Although the finding that older patients and those with later-onset disorder
have high mortality rates may not relate to lack of treatment, our study still
suggests that higher mortality rates may be associated with the poor treatment
received by older patients in rural China
(Ran et al,
2004).
Mortality and treatment
Evidence indicates that a significant proportion of treated incident cases
of schizophrenia achieve favourable long-term outcome
(Harrison et al,
2001). Suicide risk among patients with schizophrenia-spectrum
disorders declines quickly after treatment and recovery
(Qin & Nordentoft, 2005).
The results of our study indicated that never receiving treatment might
increase the mortality rate among people with schizophrenia and, conversely,
that treatment reduced mortality risk. In a 17-year follow-up study, the
number of antipsychotic drugs taken by patients with schizophrenia showed a
graded relation to mortality (Joukamaa
et al, 2006). Given that certain classes of antipsychotic
have been associated with death (Montout
et al, 2002), we suggest that basic medication is
important in decreasing the mortality and that excessive antipsychotic
administration (e.g. overdose, multiple medication) may increase the
mortality. The relationship between antipsychotics and mortality needs further
study.
The results of our study indicate that long duration of illness and inability to work, which reflect poor social functioning, may increase the risk of mortality. The finding that previous hospitalisation is not a risk factor for mortality may be related to the lower rate of hospitalisation in rural China. Evidence indicates that people with schizophrenia have high rates of potentially reversible medical morbidity that additionally increase mortality (Green et al, 2003; Goff et al, 2005). In our study, over a quarter of the sample had physical illness, which predicted increased mortality. We suggest that treating medical comorbidity might reduce premature mortality among these patients (Goff et al, 2005).
Implications for services
Our results have implications for reducing mortality and suicide rates
among people with schizophrenia in China and elsewhere. The risk factors of
mortality should be taken into account when developing interventions to
prevent premature death among these patients. Suicide prevention strategies
should also be developed. Given the limited resources in contemporary China,
prevention programmes should emphasise community-based mental healthcare to
provide earlier diagnosis, antipsychotic treatment, treatment of comorbid
medical conditions, function rehabilitation and family support. Given the
severe stigma associated with psychiatric illness
(Xiang et al, 1994),
efforts to reduce stigma in the community will be necessary to enable
individuals with schizophrenia to rejoin their community and allow
interventions to be made to decrease their mortality rate.
Our findings indicate that homelessness among people with schizophrenia is a common phenomenon in rural China. Given that homeless individuals might experience mortality and suicide rates much higher than those of their counterparts in the general population (Roy et al, 2004), we suggest that suicide rates among people with schizophrenia might have been underestimated in previous studies in China (Phillips et al, 2004) because homeless people with the disorder were not included. Community-based mental health services, especially family and housing services, should be developed to prevent patients becoming homeless.
Given the representative sample used in this study, we are confident that our findings are generalisable to the population of people with schizophrenia in rural areas in China, and even to other countries that have a similar social environment. Premature death, suicide and homelessness are serious problems in people with schizophrenia in rural China. Supplying community mental health services and medication to these people should be a mental healthcare priority to prevent these early deaths.
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Received for publication April 8, 2006. Revision received September 12, 2006. Accepted for publication October 27, 2006.
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