It is an axiom in international psychiatry that schizophrenia
has a better course and outcome in low- and middle-income
countries.1,2Although a few important cross-national studies
by the World Health Organization (WHO) support the ‘better
prognosis’ hypothesis,3–6it may be premature to conclude that
further examination of the question is not necessary.7,8
A considerable number of individuals with schizophrenia go
countries.9–11Mortality is higher in people with schizophrenia
than in the general population,5,12,13and the differential mortality
gap between people with schizophrenia and the general
population has worsened in recent decades.13Suicide is one of
the most common causes of premature death in individuals with
schizophrenia.14–17However, no studies on mortality and rates of
suicide in never-treated people with schizophrenia have been
Compared with urban areas, mental health services are less
available and more people may never accept treatment in rural
China.18Lack of knowledge of medical treatment may influence
the beliefs of individuals and their families about medication.18
Knowledge of different outcomes between never-treated and
treated people with schizophrenia may change the attitudes of
people and their families towards medication and improve the rate
of drug treatment.
Knowledge of psychopathology in untreated individuals
would be helpful to identify the natural state of the illness and
improve understanding of the pathology underlying the illness.19
Knowledge about never-treated individuals should also be
meaningful for clinical services and understanding of the
neuropathology of the illness.
The objectives of this long-term prospective follow-up study
in people with schizophrenia in rural China were: to compare
the rates of all-cause mortality and suicide between never-treated
and treated individuals with schizophrenia; and to explore the
characteristics of never-treated people.
All participants with schizophrenia (n=510) were identified from
an epidemiological investigation of 123572 people aged 15 years
and older in six townships of Xinjin County in March 1994.
Participants were identified through screening procedures for
psychosis and general psychiatric interview. The details of this
investigation have been described in previous papers.10,20All
participants lived in rural communities and met ICD–10 criteria21
for a diagnosis of schizophrenia based on standardised admin-
istration of the Present State Examination (PSE–9)22by trained
research interviewers. Using the baseline data in 1994 we followed
up and interviewed all the participants with schizophrenia and
their informants in May 2004. All respondents gave informed
The principal assessment tools included the PSE–9 and Social
Disability Screening Schedule (SDSS)23in the baseline invest-
igation in 1994.10,20For individuals still alive at the visit in
2004, at least one person familiar with each participant’s life
and circumstances and/or the participant themselves were
interviewed.7For participants now deceased, the next-of-kin or
at least one person familiar with the person was interviewed. All
interviews were conducted by trained psychiatrists using the
Patients Follow-up Schedule (PFS)7for about 30min. For all
Differences in mortality and suicidal behaviour
between treated and never-treated people
with schizophrenia in rural China
Mao-Sheng Ran, Cecilia Lai-Wan Chan, Eric Yu-Hai Chen, Wen-Jun Mao, Shi-Hui Hu,
Cui-Ping Tang, Fu-Rong Lin and Yeates Conwell
Many people with schizophrenia remain untreated in the
community. Long-term mortality and suicidal behaviour
among never-treated individuals with schizophrenia in the
community are unknown.
To explore 10-year mortality and suicidal behaviour among
never-treated individuals with schizophrenia.
We used data from a 10-year prospective follow-up study
(1994–2004) among people with schizophrenia in Xinjin
County, Chengdu, China.
The mortality rate for never-treated individuals with
schizophrenia was 2761 per 100000 person-years during
follow-up. There were no significant differences of rates of
suicide and all-cause mortality between never-treated and
treated individuals. The standardised mortality ratio (SMR) for
never-treated people was 10.4 (95% CI 7.2–15.2) and for
treated individuals 6.5 (95% CI 5.2–8.5). Compared with
treated people, never-treated individuals were more likely to
be older, poorer, have a longer duration of illness, marked
symptoms and fewer family members.
The never-treated individuals have similar mortality to and a
higher proportion of marked symptoms than treated people,
which may reflect the poor outcome of the individuals
without treatment. The higher rates of mortality,
homelessness and never being treated among people with
schizophrenia in low- and middle-income nations might
challenge presumed wisdom about schizophrenia outcomes
in these countries.
Declaration of interest
The British Journal of Psychiatry (2009)
195, 126–131. doi: 10.1192/bjp.bp.108.055301
participants, medical and psychiatric treatment records were
obtained from hospitals, village doctors’ clinics and traditional
healers. For participants now deceased, information from the
death certification and suicide note, where applicable, was also
Participants were defined as ‘never-treated’ if the individual
and/or informants reported that they had not received any
antipsychotic medication since their first episode of schizophrenia.
The never-treated participants were classified according to the
treatment information collected in 1994 and 2004, which included
participant and/or informant reports, treatment records in
hospitals, village doctor’s clinics and traditional healers.
The classification of each death as a result of suicide or other
causes represented the consensus opinion of interviewers and
independent researchers after reviewing all information obtained
during the interviews. Information from the death certification
and suicide note (where applicable) was also obtained. Parti-
cipants were defined as homeless and lost to follow-up if
informants reported that they had wandered and slept in public
places and that their whereabouts was unknown.7Participants’
physical illnesses (e.g. diseases of heart and lung, hypertension
and cancer) at some time during the follow-up period were
defined according to the informants’ report and doctors’
diagnoses. Marked symptoms (significant positive and/or negative
symptoms, mood symptoms or resulting behavioural disturbance)
were defined according to the PSE–9.22
The follow-up period for every participant started at recruitment
and ended either at interview, death or the point at which they
were 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 antipsychotic treatment on mortality and suicide rates
were tested using univariate Cox hazard regression analyses.
Survival analyses were also used to explore treatment differences
in survival rates.
Standardised mortality ratios (SMRs) were calculated by
dividing observed deaths by expected deaths, with the general
population in Xinjin County used as a standard population. Death
registration data of Xinjin County were used for the general
population. All the variables analysed were based on the measures
at baseline or follow-up.
Characteristics of the cohort participants
Of 510 individuals identified as having schizophrenia in 1994, 10
people did not complete the evaluation. The remaining 500 parti-
cipants (98.0%, 500/510) were available for follow-up (1994–
2004), of which 46.6% were male, 64.2% were married, and in
55.8% the family’s economic status was less than the mean.
All 500 participants included in 1994 were followed up from
1994 to 2004. Informants were available for all these participants
(100%). Information on 305 participants was provided by both
the individual and their informants, and information on 195
participants was provided by proxy informants alone.
Differences between never-treated and treated
At the end of the follow-up period, 132 participants (or their
proxy informants) (26.4%) reported never having received
antipsychotic treatment and 368 (73.6%) reported having received
antipsychotic treatment for their schizophrenia (Table 1). Among
the treated individuals, there were 117 people (31.8%) who had
been admitted to a mental hospital, and 133 individuals
(36.1%) who had accepted antipsychotic treatment for less than
2 months. Compared with treated participants (traditional
Chinese medicine 45.7%, treatment by traditional healers
61.7%), never-treated people had received significantly less trad-
itional Chinese medicine (13.6%) and treatment by traditional
The characteristics of never-treated and treated participants
are described in Table 2. Compared with treated participants,
never-treated participants were significantly older, less likely to
be married, had a lower education level and fewer family
members. Caregivers of never-treated people were less likely to
be a parent or spouse. The never-treated individuals were sig-
nificantly older at age at onset, more likely to live alone, had
longer duration of illness, more marked symptoms and fewer
previous suicide attempts.
Current status and mortality
In 2004, as indicated in Table 3, there were no significant differ-
ences between never-treated (70.5%) and treated participants
(75.8%) in the percentage that had survived. There were also no
significant differences between never-treated (5.3%) and treated
participants (6.3%) in the proportion that were homeless. The
percentage of never-treated individuals who died by suicide
(3.0%) was similar to that in those who had been treated
(4.6%). Deaths from other causes were significantly more frequent
in never-treated (21.2%) than treated (13.3%) people during the
There were no significant differences between male never-
treated and treated participants in the percentage surviving at
follow-up, who had died by suicide or other causes, or who were
homeless. However, deaths from other causes were significantly
more frequent in female never-treated (20.0%) than treated
(10.4%) participants during the follow-up period. Among
never-treated individuals, there were no significant differences
between men (44.8%) and women (44.6%) in the percentage
who were unable to work. Among treated participants, there were
significantly more men (41.6%) with an inability to work than
women (32.2%) (w2=10.1, d.f.=2, P50.01).
The mortality rates and SMR of never-treated and treated
participants are shown in Table 4. There was no significant
Mortality and suicidal behaviour in people with schizophrenia
Treated and never-treated groups
Treated participants, n (%)
Never-treated participants, n (%)
Antipsychotic drugs368 (100)0 (0)
Traditional Chinese medicine 168 (45.7)18 (13.6)42.63*** 3.75 (2.36–5.96)
Treatment by traditional healers227 (61.7) 45 (34.1)29.82*** 1.35 (1.20–1.51)
Ran et al
difference between the mortality rate in never-treated and treated
individuals using Cox hazard regression analyses.
There were no significant differences in suicide rates between
never-treated (345.1 per 100000 person–years) and treated parti-
cipants (520.4 per 100000 person–years) using Cox hazard
regression analyses. The SMR for never-treated individuals who
died by suicide was 32.5, and for treated individuals 46.7.
There were no significant differences in the mortality rate
from other causes (accidental and natural) between never-treated
(2415.9 per 100000 person–years) and treated participants
(1199.9 per 100000 person–years) using Cox hazard regression
analyses. The SMR for never-treated individuals who died from
other causes was 9.5, and for treated individuals 5.9.
The survival probability for never-treated people in 2004 was
0.71 (95% CI 0.61–0.80). There was no significant difference in
survival rate between never-treated and treated participants
(survival probability in 2004: 0.76, 95% CI 0.71–0.81) during
the 10 years of follow-up (Log-rank test: w2=2.13, P40.05).
Comparison between never-treated and treated participants
Variable Never-treated participants (n=132) Treated participants (n=368)Testd.f.
Gender, male: n (%) 67 (50.8)166 (45.1)
Marital status, n (%)
Education (primary school), n (%) 113 (85.6)253 (68.8)
Family economic status (< mean), n (%) 81 (61.4) 197 (53.5)
Family history of mental illness, n (%)34 (25.8) 107 (29.1)
Caregivers, n (%)
Live alone, n (%) 29 (22.0)24 (6.5)
Inability to work, n (%)30 (22.7)67 (18.2)
With marked symptoms, n (%)
Living in stable house,an (%)
Previous suicide attempts,an (%)
Physical illness,an (%)
101 (76.5)206 (56.0)
106 (80.3) 334 (90.8)1
7 (5.3) 69 (18.8)1
34 (25.8)100 (27.2)1 0.75
Age, years: mean (s.d.)50 (16.0) 42.9 (15.0)
Duration of illness: mean (s.d.)15.4 (13.1) 11.5 (10.4)
Age at onset: mean (s.d.) 34.2 (14.1)30.1 (12.5)
Number of family members: mean (s.d.)3 (1.7) 3.6 (1.4)
a. Data from 2004; all others: data from 1994.
Current status of 500 cohort participants in 2004
Never-treated participants, n (%) Treated participants, n (%)
Current status MaleFemale TotalMale FemaleTotal
Survivals44 (65.6) 49 (75.4)93 (70.5) 115 (69.3) 164 (81.2)279 (75.8)
Deaths from other causes
Homeless and lost to follow-up 4 (6.0)3 (4.6)7 (5.3)12 (7.2)11 (5.4) 23 (6.3)
Total67 (50.8)65 (49.2) 132 (26.4) 166 (45.1)202 (54.9)368 (73.6)
a. w2=4.08, d.f.=1, P50.05.
b. w2=4.65, d.f.=1, P50.05.
Death rates per 100 000 person–years and standardised mortality ratios (SMR)
Never-treated participantsTreated participants
Rate SMR (95% CI)RateSMR (95% CI)Hazard ratio (95% CI)
Suicide345.132.5 (26.8–47.0)520.446.7 (27.8–51.3)1.2 (0.4–3.7)
Deaths from other causes2415.99.5 (6.2–14.0) 1199.95.9 (4.9–7.0)1.0 (0.6–1.6)
Total deaths 2761.010.4 (7.2–15.2)1720.36.5 (5.2–8.5)1.1 (0.7–1.7)
Mortality and suicidal behaviour in people with schizophrenia
To our knowledge, this is the first long-term prospective cohort
study of mortality and suicidal behaviour in people with
schizophrenia in the community who had never been treated with
antipsychotic medication. It includes longitudinal follow-up and
analyses based on time-dependent factors. The strengths of our
study include the use of a large representative community sample
in rural China, its longitudinal 10-year follow-up design and high
rates of participant retention.
Mortality and suicide
The results of Cox hazard regression analyses did not support
differences in mortality between never-treated and treated parti-
cipants with schizophrenia. The results of survival analyses also
indicated that there was no significant difference in 10-year
survival rates between never-treated and treated individuals. The
overall mortality rates in those never-treated and those treated
are extremely high, exceeding by 6.5 times the rate observed
among people over 15 years old in the general population.
The results indicate that suicidal behaviour is common in
never-treated and treated people with schizophrenia. The results
of Cox hazard regression analyses also did not support differences
in rates of suicide between never-treated and treated individuals.
The suicide rate that we observed in never-treated participants
is similar to the rate in those who have received treatment.
Standardised mortality ratios for suicide were 32.5 in never-
treated participants and 46.7 for treated participants.
Why are there no significant differences in total mortality rates
between never-treated and treated participants? Given the higher
proportion of marked symptoms and longer duration of illness,
it could not be because never-treated individuals had less severe
illness. Thus, despite the lack of treatment, the mortality in
never-treated participants still remained the same as those who
received treatment. The reasons may be as follows. First, the
mortality of those with schizophrenia may be influenced by
multiple factors including antipsychotic medication, family care
and physical status. Second, the results indicate that antipsychotic
treatment may not reduce the long-term mortality rates and
increase survival rates in people with schizophrenia. One study
in The Netherlands indicated that there was no significant
difference in the suicide rate between placebo and active treatment
groups.24Third, the effectiveness of antipsychotic treatment may
be underestimated because a lot of people in the treated group
had not received regular antipsychotic treatment. For example,
only 31.8% of participants had been admitted to a mental hospital
and 36.1% had accepted antipsychotic treatment for less than 2
months. Fourth, many people in the never-treated group received
traditional Chinese medicine (13.6%) and treatment by traditional
healers (34.1%), interventions that could potentially influence
the outcome of schizophrenia.25Further studies of never-treated
individuals may be helpful to explore the differences.
Although evidence indicates that a significant proportion of
treated incident cases of schizophrenia achieve favourable long-
term outcomes,5certain classes of antipsychotics have been
associated with death.26
Suicide risk among people with
schizophrenia-spectrum disorders declines quickly after treatment
and recovery.27However, the results of this study indicate that
there are no significant differences in mortality and rates of
suicide between people who had received antipsychotic treatment
and those who did not. The results did not support the
expectation that antipsychotic drugs could reduce the long-term
mortality rates in these individuals. The long-term mortality of
never-treated participants is similar to, if not higher than, the
mortality of treated participants with schizophrenia.
In general, older patients are much more likely to die.28
Evidence indicated that the mortality rate was significantly higher
among individuals with later onset of schizophrenia (445 years)
than those with age at onset before 45 years of age.7However,
although people with a later onset may have a more benign course
of illness, symptom severity and cognitive deficits may be similar
in participants with early-onset and late-onset schizophrenia.29
The results of this study indicated that there were no significant
differences in mortality rates between never-treated and treated
participants even though never-treated people were older and
had a later onset of illness than treated individuals.
The results of our study indicate that never-treated people are
more likely to be older, unmarried, be of an older age at onset,
longer duration of illness, fewer family members, more marked
symptoms and accept less support than treated individuals in rural
China. All these possible risk factors of never-treated participants
identified in this study reflect the influence of both socioeconomic
characteristics of rural China and the clinical characteristics of
these participants. It is striking that there are no differences in
mortality rates even though the untreated group is associated with
a range of significant risk factors: more likely to be older, less likely
to be married, have less social support and more marked
symptoms. The influence of socioeconomic characteristics of
participants with schizophrenia on mortality and suicide risk
needs further study.
Given the similar mortality rates between never-treated and
treated participants, we suggest that antipsychotic treatment
may actually be ineffective in reducing mortality. However, the
results of this study indicate that antipsychotic treatment might
reduce long-term symptom severity. The results signified the
importance of medication on reducing the psychotic symptoms.
Differences in symptom severity might have an impact on other
dimensions of outcome such as social function. The impact of
medication on social function needs further study.
Our results indicate that there were no significant differences
between male never-treated and treated participants in the
percentage of survivals, suicide, deaths from other causes and
homelessness. However, female never-treated participants had a
higher percentage of deaths from other causes than treated parti-
cipants. Male treated participants had a worse ability to work than
female treated participants. Differences between genders regarding
medication needs further study.
Evidence indicates that the longer the psychotic symptoms
continue unchecked by medication, the greater the likelihood of
profound clinical deterioration.30The results of the present study
indicate that never-treated participants have significantly more
marked symptoms, consistent with a previous study in Bali in
which never-treated participants showed significantly higher total
Positive and Negative Syndrome Scale (PANSS) scores than did
those in the treated group.11Our results may support the
possibility that the severity of symptoms remains the same in
untreated individuals irrespective of the duration of illness.19
The results of this study indicate that never-treated parti-
cipants may be associated with lower family economic level and
fewer caregivers in rural China.7,31The small number of family
members, reflecting the nuclear family, may be a risk factor related
to non-treatment of individuals with schizophrenia that is differ-
ent from a study in India in which the larger extended/joint family
seemed to be a crucial factor associated with non-treatment.9
Caregivers were less likely to be a parent or spouse in never-treated
Ran et al
participants which might also be a risk factor related to non-
treatment of these individuals. Never-treated people were more
likely to be older in age and ill for a longer duration than those
who had been treated, which is consistent with the Indian study.9
We suggest that the traditionally supportive family network may
be broken down by prolonged illness and poor clinical status.20,32
The role of families needs further study.
Evidence indicates that people with schizophrenia have high
rates of potentially reversible medical morbidity that increase
mortality as well.33,34The results of this study indicate that there
were no significant differences in physical illness between never-
treated and treated individuals.
Implications for services
Our results have implications for reducing mortality and suicide
among never-treated and treated people with schizophrenia in
China and elsewhere. The characteristics of these individuals
should be taken into account when developing interventions to
prevent mortality. Resources and services for mental disorders
are insufficient considering the burden caused by these disorders
around the world.35Long-term outcomes of schizophrenia may
be worsened as the absence of mental health services delays
treatment.36We suggest that treatment including antipsychotic
medication and other interventions (such as traditional Chinese
medicine) may improve outcomes for untreated individuals even
though they have been ill for many years.37Given 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 severe stigma associated with psychiatric illness,18efforts
to reduce stigma in the community will be necessary for
individuals with schizophrenia to be accepted by the community
again and interventions made to decrease their mortality rate.
The results of our long-term studies among people with
schizophrenia challenge the axiom in international psychiatry that
schizophrenia has a better course and outcome in low- and
middle-income countries.1,2Given the high rates of mortality,
including suicide, homelessness and never-treated people with
schizophrenia in low- and middle-income countries, it is
premature to come to this conclusion if withdrawals or attrition
due to death and homelessness and the outcome of many never-
treated participants are not included in follow-up analyses.7,8,38
It is time to re-examine presumed wisdom about schizophrenia
prognosis in low- and middle-income countries.7,8
Given the representative sample used in our study, we are
confident that our findings are generalisable to the population
of people with schizophrenia in rural areas, and even other
low- and middle-income countries that have a similar social
environment. Overall, mortality, suicide and homelessness are
serious concerns in never-treated and treated individuals with
schizophrenia in rural China. It is crucial to supply the necessary
community mental health services and medication for these
people in rural China.
Possible misclassification of never-treated and treated participants,
and of suicide, may exist due to recall bias. Discrimination
concerning suicidal behaviour and lack of coroners’ reports may
have also had an impact on the study findings. The mortality
and suicide rates may be underestimated because most homeless
individuals were lost to follow-up. Given the diversity of socio-
cultural, economic and care provision characteristics, the results
of this rural China study may not generalise to high-income
Mao-Sheng Ran, MD, PhD, Division of Social Work, University of Guam, Mangilao,
Guam, USA; Cecilia Lai-Wan Chan, PhD, Department of Social Work and Social
Administration, The University of Hong Kong, Pokfulam, Hong Kong; Eric Yu-Hai
Chen, MD, Department of Psychiatry, The University of Hong Kong, Pokfulam, Hong
Kong; Wen-Jun Mao, MD, Shi-Hui Hu, MD, Chengdu Mental Health Center,
Chengdu, China; Cui-Ping Tang, RN, Fu-Rong Lin, MD, Xinjin Mental Hospital, Xinjin,
Chengdu, China; Yeates Conwell, MD, Department of Psychiatry, University of
Rochester Medical Center, Rochester, New York, USA
Correspondence: Mao-Sheng Ran, Division of Social Work, University of Guam,
Mangilao, Guam 96923, USA. Email: firstname.lastname@example.org
First received 29 Jun 2008, final revision 17 Nov 2008, accepted 30 Jan 2009
The 1994 Chengdu study was supported by a grant from the China Medical Board in New
York (CMB, 92-557; MZ Xiang, PI). This work was supported in part by HKJC Centre for
Suicide Research and Prevention, HKU, and ICOHRTA grant D43 TW05814 (E.D. Caine, PI)
and GRIP 1 R01 TW007260-01 (M.S. Ran, PI) from the Fogarty International Center of NIH.
The authors thank Chengdu Mental Health Center and Xinjin Mental Hospital for their
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