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AJP-671; No. of Pages 10

Asian Journal of Psychiatry xxx (2015) xxx–xxx

Contents lists available at ScienceDirect

Asian Journal of Psychiatry

j our na l ho me p a ge : w ww . e l se v i e r . com / l oc a te / a j p

Review

Course and Outcome of Schizophrenia in Asian Countries:

Review of Research in the Past Three Decades
Bharath Holla, Jagadisha Thirthalli *
Department of Psychiatry, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore

ARTICLE INFO ABSTRACT

Article history: Considerable variation has been observed in the course and outcome of schizophrenia. With regard to epidemiology of
Received 7 October 2014 schizophrenia, papers from different Asian countries have reported findings which are in contrast with literature from the
Received in revised form 5 January 2015 western countries. In this background we undertook a narrative review of literature regarding course and outcome of
Accepted 18 January 2015 Available online
schizophrenia in Asian countries. We conducted Medline search for English-language papers on long-term course and
xxx
outcome of schizophrenia conducted in Asia in the past 3 decades. We also reviewed data pertaining to Asian countries from
the World Health Organization’s International Study of Schizophrenia (ISoS). In addition to ISoS, we retrieved 14 reports
Keywords:
from 9 Asian countries. While ISoS used comparable methodology across the countries, non-ISoS studies differed
Schizophrenia
Asia
substantially in their aims, sampling, follow-up rates and assessment tools used for studying the course and outcome. Overall,
Course the percentage of patients who experienced clinical and functional outcome in the Asian countries were largely comparable to
Outcome those in the western studies. We observed significant variations in the long-term outcome and mortality in schizophrenia even
Mortality among the Asian countries. In conclusion, there is substantial variation in the long-term course and outcome and mortality
across different Asian countries. The reason for this remains unexplored. Cross-national studies exploring biological and
cultural explanations for this variation may provide clues, which may have heuristic, translational and public-health
significance.

2015 Elsevier B.V. All rights reserved.

Contents

1. Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
3.1. ISoS centres (Tables 1 and 2) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
3.2. Non-ISoS studies (Tables 3 and 4) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
3.3. Mortality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
3.4. Substance use comorbidity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
3.5. Predictors of outcome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
4.1. Mortality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
4.2. Substance use comorbidity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
4.3. Antipsychotic treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
4.4. Limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

* Corresponding author. Additional Professor, Department of Psychiatry, National Institute of Mental Health & Neurosciences (NIMHANS), Bangalore, India. Tel.: +918026995350;
fax: +918026564830.
E-mail address: jagatth@yahoo.com (J. Thirthalli).

http://dx.doi.org/10.1016/j.ajp.2015.01.001
1876-2018/ 2015 Elsevier B.V. All rights reserved.

Please cite this article in press as: Holla, B., Thirthalli, J., Course and Outcome of Schizophrenia in Asian Countries: Review of Research in the Past Three
Decades. Asian J. Psychiatry (2015), http://dx.doi.org/10.1016/j.ajp.2015.01.001
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2 B. Holla, J. Thirthalli / Asian Journal of Psychiatry xxx (2015) xxx–xxx
1. Background
Kraepelin described dementia precox as a disorder character-ized by a
chronic, progressive course with minimal chances of clinical improvement
(Kraepelin, 1899). Since then, course and outcome of this disorder, which
later came to be popularly known as schizophrenia, has drawn considerable
research interest. In fact, in an influential systematic review and meta-analysis
conducted 2 decades ago (Hegarty et al., 1994), the authors identified 320
studies that met their fairly stringent inclusion criteria. This and other reviews
(McGlashan, 1988; Stephens, 1978) have indicated that the outcome of
schizophrenia is not uniformly poor; it is rather highly heterogeneous, and, on
an average, substantially high proportion of persons who receive a diagnosis
of schizophrenia experience reasonably good clinical and functional outcome.
The heterogeneity stems from several sources: nature of sampling, criteria
used to diagnose schizophrenia, use of modern treatment, particularly
antipsychotic medications, provision of psychiatric services, etc.
In the World Health Organization (WHO) follow up studies –
International Pilot Study of Schizophrenia (IPSS) (WHO, 1979),
Determinants of Outcome of Severe Mental Disorder (DOSMeD) (Jablensky
et al., 1992) and International Study of Schizophrenia (ISoS) (Harrison et al.,
2001) – another important factor influencing the course and outcome was
noticed–patients belonging to the ‘developing’ countries had more favorable
overall outcome than those in the ‘developed’ countries. The reason for this
differential outcome has not been studied well. What is it in the developing
countries that could favourably influence the course and outcome? A number
of hypotheses have been put forth, but these have remain untested.
Differences in the level of industrialization, urbanization, social support,
family structure, expressed emotions, explanatory model for causation of the
illness, societal challenges, etc., have been proposed to explain the differential
outcome. Though countries were divided as ‘developed’ and ‘developing’ on
economic status, it is not clear as to whether the economic status per se could
be responsible for the differential outcomes. The differences observed may be
better described as ‘regional’ differences, which encompass differences due to
racial (genetic) environmental and sociocultural differences. Indeed, even
within the ‘developed’ and ‘developing’ countries included in the WHO
studies, substantial differences have been noted (Cohen et al., 2008).
Studies from several Asian countries have documented many findings,
which are in contrast to that of the rest of the world. For instance, prevalence
of schizophrenia has been reported to be more in women than in men in
Chinese studies (Cooper et al., 1996). Studies from India (Gangadhar et al.,
2002; Murthy et al., 1998; Venkatesh et al., 2008) and Pakistan (Naqvi et al.,
2005) have failed to find earlier age of onset of schizophrenia that is so well
replicated elsewhere (Hafner et al., 1993). Substance use comorbidity, which
can adversely influence the course and outcome of schizophrenia (Volkow,
2009), is found to be lower in India (Chand et al., 2014; Isaac et al., 2007);
this reflects a fairly low occurrence of substance use and psychiatric disorders
in many Asian countries (Thirthalli et al., 2012). Similarly, family expressed
emotions, which also can adversely influence the course of schizophrenia is
found to be lower in Indian families than in some of the western countries
(Leff et al., 1990). There is an argument that repeated exposure to severe
famines have possibly eliminated severest forms of schizophrenia and there is
a natural selection in the favour of milder forms of schizophrenia in some
Asian countries (Thirthalli and Jain, 2009). A recent study has also found that
the proportion of patients who had longer than 6 months of prodrome was less
than 10% (Kare et al., 2009) in contrast to the typical course of prodrome
described in text books
Please cite this article in press as: Holla, B., Thirthalli, J., Course and Outcome of Schizophrenia in Asian Countries: Review of Research in the Past Three
Decades. Asian J. Psychiatry (2015), http://dx.doi.org/10.1016/j.ajp.2015.01.001
(Sadock, 2000). With several studies showing that different dimensions of
schizophrenia are different in the Asian countries, it is of interest to see if
course and outcome of schizophrenia is different in these countries.
2. Methods
In this narrative review, we attempt to provide an overview of the past
three decades of research studies on course and outcome of schizophrenia in
Asian countries. We conducted Medline search using the following
combinations of keywords: ‘schizophrenia’, ‘psychosis’, ‘outcome’, ‘course’,
‘follow-up’, ‘Asia’ along with names of individual Asian countries. We
further conducted author searches and used cross-references from the
identified research reports. Papers published in English language, presenting
results of research conducted in an Asian country since 1980 were reviewed if
the follow-up period was at least 2 years. We reviewed only such follow-up
studies, where either clinical/functional outcomes and/or mortality were
reported (i.e., we did not review papers where other outcomes like stigma,
quality of life, medication adherence, etc., were studied) In addition, we also
reviewed data of Asian centres from the World Health Organization’s (WHO)
influential ISoS project. The ISoS is a transcultural investigation coordinated
by the WHO in 18 centres in 14 countries. It included cohorts from three
earlier WHO studies, the IPSS (WHO, 1979), DOSMeD (Jablensky et al.,
1992), Reduction and Assessment of Psychiatric Disability (RAPyD)
(Wiersma et al., 1996) and three other centres not involved in these three
studies. For this review, if more than one paper was published from a cohort,
then we considered the data from the longest follow-up period; we also
reviewed significant results from other related papers from those studies.
We reviewed each study specifically with regard to the following
characteristics: primary aim of the study, method of sampling, number of
subjects included in the original cohort, percentage of subjects whose data
was considered for outcome analysis, system and method of diagnosis, tools
used for assessing clinical, functional, course-related and overall outcomes
and mortality. Predictors of outcome were also reviewed. We specifically
reviewed the papers for data on substance use comorbidity because of the
following reasons: (a) it is known to adversely affect the outcome of
schizophrenia (Volkow, 2009); (b) earlier long-term studies of schizophrenia
have not specifically examined its influence on the course and outcome of
schizophrenia and (c) substance use comorbidity is relatively lower in the
Asian countries (Chand et al., 2014). Finally, we carefully examined the
treatment details, which could influence the course and outcome of
schizophrenia.
3. Results
In addition to ISoS, we retrieved 14 studies which met our inclusion
criteria. ISoS employed uniform method of assessing the course and outcome
of the included cohorts, though the individual cohorts themselves were
formed using substantially different methods. Hence, it would be useful to
consider the results of all ISoS cohorts and non-ISoS cohorts separately. The
results of the ISoS and non-ISoS studies are shown in Tables 1 and 2 and
Tables 3 and 4 respectively.
3.1. ISoS centres (Tables 1 and 2)
There were seven Asian sites in the ISoS, including four from India. The
samples included community-dwelling patients, inpa-tients and outpatients
with recent onset schizophrenia. The duration of follow-up ranged from 12
years to 26 years – centres from the DOSMeD study had 15 years of follow-
up. There were wide variations in the percentage of the original cohort that
was
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B. Holla, J. Thirthalli / Asian Journal of Psychiatry xxx (2015) xxx–xxx 3

Table 1
Details of cohorts in the International Study of Schizophrenia (ISoS; see text for details).

Location Sampling details Original % followed-up Duration of Males:

cohort (n) follow up (yr) Females (%)

Prevalence cohortsa
Agra, India Outpatients of mental hospital; 15-45 ears of age, 138 43.5 26 64:36
<5yr duration of illness
Beijing, China Random sampling from an urban area 89 65.2 12 50:50
b
Incidence cohorts
Chandigarh-rural, India Incidence cases: symptoms within 12 months and 55 50.7 15 50:50
treatment seeking at any place within 3 months.
Chandigarh-urban, India Incidence cases: symptoms within 12 months and 148 69.1 15 59:41
treatment seeking at any place within 3 months.
Nagasaki, Japan Incidence cases: symptoms within 12 months and 111 50.5 15 57:43
treatment seeking at any place within 3 months.
Hong-Kong, China Randomly selected from a pool of recent-onset 100 70 15 51:49
schizophrenia patients
Madras# (Chennai), India Consecutive outpatients with <2 years of illness 100 77 15 50:50
a From the original International Pilot Study of Schizophrenia (IPSS) (WHO, 1979).
b From the original Determinants of Outcome of Severe Mental Disorder (DOSMeD) (Jablensky et al., 1992).
# 25-year follow-up of this cohort has been published elsewhere (Rangaswamy, 2012); however, we have considered only the 15-year outcome for this paper because it formed part of the ISoS and
thus, the findings of this cohort can be readily compared with results of other cohorts of ISoS.

followed up across the centres; on an average, it was lower in centres from
India. ISoS study used an array of clinical, functioning and global outcomes
based on several assessment tools (see footnote to Table 2); we have
highlighted only few selected outcomes here. The reader is referred to the
source book of the study (Hopper et al., 2007) for other details.
In terms of clinical outcome, about 50% of patients were never psychotic
in the last 2 years of follow-up across all the centres (Harrison et al., 2001) of
this trans-continental study. Among the Asian countries, all three Indian sites
had nearlymore than60% patients, who were free of psychosis in the past 2
years. In contrast, the non-Indian sites (Beijing, Nagasaki and Hong-kong)
had substantially less

Table 2
Findings of International Study of Schizophrenia (ISoS; see text for details):.

Location Course and clinical Social-occupational Overall outcome Mortality Treatment details Co-morbidity Predictors
outcome outcome

Prevalence cohortsa
Agra, India 63% not psychotic; 60% best; 20% each 18% better; 23% same; 31.2% 63% never; 25.9% Though NR
13.3% continuously fair and poor 8.2 worse; 35% other (SMR = 1.86*) sometimes 11.1% studied,
psychotic; 23.7% other most times on AP not used
in analysis;
details not
available
Beijing, China 34.5% not psychotic; 25% best; 8.3% 48.3% better; 12.1% 22.5%; 8.6% never; 51.7% NR Females
51.7% continuously fair; 66.6% poor same; 25.9% worse; SMR = 2.97* sometimes; 39.7% had poorer
psychotic; 13.8% other 13.8 other most times on outcome
AP

Incidence cohortsb
Chandigarh-rural, 71.1% not psychotic; 71% best; 19.4% 57.9% better; 18.4% 18.2%; 5.3% never; 89.5% NR NR
India 7.9% continously fair; 9.6% poor same; 5.3% worse; SMR = 3.2* sometimes; 5.3%
psychotic; 11% other 18.4% other most times on AP
Chandigarh-urban, 63.8% not psychotic; 63.2% best; 28.7% better; 27.5% 6.3%; 53% sometimes; 27% NR NR
India 18.8% continously 26.5% fair; 10.3 same; 8.8% worse; SMR = 1.8* most times on AP;
psychotic 17.4% others poor 35% other 20% unknown
Nagasaki, Japan 25% not psychotic; 25% best; 16.1% 35.1% better; 31.6% 6.3%; 14% sometimes and NR NR
55.4% continuously fair; 58.9% poor same; 33.3% worse SMR = 5.71% 86% most times on
psychotic; 19.6% AP
others
Hong-Kong, China 43.5% not psychotic; 62.3& best; 46.4% better; 26.1% 11%; 4.3% sometimes and NR NR
36.2% continuously 21.9% fair; same; 27.5% worse SMR = 5.7* 95.7% most times on
psychotic; 20.3% 15.7% poor AP
others
Madras (Chennai), 61% not psychotic; 46.7% best; 17.3% 72.8% better; 16.9% 9%; SMR = 1.9 42.9% sometimes NR NR
India 18.2% continuously fairl; 36% poor same; 10.4% worse and 57.1% most
psychotic; 20.8% other times on AP

The assessment tools used were uniform across all the centres. These included the Present State Examination (PSE; Cooper et al., 1996), Diagnostic Schedule Scoresheet (DSS; developed for this
study), which records study team’s consensus diagnosis according to DSM-III-R or ICD-10; Scale for the Assessment of Negative symptoms (SANS; Andreasen et al 1989); Disability Assessment
Schedule (DAS); Substance Abuse Schedule (SAS developed for this study); Life-Chart Schedule (LCS; Harding et al), Broad Rating Schedule (BRS; developed for this study).

a From the original International Pilot Study of Schizophrenia (IPSS) (WHO, 1979).
b From the original Determinants of Outcome of Severe Mental Disorder (DOSMeD) (Jablensky et al., 1992). * p < 0.05.

Please cite this article in press as: Holla, B., Thirthalli, J., Course and Outcome of Schizophrenia in Asian Countries: Review of Research in the Past Three
Decades. Asian J. Psychiatry (2015), http://dx.doi.org/10.1016/j.ajp.2015.01.001
G Model
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4 B. Holla, J. Thirthalli / Asian Journal of Psychiatry xxx (2015) xxx–xxx

Table 3
Details of cohorts in the non-ISoS studies (See text for details).

Author/Year/Location Aim Samplinga,b,c Original Sample Follow up M:F Dia-gnosis

sample followed dura-tion
up (%) (yrs)

Chang WC et al/2011,12, To Investigate the rates and Community outreach— 700 77 3 52:48 ICD
13/Hong Kong (EASY) predictors of symptomatic first episode 10
remission and recovery in schizophreniaa
first-episode ‘psychosis’
Kua J et al/2003/Singapore Assess the course of illness First admission in 1975 at 402 72% at 10yr; 10, 15,and 20 61:39 ICD 9
and to examine the variables mental hospital in 74% at 15yr;
that are useful predictors of Singaporeb 54% at 20yr
outcome.
Liu T et al/2014/China To examine mortality among Randomly selected 2071 2071 97.5 4 56:44
those with disability due to from a national pool of ICD-10
schizophrenia patients with disability
due to schizophreniaa
Ran MS et al/2010/China To study work functioning and All patients in six rural 510 72 10yrs 47:53 ICD-10
its predictors rural area townships of Xinjin
County identified by key-
informant method a
Verma S et To describe outcomes of early Community outreach– 1175 66 2 51:49 SCID
al/2012/Singapore (EPIP) intervention programme first episode
schizophreniaa
Yang J et al/2014/China To study the prevalence, natural Random cluster sampling, 30 70 30 57:43 CIDI ICD9, 10
course and prognosis in Jinuo prevalencea
people, (national minority) every
10yrs since 1979

Johnson S et al/2012/ To study the relationship between Outpatients with first 131 72.5 5 55:45 DSM-IV
Vellore, India insight, explanatory models and contact with mental
outcome Predictors of outcome health professionalsb
Srivastava A et al/2009; after ‘10yrs of follow up Patients hospitalized for 200 57 10 73:27 DSM-IV
10/Mumbai, India first-episode in a private
hospital in Mumbai a
Suresh et al/2012/Rural to study work-functioning of All patients with 236 85.1 4yrs (mean) 51:49 MINI: ICD-10
schizophrenia patients living in a schizophrenia in a rural
Karnataka, India rural community in south India community in South India
(both treated and
untreated)c
Verghese A To study factors affecting Consecutive outpatients 386 74.4 5 63.2:36.8 Feighner’s
et al/1989/Chennai, Vellore, course and outcome of with <2yrs of illnessa criteria
Lucknow, India (SOFACOS) schizophrenia
Kurihara T et clinical outcome of Consecutively admitted 59 72 17 63:37 DSM-III-R
al/2011/Indonesia schizophrenia and its first-episode patientsa
predictors
Marom S et al/2005/Israel To study predictive value of Consecutive in-patientsa 114 95 7 Not DSM-III-R
expressed emotions for long-term reported
outcome.
Ryu Y et al/2006/Japan To investigate the effects of Chronic institutionalized 94 83 2 65:35 ICD-10
deinstitutionalization and patients transferred to
evidence-based strategies for the community-based
treatment of mental disorders facilitya
among long-stay patients after
their discharge To determine the
Haro MJ et al/2011/Korea, frequency of symptom and In/outpatients who were 1223 37.5 3 54:46 DSM
Malaysia Taiwan (W-SOHO) functional remission in initiating/changing IV/ICD 10
outpatients in different regions of antipsychoticsc
the world

EPIP, Early Psychosis Intervention Programme; EASY, Early Assessment Service for Young People with Psychosis; SOFACOS, Study Of Factors Associated With Course and Outcome of
Schizophrenia; W-SOHO, Worldwide Schizophrenia Outpatient Health Outcomes; ICD, International Classification of Diseases (ICD); DSM, Diagnostic and Statistical Manual of Mental Disorders

a
Community sample. b
Hospital sample.
c
Mixed sample.

percentage of patients who were never psychotic in the past 2 years of follow-
up.
In terms of disability, among the ‘incidence’ cohorts, 40% of the patients
across all centres of ISoS had good or excellent global functioning score on a
modified version of the WHO Disability Assessment Schedule (DAS)
(Jablensky et al., 1980). The percent-age of patients with good or excellent
global functioning among all Indian cohorts and also the Hong-Kong cohort
were higher than this; in Nagasaki only 25% had good or excellent
functioning.
Among the ‘prevalence’ cohorts, across all centres of ISoS, nearly 50% had
good or excellent functioning. It was 60% for Agra and only 25% for Beijing,
Hong-Kong and Nagasaki. The results for global evaluation of outcome was
also similar: the proportion of patients, whose overall course was classified as
‘worse’ was 10% or less across the four Indian sites. In contrast, it was more
than 25% in other centres.
When mortality was examined with regard to standardized mortality ratio
(SMR), Nagasaki and Hong-Kong had the highest

Please cite this article in press as: Holla, B., Thirthalli, J., Course and Outcome of Schizophrenia in Asian Countries: Review of Research in the Past Three
Decades. Asian J. Psychiatry (2015), http://dx.doi.org/10.1016/j.ajp.2015.01.001
 671;-AJP
Table 4
Findings of the non-ISoS studies (see text for details).

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Author/Year/Loca-tion Outcome–measurement Outcome–results Mortality Treatment Co-morbidity Predictors

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Chang WC et al/2011, CGI-S SOFAS CGI 58.8% achieved 23.7% achieved 17.4% met NA Medications & 6.5% ‘Substance Female sex, older age of
12,13/Hong symptomatic functional criteria for psychosocial; abuse’ onset, shorter DUP & early
inarticle as:press
.Decade

Kong, China(EASY) remission (CGI-SCH remission (SOFAS both adherence symptom resolution
<3 on +ve and ve >60 and symptomatic details NA predicted symptomatic
symptom domains) employment/ and remission 3yr; (education,
s .JAsian

education >12 functional onset-type, diagnosis and

months) remission substance use did not
and no predict outcome)
hospitalization
Liu T et al/2014/China NR NR NR NR NR NR 7.2%; medical:6%; NA NA (Age, education, marital
suicide:0.34%; status and income did not
Thirthalli,,.BHolla, Course,.J
,(2015)Psychiatry

others:0.8% predict mortality)

SMR = 10.17 &

B. Holla, J. Thirthalli / Asian Journal of Psychiatry xxx (2015) xxx–xxx

12.42 for men &
women
Ran MS et al/2010/ NR Interview NR NR 27.3% had full- NR 19.6%; suicide:4.2%; ‘‘once treated’’ vs. NA Work history and
China about their time work; 49.7% other causes: 15.4% ‘‘never treated’’ disability at baseline
work status had part-time predicted work status;
work; 23% had no (Age, sex, education, age of
work onset, duration of illness,
.http://d

treatment status did not

influence outcome)
x

Yang J et al/2014/China PANSS, CGI NR NR After 30yr: 18.87% NR NR 23.3%; suicide:6.6%; Only one patient NA Longer duration associated
achieved remission, Medical/ was receiving with poorer outcome (No
62.26% had accidental:16.6% antipsychotics other predictors studied)
deteriorated or had at 30yr follow up.
residual symptoms
AsianinSchizophreniaofOutcomeand

Verma S et al/2012/ PANSS GAF NR 54.1% achieved 58.4% of patients 29.4% met Nil Comprehensive Excluded Female sex, shorter DUP,
001.01.2015.ajp.1016/j.org/10.doi

Singapore, (EPIP) remission achieved criteria for treatment with substance fewer negative symptoms
significant both pharmacological abuse at baseline and early
functional symptomatic and psychosocial response at 3 months were
remission and interventions found to be significant
functional factors associated with
remission both symptomatic and
functional remission as
well as recovery at 2yr.
(Malay ethnicity was
associated with poor
functional remission &
Other ethnicity was
associated with poor
recovery as compared to
Chinese ethnicity)
Kua J et al/2003/ 1. Good: patient not 10yr: 35% poor 66% had 14.6%; suicide:9.7%; 44–48% were not NA Shorter illness
Singapore receiving treatment, well functioning; fair to others:4.9%; Suicide on treatment at duration and male
inResearchofReviewCountries:

and working. 15yr: 38% poor good about 60 times higher different points in gender associated with
2. Fair: patient not functioning outcome and death about time better outcome;
receiving treatment and 20yr: 35% poor through-out 10 times higher than (Race, family history,
not working, or receiving functioning; the study general population education, marital
out-patient treatment and 10yr: 45% period status at presentation,
working. unemployed; premorbid Personality
3. Poor: patient receiving 15yr: 52% did not predict
treatment and not unemployed; outcome)
working, or receiving in- 20yr: 53%
patient treatment. unemployed
Global Assessment Scale,

5
 Table 4 (Continued )

ModelG
671;-
Author/Year/Loca-tion Outcome–measurement Outcome–results Mortality Treatment Co-morbidity Predictors

AJP
thiscitePlease
ThreePastthe .Decades

6
details
Clinical Functioning Overall Clinical Social- Overall
occupational

10Pagesof.No
Johnson S et al/2012/ BPRS, PANSS WHODAS NR 68% remitted; 24% had Median WHODAS NR 3.8% 25.3% regular on NA Higher insight & having
Vellore, India at least one additional score 8 medication non-medical explanatory
psychotic episode model associated with
inarticle as:press

remission;
Srivastava A et al/2009; PANSS GAF CGI 100% had PANSS 61.7% had GAF >80 61% had NA 80% adherence to NA Hard to interpret because
‘10/Mumbai, India positive score <21; CGI <2 treatment ensured of insufficient data
88% had PANSS analysis
negative score <21
.JAsian

Suresh et al/2012/Rural PANSS IDEAS NR NR 60% of patients had NR 6.5%; 90% treated with NR Medication adherence;
Karnataka, India mild/no disability Suicide:3.6%; antipsychotics; sociodemographic details;
in work Others:2.9% 74% had good psychopathology
adherence
Thirthalli,,.BHolla,

Verghese A et al/1989/ PSE PPHS PPHS 64% in remission; 6% 61% had 27%-very 8.2% 85% had 8% had alcohol Treatment adherence,
,(2015)Psychiatry

Chennai, Vellore, continuous psychosis; occupational favourable; good/moderate abuse dangerous behaviour,

B. Holla, J. Thirthalli / Asian Journal of Psychiatry xxx (2015) xxx–xxx

Lucknow, India 30% other impairment 40%- adherence on change in SES, delusion of
(SOFACOS) favourable; typical persectution, agitation
31% antipsychotics explained 22% variance
intermediate;
1.7%
unfavourable
outcome
Kurihara T et al/2011/ PANSS Interview on work, NR 19 (32.2%) had cross- NR Combined 25.4%; None with No medical Shorter DUP predicted
Indonesia Independent living sectional symptomatic remission Physical disease/ combined comorbidity both remission and
and peer relationship. remission (symptomatic accident:24%; remission and at intake mortality; (age, sex,
AsianinSchizophreniaofOutcomeandCourse,.J

& functional): Suicide:1.6% 41.4% without education, marital status,

23.7% remission were premorbid functioning
001.01.2015.ajp.1016/j.org/10.doi.http://dx

on treatment and age at onset did not

predict either)
Marom S et al/2005/ Time to, number NR NR 66.9% had re- NR NR 3.5% Only data on Excluded High criticism was
Israel and duration of admission compliance at substance associated with higher
IP care baseline and not abuse rates of readmissions and
for the follow-up & longer hospital stay
duration
Ryu Y et al/2006/Japan PANSS, SAI GAF, REHAB, SFS NR Significant Significant Successful 2%; 1% each by suicide Comprehensive NA NR
improvement in improvement in community and accident medical and
PANSS scores. No many items of tenure: 76.9%, psychosocial
categories given; REHAB and SFS; no Hospitalization management
significant categories given due to physical provided to all
deterioration on SAI; illness 15.4%
no categories given and psychiatric
exacerbations:
5.1%
Haro MJ et al/2011/ CGI-SCH (a) Occupational NR 84.4% achieved clinical 24.6% achieved NR NA All patients Alcohol misuse: Baseline social
Korea, Malaysia status (b) Living remission functional received treatment 3.8%, Other functioning, being female
Taiwan (W-SOHO) arrangement (c) remission substance and previously untreated
Social interactions misuse: 3.1% were consistent predictors
inResearchofReviewCountries:

of remission across
regions. Particularly
alcohol misuse had a lower
likelihood of achieving
clinical remission in east
Asia

EPIP, Early Psychosis Intervention Programme; EASY, Early Assessment Service for Young People with Psychosis; SOFACOS, Study Of Factors Associated With Course and Outcome of Schizophrenia; W-SOHO, Worldwide Schizophrenia Outpatient Health
Outcomes; PANSS, Positive and Negative Syndrome Scale(Kay et al., 1987); PSE, Present State Examination; PPHS, Psychiatry and Personal History Schedule; GAF, Global Assessment of Function (APA, 1994); CGI-SCH, Clinical Global Impression-
Schizophrenia (Haro et al., 2003); CGI-S, Clinical Global Impression-Severity (Guy, 1976); SAI, Schedule of Assessment of Insight (David, 1990); REHAB, Rehabilitation Evaluation Hall and Baker (Baker and Hall, 1988); SFS, Social Functioning Scale
(Birchwood et al., 1990); SOFAS, Social Occupational Functioning Assessment Scale (APA, 1994); BPRS, Brief Psychiatric Rating Scale (Overall and Gorham, 1962); WHODAS, WHO Disability Assessment Schedule; IDEAS, Indian Disability Evaluation and
Assessment Scale; NA, Not Available; NR, Not Reported
G Model
AJP-671; No. of Pages 10
B. Holla, J. Thirthalli / Asian Journal of Psychiatry xxx (2015) xxx–xxx
SMRs across all ISOS centres: 5.71 and 5.76 respectively; all Indian centres
except Chandigarh rural had SMRs less than 2.
Nearly all, or most patients across all the centres were on antipsychotics
for some time ormostof thetime throughout thefollow up period. However, in
Agra, nearly 63% were never on antipsychotics. Predictors of outcome were
not reported separately for the Asian centres. Moreover, though ISoS had a
tool to assess substance use among patients with schizophrenia, we were
unable to find any analysis regarding this important determinant of outcome.
3.2. Non-ISoS studies (Tables 3 and 4)
Studies varied in their specific aims: while a few studies had specific aims
of examining the course and outcome of schizophrenia, several studies had
recorded outcome as part of some other research agenda, including examining
the effect of early intervention programmes (Chang et al., 2012; Verma et al.,
2012), deinstitution-alization (Ryu et al., 2006), expressed emotions (Marom
et al., 2005), treatment response (Haro et al., 2011), insight (Johnson et al.,
2012) etc., on the outcome. While (Liu et al., 2014) focused exclusively on
mortality, (Suresh et al., 2012) focused exclusively on work-functioning. The
variations in outcome of subjects across the studies could be a function of
such variable research agenda.
Generally, there was a slight male preponderance in all cohorts. There was
a mix of community-based, clinic (outpatient) – based and inpatient cohorts
(See footnote to Table 3). Eyeballing of the results suggest that outpatient and
community samples had overall better outcomes. Striking exceptions to this
observation are
(a) (Yang et al., 2013) cohort, in which only about 18% of a community-
dwelling patients had remission – most of them were not on any treatment for
nearly 30 years of their follow-up and (b) (Shrivastava et al., 2010) cohort,
where nearly all patients showed clinical remission after 10 years of follow-
up – all were on continuous treatment for about 80% of the follow-up period.
In contrast to ISoS study, the non-ISoS studies varied widely in their
method of assessing clinical, functional and overall out-comes: most
commonly used tool for symptoms was the Positive and Negative Syndrome
Scale, (PANSS) (Kay et al., 1987); tools used for assessing functioning were
more varied – a few studies did not even specify the tools for assessing
functioning (Kua et al., 2003; Marom et al., 2005). Such variations in
assessment tools makes comparison across different cohorts difficult–any
interpre-tation of similar or differential outcomes across the cohorts should be
made in this background.
Most studies were successful in following up about three-quarters of their
original cohorts through the follow-up period ranging from 2 years to 30
years. While this could have influenced the results, close examination of
reasons for loss to follow up suggests apparently extraneous causes like
migration, inability to trace, change of diagnosis, etc. The extent to which
such factors would influence the outcome of schizophrenia is debatable.
Most studies used different definitions of clinical remission and reported
remission in majority of their cohorts (54%–100%). In contrast, improvement
in functioning was achieved by slightly less percentage of patients – in almost
all studies, percentage of patients with functional improvement, especially in
the field of work/occupational functioning, was less than those with clinical
remission. Not surprisingly, when combined improvement in symptoms and
functionality was considered, the percentage of patients reporting
improvement fell even further.
3.3. Mortality
Nearly all studies provided data on the percentage of patients who died
during the follow-up period. However, unlike in ISoS, none of the studies
provided comparison with mortality among the
Please cite this article in press as: Holla, B., Thirthalli, J., Course and Outcome of Schizophrenia in Asian Countries: Review of Research in the Past Three
Decades. Asian J. Psychiatry (2015), http://dx.doi.org/10.1016/j.ajp.2015.01.001
7
general population except (Liu et al., 2014). This poses problems in
interpreting the mortality figures. Nevertheless, substantial percent of patients
had died at fairly young age. Generally, deaths due to non-suicidal causes
were commoner than suicide, though some exceptions where there (Kua et al.,
2003; Suresh et al., 2012). Liu et al. (2014) reported very high rates of
mortality among schizophrenia patients with SMRs of 10.17 and 12.42 for
men and women respectively. For some age group of patients like 18–29
years, the SMR was as high as 75.02 and 239.26 for men and women
respectively. These SMRs are considerably higher than those reported for the
ISoS cohorts.
3.4. Substance use comorbidity
Many studies do not mention the rates of substance use comorbidity
among their cohorts; a few excluded those with substance use comorbidity.
(Chang et al., 2012) reported 6.5% comorbidity with ‘substance abuse’;
(Verghese et al., 1989) reported 8% ‘alcohol abuse’ and (Haro et al., 2011)
reported 3.8% and 3.1% patients with ‘alcohol misuse’ and ‘substance
misuse’ respectively. The papers are not clear about the time course of
comorbidity – whether these were life-time diagnoses or current diagnoses.
3.5. Predictors of outcome
While ISoS report (Hopper et al., 2007) has provided important predictors
of long-term outcome, analysis of predictors is not available for any
individual centres, including the Asian ones. As with other issues, there was
high degree of variation in the predictors of outcome across different non-
ISoS centres. Never-theless, several good prognostic indicators were
consistently seen. These included female gender, shorter duration of illness,
better baseline status, shorter duration of untreated illness, and early treatment
response and treatment adherence.
4. Discussion
In this paper, we reviewed studies on course and outcome of
schizophrenia in Asian countries. We reviewed studies examining
clinical/functional outcomes and/or mortality data in cohorts of schizophrenia
patients recruited in diverse settings and followed up for a minimum of 2
years. We found wide variations in the course and clinical and functional
outcome of patients across different cohorts in Asia.
As discussed in the methods and results section, we reviewed the ISoS
and non-ISoS studies separately. Though ISoS cohorts were different insofar
as the settings from which they were initiated, the outcome measures were
uniform and to this extent, the results could be compared across the centres.
However, the non-ISoS studies varied widely in their settings, follow-up
duration, percentage of followed-up patients, measurement of outcome,
assessment of predictors of outcome, etc., which make comparison across
different cohort hard. Because of this, firm inferences regarding cross-
national comparisons can be made only from the ISoS report. It was
interesting to note that the outcome was better in the Indian centres than in
non-Indian centres. From this review it is not possible to speculate the
plausible explanation for this. Clearly, the ‘developing’ vs. ‘developed’
country classification would not be relevant here, as Beijing as well as all the
Indian centres were classified as from ‘developing’ countries; the status of
Hong-Kong in this regard is debated (Hopper and Wanderling, 2000). Many
researchers have suggested that involvement of the families in the care of
schizophrenia patients may explain the better outcome of the disorder
(Nunley, 1998; Wig et al., 1987). In the absence of concrete information
about the involvement of
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8 B. Holla, J. Thirthalli / Asian Journal of Psychiatry xxx (2015) xxx–xxx
family members in other centres, the assumption that this variable could
explain the differential outcome remains extremely conjec-tural.
Unfortunately, this issue of differential outcome of schizo-phrenia across
different regions remains unexplained. Notwithstanding these regional
variations, in both ISoS and non-ISoS cohorts of schizophrenia patients in
Asia the overall outcomes are largely comparable to other long-term studies,
including (Bleuler, 1978; Ciompi and Mu¨ller, 1976; Huber et al., 1975;
Tsuang et al., 1979)
4.1. Mortality
Mortality is an important outcome in any medication condition. Mortality
in schizophrenia is assuming greater importance recently, with studies
systematically suggesting that the relatively excessive mortality among
schizophrenia patients vis-a`-vis the general population is increasing over the
past decades (McGrath et al., 2008; Saha et al., 2007). We specifically
examined the issue of mortality in all the reviewed studies. All ISoS centres
had data on SMRs. Consistent with better clinical and functional outcomes in
the Indian centres, SMR was generally lower in three of the four Indian
centres. While many non-ISoS studies provided definitive data on mortality,
the interpretation of this is seriously constrained by the lack of comparison
with mortality among the general populations in the reports. Fewer studies
had reported causes of mortality: in many centres (Kurihara et al., 2011; Liu
et al., 2014; Ran et al., 2011) causes of death other than suicide were
commoner than suicidal deaths. However, in the absence of cause-specific
SMRs, interpretation of this differential rate of mortality due to suicidal and
non-suicidal causes is limited. For instance, in (Kua et al., 2003), the
percentage of patients dying due to suicide was 9.7% and those due to other
causes was 4.9%. However, when compared with general population figures,
suicide rates were as high as 80-times greater and non-suicidal deaths were
about 10-times greater in schizophrenia patients for the respective age-groups.
Only one study provided SMRs for different age- and sex-groups of patients
(Liu et al., 2014). SMR for men and women were respectively 10.17 and
12.42, higher than all centres across ISoS. Plausible explanation for this
unusually high SMR is the fact that the cohort consisted of only such patients
who had substantial disability–schizophrenia patients with milder form of
illness (i.e., without disability) were not part of this cohort. Three studies had
relatively long durations of follow-up, viz., Kua et al. (20 years), Yang et al.
(30 years), and Kurihara et al. (17 years). Percentages of patients committing
suicide in these studies – 9.7%, 6% and 1.6% respectively – were notably
much lower than the 14–22% Twenty year suicide rate reported in the
literature from the western countries.
4.2. Substance use comorbidity
Substance use comorbidity is well known to influence several short-term
outcomes of schizophrenia. It is surprising that there is relative lack of
literature on its influence on the long-term outcome. We attempted to review
this issue in the Asian schizophrenia cohorts. Though ISoS centres had
substance abuse schedule among their assessment tools, we could not find
data on this in their reports. Among the non-ISoS studies, very few studies
examined substance use comorbidity. Consistent with a previous review
(Thirthalli et al., 2012), the proportion of patients with substance abuse in the
Asian centres, in the few cohorts where it was studied, was less than 8%,
much less than some of the western studies (Barnes et al., 2006; Cantwell et
al., 1999). Plausibly owing to this, the influence of substance use comorbidity
on the course and outcome of schizophrenia was not studied in any of the
reports.
Please cite this article in press as: Holla, B., Thirthalli, J., Course and Outcome of Schizophrenia in Asian Countries: Review of Research in the Past Three
Decades. Asian J. Psychiatry (2015), http://dx.doi.org/10.1016/j.ajp.2015.01.001
4.3. Antipsychotic treatment
Treatment with antipsychotics is recommended for preventing relapse in
multi-episode patients, PORT guidelines 2009, (Kreyen-buhl et al., 2010) and
only about 10–15% of patients with schizophrenia are expected to remain free
of relapses after the first episode, APA practice guidelines 2004 (APA, 2004).
In this background, we reviewed the effect of continuation of antipsy-chotics
on the long-term outcome of schizophrenia. Different cohorts had variable
proportion of patients on antipsychotics for variable periods of time in both
ISoS and non-ISoS cohorts. Unfortunately, the issue of adherence to
antipsychotic medications and outcome was not examined in most studies.
Overall, across ISoS and non-ISoS study, there was no consistent trend in
terms of percentage of patients on medications and percentage of patients
with good outcome. The review revealed two extreme examples: in ISoS–
Agra centre 63% of patients never received treatment and in (Yang et al.,
2013) cohort, nearly none received antipsychotics through the follow-up
period. While in Agra cohort majority were free of psychosis at the end of 26
years of follow-up, most patients had substantial deterioration in the Chinese
cohort. The question about treatment continuation was complicated by the
fact that a substantial proportion of patients in (Kua et al., 2003) study were
considered to have best outcome precisely since they were not receiving
antipsychotics. While antipsychotics are the standard of care for acute
schizophrenia in the modern day psychiatric practice, it is possible that a
substantial proportion of patients may remain free of psychotic symptoms
despite not being on antipsychotics.
4.4. Limitations
The findings of this review need to be considered with a few caveats. (1)
We did not conduct a systematic review; narrative reviews like ours may have
inherent limitations in terms of objectivity of inclusion of studies and results.
Studies in the field of long-term outcome in schizophrenia in Asia were very
varied in terms of their aims, study designs and methods, and could not yield
themselves to a systematic review. (2) We searched only English language
studies from one source. We could have missed out on many Asian-language
studies. (3) We could find long-term studies on schizophrenia from only 9 of
the 48 Asian countries–evidently, the findings cannot be generalized to a
large number of unrepre-sented countries. (4) Though we set out to examine
course as well as outcome of schizophrenia, we could comment on the
‘course’ only in ISoS centres [The ISoS (Hopper et al., 2007) has a number of
other outcome measures, interested readers are referred to this source]; from
among the non-ISoS centres none of the studies had presented data on the
course of schizophrenia; they were rather focused on outcomes at different
points in time. (5) A number of studies in the past few decades have
highlighted the fact that medical comorbid-ities are substantially higher
among schizophrenia patients than in the general population (Carney et al.,
2006; Schoepf et al., 2014). Studies reviewed in this paper did not
systematically examine this important aspect of course and outcome.
5. Conclusions
In Asian countries, overall, about 60% of patients with schizophrenia
show substantial clinical improvement and slightly less percentage of patients
show functional improvement. These are consistent with findings from other
long-term studies conducted elsewhere in the world. Mortality among
schizophrenia patients relative to that of the general population is relatively
less in some Asian countries. However, variations in different outcomes
found across countries within Asia is largely similar to that found
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B. Holla, J. Thirthalli / Asian Journal of Psychiatry xxx (2015) xxx–xxx
across different countries in the WHO studies. One obvious reason for this is
variations across individual studies in terms of their scope and methodologies.
However, the ISoS study, which used comparable methods of investigation,
found substantial variation. Sadly, at this stage there is very little research
evidence to understand these variations. There is substantial evidence that a
diverse set of socio-environmental and cultural variables interact with
physiologic pathways related to psychological stress in influencing the
expression of psychosis (Howes and Kapur, 2009). As van Os et al. (van Os et
al., 2008) have elucidated, studies examining the interaction between genetic
and complex environ-mental factors would have to necessarily involve
researchers from diverse disciplines. These should include researchers from
cultural anthropology, epidemiology, psychology, psychiatry, neurosci-ence,
neuroimaging, pharmacology, biostatistics, and genetics. Measures of course
and outcome should also move from clinical to more real-life outcomes such
as role-functioning, work-function-ing, quality of life, stigma and caregiver
burden. Finally, there is an emerging interest in studying physical
comorbidities such as cardiovascular conditions, diabetes mellitus, metabolic
syndrome and cancer as measures of course and outcome of schizophrenia.
Future studies should systematically explore this important dimension of
long-term outcome of schizophrenia.
Conflict of interests
None
Acknowledgements
None
References
Andreasen, N.C., 1989. The Scale for the Assessment of Negative Symptoms (SANS):
conceptual and theoretical foundations. Br J Psychiatry Suppl. 7, 49–58.
APA, 1994. Diagnostic and 1; Statistical Manual of Mental Disorders: DSM-IV.
American Psychiatric Association, Washington, DC.
APA, 2004. Practice guideline for the treatment of patients with schizophrenia.
Amer Psychiatric Pub Inc., Washington, DC.
Baker, R., Hall, J.N., 1988. REHAB: a new assessment instrument for chronic psychiatric
patients. Schizophr. Bull. 14, 97–111.
Barnes, T.R., Mutsatsa, S.H., Hutton, S.B., Watt, H.C., Joyce, E.M., 2006. Comorbid substance
use and age at onset of schizophrenia. Br. J. Psychiatry: J. Mental Sci. 188, 237–242.
Birchwood, M., Smith, J., Cochrane, R., Wetton, S., Copestake, S., 1990. The social functioning
scale. The development and validation of a new scale of social adjustment for use in family
intervention programmes with schizophrenic patients. Br. J. Psychiatry: J. Mental Sci. 157,
853–859.
Bleuler, M., 1978. The Schizophrenic Disorders: Long-Term Patient and Family Studies. Yale
University Press, New Haven (CT).
Cantwell, R., Brewin, J., Glazebrook, C., Dalkin, T., Fox, R., Medley, I., Harrison, G., 1999.
Prevalence of substance misuse in first-episode psychosis. Br. J. Psychia-try: J. Mental Sci.
174, 150–153.
Carney, C.P., Jones, L., Woolson, R.F., 2006. Medical comorbidity in women and men with
schizophrenia: a population-based controlled study. J. Gen. Intern. Med. 21, 1133–1137.
Chand, P., Thirthalli, J., Murthy, P., 2014. Substance use disorders among treatment naive first-
episode psychosis patients. Compr. Psychiatry 55, 165–169.
Chang, W.C., Tang, J.Y., Hui, C.L., Lam, M.M., Chan, S.K., Wong, G.H., Chiu, C.P., Chen,
E.Y., 2012. Prediction of remission and recovery in young people presenting with first-
episode psychosis in Hong Kong: a 3-year follow-up study. Aust. N Z. J. Psychiatry 46,
100–108.
Ciompi, L., Mu¨ller, C., 1976. Lebensweg und Alter der Schizophrenen. Springer-Verlag,
Berlin.
Cohen, A., Patel, V., Thara, R., Gureje, O., 2008. Questioning an axiom: better prognosis for
schizophrenia in the developing world? Schizophr. Bull. 34, 229–244.
Cooper, J.E., Sartorius, N., Shen, Y., 1996. Mental Disorders in China: Results of the National
Epidemiological Survey in 12 Areas. Gaskell.
David, A.S., 1990. Insight and psychosis. Br. J. Psychiatry:J. Mental Sci. 156, 798–808.
Gangadhar, B.N., Panner Selvan, C., Subbakrishna, D.K., Janakiramaiah, N., 2002.
Age-at-onset and schizophrenia: reversed gender effect. Acta psychiatrica Scandinavica
105, 317–319.
Guy, W., 1976. Clinical global impression scale. The ECDEU Assessment Manual for
Psychopharmacology-Revised. Volume DHEW Publ No ADM 76 338, 218-222.
Please cite this article in press as: Holla, B., Thirthalli, J., Course and Outcome of Schizophrenia in Asian Countries: Review of Research in the Past Three
Decades. Asian J. Psychiatry (2015), http://dx.doi.org/10.1016/j.ajp.2015.01.001
9
Hafner, H., Maurer, K., Loffler, W., Riecher-Rossler, A., 1993. The influence of age and sex on
the onset and early course of schizophrenia. Br. J. Psychiatry:J. Mental Sci. 162, 80–86.
Haro, J.M., Kamath, S.A., Ochoa, S., Novick, D., Rele, K., Fargas, A., Rodriguez, M.J., Rele,
R., Orta, J., Kharbeng, A., Araya, S., Gervin, M., Alonso, J., Mavreas, V., Lavrentzou, E.,
Liontos, N., Gregor, K., Jones, P.B., Group, S.S., 2003. The Clinical Global Impression-
Schizophrenia scale: a simple instrument to measure the diversity of symptoms present in
schizophrenia. Acta psychiatrica Scandina-vica. Supplementum 16–23.
Haro, J.M., Novick, D., Bertsch, J., Karagianis, J., Dossenbach, M., Jones, P.B., 2011. Cross-
national clinical and functional remission rates: Worldwide Schizophrenia Outpa-tient
Health Outcomes (W-SOHO) study. Br. J. Psychiatry:J. Mental Sci. 199, 194–201.
Harrison, G., Hopper, K., Craig, T., Laska, E., Siegel, C., Wanderling, J., Dube, K.C., Ganev,
K., Giel, R., an der Heiden, W., Holmberg, S.K., Janca, A., Lee, P.W., Leon, C.A.,
Malhotra, S., Marsella, A.J., Nakane, Y., Sartorius, N., Shen, Y., Skoda, C., Thara, R.,
Tsirkin, S.J., Varma, V.K., Walsh, D., Wiersma, D., 2001. Recovery from psychotic illness:
a 15- and 25-year international follow-up study. Br. J. Psychiatry:J. Mental Sci. 178, 506–
517.
Hegarty, J.D., Baldessarini, R.J., Tohen, M., Waternaux, C., Oepen, G., 1994. One hundred
years of schizophrenia: a meta-analysis of the outcome literature. The American journal of
psychiatry 151, 1409–1416.
Hopper, K., Harrison, G., Janca, A., Sartorius, N., 2007. Recovery from Schizophre-nia: An
International Perspective: A Report from the WHO Collaborative Project, the International
Study of Schizophrenia. Oxford University Press, Oxford.
Hopper, K., Wanderling, J., 2000. Revisiting the developed versus developing country
distinction in course and outcome in schizophrenia: results from ISoS, the WHO
collaborative followup project. International Study of Schizophrenia. Schizophr. Bull. 26,
835–846.
Howes, O.D., Kapur, S., 2009. The dopamine hypothesis of schizophrenia: version III–the final
common pathway. Schizophr. Bull. 35, 549–562.
Huber, G., Gross, G., Schu¨ttler, R., 1975. A long-term follow-up study of schizophre-nia:
psychiatric course of illness and prognosis. Acta psychiatrica Scandinavica 52, 49–57.
Isaac, M., Chand, P., Murthy, P., 2007. Schizophrenia outcome measures in the wider
international community. The British Journal of Psychiatry 191, s71–s77.
Jablensky, A., Sartorius, N., Ernberg, G., Anker, M., Korten, A., Cooper, J.E., Day, R.,
Bertelsen, A., 1992. Schizophrenia: manifestations, incidence and course in different
cultures. A World Health Organization ten-country study. Psychologi-cal medicine.
Monograph supplement 20, 1–97.
Jablensky, A., Schwarz, R., Tomov, T., 1980. WHO collaborative study on impair-ments and
disabilities associated with schizophrenic disorders. Acta psychia-trica Scandinavica 62,
152–163.
Johnson, S., Sathyaseelan, M., Charles, H., Jeyaseelan, V., Jacob, K.S., 2012. Insight,
psychopathology, explanatory models and outcome of schizophrenia in India: a prospective
5-year cohort study. BMC psychiatry 12, 159.
Kare M, Thirthalli J, Reddy KS, Ross D, Jagannathan A, BN, G., 2009. Better outcome of
schizophrenia in India: possible role of short prodromal period., Oral paper presented at the
10th World Congress of World Association of Psychosocial Rehabilitation (WAPR), Nov
2009. NIMHANS, Bangalore.
Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The positive and negative syndrome scale (PANSS)
for schizophrenia. Schizophr. Bull. 13, 261–276.
Kraepelin, E., 1899. Psychiatrie: Ein Lehrbuch fur studierende und Aerzte, 5th Edition ed.
Kreyenbuhl, J., Buchanan, R.W., Dickerson, F.B., Dixon, L.B., 2010. The schizophrenia patient
outcomes research team (PORT): updated treatment recommendations 2009. Schizophr.
Bull. 36, 94–103.
Kua, J., Wong, K.E., Kua, E.H., Tsoi, W.F., 2003. A 20-year follow-up study on schizophrenia
in Singapore. Acta psychiatrica Scandinavica 108, 118–125.
Kurihara, T., Kato, M., Reverger, R., Tirta, I.G., 2011. Seventeen-year clinical outcome of
schizophrenia in Bali. European psychiatry: the journal of the Association of European
Psychiatrists 26, 333–338.
Leff, J., Wig, N.N., Bedi, H., Menon, D.K., Kuipers, L., Korten, A., Ernberg, G., Day, R.,
Sartorius, N., Jablensky, A., 1990. Relatives’ expressed emotion and the course of
schizophrenia in Chandigarh. A two-year follow-up of a first-contact sample. Br. J.
Psychiatry:J. Mental Sci. 156, 351–356.
Liu, T., Song, X., Chen, G., Paradis, A.D., Zheng, X., 2014. Prevalence of schizophrenia
disability and associated mortality among Chinese men and women. Psychiatry research.
Marom, S., Munitz, H., Jones, P.B., Weizman, A., Hermesh, H., 2005. Expressed emotion:
relevance to rehospitalization in schizophrenia over 7 years. Schizophr. Bull. 31, 751–758.
McGlashan, T.H., 1988. A selective review of recent North American long-term followup
studies of schizophrenia. Schizophr. Bull. 14, 515–542.
McGrath, J., Saha, S., Chant, D., Welham, J., 2008. Schizophrenia: a concise overview of
incidence, prevalence, and mortality. Epidemiol. Rev. 30, 67–76.
Murthy, G.V., Janakiramaiah, N., Gangadhar, B.N., Subbakrishna, D.K., 1998. Sex difference in
age at onset of schizophrenia: discrepant findings from India. Acta Psychiatrica Scand. 97,
321–325.
Naqvi, H., Khan, M.M., Faizi, A., 2005. Gender differences in age at onset of schizophrenia. J.
Coll. Physicians Surg.—Pak.: JCPSP 15, 345–348.
Nunley, M., 1998. The involvement of families in Indian psychiatry. Culture, Med.
Psychiatry 22, 317–353.
Overall, J.E., Gorham, D.R., 1962. The brief psychiatric rating scale. Psychol. Rep. 10, 799–
812.
G Model
AJP-671; No. of Pages 10
10 B. Holla, J. Thirthalli / Asian Journal of Psychiatry xxx (2015) xxx–xxx
Ran, M.S., Chen, S., Chen, E.Y., Ran, B.Y., Tang, C.P., Lin, F.R., Li, L., Li, S.G., Mao, W.J.,
Hu, S.H., 2011. Risk factors for poor work functioning of persons with schizo-phrenia in
rural China. Soc. Psychiatry Psychiatric Epidemiol. 46, 1087–1093.
Rangaswamy, T., 2012. Twenty-five years of schizophrenia: the Madras longitudinal study.
Indian J. Psychiatry 54, 134–137.
Ryu, Y., Mizuno, M., Sakuma, K., Munakata, S., Takebayashi, T., Murakami, M., Falloon, I.R.,
Kashima, H., 2006. Deinstitutionalization of long-stay patients with schizophrenia: the 2-
year social and clinical outcome of a comprehensive intervention program in Japan. Aust.
N. Z. J. Psychiatry 40, 462–470.
Sadock, B.J., 2000. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry.
Lippincott Williams & Wilkins, Philadelphia (2 Volume Set).
Saha, S., Chant, D., McGrath, J., 2007. A systematic review of mortality in schizo-phrenia: is
the differential mortality gap worsening over time? Arch. Gen. Psychiatry 64, 1123–1131.
Schoepf, D., Uppal, H., Potluri, R., Heun, R., 2014. Physical comorbidity and its relevance on
mortality in schizophrenia: a naturalistic 12-year follow-up in general hospital admissions.
Eur. Arch. Psychiatry Clin. Neurosci. 264, 3–28.
Shrivastava, A., Shah, N., Johnston, M., Stitt, L., Thakar, M., 2010. Predictors of long-term
outcome of first-episode schizophrenia: a ten-year follow-up study. Indian J. Psychiatry 52,
320–326.
Stephens, J.H., 1978. Long-term prognosis and followup in schizophrenia.
Schizophr. Bull. 4, 25–47.
Suresh, K.K., Kumar, C.N., Thirthalli, J., Bijjal, S., Venkatesh, B.K., Arunachala, U.,
Kishorekumar, K.V., Subbakrishna, D.K., Gangadhar, B.N., 2012. Work function-ing of
schizophrenia patients in a rural south Indian community: status at 4-year follow-up. Soc.
Psychiatry Psychiatric Epidemiol. 47, 1865–1871.
Thirthalli, J., Jain, S., 2009. Better outcome of schizophrenia in India: a natural selection against
severe forms? Schizophr. Bull. 35, 655–657.
Thirthalli, J., Kumar, C.N., Arunachal, G., 2012. Epidemiology of comorbid substance
use and psychiatric disorders in Asia. Curr. Opin. Psychiatry 25, 172–180.
Please cite this article in press as: Holla, B., Thirthalli, J., Course and Outcome of Schizophrenia in Asian Countries: Review of Research in the Past Three
Decades. Asian J. Psychiatry (2015), http://dx.doi.org/10.1016/j.ajp.2015.01.001
Tsuang, M.T., Woolson, R.F., Fleming, J.A., 1979. Long-term outcome of major psychoses: I.
Schizophrenia and affective disorders compared with psychiatri-cally symptom-free surgical
conditions. Arch. Gen. Psychiatry 36, 1295–1301. van Os, J., Rutten, B.P., Poulton, R., 2008.
Gene-environment interactions in schizo-phrenia: review of epidemiological findings and future
directions. Schizophr.
Bull. 34, 1066–1082.
Venkatesh, B.K., Thirthalli, J., Naveen, M.N., Kishorekumar, K.V., Arunachala, U.,
Venkatasubramanian, G., Subbakrishna, D.K., Gangadhar, B.N., 2008. Sex differ-ence in
age of onset of schizophrenia: findings from a community-based study in India. World
Psychiatry: Off. J. World Psychiatric Assoc. 7, 173–176.
Verghese, A., John, J.K., Rajkumar, S., Richard, J., Sethi, B.B., Trivedi, J.K., 1989. Factors
associated with the course and outcome of schizophrenia in India: results of a two-year
multicentre follow-up study. Br. J. Psychiatry: J. Mental Sci. 154, 499–503.
Verma, S., Subramaniam, M., Abdin, E., Poon, L.Y., Chong, S.A., 2012. Symptomatic and
functional remission in patients with first-episode psychosis. Acta Psychia-trica Scand.
126, 282–289.
Volkow, N.D., 2009. Substance use disorders in schizophrenia—clinical implications of
comorbidity. Schizophr. Bull. 35, 469–472.
WHO, 1979. Schizophrenia;1; An international Follow-Up Study. John Wiley and Sons,
Chichester, UK.
Wiersma, D., Nienhuis, F.J., Giel, R., de Jong, A., Slooff, C.J., 1996. Assessment of the need
for care 15 years after onset of a Dutch cohort of patients with schizo-phrenia, and an
international comparison. Soc. Psychiatry Psychiatric Epide-miol. 31, 114–121.
Wig, N.N., Menon, D.K., Bedi, H., Ghosh, A., Kuipers, L., Leff, J., Korten, A., Day, R.,
Sartorius, N., Ernberg, G., et al., 1987. Expressed emotion and schizophrenia in north
India. I. Cross-cultural transfer of ratings of relatives’ expressed emotion. Br. J. Psychiatry:
J. Mental Sci. 151, 156–160.
Yang, J., Kang, C., Zeng, Y., Li, J., Li, P., Wan, W., Zhao, X., Guo, W., Xu, X., Yang, X., Li,
Q., Liu, X., Pauline, S.C., 2013. Prevalence and prognosis of schizophrenia in Jinuo people
in China: A prospective 30-year follow-up study. Int. J. Soc. Psychiatry 60, 482–488.