This document summarizes research on the course and outcome of schizophrenia. It discusses several landmark studies including the International Pilot Study of Schizophrenia, Determinants of Outcome of Severe Mental Disorder study, and International Study of Schizophrenia. Overall, the studies found that outcomes tended to be better in developing countries compared to developed countries. Within developing countries, outcomes were particularly good in India, with studies in Agra and Chandigarh finding high rates of remission. Acute onset, good premorbid adjustment, younger age, and shorter duration of initial psychotic episode predicted better long-term prognosis.

1. Course and Outcome of
Schizophrenia
Presented by Dr. Karrar Husain
Moderator – Prof. SA Azmi

2. INTRODUCTION
 Schizophrenia is a major public health concern that
afflicts a sizeable population over the world.
 It manifests with multiple signs and symptoms
involving thoughts, perceptions, emotion and
behaviour.
 It is chronic and disabling condition, which shows
heterogeneity in its clinical presentation,
pharmacological response and in the long term
outcome.

3.  Historically, poor outcome has often been
considered as basic to the concept of schizophrenia.
 Emil Kraepelin (1856 to 1926) -a professor of
psychiatry, studied the objective symptoms and
clinical life histories of thousands of psychotic
patients.
 Two major patterns of insanity—manic-depressive
psychosis and dementia praecox.
Ctp 9th

4.  Hebephrenia, catatonia (Ewald Hecker and Karl
Kahlbaum) and paranoia.
 Kraepelin emphasized dementia praecox, has poor
long-term prognosis as compared to the relatively
non deteriorating course of manic-depressive
illness.
 However, 12.5% of his patients had a good outcome
Ctp 9th

5.  Bleuler, who coined the term ‘schizophrenia’
believed that it did not permit a full “restitutio ad
integrum”
 Kleist (1960) and Leonhard (1961) insisted that if a
patient recovers, he could not have had
schizophrenia.
(Alan et al.,1975)
 Scenario is less bleak and pessimistic, now

6. Defining course and outcome
Course
 Progress of the disorder or the clinical state of the
patient along the passage of time
 Bleuler (1978) and Ciompi (1980) - undulating
(phases of at least a week), simple (long term,
stable chronic state) and atypical.
 ISOS - episodic ( no episode > 6 months ),
continuous ( no remission > 6 months) , neither
episodic nor continuous (negative symptoms).
(Harrison et al , 2001)

7.  WHO - 5 patterns, which are a part of the instrument
psychiatric and personal history schedule (PPHS) :
 Complete or near complete recovery, without relapse
or exacerbations of psychotic symptoms.
 No relapse or exacerbations of psychotic symptoms
but with residual or personality change.

8.  One or more relapses or acute exacerbations of
psychotic symptoms with full or nearly full remission,
following then with no marked personality change.
 One or more relapses or exacerbations of psychotic
symptoms against a background of marked
personality change.
 Continuous psychotic illness.

9. Outcome
 State or condition of the person suffering from the
illness at a defined point of time.
 Bleuler and Ciompi categorized it as recovery, mild,
moderately severe and severe, mainly accounting for
symptomatology, social and occupational functioning
 Most studies have tried to cover similar areas –
clinical outcome, social, occupational and overall
outcome

10. PARAMETERS OF OUTCOME
 Death : more, suicide is primarily responsible for the
increased mortality.
 Continuous institutionalization : this is
progressively becoming rare
 Psychological deficit : Some studies have
included cognitive impairment, namely disturbance
in attention, orientation and memory as outcome
parameter.
 Relapse
 Functioning

11.  Global scenario (pre-IPSS)
 WHO sponsored studies
 International Pilot Study of Schizophrenia (IPSS)
 Determinants of Outcome of Severe Mental Disorder
(DOSMeD)
 International Study of Schizophrenia (ISoS)
 Indian studies (other than WHO)
 Long term follow up of Agra cohort of the IPSS
 ICMR project (2 year multicentre follow up study)
(SoFACOS)
 The Madras Longitudinal Study – 10 and 20 year follow
up.
 Chandigarh Study

12.  Afro-Carribean studies
 Comparison of recent long-term studies
(including Indian studies)

13. Global Scenario pre IPSS
 M. Bleuler - European patients –1/3rd have a
chronic and deteriorating course, 1/3rd recover
while the remaining one-third have an intermediate
course
 Brown et al (1966) – London study – 55% had a
chronic or episodic disturbance and 34% had no
disturbance at follow up

14.  12-year follow up survey in Mauritius - 64% of their
cases were independent or had no symptoms,16%
were still in hospital and 19% had symptoms of
psychosis or varying degree of dependence at the
time of the 12- year follow up.
(Murphy &Raman, 1971)

15.  5 year follow up study from North West India of
patients diagnosed based on criteria of Schneider
and Mayer –174 patients, of which 100 could be
followed up
 29% had no disturbance, 16% were improving , 23%
had an episodic course & 32% continued to be ill
(Kulhara & Wig, 1978)

16.  10 years follow up by Lo & Lo (1977) - Chinese
schizophrenic patients found that 65 percent had full
and lasting remission.
 5 year follow up of 89 first admission patients in Sri
Lanka (Waxler, 1979) reported that 45% of the
cases had no symptoms, 24% had non-psychotic
symptoms and only 31% had psychotic symptoms

17. A Comparison (with Brown et al., 1966)
 Mauritian and Sri Lankan studies – better outcome
in developing countries as compared to developed
countries

18. International Pilot Study of Schizophrenia
 First published in 1973
 9 countries; baseline, 2 year and 5 year follow up.
 Instruments – PSE, follow up Psychiatric history
schedule, follow up Social description schedule,
follow up Diagnostic assessment schedule.
 Original cohort – 1202.

19.  2 year F/U - 909 reviewed (1979)
 Agra, Cali and Ibadan had more asymptomatic
patients than Aarhus, London and Washington.
 Also, the former centres had more patients in the
category of best course as compared to the latter.

20. 5-year follow up - 807 – 76% of original cohort(1992)
 Clinical and social outcomes were significantly
better for patients in Agra and Ibadan than for those
in centers in developed countries.
 In Cali, only social outcome was significantly better
(despite high proportion of patients with worst
pattern of course)
 Agra had the highest percentage (42%) with best
outcome and least (10%) with worst outcome
(Sartorius et al., 1987, Leff et al., 1992)

21. Centre Percentage of full remission Percentage with continuous
illness
2 yrs 5 yrs 2 yrs 5 yrs
Aarhus 6 6 50 40
Agra 51 42 20 10
Cali 19 11 26 21
Ibadan 58 33 7 10
London 23 5 30 14
Moscow 7 6 18 21
Prague 17 9 30 23
Washington 21 17 47 23
Taipei 27 - 27 -
COURSE OF IPSS PATIENTS AT 2 AND 5 YRS

22. CONCLUSIONS
 Course and outcome better in developing countries.
 Centre and acuteness of onset – most significant
predictors.
 Better social outcome despite worse clinical outcome
in Cali – good family support?
 IPSS analyses showed that the rate of f/u at Cali was
high but no. of cases with best outcome was
relatively low, in contrast to Ibadan in Nigeria- rate of
f/u comparatively low but high number of best
outcomes cases.
(Leff et al., 1992)

23. Study on Determinants of Outcome of Severe
Mental Disorder ( DOSMeD)
 12 centers in 10 different countries - India had 2
centers – Agra and Chandigarh;
 1 and 2 year f/u
 Instruments – Screening schedule, PSE, Psychiatric
and Personal history schedule(PPHS), Diagnostic
and Prognostic schedule, FU-PPHS, DAS
 7 categories of pattern of course - single psychotic
episode followed by a complete remission to
continuous unremitting illness.
 Original cohort – 1379

24.  1014 (74%) could be evaluated sufficiently for pattern
of course
 Overall findings:
Mild course Severe Course
Developing 56% 24%
Developed 39% 40%

25.  Acute onset had a good pattern of course in both
developing and developed countries.
 Insidious onset + good premorbid adjustment and
younger age in developing countries - predicted a
better course. Not the case in developed countries.
 Later of age onset, female gender, married at
initial evaluation, hebephrenic and residual
subtypes of schizophrenia predicted poor outcome.

26. INDIAN CENTRES
 Agra - 81 patients, CHD (R) – 54 patients and urban
center had 155 patients.
 83% , 81% and 56% of patients had acute mode of
onset.
 54% - Agra, 42% - Chandigarh (urban) and 27.3% in
Chandigarh (rural) had single episode followed by
complete remission
 Agra & Chandigarh patients had more favorable 2
year course and outcome, had spent lesser time in
psychotic episode and had less impairment of social
functioning
Sartorius et al., 1986, Craig et al., 1997,
Kulhara, 1997

27. International Study of Schizophrenia
 3 cohorts - 2 were DOSMeD , RAPyD (assessment
& reduction of psychiatric disability) that allowed for
15-year follow up and the third cohort of IPSS
offered the opportunity of a 25 year f/u
 14 culturally diverse treated incidence cohorts – 12
from DOSMED and RAPyD and 2 invited cohorts
from HongKong and Madras – total of 1171 subjects
 Four prevalence cohorts – 3 from IPSS and one
invited from Beijing – total of 462 cases
 Total of 1633 subjects included in the study.

28.  PSE, WHO – DAS and GAF (for functioning), life
chart schedule (for course of illness) and a global
assessment of functioning by Bleuler’s criteria.
 Within center & between centers, reliability was
examined. Five centers carried out a maintenance
reliability check
 About 75% traced; 1005 living participants

29.  15.7% of schizophrenic cases in the incidence
cohort showed evidence of late improvement at the
15 – year follow up.
 In non – industrialized countries, the majority of
known deaths listed as natural, reverse true in
industrialized countries.

30. Mortality rates
Centres Cohort (n) Deaths SMR
Agra 140 43 1.86
CHD (U) 155 14 1.88
CHD (R) 55 10 3.02
Nottingham 99 9 3.31

31. CONCLUSIONS
 Global outcomes at 15 years & 25 years were
favorable for over half of all people followed up
 Baseline diagnosis of ICD – 10 schizophrenia was
consistently associated with poorer outcomes
Strongest predictors were measures of early
illness course

32.  % of time spent experiencing psychotic symptoms in
the 2 years following onset was the best predictor.
 Offered reason for therapeutic optimism and pointed
to a critical ‘window of opportunity’ in the early
period.
 Type of onset was significantly related to % time
spent with psychotic symptoms.
 Living in certain areas appear to improve chances of
recovery.

33.  Short term course of illness strongly predicted long
– term outcome.
 Premorbid signs and symptoms s/o poor social
adjustment enhance the chance of adverse long-
term outcome.
 Evidence of difference in illness trajectory in
favor of developing countries
(Sartorius et al., 1995, Harrison et al.,
2001

34. Long term follow up of Agra cohort of the
IPSS
 Course and Outcome at a 13-14 year follow up of
the Agra cases was done.
 Original cohort - 140 patients; 61% of the original
cohort could be traced (17 patients who had died
were included)
 Instruments – PSE, PPHS

35. Findings:
 46% of schizophrenics had no episode at all after 5
years of inclusion and thus considered recovered
 According to the perception of the key respondents,
41% of schizophrenics were recovered and 25%
partially recovered.

36. Conclusions
 Prospect of recovery is not as bleak as is generally
believed
 Patients who do not recover completely, do have
intervals of recovery and in those with a continuous
course, the actual state usually loses its intensity
 Thus, a diagnosis of schizophrenia is compatible
with recovery
(Dube et al., 1984)

37. ICMR project ( 2 year multicentre follow
up study)
 Also known as soFACOS
 3 centers – Lucknow in North India, Madras and
Vellore in South India – 2 year f/u
 Attending psychiatric clinic with illness of less than 2
years.
 Original Cohort - 386; 96 patients were recruited in
Madras center, 207 in Lucknow & 83 in Vellore
 Follow up – 323 patients (84%) – 174 (L), 83 (M), 64
(V)

38. FINDINGS
 45% of patients had the best clinical outcome while
66 % had a good overall outcome.
 40% showed good occupational adjustment, 34%
showed good social interaction
 Variables associated with good overall outcome
were short duration of illness, regular drug
compliance, no schizoid premorbid traits, absence of
economic difficulties , increase in socio-economic
levels, lack of dangerous behavior.

39.  Rural background was a correlate. The authors
hypothesised, that rural background assures more
social support and tolerance, and in turn, might
explain the difference in prognosis between the
developed and the developing countries.
 Thus, strongly in keeping with the findings of the
IPSS.
(Verghese et al.,
1989)

40. The Madras Longitudinal Study
 10 years follow up of ICMR cohort
 Complete assessment of 76 out of 96 cases of the
original cohort was carried out
FINDINGS
 Patten of illness was good in 67% of cases, the
commonest pattern was one with recurrent episode
with / without complete remission
 Nearly 60% of the cohort was able to hold onto a job
at the end of 10 years.
(Thara et al., 1994, Thara & Eaton, 1996)

41.  Another important finding was that of a significant
decline in positive symptoms without a concurrent
rise in negative symptoms
 At 20 year f/u
 F/u rate - 61 subjects from the initial cohort of 96
patients
 Four basic pattern of course were complete
remission / few residual symptoms, relapses with &
without complete remission and continuous illness

42. PATTERNS OF COURSE

43. Chandigarh cohort
 15 year follow up of the two incidence cohorts of
DOSMeD in urban and rural Chandigarh to examine
the implications of poor early course ( 2 year) for the
long – term prognosis
 Key Instruments for rating the course of illness –
Life Chart Schedule, Broad rating schedule (for
deceased and lost to f/u)
 Original cohort - 209 patients
 171 (82%) had a rating of course of illness at the 2-
year follow up. 111 patients could be interviewed
directly at 15 – year follow up.

44. FINDINGS:
 Patients with a poor 2-year course (a continuous
psychotic illness) had a very poor prognosis in the
long term (92% in the present study)
 No meaningful differences between the urban and
rural settings in this regard
 High rate of morality (47%) among those with a poor
2-year course
 Very few patients with a poor 2 year course had
received treatment for most or all of the f/u period

45. CONCLUSIONS
 Data results from 13 year f/u in Nottingham cohort
of DOSMeD (Harrison et al.,1996) & other ISoS
centers are similar, it can be concluded with a fair
degree of confidence that a poor 2 year course is a
strong predictor of a poor long – term course
 However, few patients in developing countries have
a poor 2- year course as compared to industrialized
countries (Jablensky et al., 1992)
 Also, urban and rural centres, though represent
different sociocultural settings had similar findings
(Mojtabai et al., 2001)

46. Studies comparing Asian, Afro- Caribbean
and White patients
 1st episode sample was assessed 12 months after
discharge
 Relapse rates lowest in the Asian (16%), as
compared to the white patients (30%) and Afro
Caribbean (49%) patients
 The authors hypothesized that extended family
networks and high frequency of stable marriage
might have reduced vulnerability in the Asians
 Employment rates were low in Afro – Caribbeans
 Similar findings by Bhugra (1997)
(Birchwood et al., 1992)

47. 16 year follow up study (ISoS) in Sofia,
Bulgaria
 60 patients (recent onset non affective psychosis)
followed up 16 years after the initial assessment in
RAPyD (WHO project)
 About 1/3rd
of the patients had a good outcome
 Subjects had a relatively low mortality rate (3.3% - 2
subjects; both committed suicide)
- 45 % patients were continuously psychotic in
last 2 years compared to 7% in Madras
longitudinal study
 Subjects had a lower rate of institutionalization
(Ganev et al., 1998)

48. Nottingham study – 13 year outcome
 Original cohort (1978-80) in Nottingham - 67 first
episode cases, of which 58 followed up
 52% were without psychotic symptoms in the last 2
years of follow up, 52% were without negative
symptoms and 55% showed good / fair social
functioning
 Comparable to other studies in the industrialized
world (5 year outcome of the London cohort of
IPSS).

49.  17% of patients achieved complete recovery over
the long term, but about half of the patients
achieved a mild/ recovered treated outcome at 13
years
 Poor 2-year course associated with poor outcome at
long term f/u
(Mason et al., 1995, Harrison et al.,
1996)

50. Sweden study (14-17 year f/u of 92 first admitted
cases) (Jonsson & Nyman, 1991)
Variable Distribution
(%)
Symptoms Well or almost well vs ill 26/74
Economic self
support
Employment v/s not
self supporting
47/53
Social
competence
Marriage/partnership or
parenthood v/s neither
32/68
Total outcome Good in at least 2
variables v/s 1 or none
28/72

51. Comparison between industrialized and non-
industrialized societies in Asia
 5 outcome measures at 5 – years follow up of
patients in Bali and Tokyo
 Cumulative length of stay in hospital and
percentage of subjects on neuroleptics was
significantly lower in Bali as compared to Tokyo
(Kurihara et al.,
2000)

52. Cali (Columbia) – 10 year follow up
 IPSS cohort – 101 patients
 84 patients – adequate information
 51% recovered (43% - complete recovery)
 Only 10% - spent 75% of follow up period in
psychosis
 50% had no or mild social impairment
 Disagreed with Kraepelin
(Leon, 1989)

53. Pattern of course over last 2 years of the follow up period
ISoS
(incidence)
ISoS
(prevalence)
Nottingham Sofia Madras
(20 years)
n 502 142 48 55
Episodic 16.6 8.5 10 12.7
Continuous 33.6 46.4 34 45.5 8.2
Neither
episodic nor
continuous
6.9 4.2 3 3.6
Never
psychotic
42.5 40.8 52 38.2

54. GAF – symptom scores
Sofia
n= 55
Nottingham
n=57
Madras (20
year) n=61
< or = 60 78% 51% 22.9%
> 60 22% 49% 77.1%

55. GAF – D Scores
ISoS
(incidence
cohort)
Sofia
n= 55
Nottingham
n=58
Madras (20
year) n=61
< 30 7.2%
31-50 50.9%
51-60 7.2%
> 60 37.8% 34.5% 50% 73.8%

56. Psychopathology : signs and symptoms
 Poor prognostic factors
 Emotional blunting and flatness
 Negativism, mutism
 Inappropriate affect
 Higher psychopathology at index discharge
 Negative symptoms

57.  Good prognostic factors
 Affective symptoms
 Confusion
 Hallucination
 Delusions
 Intact thickening

58. Conclusion
 Consistent finding - developing countries have a
larger proportion (50-60%) with a good outcome and
lesser percentage with a worst outcome as
compared to developed countries at 2-year and 5-
year follow up
 This difference continues to stay at 15 years or
longer follow up.
 Mortality rates are higher as compared to general
population; suicide is a significant cause

59.  Studies have given varying results as to whether
schizophrenia loses its intensity over time (Dube et
al., 1984), has neither ameliorating nor deteriorating
course (Mason et al., 1996) or has increase in some
subsyndromal symptoms (Thara et al., 2004)
 However, one thing is clear that the course &
outcome are not as malignant as projected by the
followers of Kraepelin.

60.  Another consistent finding in the long-term ( > 13-15
years) is that the pattern of course at 2 years
predicted the course and outcome at long –term
follow up across cultures/ countries (Harrison et al., 1996,
Thara et al., 2004)
 Also, it was found in the Mauritian study that in long-
term outcome of mild cases, environment played a
role; whereas outcome of severe cases was
independent of external factors.

61.  Various investigators have found that a family h/o
schizophrenia indicates a poor prognosis (Bland
1982; Stephens and Astrup 1963).
 On the other hand a family history of affective
disorder has a better outcome (Bland 1982, Vaillant
1964).
 If the schizophrenia onset was precipitating by some
events/ factor, the prognosis is regarded as good on
the other hand absence of a precipitating factor
indicates poor outcome.

62. Predictors of outcome:
 Acuteness of onset & centre.
 Male gender, insidious onset, lesser social support,
low level of employment predict a poor outcome.
 Being married, female gender, better premorbid
adjustment, no drug use, acute onset, short duration
of illness and short duration of untreated illness –
better outcome.
 Appears that premorbid adjustment is a better
predictor of outcome in developing countries than
developed countries.

63.  Various studies on EE across cultures show that high
level of EE are associated significantly with high rate
of relapse and poor outcome

64. Kraepelin during his stay in the islands of
Java concluded that the illness does not exist
in primitive societies; now there is enough
evidence
 Schizophrenia is universal
 Course and outcome appear to be better in the
developing world

65. Thank you