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Schizophrenia and Bipolar Disorders:
Diagnosis, Descriptive Epidemiology,
and Natural History
William W. Eaton, PhD
Johns Hopkins University
Section A
Diagnosis
Sign, Symptoms, and Diagnosis
Psychoses (ICD 8: 290-299)
Ë Mental disorders in which impairment of
mental function has developed to a degree that
interferes grossly with insight, ability to meet
some ordinary demands of life, or to maintain
adequate contact with reality
Ë It is not an exact or well defined term
Ë Mental retardation is excluded
4
DSM-IV Diagnosis of Schizophrenia
A. Characteristic symptoms
Ë Delusions
Ë Hallucinations
Ë Disorganized speech
Ë Disorganized behavior
Ë Negative symptoms
Continued
5
DSM-IV Diagnosis of Schizophrenia
A. Characteristic symptoms
Ë Delusions
Ë Hallucinations
Ë Disorganized speech
Ë Disorganized behavior
Ë Negative symptoms
Continued
6
DSM-IV Diagnosis of Schizophrenia
B. Poor functioning
C. Duration of six months
D. Not due to a mood disorder
E. Not due to substances
F. Not autism
7
DSM-IV Criteria for Mania
A. Episode of elevated mood (> one week)
B. Three or more . . .
Ë Grandiosity
Ë Decreased need for sleep
Ë Talkative
Ë Flight of ideas
Ë Distractible
Ë Increase in goal-directed activity
Ë Spending sprees, promiscuity, etc.
Continued
8
DSM-IV Criteria for Mania
C. Not mixed with major depressive episode
D. Marked impairment
E. Not due to substance or medical condition
9
Section B
International Variation in Schizophrenia: Signs
and Symptoms
U.S.–UK Project
New York
London
Schizophrenia
Hospital
Diagnosis
Affective
Psychosis
Project
Diagnosis
Diagnostic differences were mostly due to failure of
Americans to exclude affective disorders
Source: Kendell, et al. (1971), Arch Gen Psychiatry
11
0
Ps
yc
ho
5. 3 mo
Af . F to
fe or r d
ct m is
-la o o
7.
de f th rd
Ex
6
p
. P n t ink er
9.
e
Ne rie re ho in
nc de ug g
ur
es lu h
as
t
11
he 8 of sion ts
.D
ni . D con al
1
ist 0. c c el t
or La om usi rol
te ck p on
13
d
14 . A
se of lain s
1
. C u 2 lf- in ts
ha dit . D pe sig
ra or e- rce ht
c y r
16 teri hal eali ptio
. P sti luc zat n
se c h in io
18
n
u
. A 1 do allu atio
nx 7. -h cin ns
ie De allu at
ty p c io
, t re in n
en ss at s
sio ed io
n, -el ns
i a
19 rrita ted
23 22 2 . Fl bil
. D . Pe 0. I atn ity
isr rs nc es
eg on on s
27 ard ality gru
. D fo c ity
iff r s ha
icu oc ng
l t y ial e
co no
op rm
er s
at
in
g
1.
Syndrome Score (%)
International Pilot Study of Schizophrenia
Syndrome Profiles for Schizophrenics in Aarhus, Denmark
Aarhus
80
60
40
20
+
Source: WHO (1979), “Schizophrenia: An International Follow-Up Study,” Tables 9 and 23
+
Continued
12
0
Ps
yc
ho
5. 3 mo
Af . F to
fe or r d
ct m is
-la o o
7.
de f th rd
Ex
6
p
. P n t ink er
9.
e
Ne rie re ho in
nc de ug g
ur
es lu h
as
t
11
he 8 of sion ts
.D
ni . D con al
1
ist 0. c c el t
or La om usi rol
te ck p on
13
d
14 . A
se of lain s
1
. C u 2 lf- in ts
ha dit . D pe sig
ra or e- rce ht
c y r
16 teri hal eali ptio
. P sti luc zat n
se c h in io
18
n
u
. A 1 do allu atio
nx 7. -h cin ns
ie De allu at
ty p c io
, t re in n
en ss at s
sio ed io
n, -el ns
i a
19 rrita ted
23 22 2 . Fl bil
. D . Pe 0. I atn ity
isr rs nc es
eg on on s
27 ard ality gru
. D fo c ity
iff r s ha
icu oc ng
l t y ial e
co no
op rm
er s
at
in
g
1.
Syndrome Score (%)
International Pilot Study of Schizophrenia
Syndrome Profiles for Schizophrenics in Denmark and Agra
80
Aarhus
Agra
60
40
20
+
Source: WHO (1979), “Schizophrenia: An International Follow-Up Study,” Tables 9 and 23
+
Continued
13
0
Ps
yc
ho
5. 3 mo
Af . F to
fe or r d
ct m is
-la o o
7.
de f th rd
Ex
6
p
. P n t ink er
9.
e
Ne rie re ho in
nc de ug g
ur
es lu h
as
t
11
he 8 of sion ts
.D
ni . D con al
1
ist 0. c c el t
or La om usi rol
te ck p on
13
d
14 . A
se of lain s
1
. C u 2 lf- in ts
ha dit . D pe sig
ra or e- rce ht
c y r
16 teri hal eali ptio
. P sti luc zat n
se c h in io
18
n
u
. A 1 do allu atio
nx 7. -h cin ns
ie De allu at
ty p c io
, t re in n
en ss at s
sio ed io
n, -el ns
i a
19 rrita ted
23 22 2 . Fl bil
. D . Pe 0. I atn ity
isr rs nc es
eg on on s
27 ard ality gru
. D fo c ity
iff r s ha
icu oc ng
l t y ial e
co no
op rm
er s
at
in
g
1.
Syndrome Score (%)
International Pilot Study of Schizophrenia
Profiles for Schizophrenics in Denmark, India, Ibadan, and Nigeria
80
Aarhus
Agra
Ibadan
60
40
20
+
Source: WHO (1979), “Schizophrenia: An International Follow-Up Study,” Tables 9 and 23
+
Continued
14
0
Ps
yc
ho
5. 3 mo
Af . F to
fe or r d
ct m is
-la o o
7.
de f th rd
Ex
6
p
. P n t ink er
9.
e
Ne rie re ho in
nc de ug g
ur
es lu h
as
t
11
he 8 of sion ts
.D
ni . D con al
1
ist 0. c c el t
or La om usi rol
te ck p on
13
d
14 . A
se of lain s
1
. C u 2 lf- in ts
ha dit . D pe sig
ra or e- rce ht
c y r
16 teri hal eali ptio
. P sti luc zat n
se c h in io
18
n
u
. A 1 do allu atio
nx 7. -h cin ns
ie De allu at
ty p c io
, t re in n
en ss at s
sio ed io
n, -el ns
i a
19 rrita ted
23 22 2 . Fl bil
. D . Pe 0. I atn ity
isr rs nc es
eg on on s
27 ard ality gru
. D fo c ity
iff r s ha
icu oc ng
l t y ial e
co no
op rm
er s
at
in
g
1.
Syndrome Score (%)
International Pilot Study of Schizophrenia
Profiles for Schizophrenics in Five Countries
80
60
Aarhus
Agra
Ibadan
London
Cali
40
20
+
Source: WHO (1979), “Schizophrenia: An International Follow-Up Study,” Tables 9 and 23
+
Continued
15
0
Ps
yc
ho
5. 3 mo
Af . F to
fe or r d
ct m is
-la o o
7.
de f th rd
Ex
6
p
. P n t ink er
9.
e
Ne rie re ho in
nc de ug g
ur
es lu h
as
t
11
he 8 of sion ts
.D
ni . D con al
1
ist 0. c c el t
or La om usi rol
te ck p on
13
d
14 . A
se of lain s
1
. C u 2 lf- in ts
ha dit . D pe sig
ra or e- rce ht
c y r
16 teri hal eali ptio
. P sti luc zat n
se c h in io
18
n
u
. A 1 do allu atio
nx 7. -h cin ns
ie De allu at
ty p c io
, t re in n
en ss at s
sio ed io
n, -el ns
i a
19 rrita ted
23 22 2 . Fl bil
. D . Pe 0. I atn ity
isr rs nc es
eg on on s
27 ard ality gru
. D fo c ity
iff r s ha
icu oc ng
l t y ial e
co no
op rm
er s
at
in
g
1.
Syndrome Score (%)
International Pilot Study of Schizophrenia
Profiles for Schizophrenics in Five Countries
80
60
40
20
+
+
+
+
+
+
+
+
+
+
Aarhus
Agra
Ibadan
London
Cali
+ Depressive
+
+ +
Source: WHO (1979), “Schizophrenia: An International Follow-Up Study,” Tables 9 and 23
+
+
+
+ +
16
IPSS—Conclusions
Symptoms of schizophrenia are found around the
world in many cultures
Profiles of schizophrenics look similar in different
cultures
Profiles of schizophrenia look different than affective
disorder
It is possible to conduct a multinational study with
many collaborators
17
Section C
International Variation in Schizophrenia: Rates
of Occurrence
Rates of Schizophrenia
Prevalence and Incidence of Schizophrenia per 1000 Population
Area
Denmark
Date
Author
Age
Prevalence
Type
Rate
15 +
Lifetime
2.7
1977
Nielsen
1972
Munk-Jorgensen
All
Annual
Baltimore,
1963
Wing
All
One year
Maryland, USA
1963
Warthen
All
Annual
Camberwell,
1963
Wing
15+
One year
England
1971
Hailey
All
Annual
Ireland
1973
Walsh
15+
Point
1986
WHO
15-54
Annual
Portogruaro,
1982-9
de Salvia et al.
Itlay
1989
de Salvia et al.
Hampstead,
1991-5
Jeffreys et al.
England
1991-5
McNaught et al.
Incidence
0.12
7
0.7
4.4
0.11
8.3
0.22
2.7
Annual
0.19
5.1
Annual
0.21
Sources: Eaton, Epidemiol Rev., 1985; 1991; Jeffreys, et al., Br J Psychiatry, 1997;
McNaught, et al., Br J Psychiatry, 1997; de Salvia, et al., J Nerv Ment Dis.,1993
19
Incidence of Schizophrenia
WHO Collaborative Study
Place
Annual Incidence per 1000
Aarhus, Denmark
0.18
Chandigarh, India (rural)
0.42
Chandigarh, India (urban)
0.35
Dublin, Ireland
0.22
Honolulu, Hawaii
0.16
Moscow, Russia
0.28
Nagasaki, Japan
0.21
Nottingham, England
0.22
Adapted from Sartorius, et al. (1986), Psychol Med.
Continued
20
Incidence of Schizophrenia
Selected Studies Published after 1985
Buckingham
Camberwell
Dublin
Hampstead
Ireland—3 Countries
Manchester
New Zealand
Nottingham
Oxfordshire
Salford
Aarhus
Bavaria
Cantabria
Croatia
Finland
Germany
Groningen
Helsinki
Italy
Lundby
Mannheim
Moscow
Netherlands-Hague
Portogruaro
Sweden
Brazil
Jamaica
Honolulu
Saskatchewan
Surinam
Trinidad
Vancouver
Beijing
Chandigarh R
Chandigarh U
Madras
Nagasaki
0
0.1
0.2
0.3
0.4
0.5
Annual Incidence per 1000
Adapted from: Eaton and Chen (2004)
0.6
0.7
21
Incidence of Schizophrenia
WHO Collaborative Study
Place
Annual Incidence per 1000
Aarhus, Denmark
0.18
Chandigarh, India (rural)
0.42
Chandigarh, India (urban)
0.35
Dublin, Ireland
0.22
Honolulu, Hawaii
0.16
Moscow, Russia
0.28
Nagasaki, Japan
0.21
Nottingham, England
0.22
Source: Adapted from Sartorius, et al. (1986), Psychol Med.
Continued
22
Comparison of Six WHO Sites for Broad Schizophrenia
Lifetime Risk and Annual Incidence
Annual Incidence / 10,000
Honolulu
Nottingham
Males
Aarhus
Females
Males
Dublin
Females
Nagasaki
Moscow
0
2
4
6
8
10
12
14
Lifetime Risk / 1000
Goal Range for Annual Incidence is 1/5 of Range, Centered on Mean of 2.05
Adapted from: Chang, Tables 124-125; Satorius, et al. (1986)
23
Comparison of Six WHO Sites for Narrow Schizophrenia
Lifetime Risk and Annual Incidence
Annual Incidence /10,000
Honolulu
Nottingham
Males
Aarhus
Females
Males
Dublin
Females
Nagasaki
Moscow
0
1
2
3
4
5
6
7
Lifetime Risk /1000
Goal Range for Annual Incidence is 1/5 of Range, Centered on Mean of 1.02
Adapted from: Chang, Tables 124-125; Satorius, et al. (1986)
24
Prevalence and Incidence—Conclusions
Prevalence—about five per 1000
Incidence—about 0.2 per 1000 per year
Rates vary in different populations
25
Section D
Incidence by Age and Sex
Incidence by Age and Sex, Monroe County
DSM-II Schizophrenia in Monroe County, New York, 1975
Annual Incidence per 1000
1.4
Males
1.2
Females
1
0.8
0.6
0.4
0.2
0
0-14
15-24
25-34
35-44
45-54
55-64
65 +
Age in Years at First Admission
Adapted from Babigian (1985), in Comprehensive Textbook of Psychiatry IV
27
Incidence by Age and Sex, Denmark
ICD-8 Schizophrenia in Denmark, 1970–1982
Annual Rate per 1000
0.2
0.15
0.1
0.05
0
0-14
15-24
25-34
35-44
45-54
55-64
65 +
Age at Admission
Adapted from: Munk-Jorgensen (1987), Acta Psychiatr Scand.
Continued
28
Incidence by Age and Sex, Denmark
ICD-8 Schizophrenia in Denmark, 1970–1982
Annual Incidence per 1000
1.4
1.2
1
Males
0.8
Females
0.6
0.4
0.2
0
0-14
15-24
25-34
35-44
45-54
55-64
65 +
Age in Years at First Admission
29
Annual Incidence per 1000
Incidence by Age and Sex, Denmark and NY
1.4
DSM-II Schizophrenia in Monroe County, New York, 1975
ICD-8 Schizophrenia in Denmark, 1970-1982
Males
1.2
Females
1
Males
0.8
Females
0.6
0.4
0.2
0
0-14
15-24
25-34
35-44
45-54
55-64
65 +
Age in Years at First Admission
Adapted from Babigian (1985), in Comprehensive Textbook of Psychiatry IV,;
Munk-Jorgensen (1987), Acta Psychiatr Scand.
30
Age and Sex—Conclusions
Onset peaks in young adulthood
Females peak about five years later
Age-sex curve not affected by diagnostic threshold
Lifetime risk for males and females roughly equal
31
Section E
Natural History of Schizophrenia
Typologies of Course from Ciompi Follow-up
Undulating
ONSET
COURSE
OUTCOME
25%
10%
5%
40%
"Good"
Outcome
24%
8%
Schubweis
10%
12%
60%
"Poor"
Outcome
6%
Continued
33
Typologies of Course from Ciompi Follow-up
Undulating
ONSET
COURSE
OUTCOME
25%
10%
5%
40%
"Good"
Outcome
24%
8%
Schubweis
10%
12%
60%
"Poor"
Outcome
6%
34
Prodrome of Schizophrenia
Adapted from Hafner, et al. (1995), Search for the Causes of Schizophrenia, III
35
Precursor Signs and Symptoms of Schizophrenia
Sign or Symptom
Consistency of Finding
Early psychotic-like symptoms
+
Few friends, schizoid
Abnormal social behavior
Language impairment
Poor School Achievement
Neurological soft signs
+++
+++
+
++
++
Source: Done, D. John, Early developmental abnormalities—risk for what? In Gattaz, W.F. and Hafner, H., editors,
Search for the Causes of Schizophrenia, Volume V, Steinkopf Verlag, Darmstadt, 2004, pages 91-109
36
Course of Re-Hospitalization
Adapted from: Eaton, William W.; Mortensen, Preben Bo; Herrman, Helen; Freeman, Hugh; Bilker, Warren; Burgess, Philip; Woof, Kate.
Long-term Course of Hospitalization for Schizophrenia: Part 1. Risk for Rehospitalization. Schizophrenia Bulletin, 18, 217-228, 1992
37
WHO Follow-Up of Schizophrenia
First Onset Cases in Eight Centers
Place
Percent Percent with
Sample with No
Chronic
Symptoms Psychosis
Size
Developed Countries
Aarhus, Denmark
London, England
Moscow, Russia
50
64
66
6
5
17
40
14
21
Prague, Czechoslovakia
65
6
23
Washington, D.C., USA
51
3
23
Agra, India
Cali, Colombia
Ibadan, Nigeria
73
91
68
42
11
34
10
21
10
Developing Countries
Data from: Leff, et al. (1992), Psychol Med.
Continued
38
WHO Follow-Up of Schizophrenia
First Onset Cases in Eight Centers
Place
Percent Percent with
Sample with No
Chronic
Symptoms Psychosis
Size
Developed Countries
Aarhus, Denmark
London, England
Moscow, Russia
50
64
66
6
5
17
40
14
21
Prague, Czechoslovakia
65
6
23
Washington, D.C., USA
51
3
23
Agra, India
Cali, Colombia
Ibadan, Nigeria
73
91
68
42
11
34
10
21
10
Developing Countries
39
Readmission Risk for Schizophrenia in Denmark
in a Single Cohort of 8697 First Admissions
100
Percent of Sample
80
60
1st discharge n = 8697
5th discharge n = 3016
10th discharge n = 1231
15th discharge n = 567
40
1st
20
0
15th
10th
5th
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Years following Discharge
Adapted from: Mortensen, P. B., and Eaton, W. W. (1994). Predictors for readmission risk in schizophrenia.
Psychological Medicine, 24, 223-232.
40
Progressive Course of Schizophrenia
Relative Risk of Rehospitalization During 16 Years
Age of Onset
Victoria
Denmark
Total # episodes
1.33
1.13
Each additional
0.89
0.95
Total episodes
2866
3193
Additional variables controlled included gender, age of onset, and number of
hospitalizations prior to diagnosis of schizophrenia
Data from: Eaton, William W.; Bilker, Warren; Haro, Josep M.; Herrman, Helen; Mortensen, Preben Bo; Burgess, Philip,
Long-term Course of Hospitalization for Schizophrenia: Part II. Change with passage of time, Schizophrenia Bulletin, 18, 229-241,41
(1992
Natural History—Conclusions
Heterogeneity as to onset, course, and outcome
Considerable chronicity—long term course is mostly
stable, not progressive
Outcome: 33%– 33%–33%??
Extended prodrome and insidious onset
Languid negative—volatile positive symptoms
More benign course in non-modern settings
42
Section F
Natural History of Bipolar Disorder
Bipolar Disorder in Denmark and England
Aarhus Males
75
-
65
-
55
-
45
-
35
-
Aarhus
Females
Camberwell
Males
Camberwell
Females
25
-
15
-
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
Age of Onset
Source: Weeke, et al. (1995), Acta Psychiatr Scand., Figure 1;
Bebbington and Ramana, Soc Psychiatry Psychiatr Epidemiol., Figure 4
44
Syndromal Stability of the Course
Proportion of Syndromes across 20 Episodes in Male Subjects
Adapted from: Angst and Sellaro, Biol Psychiatry (2000)
45
Syndromal Stability of the Course of Bipolar I
Collaborative Depression 13 year follow-Up of 146 Patients
Symptom Level
Asymptomatic
Depression only
Subsyndromal
Minor
Major
Mania/hypomania only
Subsyndromal
Hypomania
Mania
Cycling or mixed
Data from: Judd, et al. (2002), Arch Gen Psychiatry
Mean % Weeks
52.7
31.9
9.4
13.5
8.9
9.3
2.4
4.6
2.3
5.9
46
Stability of Recurrence
Number of Cycles and Length (Zurich Study)
Adapted from: Angst and Sellaro, Biol Psychiatry (2000)
47
Natural History of Bipolar Disorder—Summary
Relatively abrupt onset in youth is common
Course is stable, not progressive
Continuing infrequent psychotic episodes
Natural History of Bipolar Disorder-- Summary
Continuing depressive and hypomanic episodes
throughout the course
48