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Psychiatric epidemiology
Nicole Vogelzangs
Department of Psychiatry / EMGO+ Institute
VU University Medical Center
GGZ inGeest
Topics
• Classification en diagnostics
• Prevalence of psychiatric disorders
• Etiology of depression
• Public mental health
• NESDA: a psychiatric epidemiological study
• Interaction mental health with somatic disease
Topics
• Classification en diagnostics
• Prevalence of psychiatric disorders
• Etiology of depression
• Public mental health
• NESDA: a psychiatric epidemiological study
• Interaction mental health with somatic disease
Psychiatric disorder
Condition characterized by disturbed mental
functioning causing distress and/or impaired
social functioning
Mental functioning: becoming aware of information
from the environment, appreciating this
information, weighing and testing this by previous
experiences, leading to automatic muscle
movements and acting on the environment
Psychiatric disorder
Most psychiatric disorders:
Pathologic-anatomical of pathophysiological disease
process unknown

Diagnosis is based on pattern of complaints
and symptoms

Emphasis on diagnosing based on subjective
disease perception, social dysfunctioning and
need for care
Classification and Diagnostics
• <1968: Categories and dimensions without clear
definition; different “schools”
• 1968: ICD-8 - Categories with glossary
• 1980: DSM-III - Categories with explicit inclusion- and
exclusion criteria (currently DSM-IV)
• 1980: Semi-structured and fully structured interviews –
for example CIDI psychiatric interview
Depression
Anxiety disorder
Panic disorder
1
2
3
4
5
6
7
8
9
Depressed mood
Lack of interest
Sleep disorders
Appetite/weight changes
Low energy
Concentration problems
Retardation or agitation
Guilt or worthlessness
Suicidal ideation
Specific phobia
Social phobia
Generalized
anxiety disorder
Obsessive
compulsive disorder
Depressive Disorders
Major Depressive Disorder
• ≥ 5 of the 9 key DSM depression criteria
• present for at least 2 weeks, most of the day
• limiting daily functioning
Dysthymia
•
•
depressed mood, not always as severe
present very chronic: > 2 years
Subthreshold depression (minor depression)
•
different definitions: DSM-criteria or screening
questionnaire (CES-D, BDI, IDS)
•
prevalence depending on definition
Depression = container concept
Manic
Anxiety Disorders
Panic disorder
• Attacks of recurrent, severe fear with ‘somatic’ symptoms,
e.g. sweating, shortness of breath, trembling, palpitations,
fear of going crazy
• Often accompanied with agoraphobia: avoidance behavior
Specific phobia
• Fear for 1 situation, thing or animal
(e.g. spiders, flying, water)
• Limits daily functioning
Anxiety Disorders
Social phobia
• Fear for social circumstances (e.g. speaking in public)
Generalized Anxiety Disorder (GAD)
• Nervousness / worrying much more than usual
• Without clear reasons
• Rather large overlap with depression
Obsessive Compulsive Disorder (OCD)
• Compulsions and/or obsessions that cause stress
Measuring in a research setting?
• Psychiatric interview - symptom questionnaire
• Self-report - observation
Problems
• Overlap between normal and pathology
• Overlap between disorders
• Heterogeneity within disorders
• Little specificity (biological) markers
Psychiatric epidemiology
Normal and special
Normal:
• Population description / case definition / risk factors /
analysis techniques
Special:
• Stigmatizing character disease / illegal drugs
• Case definitions more ambiguous
• Reduced response rates in research
• Reduced therapy adherence in clinical trials
• High drop-out
• High placebo-response in RCTs
• Self selection & motivation important for treatment effects
Topics
• Classification en diagnostics
• Prevalence of psychiatric disorders
• Etiology of depression
• Public mental health
• NESDA: a psychiatric epidemiological study
• Interaction mental health with somatic disease
The ‘soul’ in numbers: world wide in 2001
•
•
•
•
Depression
Alcohol use disorder
Alzheimer’s disease
Schizophrenia
=>
121 million
70 million
37 million
24 million
Lifetime psychiatric disorder:
25% of world population
World Health Report, WHO 2001
Prevalence of psychiatric disorders per year
%
Netherlands (NEMESIS study, n > 7000)
6
4
2
depression anxiety
alcohol
drug
schizodependence depend. phrenia
eating
disorder
Bijl et al. Soc Psychiatry Psychiatr Epidemiol 1998
Lifetime prevalence across gender
(NEMESIS)
45
40
35
30
25
Men
Women
Total
20
15
10
5
0
Depression
Anxiety
Addiction
Schizo
Any
Depressive disorder in last year in 15 countries
Country
% psych.
disorder
% depres.
disorder
Country
% psych.
disorder
% depres.
disorder
Belgium
12.0
6.2
Libanon
16.9
6.6
France
18.4
8.5
Nigeria
4.7
0.8
Germany
9.1
3.6
Japan
8.8
3.1
Italy
8.2
3.8
Beijing
9.1
2.5
Netherlands
14.9
6.9
Shanghai
4.3
1.7
Spain
9.2
4.9
Colombia
17.8
6.8
Ukraine
20.5
9.1
Mexico
12.2
4.8
USA
26.4
9.6
Demytteenaere K et al. JAMA 2004;291:2581-2590
WHO 2001
“psychiatric illnesses are not
present in selected areas or groups:
they are everywhere!”
Prevalence of depression in the Netherlands
(NEMESIS study: 18-64 years)
% 25
major depression
dysthymia
Life time prev.
20
1-year prev.
15
10
5
0
men
women
men
women
Bijl et al. Soc Psychiatry Psychiatr Epidemiol 1998
Major depression by age and sex
% 25
20
15
10
*
men
women
*
*
5
* p<.05
0
55-64 yrs
65-74 yrs
75-84 yrs
Results from the Longitudinal Aging Study Amsterdam
Subthreshold depressive symptoms
by age and sex
*
% 25
*
20
15
*
men
women
* p<.05
10
5
0
55-64 yrs
65-74 yrs
75-84 yrs
Results from the Longitudinal Aging Study Amsterdam
Prevalence of anxiety in the Netherlands
(NEMESIS study: 18-64 years)
% 25
20
panic
disorder
specific
phobia
social
phobia
GAD
15
10
5
0
m
w
Life-time
1-year
m
w
m
w
m
w
Bijl et al. Soc Psychiatry Psychiatr Epidemiol 1998
Comorbidity of
depression & anxiety disorders
n=2981
Comorbid
anxiety
Comorbid
depression
Comorbid
total
Current*
depressive
disorder
59%
23%
63%
Current*
anxiety
disorder
31%
59%
65%
* last 6 months
Mechanisms to comorbidity
1. Disorder 1 and 2 occur together coincidentally
2. Disorder 1 and 2 are part of a third underlying disorder
3. Disorder 1 and 2 have overlapping diagnostic items
4. Disorder 1 predisposes or causes disorder 2
5. Disorder 2 predisposes or causes disorder 1
6. Disorder 1 and 2 are the result of a causal of
predisposing factor 3
Prevalence of depression across time
(NCS en NCS-R studies, n>18,000)
% 10
8
6
4
2
0
1992
2003
Kessler et al. JAMA 2003; NEJM 2005
36-50% of serious cases in developed countries
and
76-85% of serious cases in less-developed countries
DO NOT RECEIVE TREATMENT
Demyttenaere K et al. JAMA 2004;291:2581-2590
Filter model of Goldberg & Huxley
Depression in general population
• (1-MP: N=250.000)
Depression in general practice (search for care)
• (1-MP: 80%  N=200.000)
Recognition depression by GP (recognition)
• (1-MP: 50-70%  120.000)
Referral to ambulant GGZ (referral)
• (1-MP: 7-9%  8.500)
Intramural GGZ (referral)
• (1-MP: 1%  1.000)
Topics
• Classification en diagnostics
• Prevalence of psychiatric disorders
• Etiology of depression
• Public mental health
• NESDA: a psychiatric epidemiological study
• Interaction mental health with somatic disease
….depression manifests in many ways….
Depression is a complex disorder:
many interacting contributing mechanisms
Identified contributing factors include stressors as
well as vulnerabilities:
- Genetic factors
- Somatic health factors
- Psychosocial factors
- Behavioral factors
Vulnerability - Stress Model
Grouping of most mentioned etiological factors
Vulnerability
Environment
lack of social support
deprivation
Stressors
Recent life events / loss
(lasting) conflicts
adverse conditions
Personal vulnerability
genetic load
vulnerable personality
childhood experiences
previous depression
Physical unhealthiness
diseases
medication
disability or handicap
Depression
adapted from Brown & Harris, 1978; Beekman & Ormel, 1999
Genetic factors
Twin studies: heritability = 30 – 40%
Overview of genome wide linkage studies
Neale Neuroticism
Nash Neuroticism-male
Nash Neuroticism
Nash Composite-female
Nash Composite
Fullerton Neuroticism
Zubenko MDRE
Zubenko MDR
McGuffin MDR-male
McGuffin MDR-female
McGuffin MDR
Holmans MDRE-male
Holmans MDRE
Camp MDRE/anxiety-male
Camp MDRE/anxiety
Camp MDRE & anxiety
Abkevich MD-male
Cyto Band
Chr
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
Somatic health risk factors for depression
- Heart disease / diabetes / stroke
- Pain / migraine / arthritis
- Physical disability / frailty
- Vision and hearing impairment
- Cognitive impairment
- Inflammation, low sex steroid hormones (in aging)
Psychosocial risk factors for depression
Psychological
- Personality (esp. neuroticism)
- Locus of control / mastery
- Cognitive vulnerability (rumination, irritability, etc)
Social
- Childhood trauma and life events
- Social network and support
- Work (circumstances)
Behavioral factors
associated with depression
Smoking
Depressed persons: smoke more often + less likely to quit
inhale more + smoke more of cigarette
NHANES: Anda et al. JAMA 1990
Alcohol use
Depressed persons are more often excessive drinkers.
Reversed causality is likely:
- Alcohol use causes depression – ‘consequence theory’
- Depression causes alcohol use - ‘medicating theory’
- Third factors underlie both
Behavioral factors
associated with depression
Physical activity
Depressed persons are more sedentary
Physical exercise interventions improve mood
Nutrition
Vitamin B12 + folate deficiency may increase depression
Metabolic syndrome (e.g. cholesterol) & obesity may
increase depression
N-3 fatty acids  some – not consistent - evidence
Topics
• Classification en diagnostics
• Prevalence of psychiatric disorders
• Etiology of depression
• Public mental health
• NESDA: a psychiatric epidemiological study
• Interaction mental health with somatic disease
Worldwide disease burden*
Rank 2030
1
2
3
4
5
6
7
8
9
10
Disease
Depression
Heart disease
Alzheimer, dementia
Alcohol problems
Diabetes
Stroke
Hearing loss
Cancer
Arthritis
Lung disease
% DALYs
9.6%
5.9%
5.8%
4.7%
4.5%
4.5%
4.1%
3.0%
2.9%
2.5%
* in disability-adjusted life years (DALYs)= lost life years + loss of quality of life,
Western countries WHO : Mathers; Plos Medicine 2006
‘Dutch’ top ten diseases with largest disease burden
Assessed in healthy life expectancy
Source: RIVM, Nationaal Kompas Volksgezondheid
1
2
3
4
5
6
7
8
9
10
Coronary heart disease
Anxiety disorders
Stroke
Depression
COPD
Diabetes Mellitus
Lung cancer
Alcohol dependency
Arthritis
Dementia
Why high disease burden of depression?
High prevalence
Chronic disease: high relapse rate and chronicity
Episodes cause substantial loss of quality of life
Onset at relatively young age –
on average between 25-30 years of age
Course of depression is very variable
symptoms
disease
sub-clinical
normal
time
Course of depression
Various studies:
After 1-3 years: 50% still depressed
“ Single episodes are extremely rare
if the period of observation is
significantly extended “
Angst et al. Psychiatr Neurol Neurochir 1973
Costs of depression
• €132 million per million adults
• About the same costs in minor depression
• About twice as much in dysthymia
 Total costs about € 600 million per million adults
Smit et al. Journal of Mental Health Policy and Economics, 2006
Cuijpers et al. Acta Psychiatrica Scandinavica, 2007
So why is prevention necessary?
• Because of high
– Prevalence
– Incidence
– Costs
– Burden of disease
• Limited possibilities of treatment
• But: Prevention how and for whom?
Epidemiology of depression in The Netherlands
Prevention
relapse
Influx
357.000
Prevalence
738.000
recovery
Cure
Mortality
Natural course of disorders
Healthy
Risk group
Prodromal
universal
prevention
selective
prevention
indicated
prevention
Remission
Disease
treatment
Chronicity: disability & handicap
Topics
• Classification en diagnostics
• Prevalence of psychiatric disorders
• Etiology of depression
• Public mental health
• NESDA: a psychiatric epidemiological study
• Interaction mental health with somatic disease
Netherlands Study of Depression and Anxiety
www.nesda.nl
Funded through the mental health program of the Netherlands
Organization of Health Research (ZonMW)
and matching funds from participating institutes
Four central goals of NESDA
1. Describing course and consequences
2. Predicting course (demographic, psychosocial,
somatic, biological and genetic determinants)
3. Role of stress regulating mechanisms and brain
structures on course
4. Quality of care and perceived need for care
Key factors relevant for NESDA design
1. Depression AND anxiety (high comorbidity)
2. Different ‘settings’
3. Long term course
4. Integrating psychosocial, clinical, genetic and
(neuro)biological research paradigms
NESDA design
Naturalistic cohort study
Baseline assessment and after 1, 2, 4, 6, 8 years
Depression: - Major depression
- Dysthymia
- Minor depression
Anxiety:
- Generalized anxiety disorder
- Social phobia
- Panic disorder
NESDA design
• Persons with depression/anxiety from the general
population (NEMESIS)
• Adults with parents with depression/anxiety (ARIADNE)
• Primary care: 3-step screening in 65 general practices
– depression/anxiety patients
– ‘healthy’ controls
• Depression/anxiety patients from secondary care
New cases at 17 GGZ locations with (primary) anxiety
and/or depression
NESDA population
2981 persons
1979 women (66%), 1002 men (34%)
18-65 year, mean age = 41.9 ± 13.0 year
Mean education = 12.1 ± 3.3 year
97% has Dutch nationality
92% born in the Nederlands
NESDA population
Total
N
No. with
current
Depr/Anx
No. with
lifetime
Depr/Anx
General population:
- lifetime depression / Anxiety
- parents with depression / Anxiety
303
261
104
47
303
123
Primary care:
- controls: no symptoms/disorder
- subthreshold symptoms
- lifetime depression / Anxiety
- current depression / Anxiety
373
141
353
743
0
0
0
743
0
0
353
743
Secondary care:
- current depression / Anxiety
807
807
807
Total
2981
1701
2329
* Current = in the last 6 months
NESDA baseline measurement
3.5 - 4 hours
•
•
•
•
•
•
•
•
•
•
•
At home: questionnaire 1 (a.o. severity, functioning, lifestyle)
Informed consent
Blood draw
Breakfast
Interview part 1 (demography, CIDI-diagnoses)
Medical interview (a.o. blood pressure, heart rate, muscle strength)
Interview part 2 (a.o. diseases, functioning, use of care)
Psychological computer task
Interview part 3 (mental history)
At clinic or at home: questionnaire 2 (psychological characteristics)
At home: salivary swaps for cortisol
Example of use of NESDA data
Coronary heart disease
No MDD or anxiety
Remitted MDD or anxiety
Current MDD
Current anxiety
Current MDD and anxiety
OR*
95%CI
1.65
1.41
2.70
3.54
0.79-3.43
0.61-3.23
1.31-5.56
1.79-6.98
* Adjusted for age, sex, education and lifestyle
OR a for CHD in persons with a current depressive and/or anxiety disorder
OR
5
4
3
2
1
0
Current
depressive disorder
N = 418
Current
anxiety disorder
N = 504
Current
depressive and
anxiety disorder
N = 848
See
www.NESDA.nl
for more study info and results
Topics
• Classification en diagnostics
• Prevalence of psychiatric disorders
• Etiology of depression
• Public mental health
• NESDA: a psychiatric epidemiological study
• Interaction mental health with somatic disease
Somatic consequences of depression
Evidence from systematic reviews
Heart disease
Review
Wulsin 1999
Cuijpers 2002
Rugulies 2002
Wulsin 2003
Nicholson 2006
Van der Kooy 2007
Diabetes
Stroke
Knol 2006
-
n=9
n=7
Evidence
+, RR=1.9
+, RR=1.8
+, RR=1.6
+, RR=1.6
+, RR=1.8
+, RR=1.6
+, RR=1.4
+
Hypertension
Cancer
-
n=7
n=4
+/-, -/+
Mortality
No. of studies
n=21
n=25
n=11
n=10
n=21
n=28
Possible explanations
•
•
•
•
Life style
Diminished self care
First signs of disease (‘reverse causality’)
Pathophysiological
Depression
Inflammation
HPA-axis
Sex steroid
hormones
Metabolic disturbances & obesity
atherosclerosis
Cardiovascular disease
Autonomic
nervous system
Depression
Inflammation
HPA-axis
Sex steroid
hormones
Metabolic disturbances & obesity
atherosclerosis
Cardiovascular disease
Autonomic
nervous system
Obesity and depression
Cross-sectional studies show that (abdominal) obesity and
depression are associated, but …
?
Abdominal
obesity
Depression
?
“Longitudinal associations between
Abdominal Obesity and Depression”
Methods
Design
• Health, Aging, and Body Composition (ABC) Study
• Prospective cohort study in general population
• 3075 well-functioning black (41%) and white (59%) older
persons, 70-79 years old
• Random sample of residents from Pittsburgh,
Pennsylvania and Memphis, Tennessee
“Longitudinal associations between
Abdominal Obesity and Depression”
Methods
Depression
• CES-D (CES-D-20 and CES-D-10)
• Depression on baseline: CES-D-20 ≥ 16 => 4.0%
• Depression onset:
CES-D-10 ≥ 10 or new antidepressant use on any of the annual
follow-up assessments in persons without baseline
depression/antidepressant use
- Mean follow-up: 4.3 ± 1.0 years
- Onset in 23.7%
“Longitudinal associations between
Abdominal Obesity and Depression”
Methoden
Obesity
Baseline and 5-year follow-up
• Overall obesity:
- Body Mass Index: weight / height2 (kg/m2)
- % body fat (dual X-ray absorptiometry scan)
• Abdominal obesity:
- Waist circumference (cm)
- Sagittal diameter (cm)
- Visceral fat (CT scan at L4-L5 level; cm2)
Statistical analyses
1. Cox regression: N=2540
[excl baseline depression]
baseline obesity
2. Linear regression: N=2088
depression onset
[obesity at follow-up]
baseline depression
Covariates:
Sociodemographic: age, sex, race, site, education
Lifestyle: smoking, alcohol use, physical activity
Disease: cardiovascular disease, diabetes
Overall obesity: BMI
5-year change in
obesity
Sample characteristics
% or mean (SD)
Men
Women
73.7 (2.8)
73.5 (2.9)
Black
35.5
44.7
Baseline depression
3.4
4.5
Depression onset rate / 1000 PY
45.9
63.5
BMI (kg/m2)
27.1 (3.8)
27.7 (5.4)
% body fat
29.4 (4.9)
40.7 (5.7)
101.1 (10.6)
98.2 (13.4)
23.7 (3.3)
23.4 (3.4)
156.0 (71.6)
131.9 (60.3)
Change in BMI (kg/m2)
-0.1 (1.6)
0.0 (2.0)
Change in % body fat
0.8 (2.6)*
-0.1 (2.8)
Change in waist circumference (cm)
0.6 (6.1)*
-2.0 (11.5)*
Change in sagittal diameter (cm)
0.4 (2.2)*
0.1 (2.0)
Change in visceral fat (cm2)
-1.0 (46.1)
-11.4 (34.6)*
Age (years)
Waist circumference (cm)
Sagittal diameter (cm)
Visceral fat (cm2)
baseline obesity
depression onset
Vogelzangs et al. J Clin Psychiatry 2009
Risk of depression onset
N=2540
HRa
MEN *
N=1233
95%CI
P
HRa
WOMEN *
N=1307
95%CI
P
Overall obesity
BMI
1.17
1.00-1.37
.05
0.99
0.91-1.09
.87
% body fat
1.17
1.01-1.34
.04
0.98
0.89-1.08
.65
Waist circumference
1.19
1.03-1.39
.02
1.01
0.92-1.11
.82
Sagittal diameter
1.20
1.05-1.37
.007
1.04
0.93-1.15
.53
Visceral fat
1.17
1.04-1.31
.009
1.01
0.90-1.13
.84
Abdominal obesity
a
Adjusted for sociodemographics, life-style and diseases;
* P sex-interactions: .05-.11; no race interactions
Risk of depression onset
MEN N=1233
HRa 95%CI
P
- SIMULTANEOUSLY ENTERED -
a
BMI
1.10
0.92-1.31
.29
Visceral fat
1.17
1.03-1.33
.01
Adjusted for sociodemographics, life-style and diseases
Cumulative onset of depression
according to sex and visceral fat
Cumulative onset of depressive symptoms
0.3
Onset rate a
Men
Normal visceral fat
High visceral fat
4.2% / year
5.5% / year
Onset rate a
Women
Normal visceral fat
High visceral fat
6.2% / year
6.9% / year
Adjusted Hazard ratio b
Ref
HR=1.33 (1.00-1.77), p=.05
Adjusted Hazard ratio b
Ref
HR=1.04 (0.82-1.32), p=.75
0.2
0.1
0.0
0
1
2
3
Years to onset of depressive symptoms
4
5
baseline depression
5-year change in
obesity
Vogelzangs et al. Arch Gen Psychiatry 2008
Depression and
5-year change in obesity
N=2088
CES-D Score
βa P
CES-D ≥ 16
βa
P
Overall obesity
BMI
.035
.11
.030
.18
% body fat
.007
.76
-.002
.94
Waist circumference
.026
.15
.031
.08
Sagittal diameter
.037
.10
.054
.01
Visceral fat
.042
.08
.080
.001
Abdominal obesity
a
Adjusted for sociodemographics, life-style, diseases, and BMI (for abdominal obesity)
Within women: race-interactions: P = .06-.09
Adjusted mean 5-year change in visceral fat
cm2 40
30
White men
White women
34.9
p < .001
Black men
Black women
p overall = .001
p = .05
p = .06
p = .54
18.3
20
10
5.3
2.9
0
-6.9
-10
-11.0
-20
-30
-17.2
No baseline depression
Baseline depression
-23.2
Conclusions
• In an older population, abdominal obesity is independently
and more strongly associated with depression than overall
obesity
• In older men, but not older women abdominal obesity
predicts the onset of depression over 5 years
• In both men and women (except black women) depression
predicts an increase in abdominal obesity fat over 5 years
Vicious cycle
between depression and
abdominal obesity
Abdominal
obesity
Depression