Transcript Metabole depressie: een nieuw subtype depressie?

1
Depression
Diagnosis, epidemiology and etiology
Nicole Vogelzangs
Department of Psychiatry / EMGO+ Institute
VU University Medical Center
GGZ inGeest
[email protected]
Topics
2
 Classification en diagnostics
 Prevalence of depressive disorders
 Public mental health
 Etiology of depression
 Biological factors and somatic comorbidity
Psychiatric disorder
3
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
4
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
5
 <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
6
Depression
7
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
Depressive Disorders
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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
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Measuring in a research setting?
10
 Psychiatric interview - symptom questionnaire
 Self-report - observation
Problems
 Overlap between normal and pathology
 Overlap between disorders
 Heterogeneity within disorders
 Little specificity (biological) markers
Topics
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 Classification en diagnostics
 Prevalence of depressive disorders
 Public mental health
 Etiology of depression
 Biological factors and somatic comorbidity
The ‘soul’ in numbers: world wide in 2001
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 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)
13
%
6
4
2
depression anxiety alcohol
depend.
drug
schizodepend. phrenia
eating
disorder
Bijl et al. Soc Psychiatry Psychiatr Epidemiol 1998
Lifetime prevalence across gender (NEMESIS)
14
25
20
15
Men
Women
Total
10
5
0
Depression
Depressive disorder in last year
15 countries
15
Country
% depres.
disorder
Country
% depres.
disorder
Belgium
6.2
Libanon
6.6
France
8.5
Nigeria
0.8
Germany
3.6
Japan
3.1
Italy
3.8
Beijing
2.5
Netherlands
6.9
Shanghai
1.7
Spain
4.9
Colombia
6.8
Ukraine
9.1
Mexico
4.8
USA
9.6
Demytteenaere K et al. JAMA 2004;291:2581-2590
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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)
17
% 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
18
* p<.05
%
25
20
15
men
women
10
5
*
*
*
0
55-64 yrs
65-74 yrs
75-84 yrs
Results from the Longitudinal Aging Study Amsterdam
Subthreshold depressive symptoms
by age and sex
19
*
% 25
20
15
* p<.05
*
men
women
*
10
5
0
55-64 yrs
65-74 yrs
75-84 yrs
Results from the Longitudinal Aging Study Amsterdam
Comorbidity of
depression & anxiety disorders
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N=2981
Comorbid
anxiety
Comorbid
depression
Comorbid
total
Current*
depressive
disorder
59%
23%
63%
Current*
anxiety
disorder
31%
59%
65%
* last 6 months
Prevalence of depression across time
(NCS en NCS-R studies, n>18,000)
21
% 10
8
6
4
2
0
1992
2003
Kessler et al. JAMA 2003; NEJM 2005
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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
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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
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 Classification en diagnostics
 Prevalence of depressive disorders
 Public mental health
 Etiology of depression
 Biological factors and somatic comorbidity
Worldwide disease burden*
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Rank 2030 Disease
1
2
3
4
5
6
7
8
9
10
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
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1
Coronary heart disease
2
Anxiety disorders
3
Stroke
4
Depression
5
COPD
6
Diabetes Mellitus
7
Lung cancer
8
Alcohol dependency
9
Arthritis
10 Dementia
Assessed in healthy life expectancy
Source: RIVM, Nationaal Kompas Volksgezondheid
Why high disease burden of depression?
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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
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symptoms
disease
sub-clinical
normal
time
Course of depression
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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
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 €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?
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 Because of high
•
•
•
•
Prevalence
Incidence
Costs
Burden of disease
 Limited possibilities of treatment
Epidemiology of depression
in the Netherlands
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Prevention
relapse
Influx
357.000
Prevalence
738.000
recovery
Cure
Mortality
Topics
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 Classification en diagnostics
 Prevalence of depressive disorders
 Public mental health
 Etiology of depression
 Biological factors and somatic comorbidity
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….depression manifests in many ways….
Depression is a complex disorder:
many interacting contributing mechanisms
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Identified contributing factors include stressors as well as
vulnerabilities:
- Genetic factors
- Psychosocial factors
- Behavioral factors
- Somatic health factors
- Biological factors
Vulnerability - Stress Model
Grouping of most mentioned etiological factors
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Vulnerability
Stressors
Environment
lack of social support
deprivation
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%
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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
Psychosocial risk factors for depression
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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 (lifestyle) factors
associated with depression
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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 (lifestyle) factors
associated with depression
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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
Unhealthy lifestyle
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Controls Remitted
MDD
n=524
n=774
Current
MDD
n=1075
p
Physical activity -low
-moderate
-high
12.8%
37.2%
50.0%
15.2%
37.3%
47.5%
21.1%
36.3%
42.6%
.001
Alcohol dependence
1.4%
5.2%
9.1%
<.001
Smoking
26.5%
39.5%
45.2%
<.001
25.1
25.6
25.9
.01
Body Mass Index
Topics
43
 Classification en diagnostics
 Prevalence of depressive disorders
 Public mental health
 Etiology of depression
 Biological factors and somatic comorbidity
Somatic health risk factors for depression
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• Heart disease / diabetes / stroke
• Pain / migraine / arthritis
• Physical disability / frailty
• Vision and hearing impairment
• Cognitive impairment
Somatic comorbidity of depression
Evidence from systematic reviews
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Review
No. of studies
Evidence
Mortality
Wulsin 1999
Cuijpers 2002
n=21
n=25
+, RR=1.9
+, RR=1.8
Heart disease
Rugulies 2002
Wulsin 2003
Nicholson 2006
Van der Kooy 2007
n=11
n=10
n=21
n=28
+, RR=1.6
+, RR=1.6
+, RR=1.8
+, RR=1.6
Diabetes
Knol 2006
n=9
+, RR=1.4
Stroke
-
n=7
+
Hypertension
-
n=7
+/-
Cancer
-
n=4
-, -/+
Possible explanations
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 Life style
 Diminished self care
 First signs of disease (‘reverse causality’)
 Pathophysiological
Depression
47
Inflammation
HPA-axis
Autonomic
nervous system
Metabolic disturbances, obesity
& atherosclerosis
Cardiovascular disease
Meta-analyses:
inflammation in depression
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Marker
#
Effect size
studies
/ MD
p
CRP
49
0.15
.001
IL-6
61
0.25
<.001
IL-1
14
0.35
.03
TNF
13
3.97 pg/ml
<.001
Howren et al., Psychosomatic Medicine, 2009
Dowlati et al., Biological Psychiatry, 2010
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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
NESDA design
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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
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 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
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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 baseline measurement
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










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
Depression Status and Inflammation
54
Sex, age, education
adjusted model
n
P sex interaction
Fully adjusted model
CRP
IL-6
TNF-α
CRP
IL-6
TNF-α
**
*
ns
**
*
ns
MEN
Controls
193
Ref
Ref
Ref
Ref
Ref
Ref
Remitted DD
238
.089*
.061
-.017
.036
-.004
-.019
Current DD
369
.158** .111**
.106** .106*
-.002
.009
WOMEN
Controls
301
Ref
Ref
Ref
Ref
Ref
Ref
Remitted DD
551
-.017
-.043
-.012
-.017
-.043
-.012
Current DD
763
.003
-.016
.018
** p<.01, p<.05
.003
-.016
.018
Adjusted mean CRP levels
across age of onset
55
2,1
1,9
p=.001
p=.001
CRP, mg/l
1,7
p=.001 p=.002
p=.04
1,5
1,3
p=.10
1,1
0,9
0,7
0,5
n=489
Controls
n=890
n=381
n=196
n=129
n=58
< 20
20-29
30-39
40-49
50-65
Age of disorder onset
Depression and Cortisol
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Increased HPA-as activity
Caroll (1976), Holsboer (1984), Nemeroff
(1984), Gold (1986), Young (1994),
Bhagwagar (2005)
Decreased HPA-as activity
Chrousos en Gold (1992), Asnis (1995),
McGinn (1996), Levitan (2002), Stetler
en Miller (2005)
No association
Schlechte (1986), Strickland (1998),
Anisman (1999), Posener (2000), Young
(2002)
Saliva cortisol collection
57
Saliva sampling at home
73% of samples returned
Cortisol awakening response:
T1: at awakening
T2: +30 minutes
T3: +45 minutes
T4: +60 minutes
Cortisol Awakening Rise in MDD
58
Current MDD
Remitted MDD
Control
24
Cortisol (nmol/l)
22
20
18
16
14
12
Remitted MDD vs controls
Current MDD vs controls
p=.03
p=.005
10
T1
T2
T3
T4
* Adjusted for sociodemographics, sampling factors, health indicators
Vreeburg et al., Arch Gen Psychiatry 2009
Meta-analysis:
depression and heart reate variability
59
13 studies, n depressed = 312, n control = 374, overall effect size d=0.332
Depression is associated with overall reduction in HRV.
This effect is of small-to-medium size.
J. Rottenberg in Biological Psychology (2007)
Measurement of
autonomic nervous system activity
60
VU-AMS
(Ambulatory Monitoring System)
Continuous registration of a.o.:
- Heart Rate
- Heart Rate Variability
registration during NESDA interview
(~ 80 minutes)
 available for 98% of respondents
Heart rate variability per depression group
61
p<.001
55
p<.001
Effect size d= 0.22
50
RSA
(ms)
45
40
35
30
Control
Remitted MDD
Current MDD
adjusted for age, sex, education, BMI, physical activity, smoking, alcohol use, heart diseases,
heart medication, chronic disease
Licht et al, Arch Gen Psychiatry 2008
Heart rate variability
according to medication
62
55
50
p=.05
p=.05
MDD no
med, mild
MDD no
med, sev.
p<.001
p<.001
p<.001
p=.12
45
RSA
(ms)
40
35
30
Control
IDS
N
5.6
515
15.9
585
35.9
433
MDD +
TCA
34.3
67
MDD +
SSRI
34.4
435
MDD +
other ad
34.8
134
MDD +
benzo
37.0
63
Licht et al, Arch Gen Psychiatry 2008
Depression
63
Inflammation
HPA-axis
Autonomic
nervous system
Metabolic disturbances, obesity
& atherosclerosis
Cardiovascular disease
Metabolic syndrome
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≥ 3 of the following 5:
 Waist circumference
 Triglycerides
 HDL cholesterol
 Blood pressure
 Fasting glucose
> 102 cm (men)
> 88 cm (women)
≥ 150 mg/dl
< 40 mg/dl (men)
< 50 mg/dl (women)
≥ 130/85 mmHg or medication
≥ 110 mg/dl or medication
InChianti study
65
Methods
• Prospective cohort study in general population
• 1155 men and women, 65 year and older
867 included in these analyses
• Depression (CES-D ≥ 20): 20%
• Metabolic syndrome: 25%
Metabolic syndrome across
depression and cortisol groups
66
%
50
p = .008
42,2
40
20,5
20,8
30
26.0
27,2
20
23,1
Cortisol tertiles
High (> 110 μg)
10
0
Depressed
mood
No depressed
mood
Middle (76-110 μg)
Low (< 76 μg)
Vogelzangs et al., Psychoneuroendocrinology, 2007
Health, Aging, and Body Composition
(ABC) study
67
Methods
 Prospective cohort study in general population
 3075 well functioning black (41%) and white (59%) older
persons, 70-79 year
 Depressive symptoms (CES-D; 20 items, 0-60)
mean (SD) = 4.7 (5.3)
 Metabolic syndrome: 39%
Depressive symptoms and 5-year change
in visceral fat and BMI
68
Visceral fat
BMI
cm2
9.4
10
0,4
p = .18
p = .001
6
0.23
0,2
2
0
-2
-0,2
-6
-10
- 7.1
- 0.04
-0,4
No depressive symptoms
Depressive symptoms
Vogelzangs et al., Arch Gen Psychiatry 2008
Visceral fat and onset of depressive
symptoms over 5 years
69
Men, normal visceral fat
Men, high visceral fat (≥194 cm2)
Women, normal visceral fat
Women, high visceral fat (≥ 168 cm2)
% with new depression
30
20
10
0
0
1
2
3
4
5
years of research
Vogelzangs et al., J Clin Psychiatry 2010
Metabolic syndrome
& course of depression
70
OR
95%CI
p
Metabolic syndrome
2.71
1.00-7.33
.05
Waist circumference
1.39
0.95-2.01
.09
Triglycerides
1.61
0.90-2.88
.11
HDL cholesterol
0.72
0.49-1.06
.10
Systolic blood pressure
1.21
0.82-1.80
.34
Diastolic blood pressure
1.31
0.90-1.92
.16
Glucose
1.02
0.63-1.66
.93
Number of metabolic
syndrome components
1.66
1.16-2.38
.005
a
Adjusted for sociodemografics, life style and disease
Vogelzangs et al., J Clin Psychiatry 2011
Conclusion
71
Depression = heterogeneous disorder
• Etiology
• Clinical presentation
Defining subgroups of depression based on link between
etiology, genetic vulnerability, clinical characteristics and
course
e.g. metabolic depression…..
The end….
72
Questions….?