Transcript Slides - Eiko Fried

"The differential impact of individual
depression symptoms on impairment of
psychosocial functioning"
Eiko Fried
University of Leuven, Belgium
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Major Depressive Disorder (MDD)
• Prevalent
(Kessler et al., 2003)
• Recurrent
(McClintock et al., 2010)
• Costly
(Lopez et al., 2006)
Introduction
2
Depression symptoms
• DSM-5 MDD diagnosis:
1.
2.
3.
4.
5.
6.
7.
8.
9.
Diminished interest or pleasure
Depressed mood
Increase or decrease in either weight or appetite
Insomnia or hypersomnia
Psychomotor agitation or retardation
Fatigue or loss of energy
Worthlessness or inapproriate guilt
Problems concentrating or making decisions
Thoughts of death or suicidal ideation
Introduction
3
Depression symptoms
• DSM-5 MDD diagnosis:
1.
2.
> 3.
> 4.
> 5.
6.
7.
8.
9.
Diminished interest or pleasure
Depressed mood
Increase or decrease in either weight or appetite
Insomnia or hypersomnia
Psychomotor agitation or retardation
Fatigue or loss of energy
Worthlessness or inapproriate guilt
Problems concentrating or making decisions
Thoughts of death or suicidal ideation
Introduction
4
Disease model
Introduction
5
Disease model
s1
• Depression is a latent disorder
s2
D
s3
s4
s5
Introduction
6
Disease model
s1
• Depression is a latent disorder
• Depression is the common cause of its symptoms
s2
D
s3
s4
s5
Introduction
7
Disease model
s1
s2
D
s3
• Depression is a latent disorder
• Depression is the common cause of its symptoms
• Measure MDD symptoms and use them to indicate
presence of depression
s4
s5
Introduction
8
Disease model
s1
s2
D
s3
s4
s5
Consequences:
• Symptoms are passive indicators
• Symptoms are interchangeable: irrelevant what
particular symptoms a person has (DSM: 5/9)
– Symptom number, not symptom nature matters
• This disease model justifies adding up symptoms to
sum-scores
Introduction
9
Disease model
• Common-cause model implausible considering the
pronounced symptomatic variability among MDD patients
> 1500 unique symptom profiles qualifying for DSM-5 MDD diagnosis
• Alternative: understand symptoms as distinct entities worth
studying individually
• Prior research: symptoms differ from each other in important
aspects
– Symptoms have different risk factors
(Fried et al., 2013)
– Symptoms differ in their genetic background
(Kendler et al., 2013; Myung et al., 2012)
– Symptoms and their impact on impairment psychosocial functioning
(Fried & Nesse, 2014)
Introduction
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Depression & impairment
• Majority of MDD patients: moderate to severe impairment
(Kessler et al., 2003)
• Impairment long-lasting and affects various domains of living
(e.g., home, workplace, friendships)
(Hays et al., 1995; Hirschfeld et al., 2002)
• Unknown whether individual symptoms differ in their impact
on impairment
STAR*D: impaired functioning
11
Methods
• NIMH dataset: "Sequenced Treatment Alternatives to Relieve
Depression" (STAR*D)
• Enrollment stage: 3,703 MDD outpatients
– Cross-sectional
– Age M ~ 41, ~ 60% female
– No antidepressants
• Goal: test the impact of MDD symptoms on impairment
– Depression symptoms (QIDS-16) (e.g., insomnia & hypersomnia)
– Psychosocial impairment (WSAS); example question: "Because of my
depression, my ability to work is impaired"
STAR*D: impaired functioning
12
Question 1
• Do symptoms have differential effects on impairment?
H1 - heterogeneity model:
IMPAIRMENT ~ S1 + S2 + S3 ... AGE + SEX
differential impact
vs.
H0 - homogeneity model:
IMPAIRMENT ~ S1 + S2 + S3 ... AGE + SEX
STAR*D: impaired functioning
equal impact
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Question 1
• Do symptoms have differential effects on impairment?
– Yes.
H1 - heterogeneity model:
IMPAIRMENT ~ S1 + S2 + S3 ... AGE + SEX
²diff = 394.5, dfdiff = 13
p < 0.001
R² = 41%
H0 - homogeneity model:
IMPAIRMENT ~ S1 + S2 + S3 ... AGE + SEX
STAR*D: impaired functioning
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Question 2
• How much variance of impairment does each individual
symptom explain?
• Relative importance analysis
Impairment, total variance = 100%
STAR*D: impaired functioning
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Question 2
• How much variance of impairment does each individual
symptom explain?
• Relative importance analysis
Impairment, total variance = 100%
STAR*D: impaired functioning
Variance explained
by symptoms
R² = 41%
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Question 2
• How much variance of impairment does each individual
symptom explain?
• Relative importance analysis
100%
Impairment, total variance = 100%
S1
20%
S2
10%
S4
40%
S3
30%
STAR*D: impaired functioning
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20.7
Sad Mood
16.5
Concentration
13.8
Fatigue
13.1
Interest Loss
8.8
Slowed
<
• Symptoms vary
dramatically in their
explained variance of
impairment
• Coefficients within
compound symptoms
differ from each other
6.4
Self-blame
6.1
Suicidal Ideation
3.6
Early insomnia
3.0
Appetite
2.5
Late insomnia
2.1
Agitated
<
– Slowed vs. agitated
p < 0.05
1.3
Weight
Middle insomnia
0.9
Hypersomnia
0.7
0.4
Age
0.1
Sex
0
5
10
15
20
Relative importance estimation in %
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Question 3
• Do symptoms vary in their associations across 5 impairment
subdomains?
– work, home, social activities, private activities, close relationships
– Yes
– ²diff = 299.8 (dfdiff = 56); p < 0.001
STAR*D: impaired functioning
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D1: work; D2: home; D3: social act.; D4: private act.; D5: relationships
fatigue
interest loss
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Conclusions
• Some depression symptoms are much more impairing than
others
– Two MDD patients with similar symptom sum-scores potentially suffer
from different levels of impairment
• Analyses of individual symptoms reveal important clinical
information that are obfuscated by analyses of sum-scores
STAR*D: impaired functioning
23
Implications
• Main problems of modern psychiatry
– Antidepressants only marginally efficacious compared to placebos
(Kirsch et al., 2008; Pigott et al., 2010; Turner et al., 2008)
– "Questionable" reliability of MDD diagnosis in DSM-5 field trials
(Regier et al., 2013)
– In the largest GWAS study with > 34,000 subjects, no single locus was
significantly associated with depression diagnosis
(Hek et al., 2013; see also: Lewis et al., 2010; Shi et al., 2011; Wray et al., 2012)
• Current psychiatric research and practice lumps individuals
suffering from a wide range of disparate symptoms into one
undifferentiated category, obfuscating dramatic differences
between patients diagnosed with MDD.
STAR*D: impaired functioning
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Thanks to …
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