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Eiko FriedUniversity of Leuven, Belgium

"The differential impact of individual depression symptoms on impairment of

psychosocial functioning"

Introduction 2

Major Depressive Disorder (MDD)

• Prevalent (Kessler et al., 2003)

• Recurrent(McClintock et al., 2010)

• Costly(Lopez et al., 2006)

Introduction 3

Depression symptoms

• DSM-5 MDD diagnosis:1. Diminished interest or pleasure2. Depressed mood3. Increase or decrease in either weight or appetite4. Insomnia or hypersomnia5. Psychomotor agitation or retardation6. Fatigue or loss of energy7. Worthlessness or inapproriate guilt8. Problems concentrating or making decisions9. Thoughts of death or suicidal ideation

Introduction 4

Depression symptoms

• DSM-5 MDD diagnosis:1. Diminished interest or pleasure2. Depressed mood3. Increase or decrease in either weight or appetite4. Insomnia or hypersomnia5. Psychomotor agitation or retardation6. Fatigue or loss of energy7. Worthlessness or inapproriate guilt8. Problems concentrating or making decisions9. Thoughts of death or suicidal ideation

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Introduction 5

Disease model

Introduction 6

Disease model

• Depression is a latent disorder

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Introduction 7

Disease model

• Depression is a latent disorder• Depression is the common cause of its symptoms

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Introduction 8

Disease model

• Depression is a latent disorder• Depression is the common cause of its symptoms• Measure MDD symptoms and use them to indicate

presence of depression

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Introduction 9

Disease model

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

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Introduction 10

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)

STAR*D: impaired functioning 11

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 12

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 13

Question 1

• Do symptoms have differential effects on impairment?

H1 - heterogeneity model:IMPAIRMENT ~ S1 + S2 + S3 ... AGE + SEX

vs.

H0 - homogeneity model:IMPAIRMENT ~ S1 + S2 + S3 ... AGE + SEX

differential impact

equal impact

STAR*D: impaired functioning 14

Question 1

H1 - heterogeneity model:IMPAIRMENT ~ S1 + S2 + S3 ... AGE + SEX

H0 - homogeneity model:IMPAIRMENT ~ S1 + S2 + S3 ... AGE + SEX

²diff = 394.5, dfdiff = 13p < 0.001R² = 41%

• Do symptoms have differential effects on impairment?– Yes.

STAR*D: impaired functioning 15

Question 2

• How much variance of impairment does each individual symptom explain?

• Relative importance analysis

Impairment, total variance = 100%

STAR*D: impaired functioning 16

Question 2

• How much variance of impairment does each individual symptom explain?

• Relative importance analysis

Impairment, total variance = 100% Variance explained by symptomsR² = 41%

STAR*D: impaired functioning 17

Question 2

• How much variance of impairment does each individual symptom explain?

• Relative importance analysis100%

S120%

S210%

S440%

S330%

Impairment, total variance = 100%

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• Symptoms vary dramatically in their explained variance of impairment

• Coefficients within compound symptoms differ from each other– Slowed vs. agitated

p < 0.05

<

<

STAR*D: impaired functioning 19

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

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D1: work; D2: home; D3: social act.; D4: private act.; D5: relationships

fatigue

interest loss

STAR*D: impaired functioning 23

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 24

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.

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Thanks to …