What are 'good' depression symptoms? Comparing the centrality of DSM and non-DSM symptoms of depression in a network analysis Eiko Fried University of Leuven Network Analysis Approach to Psychopathology and Comorbidity ABCT, November 14, 2015

Diagnosis of Major Depression (MD) Reliable diagnosis is essential to study and treat mental disorders Reliable diagnosis of MD is difficult: biomarkers have very limited explanatory power, and MD was among the least reliable diagnosis in DSM-5 field trials (kappa = 0.28) Current state: we measure depression symptoms to indicate the presence of MD. We add them to a sum-score, and suppose this adequately represents depression severity 2

Common cause model 3 s1 s2 s3 s4 s5 M M

Common cause model 4 s1 s2 s3 s4 s5 M M Red eyes

Common cause model 5 s1 s2 M M Red eyes Fever s3 s4 s5

Common cause model 6 s1 s2 s3 s4 s5 M M Red eyes Fever Runny nose Koplik's spots Cough

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Common cause model 8 There is a specific relationship between symptoms of a disorder and the disorder itself (common cause model) s1 s2 s3 s4 s5 M M Red eyes Fever Runny nose Koplik's spots Cough

Common cause model 9 There is a specific relationship between symptoms of a disorder and the disorder itself (common cause model) 1.Symptoms are somewhat interchangeable s1 s2 s3 s5 M M Red eyes Fever Runny nose Cough s4 Koplik's spots

Common cause model 10 There is a specific relationship between symptoms of a disorder and the disorder itself (common cause model) 1.Symptoms are somewhat interchangeable s1 s3 s4 s5 M M Red eyes Runny nose Koplik's spots Cough s2 Fever

Common cause model 11 There is a specific relationship between symptoms of a disorder and the disorder itself (common cause model) 1.Symptoms are somewhat interchangeable 2.Symptoms are unrelated beyond their common cause s1 s2 s3 s4 s5 M M Red eyes Fever Runny nose Koplik's spots Cough Red eyes Fever Runny nose Koplik's spots

Common cause model 12 There is a specific relationship between symptoms of a disorder and the disorder itself (common cause model) 1.Symptoms are somewhat interchangeable 2.Symptoms are unrelated beyond their common cause 3.A 'good' symptom is one that indicates the latent disease well M M s1 s2 s3 s4 s5 Red eyes Fever Runny nose Koplik's spots Cough

Psychiatry 13 s1 s2 s3 s4 s5 D Common cause model ubiquitous in psychiatry

Measuring Major Depression 14 s1 s2 s3 s4 s5 MD Insomnia Fatigue Concentration problems Psychomotor problems Weight loss Common cause model

– We measure symptoms to indicate the disorder – Add symptoms to total-score to indicate severity Measuring Major Depression 15 s1 s2 s3 s4 s5 MD Insomnia Fatigue Concentration problems Psychomotor problems Weight loss

Common cause model – We measure symptoms to indicate the disorder – Add symptoms to total-score to indicate severity – Symptoms roughly interchangeable – We want to treat the disease so symptoms disappear Measuring Major Depression 16 s1 s2 s3 s4 s5 MD Insomnia Fatigue Concentration problems Psychomotor problems Weight loss

Common cause model (overly simplistic) – We measure symptoms to indicate the disorder – Add symptoms to total-score to indicate severity – Symptoms roughly interchangeable – We want to treat the disease so symptoms disappear Measuring Major Depression 17 s1 s2 s3 s4 s5 MD Insomnia Fatigue Concentration problems Psychomotor problems Weight loss

Measuring Major Depression 18 s1 s2 s3 s4 s5 MD Insomnia Fatigue Concentration problems Psychomotor problems Weight loss Problem: there is a dramatic lack of consensus what depression symptoms (or good depression symptoms) are. Different depression instruments measure very different things.

What are 'good' depression symptoms? DSM-5: 9 symptoms None of the common rating scales of depression measure all DSM symptoms; all of them measure a number of symptoms not featured in the DSM – BDI: irritability, pessimism, feelings of being punished, … – HRSD: anxiety, genital symptoms, hypochondriasis, insights into the depressive illness, paralysis, … – CESD: frequent crying, talking less, perceiving others as unfriendly, … As a result, there is little consistency across depression studies because patients are enrolled based on very different criteria 19

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Measurement of depression "The measurement of depression of depression is as confused as the basic construct of the state itself." 21

Network model Symptoms co-occur due to their common cause 22

Network model Symptoms co-occur because they cause each other 23 Psychomotor problemsInsomnia Concentration problems s1 s2 s3 s4 s5 Fatigue Weight loss

Network model Symptoms co-occur because they cause each other Symptoms are roughly equally important indicators 24 Psychomotor problemsInsomnia Concentration problems s1 s2 s3 s4 s5 Fatigue Weight loss

Network model Symptoms co-occur because they cause each other Symptoms are distinct entities with different characteristics 25 Psychomotor problemsInsomnia Concentration problems s1 s2 s3 s4 s5 Fatigue Weight loss

Network model Symptoms co-occur because they cause each other Symptoms are distinct entities with different characteristics Reinforcing feedback loops (attractor state) 26 Psychomotor problemsInsomnia Concentration problems s1 s2 s3 s4 s5 Fatigue Weight loss

Network model Important new questions arise: what symptoms are most central to driving depressive processes? 27 Psychomotor problemsInsomnia Concentration problems s1 s2 s3 s4 s5 Fatigue Weight loss

Network model Important new questions arise: what symptoms are most central to driving depressive processes? 28 Psychomotor problemsInsomnia Concentration problems s1 s2 s3 s5 Fatigue s4 Weight loss

Network model Important new questions arise: what symptoms are most central to driving depressive processes? 29 Psychomotor problems Concentration problems s2 s3 s4 s5 Fatigue Weight loss Insomnia s1

What are 'good' depression symptoms? Comparing the centrality of DSM and non-DSM symptoms of depression in a network analysis 30 Journal of Affective Disorders Eiko I. Fried Sacha Epskamp Randolph M. Nesse Francis Tuerlinckx Denny Borsboom

Research questions What is the network structure of depression? – DSM symptoms – A large number of symptoms above and beyond the DSM criteria What symptoms are most central, i.e. most connected in the network? 31

Sample 3463 depressed outpatients from the enrollment stage of the STAR*D study – Mean age 41 years (SD=13), 63% female IDS-C: 28-item questionnaire that covers 15 disaggregated DSM symptoms and 13 common non-DSM symptoms (e.g., anxiety, irritability) Network estimation – Gaussian graphical model (special case of the Pairwise Markov Random Field): edges are partial correlation coefficients – Regularization via least absolute shrinkage and selection operator (lasso); very small edges set exactly to 0, results in a conservative (sparse) network 32

33 Estimation -Edges equal partial correlations -Sparse network Interpretation -Heterogeneous network -Some clusters emerge Network structure of MD DOI | /j.jad

34 Symptom importance DOI | /j.jad

35 Symptom importance DOI | /j.jad

Permutation test to examine differences in centrality between DSM and non-DSM symptoms: – Betweenness centrality: p = 0.12 – Closeness centrality: p = 0.64 – Node strength: p = 0.03 (0.08) Controlling for outliers: – Betweenness centrality: p = 0.28 – Closeness centrality: p = 1 – Node strength: p = 0.13 DSM symptoms are not more central than non-DSM symptoms 36 Full IDS symptom network DOI | /j.jad

Robustness analysis 37

Conclusions Core assumptions of the common cause model do not seem remotely tenable for depression "Depression sum-scores don't add up: why analyzing specific depression symptoms is essential" (Fried & Nesse, 2015) Centrality measures may provide new insights regarding the clinical significance of specific depression symptoms. These insights likely have major clinical implications and suggest new approaches that may better predict outcomes such as the course of illness, probability of relapse, and treatment response. 38

Limitations STAR*D population Cross-sectional (indegree vs outdegree centrality) Heterogeneity of depression Topological overlap 39

Thank you

Eiko Fried University of Leuven University of Amsterdam eiko-fried.com

Discussion Robustness: – DSM and non-DSM symptoms do not differ regarding means (W = 121, p = 0.30) or SD (W = 89, p = 0.72) – 10 disaggregated symptoms not more central than the other 18 symptoms (node strength: p = 0.86; betweenness and closeness: p = 1) 42

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