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Polygenic analyses show important differences between MDD symptoms collected using PHQ9 and CIDI-SF.

Lianyun Huang1,2,3, Sonja Tang4,5, Jolien Rietkerk1,2,3

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Major Depressive Disorder (MDD) symptom assessments using PHQ9 and CIDI-SF show distinct genetic underpinnings. These differences impact the identification of genetic factors for MDD symptom dimensions and heterogeneity.

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Area of Science:

  • Psychiatry
  • Genetics
  • Epidemiology

Background:

  • Major Depressive Disorder (MDD) diagnosis relies on self-report symptom assessments.
  • Common instruments include the Patient Health Questionnaire 9 (PHQ9) for current symptoms and the Composite International Diagnostic Interview Short-Form (CIDI-SF) for lifetime worst-episode symptoms.

Approach:

  • Utilized UKBiobank data to analyze genetic correlations between PHQ9 and CIDI-SF symptom endorsements.
  • Employed Mendelian Randomization (MR) and polygenic prediction analyses to investigate genetic associations.
  • Examined the influence of severity thresholds and CIDI-SF's skip-structure on genetic correlations.

Key Points:

  • PHQ9 and CIDI-SF symptom endorsements exhibit low to moderate genetic correlations (rG=0.43-0.87).
  • PHQ9 symptoms associate more strongly with general dysphoria traits.
  • The CIDI-SF's skip-structure aids in identifying heterogeneity among MDD cases.

Conclusions:

  • Genetic correlations between PHQ9 and CIDI-SF symptoms are not solely due to differing severity thresholds or skip-structures.
  • Findings have significant implications for factor analysis of genetic covariance matrices in MDD research.
  • Distinguishing genetic factors for MDD symptom dimensions and heterogeneity requires careful consideration of assessment instruments.