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Predicting Cognitive Executive Functioning with Polygenic Risk Scores for Psychiatric Disorders.

Chelsie E Benca1,2, Jaime L Derringer3, Robin P Corley4

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|October 16, 2016
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Summary

This study investigated executive functions (EFs) as potential endophenotypes for psychiatric disorders. Findings suggest EFs may not be larger effect endophenotypes for conditions like ADHD, depression, or schizophrenia.

Keywords:
Cognitive controlExecutive controlIntermediate phenotypesPolygenic risk scores

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Area of Science:

  • Psychiatric Genetics
  • Neuroscience
  • Cognitive Psychology

Background:

  • Executive functions (EFs) are frequently impaired in psychiatric disorders.
  • EF deficits are hypothesized to serve as an endophenotype for psychopathology.
  • Endophenotypes bridge genetic risk and observable symptoms.

Purpose of the Study:

  • To test the hypothesis that EFs are endophenotypes for major psychiatric disorders.
  • To examine the relationship between polygenic risk scores and EF components.
  • To assess genetic risk for ADHD and major depressive disorder (MDD) against symptom counts and diagnoses.

Main Methods:

  • Derived polygenic risk scores for autism, ADHD, bipolar disorder, MDD, and schizophrenia.
  • Utilized genome-wide data from the Psychiatric Genomics Consortium.
  • Employed a latent variable model to assess three distinct EF components.
  • Examined genetic risk correlations with symptom counts and lifetime diagnoses for ADHD and MDD.

Main Results:

  • No significant evidence was found supporting larger effect sizes for EFs as endophenotypes across the studied psychiatric disorders.
  • Polygenic risk scores for psychiatric disorders were analyzed in relation to executive function components.
  • Further investigation into the genetic underpinnings of executive functions and psychopathology is warranted.

Conclusions:

  • The current study did not find robust support for executive functions as significant endophenotypes for major psychiatric disorders.
  • Larger sample sizes are crucial for future research to adequately examine the endophenotype hypothesis.
  • The relationship between genetic risk, executive functions, and psychopathology requires further exploration.