Shared polygenic risk for ADHD, executive dysfunction and other psychiatric disorders.
Suhua Chang1,2, Li Yang3, Yufeng Wang1
1Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China.
Translational Psychiatry
|June 11, 2020
Summary
Polygenic risk scores for major depressive disorder, ADHD, and bipolar disorder are linked to executive dysfunction in children with ADHD. Specific genetic liabilities influence distinct executive function components, offering insights into potential diagnostic markers.
Area of Science:
- Neuroscience
- Psychiatry
- Genetics
Background:
- Executive functioning (EF) deficits are common in psychiatric disorders, with variations potentially linked to genetic factors.
- Understanding the genetic overlap between different psychiatric conditions and specific EF components is crucial for clarifying underlying mechanisms.
Purpose of the Study:
- To investigate the genetic associations between five psychiatric disorders (ADHD, MDD, SZ, BIP, Autism) and executive functioning in children with ADHD.
- To explore how polygenic risk scores (PRS) for these disorders relate to specific components of executive functioning and ADHD symptoms.
Main Methods:
- Utilized genome-wide association study (GWAS) summary data to calculate polygenic risk scores (PRS) for five psychiatric disorders.
- Assessed executive functioning in a Chinese ADHD cohort (n=1147) using the Stroop test (inhibitory control), trail-making test (cognitive flexibility), and digital span test (working memory).
- Employed exploratory factor analysis, linear regression, and mediation analyses to examine PRS associations with EF and ADHD symptoms.
Main Results:
- PRS for major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), and bipolar disorder (BIP) were significantly associated with the overall executive functioning principal component (EF-PC).
- Specific EF components showed differential PRS associations: ADHD and MDD PRS linked to inhibitory control, BIP PRS to working memory, and schizophrenia (SZ) PRS to cognitive flexibility.
- Inhibitory control mediated the indirect effects of ADHD and MDD PRS on ADHD symptoms.
Conclusions:
- Polygenic risks from multiple psychiatric disorders contribute to specific executive dysfunctions in children with ADHD.
- Findings clarify the relationship between genetic liabilities for psychiatric disorders and intermediate cognitive domains.
- Highlights the potential of executive functioning measures as diagnostic markers and therapeutic targets.
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