Executive Function as an Underlying Mechanism of Alcohol Use, Aggression, and ADHD

Area of Science:

• Neuroscience
• Psychiatry
• Behavioral Genetics

Background:

• Executive functioning (EF) is a proposed transdiagnostic risk factor for externalizing disorders.
• Previous research indicates phenotypic and genetic overlap between EF and behaviors such as ADHD, aggression, and alcohol use.
• The common causal role of EF in these behaviors remains under-examined.

Purpose of the Study:

• To investigate reciprocal causal associations between EF and externalizing behaviors.
• To utilize a Mendelian randomization (MR) approach to explore these relationships.

Main Methods:

• Employed a two-sample MR design.
• Utilized genome-wide association study (GWAS) summary statistics for EF, ADHD, alcohol consumption, aggressive behavior, and alcohol use disorder (AUD).
• Applied multiple estimation methods (e.g., inverse variance weighted, MR-PRESSO, MR-MIX) to address potential horizontal pleiotropy.

Main Results:

• EF showed significant causal effects on ADHD, AUD, and alcohol consumption.
• ADHD demonstrated a significant reciprocal causal influence on EF.
• No significant causal associations were found for aggression.
• Evidence of horizontal pleiotropy and heterogeneity in variant effects warrants cautious interpretation.

Conclusions:

• Findings suggest EF plays a causal role in ADHD and alcohol use.
• ADHD may also negatively impact EF.
• These results highlight the complex interplay between cognitive functions and externalizing behaviors.