Alcohol milestones and internalizing, externalizing, and executive function: longitudinal and polygenic score...

Area of Science:

• Addiction research
• Behavioral genetics
• Psychiatry

Background:

• The relationship between alcohol use and behavioral phenotypes (e.g., impulsivity, negative affect, executive function) is known, but directionality and shared genetic factors are unclear.
• Understanding these dynamics is crucial for developing effective prevention and intervention strategies for alcohol use disorder (AUD).

Purpose of the Study:

• To investigate the longitudinal associations between transitions in alcohol involvement, behavioral phenotypes, and genetic risk.
• To clarify the directionality and shared genetic liability in the development of alcohol use disorder.

Main Methods:

• Utilized data from the Collaborative Study on the Genetics of Alcoholism (n=3681, ages 11-36).
• Assessed alcohol transitions (first drink, intoxication, AUD symptoms/diagnosis), internalizing/externalizing phenotypes, and executive function (EF).
• Computed polygenic scores (PGS) for alcohol and behavioral phenotypes and used Cox models to analyze associations.

Main Results:

• Externalizing phenotypes predicted future alcohol initiation and problems; internalizing phenotypes predicted progression to severe AUD.
• Alcohol initiation and AUD were linked to increased risks for later depressive symptoms and suicidal ideation.
• Polygenic scores for alcohol consumption and problematic use were associated with increased risks for alcohol transitions and suicidal ideation, respectively.

Conclusions:

• Behavioral markers of addiction vulnerability can precede and follow alcohol involvement, indicating dynamic, bidirectional relationships.
• These findings underscore the complex interplay between behavior and the development of addiction.