Measuring the Associations Between Brain Morphometry and Polygenic Risk Scores for Substance use Disorders in...

Area of Science:

• Neuroscience
• Genetics
• Developmental Psychology

Background:

• Substance use is linked to adult brain differences, but causality remains unclear.
• Investigating genetic predisposition in early development is crucial for understanding substance use etiology.
• Adolescence is a critical period for brain development and substance use initiation.

Purpose of the Study:

• To examine the impact of polygenic risk scores (PRSs) for cannabis use disorder (CUD) and general substance use/substance use disorder liability (SU/SUD) on brain morphology in drug-naïve adolescents.
• To determine if genetic risk for substance use precedes observed brain differences.
• To assess the association between PRSs and specific brain phenotypes in early adolescence.

Main Methods:

• Utilized baseline data from the Adolescent Brain Cognitive Development Study (N=1874, ages 9-11, European descent).
• Employed multivariate twin models to estimate genetic and environmental influences on brain morphology.
• Calculated PRSs for CUD and SU/SUD using large-scale Genome-Wide Association Studies (GWAS) and applied region-specific PRSs.

Main Results:

• No significant association was found between CUD PRS and brain morphometry in drug-naïve adolescents.
• General SU/SUD PRS showed small, marginally significant effects on cortical surface area and nucleus accumbens volume (0.2-0.4% variance explained).
• Overall, genetic risk for substance use did not substantially predict brain morphology in this cohort.

Conclusions:

• This study found no evidence that genetic risk for CUD influences brain morphology in drug-naïve adolescents.
• A weak association between general substance use genetic risk and specific brain regions (nucleus accumbens, cortical surface area) was observed.
• The findings suggest that genetic predisposition alone may not be a strong determinant of brain morphology differences detectable at baseline in early adolescence.