The Regional Vulnerability Index (RVI) as a Neuroimaging-Based Biomarker for Autism: Associations with Likelihood,...

Area of Science:

• Neuroscience
• Genetics
• Developmental Psychology

Background:

• Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with lifelong challenges, influenced by heritable factors.
• Existing neuroimaging consortia (ENIGMA-ASD, COCORO) have identified consistent patterns of brain differences in individuals with autism.
• Understanding the specific genetic and environmental factors shaping ASD's neurodevelopmental trajectory remains a challenge.

Purpose of the Study:

• To develop and evaluate a novel Regional Vulnerability Index for autism (RVI-ASD), a metric quantifying brain pattern similarity to autism.
• To assess the RVI-ASD's effectiveness in differentiating individuals with autism from controls and its association with autism phenotypes.
• To investigate the longitudinal stability, heritability, and correlations of RVI-ASD with cognitive measures and environmental factors in typically developing individuals.

Main Methods:

• Developed RVI-ASD by combining regional effect sizes from ENIGMA-ASD and white matter integrity data from COCORO.
• Evaluated RVI-ASD in a large sample of individuals with autism (N=2,577) and typically developing children (N=4,201) from the ABCD study.
• Assessed longitudinal stability, heritability, gene-by-age interactions, and correlations with cognitive and behavioral measures.

Main Results:

• RVI-ASD demonstrated a significantly higher effect size for case-control differences compared to individual brain measures (d=0.30).
• RVI-ASD showed high longitudinal stability (ICC=0.76-0.92) and significant heritability (h²=0.55-0.83) in typically developing children.
• RVI-ASD correlated positively with paternal age, negatively with cognitive measures, and tracked with core autism phenotypes and early symptom onset.

Conclusions:

• RVI-ASD is a robust, neuroimaging-based biomarker reflecting stable and reproducible brain patterns associated with autism.
• This metric facilitates research into autism's biological pathways by enabling analysis across large, non-clinical samples.
• RVI-ASD offers a valuable tool for studying associations between autism likelihood, cognition, and various influencing factors beyond traditional case-control models.