XKR4 Gene Effects on Cerebellar Development Are Not Specific to ADHD

Area of Science:

• Neuroscience
• Genetics
• Developmental Psychology

Background:

• Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder.
• The XKR4 gene, particularly a single-nucleotide polymorphism (SNP) rs2939678, has been associated with ADHD.
• XKR4 is expressed in the cerebellum, a brain region involved in ADHD.

Purpose of the Study:

• To investigate the impact of the XKR4 rs2939678 SNP on cerebellar development in children with and without ADHD.
• To analyze longitudinal changes in cerebellar gray matter volume based on genotype and diagnosis.

Main Methods:

• Collected longitudinal T1-weighted MRI scans and DNA from 58 children with ADHD and 64 typically developing (TD) children.
• Segmented cerebellar lobular volumes into 35 regions using the MAGeTBrain automated pipeline.
• Analyzed data using linear mixed models to assess age, gene (XKR4 SNP), and diagnosis interactions.

Main Results:

• Children with ADHD showed reduced gray matter volume in specific cerebellar lobules (VIIIA, VIIIB, VIIB, VI) compared to TD children.
• A linear age-by-gene interaction was observed in left lobule VIIB, with G-allele homozygotes showing volume decrease over time.
• Quadratic age-by-gene and age-by-diagnosis interactions were found in left lobule IV, with G-allele homozygotes exhibiting suppressed growth curves.

Conclusions:

• The XKR4 rs2939678 SNP influences cerebellar development, particularly gray matter volume trajectories in specific lobules.
• While G-allele homozygotes display altered cerebellar growth patterns, these effects were not found to be specific to ADHD diagnosis.
• Findings suggest the XKR4 SNP may contribute to neurodevelopmental variations, but its role in ADHD pathogenesis requires further investigation.