Putative epicenters identified by transcriptome-neuromorphic interactions in attention-deficit/hyperactivity disorder...

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Attention-deficit hyperactivity disorder (ADHD) is a complex behavioral disorder characterized by inattention, hyperactivity, and impulsivity.
• Understanding ADHD heterogeneity, including distinct biotypes and their underlying mechanisms, is crucial for advancing disease pathogenesis knowledge.
• Identifying disease epicenters can illuminate network-spreading patterns and their clinical correlations.

Purpose of the Study:

• To investigate neuromorphic heterogeneity and transcriptional similarity architecture in ADHD.
• To analyze the epicenters of network-spreading within each identified ADHD biotype.
• To explore correlations between ADHD biotypes, network epicenters, and clinical characteristics.

Main Methods:

• Utilized partial least squares (PLS1) to analyze regional cortical thickness deviation and gene expression patterns.
• Identified distinct ADHD biotypes based on neuromorphic and transcriptional profiles.
• Mapped disease epicenters within cognitive control and attention networks for each biotype.

Main Results:

• Two discriminative ADHD biotypes were identified, each exhibiting unique neuromorphic aberrances.
• Gene expression patterns (PLS1 positively weighted genes over-expressed, negatively weighted genes under-expressed) correlated with cortical thickness deviation.
• Distinct disease epicenters were observed in cognitive control and attention networks for both ADHD biotypes, showing significant heterogeneity.

Conclusions:

• The study successfully identified two distinct ADHD biotypes with unique transcriptome-neuroimaging relationships.
• Disease epicenters in cognitive and attention networks vary between biotypes, offering insights into ADHD pathogenesis.
• These findings hold promise for advancing the understanding and personalized treatment of ADHD.