Cell-type-specific genes associated with cortical structural abnormalities in pediatric bipolar disorder

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Pediatric bipolar disorder (PBD) is linked to abnormal brain structural connectivity.
• The correlation between PBD abnormalities and gene expression remains debated.

Purpose of the Study:

• Identify cell-type-specific gene modules associated with cortical structural differences in PBD.
• Investigate the genetic underpinnings of neurodevelopmental abnormalities in pediatric mental health.

Main Methods:

• Computed morphometric similarity networks (MSN) from MRI data of 102 participants (59 PBD patients, 43 controls).
• Used partial least squares (PLS) regression to link MSN differences with transcriptomic data from the Allen Human Brain Atlas (AHBA).
• Employed gene enrichment tools to determine biological processes and cortical cell types involved.

Main Results:

• MSN analysis revealed significant cortical structural differences between PBD patients and controls.
• PBD-related genes were spatially correlated with MSN differences.
• Enriched gene sets included "trans-synaptic signaling" and "regulation of ion transport", with specific expression in excitatory and inhibitory neurons.

Conclusions:

• Identified specific genes contributing to structural network aberrations in PBD.
• Suggests that transcriptional changes in excitatory and inhibitory neurons are associated with abnormal brain structural connectivity in PBD.