Per1 gene polymorphisms influence the relationship between brain white matter microstructure and depression risk

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Circadian rhythm disruption is implicated in depression pathogenesis.
• Early prediction and diagnosis of major depressive disorder (MDD) increasingly focus on circadian genes and white matter (WM) integrity.
• PER1 gene polymorphisms are key circadian regulators.

Purpose of the Study:

• To investigate the impact of PER1 gene polymorphisms (rs7221412) on the relationship between depressive symptoms and WM microstructural integrity.
• To explore the role of PER1 genotypes in the association between depression levels and brain white matter characteristics.

Main Methods:

• Diffusion tensor imaging (DTI) and Beck Depression Inventory (BDI) were used in 77 healthy college students.
• Participants were genotyped for PER1 polymorphisms, categorized into AG and AA groups.
• Tract-based spatial statistics (TBSS) analyzed the effects of PER1 genotypes on WM integrity and BDI scores.

Main Results:

• Individuals with the PER1 AG genotype had higher depression scores (BDI cutoff of 14) compared to the AA genotype (p=0.007).
• Poorer WM integrity was observed in the AG group within the corpus callosum, internal capsule, corona radiata, and fornix.
• Significant genotype × BDI interactions revealed that BDI scores correlated with WM integrity in emotion-related tracts (corpus callosum, internal capsule, etc.) exclusively in the AG group.

Conclusions:

• PER1 genotypes and emotion-related WM microstructure may serve as early indicators of depression risk.
• This study highlights the interplay between circadian gene variants and brain structural integrity in the context of depression.