SREBF-2 polymorphism influences white matter microstructure in bipolar disorder

Area of Science:

• Neuroscience
• Genetics
• Biochemistry

Background:

• Bipolar disorder (BD) is associated with white matter (WM) microstructure alterations.
• Sterol regulatory element binding proteins (SREBP-1 and SREBP-2) are key regulators of lipid and cholesterol metabolism.
• The role of SREBP gene polymorphisms in BD-related WM changes is not well understood.

Purpose of the Study:

• To investigate the association between gene polymorphisms in SREBF-1 and SREBF-2 and WM microstructure in patients with bipolar disorder.
• To explore the potential role of the SREBP pathway in central nervous system (CNS) myelination processes in BD.

Main Methods:

• Study included 93 patients diagnosed with bipolar disorder (BD).
• Investigated SREBF-1 rs11868035 and SREBF-2 rs1052717 polymorphisms.
• Utilized diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) to assess WM microstructure.

Main Results:

• The SREBF-2 rs1052717 A/A genotype showed increased radial diffusivity compared to A/G and G/G genotypes.
• Reduced fractional anisotropy (FA) was observed in the SREBF-2 rs1052717 A/A genotype compared to G carriers.
• Affected WM tracts included the cingulum, corpus callosum, longitudinal fasciculi, and anterior thalamic radiation.

Conclusions:

• Findings suggest SREBF-2 gene polymorphisms are associated with altered WM microstructure in bipolar disorder.
• These results indicate a potential involvement of SREBP-2 in maintaining white matter tract integrity in BD.
• The SREBP pathway may play a role in CNS myelination processes relevant to bipolar disorder pathophysiology.