Abnormal white matter integrity as a structural endophenotype for bipolar disorder

Area of Science:

• Neuroimaging
• Psychiatry
• Neuroscience

Background:

• Bipolar disorder (BD) is increasingly associated with white matter (WM) pathology.
• Investigating unaffected first-degree relatives can identify genetic risk markers for BD, independent of illness burden or treatment.
• Tract-based spatial statistics (TBSS) is a key neuroimaging technique for analyzing WM integrity.

Purpose of the Study:

• To investigate white matter (WM) structural differences in patients with bipolar disorder (BD) and their unaffected first-degree relatives.
• To identify potential neuroimaging biomarkers associated with genetic predisposition to BD.
• To differentiate between illness-related changes and trait-based markers in BD.

Main Methods:

• Enrolled 27 euthymic BD type I patients, 20 unaffected siblings, and 29 healthy controls.
• Utilized tract-based spatial statistics (TBSS) to analyze white matter (WM) integrity.
• Performed region-of-interest (ROI) analyses to compare fractional anisotropy (FA) values across groups.

Main Results:

• BD patients exhibited significantly lower fractional anisotropy (FA) in multiple WM tracts compared to controls.
• Both BD patients and unaffected siblings showed reduced FA in the fornix, left posterior thalamic radiation, and left sagittal stratum.
• FA values in unaffected siblings were intermediate between controls and BD patients in these specific ROIs.

Conclusions:

• Reduced FA in the fornix, left posterior thalamic radiation, and left sagittal stratum may serve as a structural endophenotype for bipolar disorder (BD).
• These findings suggest a potential trait-based marker for BD, observable even in genetically at-risk but unaffected individuals.
• WM integrity differences in relatives highlight the genetic component of bipolar disorder.