Differential relationships between apathy and depression with white matter microstructural changes and functional...

Area of Science:

• Neurology
• Neuroimaging
• Psychiatry

Background:

• Small vessel disease (SVD) is a stroke subtype affecting small arteries supplying sub-cortical brain structures.
• SVD is linked to high rates of apathy and depression, potentially due to disrupted white matter pathways crucial for emotion regulation.
• SVD serves as a model for studying the mechanisms of these neuropsychiatric disorders.

Purpose of the Study:

• To differentiate apathy and depression in SVD patients based on their relationship with white matter microstructure.
• To determine if apathy and depression independently predict functional outcomes in SVD.
• To investigate the specific white matter regions associated with apathy and depression in SVD.

Main Methods:

• Recruited 118 SVD patients (lacunar stroke with leukoaraiosis) and 398 healthy controls.
• Utilized multilevel structural equation modeling to analyze relationships between white matter integrity (fractional anisotropy), apathy, depression, and quality of life.
• Employed whole-brain voxel-based analysis to identify white matter regions associated with apathy and depression, controlling for covariates.

Main Results:

• Both apathy and depression independently predicted quality of life in SVD patients.
• Reduced white matter integrity (fractional anisotropy) was significantly associated with apathy, but not depression.
• Apathy was linked to widespread white matter integrity loss in limbic association tracts; depression showed no significant association when controlling for apathy.

Conclusions:

• White matter microstructural changes in SVD are associated with apathy, not directly with depressive symptoms.
• Apathy in SVD appears related to damage in cortical-subcortical networks governing emotion regulation, reward, and goal-directed behavior.
• These findings suggest distinct underlying mechanisms for apathy and depression in the context of SVD.