Association Between Behavioral Activation System, White Matter Microstructure, and Depressive Symptoms in Major Depressive Disorder

Abstract Reduced behavioral activation system (BAS) sensitivity is a core behavioral phenotype of anhedonia, a key symptom of major depressive disorder (MDD) that involves multifaceted dysfunctions in the reward processing system. However, the white matter microstructural basis of this phenotype remains unclear. We examined fractional anisotropy (FA) in 54 MDD patients and 72 healthy controls (HC) and explored relationships among FA, BAS Total scores, and depressive symptom severity (Beck Depression Inventory, BDI) in MDD patients. All participants underwent diffusion-weighted imaging (DWI) and completed the BDI, BAS, and Behavioral Inhibition System (BIS) scales. Tract-based spatial statistics (TBSS) was used to extract FA values from seven a priori white matter tracts. Compared with HC, the MDD group showed significantly lower FA values in six tracts (right superior corona radiata, superior longitudinal fasciculus, posterior thalamic radiation, genu of corpus callosum, sagittal stratum, and fornix), as well as significantly lower BAS Total scores and higher BDI scores. Partial correlation analyses within the MDD group showed that FA values in four tracts (right superior corona radiata, superior longitudinal fasciculus, posterior thalamic radiation, and sagittal stratum) were significantly positively correlated with BAS Total scores. Mediation analyses controlling for age, sex, and BIS score revealed that BAS Total scores significantly mediated the relationship between FA values in these four tracts and BDI scores, with an indirect-only mediation pattern. When BIS was tested as an alternative mediator, none of the indirect effects were significant, supporting the specificity of the BAS-mediated pathway. These findings provide new imaging evidence for a "white matter microstructure–behavior–symptom" pathway, suggesting that targeting white matter microstructure and BAS function may help alleviate anhedonia in MDD.