Associations among bipolar II depression white matter subgroups, inflammation, symptoms and childhood maltreatment

Childhood maltreatment has long-term effects on brain structure, inflammation and psychiatric symptoms, yet its impact on white matter (WM) integrity in bipolar disorder type II depression (BDII-D) remains understudied. Here, we investigate WM alterations in BDII-D and their associations with childhood maltreatment, inflammation and psychiatric symptoms. Using TractSeg, we analyzed WM integrity in 146 patients with BDII-D and 151 healthy controls, identifying significantly lower fractional anisotropy (FA) in the corpus callosum, left inferior longitudinal fasciculus and right striato-fronto-orbital tract, alongside higher FA in sensory-motor regions. WM alterations were correlated with inflammatory markers and psychiatric symptoms. Non-negative matrix factorization and clustering analysis revealed two BDII-D subgroups, with one subgroup showing lower corpus callosum FA, higher inflammatory markers, greater childhood emotional maltreatment and psychiatric symptoms. These findings suggest deficits in WM integrity in thalamo-subcortical-cortical and somatosensory areas in BDII-D. Childhood emotional maltreatment may contribute to long-term effects on inflammation and psychiatric symptoms in adulthood BDII-D. The authors analyze white matter alterations in bipolar II depression, revealing significant correlations with inflammation and psychiatric symptoms. These findings suggest that childhood emotional maltreatment may exacerbate these effects and offer insights into potential therapeutic targets.