Free water diffusion MRI differentiates suicide ideators from attempters with treatment-resistant depression

Abstract Suicide attempt is highly prevalent in treatment-resistant depression (TRD), however, the neurobiological profile of suicidal ideation versus suicide attempt is unclear. Neuroimaging methods including diffusion MRI (dMRI) based free water imaging may identify neural correlates underlying the progression from suicidal ideation to attempts in individuals with TRD. dMRI data were obtained from 64 participants, including 39 patients with TRD (n=21 suicide ideators and n=18 suicide attempters), and 25 age- and sex-matched healthy controls. Depression and suicidal ideation severity were examined using clinician-rated and self-report measures. Whole-brain analysis of neuroimaging data was conducted using tract-based spatial statistics via FMRIB Software Library to identify between-group differences in white matter microstructural integrity in suicide ideators versus attempters, and in patients with TRD versus controls. Free water imaging revealed elevated axial diffusivity (AD) and extracellular free water (FW) in fronto-thalamo-limbic white matter tracts of suicide attempters compared to ideators (thresholded p<0.05, FWE corrected). In a separate comparison, patients with TRD were found to have widespread reductions in fractional anisotropy (FA) and axial diffusivity (AD), as well as elevated radial diffusivity (RD) compared to healthy controls. A unique neural signature consisting of elevated AD and FW is identified for the first time in suicide attempters with TRD. Findings of reduced FA, AD, and elevated RD in patients versus controls are consistent with previously published studies. Multimodal and prospective investigations are recommended to better understand biological correlates of suicide attempt.