White Matter Microstructural Alterations and their Association with Decision-Making Deficits in Suicide Attempters

Decision-making and inhibition deficits are well documented among individuals with a history of suicide attempt (SAs), but the underlying neurobiological mechanisms remain unclear. This study investigated white matter (WM) tracts associated with intermediate phenotypes, namely, decision-making and inhibition, among SAs (n=48), patient controls (PCs; n=34), and healthy controls (HCs; n=49) using diffusion tensor imaging and tractometry, a novel method allowing pointwise investigation of WM microstructure. We hypothesized alterations in the striato-fronto-orbital tract (ST-FO), superior longitudinal fasciculus II (SLF-II), and cingulum bundle in SAs and subgroups, as well as associations between diffusion metrics and cognitive performance on the Iowa Gambling (IGT) and Go/No-Go tasks. As hypothesized, compared with the PCs and HCs, the SAs presented significant alterations in the right ST-FO, with elevated fractional anisotropy (FA) in the central segment and lower FA in the anterior segment; similar effects were observed for radial diffusivity (RD). RD values bilaterally and FA values in the left ST-FO correlated significantly with IGT performance. Additional RD and FA alterations were detected in the SLF-II, although no differences emerged between patient groups. No significant group differences were found in the cingulum bundle, although SAs made more Go/No-Go commission errors than both control groups. In addition, SAs who used violent suicide methods differed from nonviolent SAs in the central segments of the ST-FO tract in the RD. This is the first study to apply tractometry in SAs, providing novel evidence that WM alterations, mainly in orbitofronto-striatal pathways, are linked to cognitive deficits relevant to suicidal behavior.