BackgroundClinical depression is associated with reductions in white-matter integrity in several long tracts of the brain. The extent to which these findings are localized or related to depressive symptoms or personality traits linked to disease risk remains unclear.MethodMembers of the Lothian Birth Cohort 1936 (LBC936) were assessed in two waves at mean ages of 70 and 73 years. At wave 1, they underwent assessments of depressive symptoms and the personality traits of neuroticism and extraversion. Brain diffusion magnetic resonance imaging (MRI) data were obtained at the second wave and mood assessments were repeated. We tested whether depressive symptoms were related to reduced white-matter tract fractional anisotropy (FA), a measure of integrity, and then examined whether high neuroticism or low extraversion mediated this relationship.ResultsSix hundred and sixty-eight participants provided useable data. Bilateral uncinate fasciculus FA was significantly negatively associated with depressive symptoms at both waves (standardized β=0.12–0.16). Higher neuroticism and lower extraversion were also significantly associated with lower uncinate FA bilaterally (standardized β=0.09–0.15) and significantly mediated the relationship between FA and depressive symptoms.ConclusionsTrait liability to depression and depressive symptoms are associated with reduced structural connectivity in tracts connecting the prefrontal cortex with the amygdala and anterior temporal cortex. These effects suggest that frontotemporal disconnection is linked to the etiology of depression, in part through personality trait differences.