['Mood disorders in old age increase the risk of morbidity and mortality for individuals and healthcare costs for society. Trait Neuroticism, a strong risk factor for such disorders into old age, shares common genetic variance with depression, but the more proximal biological mechanisms that mediate this connection are not well understood. Further, whether sex differences in the neural correlates of Neuroticism mirror sex differences in behavioral measures is unknown. The present research identifies sex differences in the stable neural activity associated with Neuroticism and tests whether this activity prospectively mediates Neuroticism and subsequent depressive symptoms.', 'A total of 100 (46 female) older participants (>55years) underwent a resting-state PET scan twice, approximately two years apart, and completed measures of Neuroticism and depressive symptoms twice.', 'Replicating at both time points, Neuroticism correlated positively with resting-state regional cerebral blood-flow activity in the hippocampus and midbrain in women and the middle temporal gyrus in men. For women, hippocampal activity mediated the association between Neuroticism at baseline and depressive symptoms at follow-up. The reverse mediational model was not significant.'] Do the neural correlates of Neuroticism differ by sex prospectively mediate depressive symptoms among older women?