title: The neural correlates of Neuroticism differ by sex prospectively mediate depressive symptoms among older women.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Neuroticism was associated with stable neural activity in regions implicated in emotional processing and regulation for women but not men. Among women, Neuroticism prospectively predicted depressive symptoms through greater activity in the right hippocampus, suggesting one neural mechanism between Neuroticism and depression for women. Identifying responsible mechanisms for the association between Neuroticism and psychiatric disorders may help guide research on pharmacological interventions for such disorders across the lifespan.
authors.affiliation: Laboratory of Personality and Cognition, National Institute on Aging, NIH, DHHS, Baltimore, MD 21224, USA. sutina@mail.nih.gov
authors.forename: Angelina R
authors.initials: AR
authors.lastname: Sutin
authors.forename: Lori L
authors.initials: LL
authors.lastname: Beason-Held
authors.forename: Vonetta M
authors.initials: VM
authors.lastname: Dotson
authors.forename: Susan M
authors.initials: SM
authors.lastname: Resnick
authors.forename: Paul T
authors.initials: PT
authors.lastname: Costa
mesh_terms: D000368:Aged; D015142:Baltimore; D001783:Blood Flow Velocity / Q000502:physiology; D001921:Brain / Q000098:blood supply* / Q000000981:diagnostic imaging; D001931:Brain Mapping; D002605:Character; D003866:Depressive Disorder / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008297:Male; D008636:Mesencephalon / Q000098:blood supply / Q000000981:diagnostic imaging; D008875:Middle Aged; D009497:Neurotic Disorders / Q000000981:diagnostic imaging*; D010555:Personality Inventory / Q000706:statistics & numerical data; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D011594:Psychometrics; D012039:Regional Blood Flow / Q000502:physiology; D012737:Sex Factors; D013223:Statistics as Topic; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000503:physiopathology