title: Prefrontal cortex function in remitted major depressive disorder.
abstract: BACKGROUND
  Recent models of major depressive disorder (MDD) have proposed the rostral anterior cingulate (rACC) and dorsomedial prefrontal cortex (dmPFC) as nexus sites in the dysfunctional regulation of cognitive-affective state. Limited evidence from remitted-state MDD supports these theories by suggesting that aberrant neural activity proximal to the rACC and the dmPFC may play a role in vulnerability to recurrence/relapse within this disorder. Here we present a targeted analysis assessing functional activity within these two regions of interest (ROIs) for groups with identified vulnerability to MDD: first, remitted, high predicted recurrence-risk patients; and second, patients suffering observed 1-year recurrence. Method Baseline T2* images sensitive to blood oxygen level-dependent (BOLD) contrast were acquired from patients and controls during a Go/No-Go (GNG) task incorporating negative feedback, with 1-year patient follow-up to identify recurrence. BOLD contrast data for error commission (EC) and visual negative feedback (VNF) were used in an ROI analysis based on rACC and dmPFC coordinates from the literature, comparing patients versus controls and recurrence versus non-recurrence versus control groups.
  
  
  RESULTS
  Analysis of patients (n = 20) versus controls (n = 20) showed significant right dmPFC [Brodmann area (BA) 9] hypoactivity within the patient group, co-localized during EC and VNF, with additional significant rACC (BA 32) hypoactivity during EC. The results from the follow-up analysis were undermined by small groups and potential confounders but suggested persistent right dmPFC (BA 9) hypoactivity associated with 1-year recurrence.
  
  
  CONCLUSIONS
  Convergent hypoactive right dmPFC (BA 9) processing of VNF and EC, possibly impairing adaptive reappraisal of negative experience, was associated most clearly with clinically predicted vulnerability to MDD.
authors.affiliation: Division of Psychiatry, The Institute of Mental Health, University of Nottingham, Nottingham, UK. neil.nixon@nottingham.ac.uk
authors.forename: N L
authors.initials: NL
authors.lastname: Nixon
authors.forename: P F
authors.initials: PF
authors.lastname: Liddle
authors.forename: G
authors.initials: G
authors.lastname: Worwood
authors.forename: M
authors.initials: M
authors.lastname: Liotti
authors.forename: E
authors.initials: E
authors.lastname: Nixon
mesh_terms: D000328:Adult; D001931:Brain Mapping; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000503:physiopathology*; D005260:Female; D059907:Functional Neuroimaging; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012008:Recurrence; D055815:Young Adult