title: Age, rapid-cycling, and pharmacotherapy effects on ventral prefrontal cortex in bipolar disorder: a cross-sectional study.
abstract: BACKGROUND
  Neuroimaging data suggest that deficits in ventral prefrontal cortex (VPFC) function in bipolar disorder (BD) progress during adolescence and young adulthood. However, the developmental trajectory of VPFC morphological abnormalities in BD is unknown. This study investigated potential age-dependent volume abnormalities in VPFC in BD.
  
  
  METHODS
  Thirty-seven individuals diagnosed with BD I (14 adolescents, 10 young adults and 13 older adults) and 56 healthy comparison subjects (HC) participated in imaging. Gray and white matter volumes of VPFC were measured using high-resolution structural magnetic resonance imaging (MRI). We used a mixed model, repeated measures analysis to examine VPFC volumes across age groups while co-varying for total brain volume. Potential effects of illness features including rapid-cycling and medication were explored.
  
  
  RESULTS
  VPFC volumes declined with age (p < .001). The diagnosis-by-age group interaction was significant (p = .01). Relative to HC subjects, VPFC gray and white matter volumes were significantly smaller in BD patients only in young adulthood (p = .04). In participants with BD, VPFC volumes were significantly smaller in participants with rapid-cycling than participants without rapid-cycling (p = .02). Conversely, current use of medication was associated with larger VPFC gray matter volumes (p = .005), independent of age.
  
  
  CONCLUSIONS
  These preliminary findings suggest the presence of a more rapid initial decline in VPFC volumes with age in adolescents and young adults with BD than HC. These findings also suggest that the rapid-cycling subtype of BD is associated with larger VPFC volume deficits than the non-rapid-cycling subtype, and that pharmacotherapy may have trophic or protective effects on VPFC volumes in BD patients.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06511, USA. hilary.blumberg@yale.edu
authors.forename: Hilary P
authors.initials: HP
authors.lastname: Blumberg
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.forename: Ravi
authors.initials: R
authors.lastname: Bansal
authors.forename: Andrés
authors.initials: A
authors.lastname: Martin
authors.forename: James
authors.initials: J
authors.lastname: Dziura
authors.forename: Kathleen
authors.initials: K
authors.lastname: Durkin
authors.forename: Laura
authors.initials: L
authors.lastname: Martin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gerard
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Charney
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Peterson
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000188:drug therapy*; D003430:Cross-Sectional Studies; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004358:Drug Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010507:Periodicity; D017397:Prefrontal Cortex / Q000033:anatomy & histology / Q000187:drug effects* / Q000503:physiopathology*