title: Altered functioning of the executive control circuit in late-life depression: episodic and persistent phenomena.
abstract: OBJECTIVE
  To characterize the functional neuroanatomy of late-life depression (LLD) by probing for both episodic and persistent alterations in the executive-control circuit of elderly adults.
  
  
  METHODS
  Event-related functional magnetic resonance imaging (fMRI) data were collected while participants performed an executive-control task.
  
  
  METHODS
  Participants were recruited through a depression-treatment study within the Pittsburgh, PA, Intervention Research Center for Late-Life Mood Disorders.
  
  
  METHODS
  Thirteen nondepressed elderly comparison participants and 13 LLD patients.
  
  
  METHODS
  The depressed patients underwent imaging before initiating and after completing 12 weeks of paroxetine.
  
  
  METHODS
  Regional fMRI activity was assessed in the dorsolateral prefrontal cortex (dLPFC: BA9 and BA46 bilaterally) and the dorsal anterior cingulate cortex (dACC). Functional connectivity was assessed by correlating the fMRI time-series in the dLPFC and dACC.
  
  
  RESULTS
  Both depressed and comparison participants performed the task as expected, with greater response latency during high versus low-load trials. The response-latency load-effect did not differ between groups. In contrast to the null findings for behavioral data, pretreatment, depressed patients showed diminished activity in the dLPFC (BA46 left, t(25)=1.9, p = 0.035) and diminished functional connectivity between the dLPFC and dACC. Moreover, right dLPFC (BA46 right, t(25)=2.17, p < 0.02) showed increased activity after treatment.
  
  
  CONCLUSIONS
  These results support a model of both episodic and persistent neurobiologic components of LLD. The altered functional connectivity,perhaps due to vascular damage to frontal white matter, appears to be persistent. Further, at least some of the prefrontal hypoactivity (in the right dLPFC) seems to be an episodic characteristic of acute depression amenable to treatment.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, and Western Psychiatric Institute and Clinic, 3811 O'Hara Street, Pittsburgh, PA 15213, USA. aizen@pitt.edu
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Aizenstein
authors.forename: Meryl A
authors.initials: MA
authors.lastname: Butters
authors.forename: Minjie
authors.initials: M
authors.lastname: Wu
authors.forename: Laura M
authors.initials: LM
authors.lastname: Mazurkewicz
authors.forename: V Andrew
authors.initials: VA
authors.lastname: Stenger
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gianaros
authors.forename: James T
authors.initials: JT
authors.lastname: Becker
authors.forename: Charles F
authors.initials: CF
authors.lastname: Reynolds
authors.forename: Cameron S
authors.initials: CS
authors.lastname: Carter
mesh_terms: D017668:Age of Onset; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D003071:Cognition / Q000502:physiology; D003866:Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology*; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D009482:Neurophysiology; D009483:Neuropsychological Tests; D017374:Paroxetine / Q000627:therapeutic use; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011930:Reaction Time
chemical_list: D018687:Antidepressive Agents, Second-Generation; D017374:Paroxetine