title: Apoptosis-related proteins and proliferation markers in the orbitofrontal cortex in major depressive disorder.
abstract: BACKGROUND
  In major depressive disorder (MDD), lowered neural activity and significant reductions of markers of cell resiliency to degeneration occur in the prefrontal cortex (PFC). It is still unclear whether changes in other relevant markers of cell vulnerability to degeneration and markers of cell proliferation are associated with MDD.
  
  
  METHODS
  Levels of caspase 8 (C8), X-linked inhibitor of apoptosis protein (XIAP), direct IAP binding protein with low pI (DIABLO), proliferating cell nuclear antigen (PCNA) and density of cells immunoreactive (-IR) for proliferation marker Ki-67 were measured in postmortem samples of the left orbitofrontal cortex (OFC) of subjects with MDD, and psychiatrically-normal comparison subjects.
  
  
  RESULTS
  There was significant increase in C8, a higher ratio of DIABLO to XIAP, lower packing density of Ki-67-IR cells, and an unexpected age-dependent increase in PCNA in subjects with MDD vs. controls. PCNA levels were significantly higher in MDD subjects unresponsive to antidepressants or untreated with antidepressants. The DIABLO/XIAP ratio was higher in MDD subjects without antidepressants than in comparison subjects.
  
  
  CONCLUSIONS
  Qualitative nature of responsiveness assessments; definition of resistance to antidepressant treatment is still controversial; and unclear role of PCNA.
  
  
  CONCLUSIONS
  Markers of cell vulnerability to degeneration are increased and density of Ki67-positive cells is low MDD, but accompanied by normal XIAP levels. The results suggest increased vulnerability to cell pathology in depression that is insufficient to cause morphologically conspicuous cell death. Persistent but low-grade vulnerability to cell degeneration coexisting with reduced proliferation readiness may explain age-dependent reductions in neuronal densities in the OFC of depressed subjects.
authors.affiliation: Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA. Electronic address: Jmiguel-hidalgo@umc.edu.
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Miguel-Hidalgo
authors.affiliation: Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Whittom
authors.affiliation: Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Villarreal
authors.affiliation: Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Madhav
authors.initials: M
authors.lastname: Soni
authors.affiliation: Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Ashish
authors.initials: A
authors.lastname: Meshram
authors.affiliation: Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Pickett
authors.affiliation: Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Rajkowska
authors.affiliation: Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA; Psychiatry, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Stockmeier
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D053181:Caspase 8 / Q000378:metabolism*; D049109:Cell Proliferation; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D024101:Mitochondrial Proteins; D018809:Proliferating Cell Nuclear Antigen; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C505530:CASP8 protein, human; D053181:Caspase 8
keywords: Comorbidity; Depression; Postmortem; Prefrontal cortex; Vulnerability