Peripheral antioxidant markers are associated with total hippocampal and CA3/dentate gyrus volume in MDD and healthy controls-preliminary findings

Psychiatry Res. 2014 Dec 30;224(3):168-74. doi: 10.1016/j.pscychresns.2014.09.002. Epub 2014 Sep 16.


Several psychiatric disorders, including major depressive disorder (MDD), are associated with increased blood markers of oxidative stress. The relevance of this to the oxidation-sensitive hippocampus (HC) is unknown. We investigated the relationship between peripheral oxidative stress markers and HC volume in unmedicated individuals with MDD (n=16) and healthy controls (n=19). To conserve power, our primary analysis was carried out in the combined group of subjects, and secondary analyses examined each group separately. Oxidative stress markers (oxidized glutathione (GSSG)) and antioxidants (reduced glutathione (GSH), glutathione peroxidase (Gpx), and Vitamin C) were assessed, and a "total net antioxidant score" was calculated. 4-T MRI estimated total HC volume and HC subfield (CA1, CA1-CA2 transition zone, subiculum and CA3/dentate gyrus [CA3&DG]) volumes. Across groups, the antioxidant score was significantly and positively correlated with total HC volume and CA3&DG subfield volume (normalized to total intracranial volume), adjusting for age and sex. Similar relationships were observed in each individual group but missed statistical significance, likely due to type II errors, with the exception of a significant correlation between the antioxidant score and CA3&DG volume in the MDD group. These preliminary data are consistent with oxidative stress being associated with smaller total HC and CA3&DG subfield volumes.

Keywords: Aging; Glutathione; Hippocampus; Oxidative Stress; Subfields; Vitamin C.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • CA3 Region, Hippocampal / pathology
  • Dentate Gyrus / pathology
  • Depressive Disorder, Major / blood*
  • Depressive Disorder, Major / pathology*
  • Female
  • Hippocampus / pathology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Oxidative Stress / physiology*


  • Biomarkers