Peripheral indices of oxidative stress are correlated with hippocampal volume in major depression and in controls

Oxidative stress (an imbalance between free radicals and the ability to neutralize them with antioxidants) occurs in several mental illnesses, including major depression (MDD). A major antioxidant in humans is glutathione peroxidase, which reduces GSSH to GSH, increasing glutathione's ability to scavenge free radicals. The brain, and the hippocampus (HC) in particular, is particularly sensitive to oxidative stress, and HC oxidative stress (particularly in the CA1 and CA3 & dentate gyrus [CA3&DG] subfields) may contribute to major depression.Nineteen medication-free subjects with MDD and 19 matched controls underwent 4T MRI scanning of the HC and had fasting morning venipuncture for peripheral oxidative stress assessment. Two of the MDD subjects did not have glutathione (GSH) and/or glutathione (GSSG) data. Because of the preliminary nature of the study, no corrections for multiple comparisons were applied.Across all subjects, the antioxidant Vitamin C was directly correlated with total HC (p<0.03) and CA3&DG (p<0.04) subfield volumes. Glutathione peroxidase was directly correlated with total HC (p<0.006) and CA1 (p<0.009) and CA3&DG (p<0.002) subfield volumes. Levels of the antioxidant and GSH were directly correlated withCA2 (p<0.02) and CA3&DG (p<0.03) subfield volumes. In the controls, a similar pattern was observed at or near the significance threshold. In the MDD group alone, glutathione peroxidase activity was directly correlated with total HC volume (p<0.05) and tended to be directly correlated with CA3&DG subfield volume (p<0.07). The antioxidant ratio of GSH/GSSG (an index of antioxidant reserves) was directly correlated with CA2 (p <0.02) and CA3&DG (p<0.03) subfield volumes.These exploratory data are consistent with the hypothesis that oxidative stress is related to diminished hippocampal volume, with the CA3&DG subfield perhaps being the most sensitive. The relationship of peripheraloxidative stress to local oxidative stress in the HC is unknown, but studies in humans have suggested some degree of direct correlation between blood and cerebrospinal fluid (CSF) and peripheral oxidative stress measures are increased in several neurodegenerative diseases