IEPA 11

Jeffrey K. Yao1,2,3, Paulo L. Lizano4, Xiang Zhou1,3, Ravinder D. Reddy5, Gretchen L. Haas1,2, Debra M. Montrose2, Olivia Lutz4, Kiranpreet Dhaliwal4, Matcheri S. Keshavan2,4; 1VA Pittsburgh Healthcare System, Pittsburgh, PA, 2University of Pittsburgh School of Medicine, Pittsburgh, PA, 3University of Pittsburgh School of Pharmacy, Pittsburgh, PA, 4Beth Israel Deaconess Medical Center and Harvard University, Boston, MA, 5University of California San Diego, San Diego, CA
               
In human plasma, levels of total antioxidant status (TAS) and malondialdehyde (MDA) often serve as biomarkers for studying antioxidant defense system (AODS) in psychiatric disorders. Increased oxidative stress has been linked to the schizophrenia (SZ) pathology. However, it is not clear whether changes in these peripheral markers are also related to structural changes in brain. Using enzyme immunoassay, we compared TAS and MDA in plasma among healthy controls (HC, n=62), first-episode antipsychotic-naïve patients with schizophrenia (FEAN-SZ, n=85) and patients with other first-psychosis (POFP, n=24). Comparisons were also made in frontal and temporal regional gray matter volume and thickness, white matter volume, as well as hippocampal and caudate volume between HC (TAS n=14, MDA n=10) and FEAN-SZ (TAS n=26, MDA n=23) groups using 1.5T T1-weighted MRI. In accordance with previously published data, significantly lower levels of TAS (p=0.0001) and higher levels of MDA (p=0.0111) were found in FEAN-SZ compared to HC and POFP groups. TAS levels were inversely correlated with MDA levels (p<0.0001) in all groups. In addition, brain volume/thickness trajectories were positively correlated with plasma TAS levels, but inversely correlated with plasma MDA levels in HC group. However, such correlations were not present in the FEAN-SZ group.  Together, the present data showing inverse correlations suggest that both TAS and MDA are useful biomarkers to predict homeostatic imbalance of AODS. Moreover, our MRI findings lend further support that increased oxidative stress during early course of illness may confer vulnerability to reduced brain volume/thickness in SZ patients.