Antioxidative Defense Genes and Brain Structure in Youth Bipolar Disorder

Abstract

Background Oxidative stress is implicated in the neuropathology of bipolar disorder (BD). We investigated the association of single-nucleotide polymorphisms (SNPs) in the antioxidative genes superoxide dismutase 2 (SOD2) and glutathione peroxidase 3 (GPX3) with structural neuroimaging phenotypes in youth BD. Methods SOD2 rs4880 and GPX3 rs3792797 SNP genotypes, along with structural magnetic resonance imaging, were obtained from 147 youth (BD=75; healthy controls (HC)=72). Images were processed using FreeSurfer, yielding surface area, volume, and thickness values for regions of interest (ROI; prefrontal cortex (PFC), caudal anterior cingulate cortex (cACC), hippocampus) and for vertex-wise whole brain analysis. Analyses controlled for age, sex, race, and intracranial volume for volume area, and thickness analyses. Result ROI analyses revealed diagnosis-by-SOD2 rs4880 interaction effects for cACC volume and surface area, and PFC volume; in each case, there was lower volume/area in the BD GG genotype group vs. the HC GG genotype group. There was a significant BD diagnosis x GPX3 rs3793797 interaction effect for PFC surface area, where area was lower in the BD A-allele carrier group vs. the other genotype groups. Vertex-wise analyses revealed significant interaction effects in frontal, temporal, and parietal regions, related to smaller brain structure in the BD SOD2 rs4880 GG group and BD GPX3 rs3793797 A-allele carrier group. Conclusion We found preliminary evidence that SOD2 rs4880 and GPX3 rs3792797 are differentially associated with brain structure in youth with BD, in regions that are relevant to BD. Further studies incorporating additional neuroimaging phenotypes and blood levels of oxidative stress markers are warranted.

Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine

“…Oxidative stress itself suppresses mitochondrial function, which contributes to diminished neuroplasticity and neurogenesis, with increased apoptosis and neurodegeneration in BD [ 23 , 25 , 81 ]. Indeed, increased oxidative stress evidenced by DNA, RNA, protein, and enzymatic analyses has been consistently reported in bipolar depression [ 82 – 85 ]. Pharmacotherapeutic evidence also supports the association between bipolar depression treatment efficacy and antioxidant activity [ 86 ].…”

The Disease Model of Addiction: The Impact of Genetic Variability in the Oxidative Stress and Inflammation Pathways on Alcohol Dependance and Comorbid Psychosymptomatology

“…More specifically, the caudal anterior cingulate cortex surface area and volume, as well as the prefrontal cortex volume, were lower in GG carriers. Also, GG BD patients had significant interaction effects in a temporal lobe brain region associated with smaller brain structures [42]. Chronic alcohol consumption has been associated with a reduction in gray and white matter volume, which leads to whole-brain volume decline.…”

“…Moreover, the rs4880 T allele is associated with an increased risk of developing schizophrenia [42] and depression. Interestingly, sex was an influencing factor, given that the depression risk was only in males [40].…”

Higher Levels of C-reactive Protein Are Associated With Higher Cortical Surface Area and Lower Cortical Thickness in Youth With Bipolar Disorder

“…Dysfunctions observed in both the superior frontal gyrus and transverse temporal gyrus in individuals with BD may render these regions more susceptible to the effects of CRP. Moreover, our group has previously reported an oxidative stress-by-diagnosis interaction effect within the superior frontal gyrus ( Zou et al, 2022b ). Given the association of higher CRP levels with higher oxidative stress, these findings collectively suggest that the superior frontal gyrus may be more susceptible to neuroinflammation.…”