Research Article Val16Ala-SOD2 Polymorphism Modulates Hypothalamic-Pituitary-adrenal Axis Molecules and BDNF Levels in Healthy Adults under No Psychological Stress

Chronic psychological stress alters the hypothalamic-pituitary-adrenal axis (HPA-axis), triggering chronic oxidative-inflammatory states that are associated with physical and psychiatric conditions. However, it is not clear if basal oxidative-inflammatory states triggered by genetic variation affect the HPA-axis by altering cortisol, adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEA-S) levels. Humans have a single nucleotide polymorphism (SNP) found in manganese-dependent superoxide dismutase (Val16Ala-SOD2, rs4880), which has two alleles (V and A) which affect the basal efficacy of SOD2 antioxidant enzyme in the mitochondria. The VV-genotype, which presents low SOD2-efficacy, has been associated with chronic inflammatory states, as well as higher risk of depression and self-reported psychological stress. Therefore, basal oxidative imbalance could have some influence on modulation of HPA-axis physiology. We tested this hypothesis comparing morning blood levels of cortisol, ACTH and DHEA-S and other biochemical markers in 90 healthy adult university students previously genotyped for the SOD2-SNP (30 volunteers for each genotype, 26.5 +/- 8.7 years old). Only volunteers who self-reported no perception of psychological stress were included in the study. The VV group had higher morning cortisol and ACTH, and lower DHEA-S and brain-derived neurotrophic factor (BDNF) than A-allele subjects. These results indicate some influence of S-imbalance on modulation of this molecule. Therefore, we suggest that genetically controlled pro-oxidative and inflammatory states could modulate physiological markers for stress and neurogenesis.