Gender Differences in the Effects of Cortisol and Dehydroepiandrosterone on Brain Derived Neurotrophic Factor in Patients with Major Depression

Levels of serum brain derived neurotrophic factor (BDNF) are lower in patients with major depressive disorder (MDD). The adrenal cortex secretes the corticosteroids cortisol and dehydroepiandrosterone (DHEA) under stress condition, and serum levels of DHEA are gender-dependent. Although BDNF expression is associated with these corticosteroids, the effect of gender on this association is not clear. To examine gender differences in the relationship between BDNF and corticosteroids in patients with MDD, we measured serum levels of cortisol, DHEA-sulfate (DHEA-S) and BDNF in men and women with depression. We recruited 189 inpatients with MDD (76 men and 113 women) from Juntendo Koshigaya Hospital. Serum cortisol, DHEA-S and BDNF levels were measured on the morning after admission. Multiple regression analyses were conducted to assess the effects of cortisol and DHEA-S on BDNF. After controlling for age, we found that serum BDNF levels were significantly influenced by the DHEA-S/cortisol ratio (p = 0.010) in female participants. However, this association was absent in male participants. These results suggest gender differences exist in the effects of corticosteroids on BDNF. In female participants, the balance between neurotoxicity induced by cortisol and neuroprotection associated with DHEA-S may influence the pathology and symptoms of depression via BDNF.