BDNF and depressive disorder: In addition, excessive activation of the HPA axis can cause an increase in circulating inflammatory cytokines (Zajkowska et al., 2022), such as indoleamine-2-3-dioxygenase, an enzyme that causes a decrease in serotonin via the kynurenine pathway (Miller and Raison, 2016), and brain-derived neurotrophic factor (BDNF), which is thought to be involved in neuroprotection in depression and anxiety (Lee and Kim, 2010).