ESR1 and major depressive disorder: Subsequently, Chhibber et al. reported that decreased estrogen receptor (ER) expression reduces brain-derived neurotrophic factor (BDNF) levels in the hippocampus, thereby inhibiting the tropomyosin receptor kinase B (TrkB) signaling pathway, leading to 5-HT2A dysfunction, attenuated synaptic plasticity, and increased susceptibility to depression in menopausal women [14].