Fig. 4

The pathogenesis of MDD is closely related to synapses, astrocytes, microglia, and their interactions as well as interactions among organ. Genetic factors, stress and comorbidities are considered the most common pathogenic factors of MDD³. The traditional monoamine theory contends that MDD may cause by the deficits in monoamine neurotransmitters.⁴⁹ Moreover, the other abnormal increase of neurotransmitters in the synaptic cleft, such as glutamate, GABA and ATP, has the high relationship with the pathogenesis of MDD.^41,496 The interaction between neurons and glial cells can induce the oxidative stress, pro-inflammatory cytokines released, the reduction of neurotrophic factors. The microbiota-gut-brain axis is clearly disrupted in MDD.^243,248 When liver dysfunction occurs and causes OS and neuroinflammation in the brain, which also contribute to the pathophysiology of MDD.⁴⁹⁷ Adobe Illustrator was used to generate this figure