Liver depression syndrome is commonly observed in various clinical diseases. Extensive studies have demonstrated that chronic stress serves as a primary trigger for liver depression syndrome, and its biological mechanisms are closely related to changes in the morphology and function of multiple central brain regions. The relevant evidence, however, remains scattered across numerous studies, necessitating further synthesis and review. This review accordingly summarizes the relationships between the pathogenesis of liver depression syndrome and morphological,functional, and molecular changes in brain regions, including the hippocampus, cortex, hypothalamus, locus coeruleus, and amygdala. Among these, the pathological changes in liver depression syndrome models are predominantly concentrated in the hippocampus and hypothalamus. However, distinct liver depression syndrome models exhibit variations in the affected brain regions. This review summarizes and explores the common biological alterations and specific differences among different liver depression syndrome models. The findings provide a foundation and direction for further research into the biological basis of liver depression syndrome and the identification of syndrome-specific targets.