Depression is a complex, multifactorial, and highly heterogeneous clinical syndrome. As a common mental disorder, it severely impacts patients' quality of life and social functioning. Its pathogenesis is complex, involving interaction of multiple factors including genetic, environmental, neurobiological, and psychosocial factors. Furthermore, the condition is characterised by treatment resistance and recurrence, which significantly limits the clinical efficacy of existing treatment strategies. At present, hypotheses primarily cover a range of areas, including epigenetic modifications, monoamine neurotransmitter dysfunction, hypothalamic-pituitary-adrenal axis dysregulation, brain structural and neuroplasticity alterations, brain-derived neurotrophic factor abnormalities, the intestinal flora disturbances and inflammation. Therefore, there is a need to develop new treatment strategies, and the construction of animal models that effectively simulate the core phenotypes and pathological mechanisms of human depression is a key foundation for advancing this objective. Pigs exhibit marked similarities to humans in neuroanatomy, physiology, and behaviour, and are increasingly recognized as a valuable translational bridge between basic research and clinical application. This paper provides a systematic review of methods for establishing and evaluating models of depression in pigs. Regarding model development, it focuses on research advances in stress-induced modeling—such as acute stress, chronic unpredictable mild stress, maternal separation, and social defeat—as well as surgical, pharmacological, and gene-editing-based modeling approaches, and compares the advantages and limitations of these different methods. Regarding model evaluation, the paper focuses on behavioral indicators—such as feeding behavior and sucrose preference tests, open-field tests, novel object recognition tests, maze tests, and social interaction tests—as well as physiological and biochemical indicators, including monoamine neurotransmitters, hypothalamic-pituitary-adrenal axis hormones, brain-derived neurotrophic factors, and inflammatory factors. At the same time, the paper analyzes the challenges currently faced in the construction and evaluation of porcine depression models, including those related to model construction and evaluation systems, costs, equipment, and ethical considerations. In conclusion, the paper outlines future directions for research into porcine models of depression, emphasising the need to integrate multimodal assessment methods—including behavioural, neuroimaging, physiological, biochemical and molecular biological approaches—as well as the urgent requirement to accurately simulate human depression, with a view to providing guidance and insights for basic research and clinical translation in this field.
