Advances in Multi-Omics Research on Post-Stroke Depression: From Molecular Mechanisms to Therapeutic Strategies

Post-stroke depression (PSD) is a common neuropsychiatric complication after stroke and has a substantial impact on functional recovery, quality of life, and long-term outcomes. Because stroke-related manifestations, including aphasia, cognitive impairment, fatigue, and somatic symptoms, overlap with depressive symptoms, the clinical identification of PSD still largely relies on symptom assessment and clinical interviews, resulting in delayed diagnosis and intervention in some patients. Recent studies indicate that the development of PSD is not driven by a single pathological process but involves multiple mechanisms, including neuroinflammation, neural network alterations, dysfunction of the neurovascular unit, disturbances in energy and lipid metabolism, imbalance of the microbiota-gut-brain axis, and psychosocial factors following brain injury. The advancement of multi-omics technologies has provided new approaches for investigating the biological mechanisms underlying PSD. This review systematically summarizes recent progress in the application of multi-omics approaches in PSD research, focusing on molecular alterations identified across different omics platforms and potential biomarkers. Furthermore, the role of the hypothalamic-pituitary-adrenal (HPA) axis in stress response regulation and PSD development is discussed within the context of neuro-immune-metabolic interactions. Overall, multi-omics studies have provided new insights into the molecular basis of PSD and facilitated the identification of potential biomarkers and therapeutic targets. However, their clinical utility requires further evaluation through standardized cohorts and validation studies.