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Depressive symptoms, feelings of sadness, anger, and loss that interfere with a person's daily life, are prevalent health concerns across populations that significantly result in adverse health outcomes with direct and indirect economic burdens at a national and global level. This article aims to synthesize known mechanisms of depressive symptoms and the established and emerging methodologies used to understand depressive symptoms; implications and directions for future nursing research are discussed. A comprehensive search was performed by Cumulative Index to Nursing and Allied Health Literature, MEDLINE, and PUBMED databases between 2000-2021 to examine contributing factors of depressive symptoms. Many environmental, psychological, and physiological factors are associated with the development or increased severity of depressive symptoms (anhedonia, fatigue, sleep and appetite disturbances to depressed mood). This paper discusses biological and psychological theories that guide our understanding of depressive symptoms, as well as known biomarkers (gut microbiome, specific genes, multi-cytokine, and hormones) and established and emerging methods. Disruptions within the nervous system, hormonal and neurotransmitters levels, brain structure, gut-brain axis, leaky-gut syndrome, immune and inflammatory process, and genetic variations are significant mediating mechanisms in depressive symptomology. Nursing research and practice are at the forefront of furthering depressive symptoms' mechanisms and methods. Utilizing advanced technology and measurement tools (big data, machine learning/artificial intelligence, and multi-omic approaches) can provide insight into the psychological and biological mechanisms leading to effective intervention development. Thus, understanding depressive symptomology provides a pathway to improve patients' health outcomes, leading to reduced morbidity and mortality and the overall nation-wide economic burden.Supplemental data for this article is available online at https://doi.org/10.1080/01612840.2021.1998261 .

Mechanisms and Methods to Understand Depressive Symptoms