The article explores the role of inflammation and oxidative and nitrosative stress (O&NS) as mediators of environmental risk factors in depression. It discusses how various factors, such as psychosocial stressors, poor diet, physical inactivity, obesity, smoking, altered gut permeability, atopy, dental care, sleep, and vitamin D deficiency, increase the risk for depression and are associated with systemic inflammation. The review highlights the importance of these factors in both the development and neuroprogression of depression, emphasizing that many of these sources of inflammation are plastic and potentially amenable to therapeutic and preventative interventions. The article also suggests that these mechanisms may play a role in other psychiatric disorders, such as bipolar disorder, schizophrenia, autism, and post-traumatic stress disorder. The summary emphasizes the need to understand and address these inflammatory processes to develop novel therapeutic and preventive approaches for depression.The article explores the role of inflammation and oxidative and nitrosative stress (O&NS) as mediators of environmental risk factors in depression. It discusses how various factors, such as psychosocial stressors, poor diet, physical inactivity, obesity, smoking, altered gut permeability, atopy, dental care, sleep, and vitamin D deficiency, increase the risk for depression and are associated with systemic inflammation. The review highlights the importance of these factors in both the development and neuroprogression of depression, emphasizing that many of these sources of inflammation are plastic and potentially amenable to therapeutic and preventative interventions. The article also suggests that these mechanisms may play a role in other psychiatric disorders, such as bipolar disorder, schizophrenia, autism, and post-traumatic stress disorder. The summary emphasizes the need to understand and address these inflammatory processes to develop novel therapeutic and preventive approaches for depression.