In relation to inflammation, the real world of people living with depressive symptoms is diagnostically divided in two. On one side of the line is the large group of patients who have depressive and other mental health symptoms associated with physical health disorders, like rheumatoid arthritis, inflammatory bowel disease or psoriasis (1; 2; 3). These are typically categorized as cases of ‘comorbid’ depression, induced by the demoralizing effects of physical illness and its treatment, and the patient’s mental reflection on the implications of their physical disease. They cannot be formally diagnosed as cases of major depressive disorder (MDD) because the standard DSM criteria for MDD explicitly exclude cases associated with a medical disorder. On the other side of this diagnostic fault line is another large group of patients with depressive symptoms that are not associated with a major medical disorder and are therefore eligible for a diagnosis of MDD (4). One of the interesting aspects of an immune strategy for new antidepressant interventions is that it cuts across this categorical distinction between comorbid depression and MDD: It offers a potentially interesting way forward for depression caused by inflammation – ‘inflamed depression’ – whether there is an obvious medical disorder with potentially very high levels of innate immune system activation in comorbid depression, or low-grade inflammation detectable only by a biomarker or blood test in a subset of patients with MDD.