Uprising, Probably the best reference for this is, ironically, the DSM itself. DSM-5 has a category called “Depressive Disorder Due to Another Medical Condition”. One of the criteria is: “B. There is evidence from the history, physical examination, or laboratory findings that the disturbance is the direct pathophysiological consequence of another medical condition.” (p 180) Here are two quotes from the text: “In determining whether the mood disturbance is due to a general medical condition, the clinician must first establish the presence of a general medical condition. Further, the clinician must establish that the mood disturbance is etiologically related to the general medical condition through a physiological mechanism.” (p 181) “Etiology (i.e., a causal relationship to another medical condition based on best clinical evidence) is the key variable in depressive disorder due to another medical condition. The listing of the medical conditions that are said to be able to induce major depression is never complete, and the clinician’s best judgment is the essence of this diagnosis. There are clear associations, as well as some neuroanatomical correlates, of depression with stroke, Huntington’s disease, Parkinson’s disease, and traumatic brain injury. Among the neuroendocrine conditions most closely associated with depression are Cushing’s disease and hypothyroidism. There are numerous other conditions thought to be associated with depression, such as multiple sclerosis. However, the literature’s support for a causal association is greater with some conditions, such as Parkinson’s disease and Huntington’s disease, than with others…” (p 181) So, as you can see, it’s a bit vague. Of course, all serious illness can precipitate feelings of sadness and despondency, but the issue here is that the illness produces the feelings of sadness through a direct physiological mechanism. And, of course, this mechanism itself isn’t fully understood, so there will always be disagreement in this area.