"The Fall of the House of Usher" can be read as having both supernatural elements and as a psychological drama. Roderick Usher, by his own admission, suffers from psychological illness. As the narrator says of Roderick's letter, "The MS. gave evidence of nervous agitation. The writer spoke of acute bodily illness -- of a mental disorder which oppressed him." These ailments are most likely signs of modern psychological diagnoses such as anxiety, depression, and perhaps somatic disorders. Roderick also suffers from sensory issues, which the narrator describes as "a morbid acuteness of the senses."

The narrator also seems to suffer from depression, and the story is in fact more interested in his psychology than Roderick's. Upon seeing the House of Usher, the narrator says he saw it "with an utter depression of soul which I can compare to no earthly sensation more properly than to the after-dream of the reveller upon opium -- the bitter lapse into everyday life." In other words, perhaps the narrator himself suffers from unmitigated depression that he tries unsuccessfully to relieve with opium use.

Madeline, Roderick's sister, suffers from what Roderick describes as, "a settled apathy, a gradual wasting away of the person, and frequent although transient affections of a partially cataleptical character." In other words, she is wasting away and in a trance.

All three characters clearly suffer from psychological ailments, and many critics have said Roderick and his sister represent two sides of mental illness. They are both mentally ill, but she is passively ill, while he is actively agitated. Roderick and Madeline are twins and are described as having "sympathies of a scarcely intelligible nature," which could mean they are simply emotionally close or that they had an incestuous relationship.

At the end of the story, when Madeline's body falls on Roderick and kills him, the event can be understood as the demise caused by mental failing or as an event that could only be caused by the supernatural. Another possibility is that the narrator has become so deranged by his own mental illness that he imagines things and has delusions that are not real but only emanations of his sick mind. The interpretation is up to the reader as to whether the elements in the story come from the narrator's diseased mind or from the supernatural.

Roderick calls the narrator a "madman" at the end of the story because in Roderick's diseased world, everyone must become mad. To be sane is to be deranged because the narrator does not understand the evil that lurks in the house of Usher. It is clear that the narrator has been driven mad by the end of the story, and the question is whether what he sees comes from his own mind or from the supernatural.