The exact diagnosis of Roderick Usher's affliction is unknown, but there is much evidence to say that at least one of his problems is grief. The narrator provides some of the afflictions of the mind that Usher suffers from: incoherence/inconsistency, nervous agitation, alternatively vivacious and sullen, acute senses, inability to eat, superstition, and sensitivity to fabric texture, scent, light, and certain sounds. Usher himself has a theory that his problem is "a constitutional and family evil" and a "nervous affection," which he thought would simply go away. Though not much later, Usher admits that his mental sickness could stem from the long drawn out illness of his sister, whom we later learn is actually his twin sister. More evidence of this being grief for his sister is shown by the fact that he gets worse after his sister dies. The narrator tries to distract Usher from his grief, but it does not work, as is evidenced by how Usher arrives in the narrator's room late one night; he had a "mad hilarity in his eyes" and "an evidently restrained hysteria in his whole demeanor."
The grief from losing his twin sister was bad enough, but one can scarcely imagine the pain caused by burying your twin alive on accident, spending the next few days hearing sounds from her tomb, and then having her appear in front of him, covered in blood, only to fall dead on top of him. We do not get to see Usher's reaction to this because the narrator flees the manor house very quickly; and apparently not a moment too soon because something caused the fissure in the house to widen, which broke apart the entire house, and then the whole house was swallowed by the lake that was nearby.