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Le Guin's Syndrome was a disease that apparently only afflicted Mentites. For the most part, Mentites traditionally did not get sick, but Le Guin's Syndrome was a rare exception to this rule, although it only affected one Mentite in three hundred million.

Initially, symptoms of the disease just consisted of a temperature and headaches, but eventually it would escalate to the point where the Mentite could become trapped in a delusion, potentially trapping others in their 'fantasy' in the process. It was possible to treat the affliction with time, but it would require the afflicted Mentite to suppress their telepathy until it could be completed.

Lieutenant Castille of the USS Enterprise-A became a victim of Le Guin's Syndrome in the 2280s, which culminated in him unintentionally trapping almost the entire crew of the ship in his delusion of Hell after he had been reading Dante's Inferno. As he experienced his final 'attack' of the syndrome when he was in the ship's arboretum, only the current bridge crew remained unaffected due to their distance from the arboretum, while the rest of the crew subconsciously 'judged' themselves and were 'assigned' to a circle of Hell. After the bridge staff were able to make their way from the bridge to the arboretum, Spock was able to initiate a mind-meld with Castille (currently in the form of Lucifer) that broke him out of his delusion. This allowed Doctor McCoy to begin treating Castille's condition with a telepathy-suppressing helmet to keep his condition under control. (TOS - Who Killed Captain Kirk? comics: "Haunted Honeymoon", "Hell in a Handbasket")