When a character is incapable of relating normally to the people around him, and can\\\'twon\\\'t escape that condition.
- Neon Genesis Evangelion achieves a very interesting (and genocidally explosive) combination by having a Dysfunction Junction as a cast, unwilling or unable to seek professional help, and suffering from the subtle version of this trope, making them incapable of helping each other, or themselves for that matter. Now put the fate of the world in their hands, and watch the spectacle as it unfolds.
- Rising Star's Poet has a bad case of this, largely but not exclusively out of choice. Many of the other Specials have some serious loneliness issues, and it takes the serial killings to unite them as Fire-Forged Friends.
- The Big Bang Theory manages to subvert this when it comes to keeping the Omega Cast together, but played it straight for a long time when it came to enforcing that cast. The main male characters are of remarkable social ineptitude, but they still manage to stick together, largely because their interests and jobs allow them to relate to each other. Sheldon Cooper, Insufferable Genius that he is, is an even greater subversion since he constantly annoys, insults, uses and belittles everyone else in the cast, but a Life Debt binds the protagonist, Leonard, to him, and everyone else merely tolerates him because of that. Penny, the Audience Surrogate, suffers from the subtle version of this, being unable to relate to other people on a meaningful level and having lived a very shallow life until she met Leonard, with whom she seems to have found a True Love of sorts. Again, initially mostly because of him, she merely tolerates everyone else. The trope is otherwise played straight when it comes to any of these characters trying to relate to people outside of the Omega Cast: it is, in fact, one of the main themes of the series, and often played for laughs. Eventually, the trope is subverted with the introduction and shuffling of romantic pairings among the cast, and the focus of the comedy shifts to the very quirky couples working around each other's unusual or annoying traits, as well as improving themselves (or, conversely, compromising their personal integrity) for the sake of the relationships.
- The main motivation for the villian of Ghost Trick was that his body was stuck in a timeless limbo where it never ages. Unable to connect to reality, like his every sense was blunted, he when a bit crazy from the isolation.
- In Team America: World Police, Kim Jong Il sings a song about how he's "So Ronery" and can't understand why. Maybe if he didn't kill people for disagreeing with him....
- In Friendship Is Magic, the main premise of the show is demonstrating how a character who has a bad (and voluntary) case of Chronic Solitude can not only make friends, but serve as a nexus for those to become friends with each other, and, together, learn how to master the intricacies of dealing with the conflicts that might arise in a cast with such diverse and contrasting personalities.
- In Code Geass, you could argue that all of the main heroes and villains have a case of this[[hottip:*:Partly Intelligence Equals Isolation, partly Lonely at the Top, but mostly it's their circumstances, fates and backstories that get in the way of relating to other people normally]], and that the Big Bad's Assimilation Plot was to solve this issue. Somehow. The secondary villain is perfectly happy with this state of affairs, though, and has other plans entirely. Geas in general are condemnations to solitude, especially as they gain Power Incontinence. One telepath with such a problem might have been inspired by Dan Simmons. See below.
- In Bleach, the Big Bad allegedly suffers from a bad case of this, and all his acts of violence and cruelty were his way to reach out to others, and find an equal.
- Death Note, like Code Geass, has its movers and shakers be extreme loners, out of Intelligence Equals Isolation mostly.
- Naruto is mostly about how a kid who was lonely and hated by all overcomes this and grows up into an international hero with (almost) 100% Adoration Rating. It took lots of work.
- In One Piece There are very few examples of this among the Loads and Loads of Characters: almost everyone has True Companions, deep, personal friends, a shoulder on which to cry or to cheer, and most people are very open about their emotions. Nevertheless, there's at least Captain Kuro (who treated his crew as expendable pawns and did not reciprocate their loyalty), Crocodile (same deal), Nico Robin (same deal, but caused by having been branded Public Enemy Number One at age eight and through no fault of ther own) and the Thunder God Eneru. All except Robin were sociopaths.
- Harry Potter had a bad case of this until he went to Hogwarts, mostly thanks to the efforts of his abusive foster parents. When he joins the school, he almost-immediately makes one friend and one enemy. And, later on, made another, who also had a case of this (again through Intelligence Equals Isolation plus a Lisa Simpson level of preachiness). From then on, though, they bond with lots of new people, for better or for worse.
- The Simpsons: Lisa Simpson is always alone. Even the audience hates her. Once, Homer became smart for a while, and they truly bonded for the first time, but then he had to be a coward and go back to being stupid, because he thought it was more enjoyable.
- The Rage Comics featuring Forever Alone guy take this trope to its most ridiculous extremes: usually it's his own failings (despite his best intentions) that prevent him from making friends or entering a (reciprocal) romantic relationship, in spite of (or often because of) his or her eagerness to relate to others. But sometimes it seems like the Universe goes out of its way to ensure that his Loneliness remains Chronic. This is to the point that Philosoraptor once wondered: "If Rule Forty Three has no exceptions, will Forever Alone Guy ever get laid?".Presumably, the paradox would be resolved by having him hire a prostitute. The comic would present her as a normal girlfriend, then the punchline woud be the payment.
- Mahou Shoujo Madoka Magica: Mami's wish was not to die alone. She lived for a long time after. She was so eager to make friends, she put that before said friends' personal safety. Then she died. Kyoko was... in a similar situation to Mami's, but unlike her, she actively drove people away. Homura had a version of this trope due to being a Shrinking Violet. Then very very spoilery things happen. Let's just say that her entire character is deeply, deeply entrentched in this trope. In general, this is a trouble Magical Girls have (had?) to struggle with in that verse.
- Dan Simmons had a novel called The Hollow Man, about a man who is helplessly telepathic. Because of this condition, he purposefully is a hermit, trying to live as far away as possible from other people, since he doesn't want to be hearing their thoughts all the time.
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