For those of you not familiar with Tweek, allow me to explain his character in the show itself. Tweek is a nervous, paranoid, and slightly schizophrenic boy who mainly focuses on the negatives, and always is afraid for the worst outcome of an situation. I view his story a bit differently. Tweek's troubled behavior in the show has led me to the theory that Tweek was once a ordinary, yet shy person. Mentally stable, but too afraid to talk with anyone except for his family. It is said in the show that coffee was the reason for his jittery behavior. However I believe that this was only a contributing factor. When Tweek is alone, he is calm (although jittery from the coffee). However, when confronted by people or forced into unwanted conversations, his schizophrenic personality kicks in, and he slowly starts to lose his mind.
My theory is this: After a forced playdate setup by Tweek's mother, Tweek was fully engulfed in his own insanity. This became such a burden and disturbance to his parents, that they decided to send Tweek to a mental institution. Tweek, while confined to the room where he was staying, thought of his own imaginary world, a world where he was accepted. A world where he could be calm. The imaginary place he imagined was South Park, Colorado. For a short time, Tweek felt safe there. Unfortunately, the inner workings of his insane mind started to work against him. Instead of a wondrous land where he could talk with other children and live a normal life, his mind turned it into a harsh reality-like world. Tweek knew he was insane. He knew he would never be accepted. In his mind, him being accepted was an unknown concept. For the rest of his life, he would be forced to live in a hell of an imaginary world of his own creation, where he came face-to-face with his fear: A social life.