I think getting a position he wanted while he was healthy, then being unable to actually function in the position without someone telling him how to vote and when. Being entirely unable to participate in debates on the floor of the Senate, etc. has forced a man who normally would be thoroughly enjoying his new job into a severe depression. (I'm basing this on how I would feel in the same position as he is in).
I still predict that Fetterman will not serve a full 6 years. They'll want someone who has the ability to use the language and understand questions to run next time, they won't be running against a carpetbagger "celebrity" and will want a chance to win.