Imagine this: You volunteer to go on a rescue mission to not only discover the ship infested with the most horrific kinds of monsters that the imagination can conjure, but that it's all part of a larger conspiracy involving a pseudo-cult that believes these monsters are the next phase of evolution. Oh wait, it gets worse. You manage to escape with your life, destroy the giant marker device that drove everyone insane and led to this mess, and find yourself suffering from delusions and severe mental trauma as a result. Finally, once you make it back to civilization, the first thing anyone does is lock you up because they're convinced you're crazy and that these 'Necromorphs' are just figments of your damaged mind.
This is Isaac Clarke's situation at the beginning of Dead Space 2. The real problem for him, and everyone else for that matter, is that just because he's losing his mind doesn't mean he's not right.