It's the little things that give it away. The fact that he never smiles anymore, no matter how many stupid jokes Dean makes. It's the extra time he takes in the bathroom with the locked door and the water running. It's the way his body stiffens when the news comes on, just waiting to hear about yet another hurricane or an earthquake or a river turning to blood - another proof of apocalypse; as if they needed one. It's the fact that the only time he seems alive, engaged is when they're deep in a new case; the way he buries himself so completely in every little detail of the job, regardless of how simple or complicate it is. But mostly, it's those rare moments between cases when he stares off into space, when he doesn't think Dean's watching. That's when Dean sees it.
Sam's drowning.
So Dean digs in deeper and does whatever it takes to pull him back up - a stupid joke, a trip to the bar, a new case - anything to make Sam come to life again. Because the alternative is not something he ever wants to experience again.
