Since he was a teenager he has been fighting untill the current events, allies coming and going.
But the one that always was with him throughout the entire campaign, the one that was given to him to be his one and only companion, the one to eliminate his loneliness was Cortana.
Losing her must've had a tremendous impact on him and somewhere beneath that Mark VI armor he's still a human being. No training, indoctrination or containment can take that out of you unless they turn you into an actual machine.
At the end of Halo 4 you see that he's devestaded even though he's trying to hide it and if he's found any way to bring his lifelong companion back... What would you have done?