I've been thinking about what Shura said about Shiro changing after he started taking care of the Okumura twins. We saw that when Shiro was forced into taking care of a kid previously, he tolerated her until he could dump her in an orphanage. He was a cold guy. Later on he took in the Okumura twins, who are pretty clearly adopted.
I wonder if the only reason Shiro took in the twins is because they were Yuri's children.
*All on-board the crack theory train!
What if Shiro loved Yuri, but that love wasn't reciprocated? To her, he was only a friend. She made it clear she didn't love him and was mad that he persisted in having romantic interest on her. Maybe, she went on a ill-fated mission one day. There were signs it wouldn't go well, but she was stubborn about gong. When he tried to stop her, she yelled at him "don't ever call yourself my friend again!" That was the mission where Satan raped her.
Then, years later, Shiro gets into an argument with Yuri's son who finally yells "don't ever call yourself my father again". In that moment it all comes right back to him, and he snapped.