Regressor Zoro + the two year separation
After being separated from everyone I think the first while of staying on Kuraigana would have been when it hit Zoro the hardest. He'd been alone for so long before the Straw Hats and then suddenly there were people, people who cared about him and as much as he didn't know how to show it he cared deeply about them and wanted to protect them as much as he could. And then he was the first one to get sent away by Kuma's power. He had no way of knowing what happened to everyone else and the only way he found out they were all safe (assumedly) was through Luffy's message
But he was alone again. Yes, there was Mihawk and Perona but he wasn't close with either, and going off the fact that Mihawk lives in such a large castle he was for sure sleeping alone again and all the empty space only served to enhance that feeling. He'd finally known what it was like to have people care about him only to be alone again knowing how it felt to sleep surrounded by people he trusted, and now knowing how it felt to miss them.
I think he regressed a few times during those two years, once at the very start, once after he lost his eye, and once nearing the end of the two years.
The first time he regressed was a result of just everything that had been building up hitting at once. There had been so much happening ever since thriller bark from him hiding how bad his injuries were, to being the first sent away during Sabaody, and then knowing he couldn't have been there to help Luffy during and after Marineford and everything just piled up resulting in him regressing while Perona was dressing his wounds. That mixed with his current condition, injured and unable to move very much, resulted in him regressing young. For a while he just cried out of frustration as much as he didn't want to in front of Perona and as much as she would try to help they really didn't know each other and she really couldn't do much aside from try to understand and let him get it out.
The second time does stem from a fan comic I am no longer able to find so I do hope my point comes across without it. It was a comic about Zoro losing his eye to Mihawk during training and how it could have gone down and its so canon to me because it's a very in character view of it which is why I really do wish I could find it again. Either way, the point of it is that Zoro loses his eye when he doesn't limit himself in his training and tries to push Mihawk to keep going as he can still go on and wants to keep pushing himself. In retaliation and to show Zoro he isn't at the point to do so yet Mihawk slashes Zoros eye.
Headcanons about how it happened aside though, no matter how it went down he would regress. Be it once the shock wore off, or while Perona was once again tending to the injury like she had been doing for all his injuries he'd been getting during training, he would regress. It wouldn't be over losing his eye, to him it doesn't matter that he lost it (at least until the reality of this being something that has left him essentially disabled until he learns observation haki (I could talk about this so much do not let me) and will take a good while to adjust to sets in) as he could still breathe and fight which was all that mattered to get stronger. So while he wouldn't regress over the loss of his eye it would cause a short bout of doubt that he wouldn't be able to come back stronger for the crew as he hadn't been enough to stop himself from pushing too hard and this loss from happening.
By this time him and Perona have gotten closer and come to care for each other in their own ways (I would very much recommend going to read the One Piece Heroines novel chapter 4 long summary here to get an idea of this as its not yet translated into English officially and check here for a rough fan translation for a better idea of it) and she would be at least able to support him this time having more of an idea of what's going on this time until he comes back to his senses and learns from it.
Perona, despite getting annoyed at Zoro a lot over his lack of self care, self preservation, and sense of direction, manages to do pretty well at taking care of him. Once Zoros initial crying and anxieties calm down she finally gets to see the side of him that just hasn't had any care and has come to trust her as someone who he can let himself be taken care of by.
Finally, he would regress one last time during the two years. This would happen maybe a few months before the end of them, a mix of missing the crew from being separated for so long while also knowing it's almost time to see them again. Once again this is the point where going forward this is more for my AU rather than general headcanons so it pertains more to future fics. It wouldn't be anything too much and it would be more of a quiet regression where he would find a place to hide away for a while because this is also where he fully decides that to come back stronger this is something he cannot do anymore. The whole point of the two year separation was for them all to come back stronger and to him regressing was something he needed to leave behind to do so.
