I mean, when I was at my absolute peak fitness and health, I was still medically obese - but by most measures in perfect health. Would I be different in Star Trek's future?

Yes, exactly!

Is it because the world has been made even more hostile to disabled bodies and he literally can't move around outside? Is it because the perfect mind can still be depressed?

Good questions.

I haven't encountered many mutants who aren't Super in my forays into the Xmen universe, but I can see how they could be interesting.