I used to write resumes for graduating students, and I can say that when you have a long gap in your employment history, sure, you'll probably have to explain it. And yes, if you do so honestly I'd be surprised if you didn't run into prejudice about your condition. If I were in your situation I'd be up front about it, and maybe counter some of the seriousness with light humor, although not excessively self-deprecating.
Then again, I've never had to deal with this. Has anyone here? What they have to say would be of a lot more value than what I think.
-=Steve=-