Director reveals she suffered depression and hoped she would die rather than confront her issues. In an interview with the New Yorker, she says she feared she would be rejected by her family on revealing her identity as a woman, and suffered depression during the production of 'The Matrix', which she directed with her brother Andy.
There might be more difficult things BUT I don't know what that might be - to be born w/ a body that doesn't match what you feel you are. I have watched several people, most recently Chaz Bono, who have transitioned to the other sex & can't imagine how hard that would be. You really have to give these people a lot of admiration.