The Oscar-nominee's grandpa, writer Ernest Hemingway, committed suicide just months before she was born, her model sister Margaux overdosed in 1996, and her youngest sibling, Joan, has been in and out of psychiatric institutions for years.
A total of five other relatives also took their own lives, and the Manhattan star admits she worried she was destined to follow in their footsteps as she started struggling with her own demons.
Breaking her silence on her cursed family legacy in new film Running from Crazy, she tells the Associated Press, "Some people are like, 'Wow, that's a heavy title.' Well, I don't see it as a heavy title. I'm like, 'Dude, thank God.' Crazy's gone... There's fun in my life and I'm joyful. But there was a time when I really was not... But I truly am no longer depressed. It's gone. I can honestly say that it's been years. I laugh at myself now, which is fun."
And director Barbara Kopple is glad Mariel is going public with her story so others can recognise a pattern of unhealthy thoughts and get help: "She's the dream of a documentarian, because you sit at the table with her and talk to her, and everything comes out, because she has a higher purpose for it.
"She really wants to shed light on suicide and mental illness. If people see that she's doing it and how she has constructed such a healthy, wonderful lifestyle, that they can do it too."