The 52-year-old actor portrays identical twins in 'I Know This Much Is True' but the characters have very different appearances because of their completely different lives.
Mark first filmed his scenes as Dominic for 15 weeks then shooting stopped on the HBO miniseries while he transformed his body to play schizophrenic Thomas, who has been on medication for years.
He explained at the TV Critics Association Winter Press Tour: "We didn't want it to be like I run and throw a wig on and do the same scene in the same day, so we took six weeks off to really separate these two guys.
"And Thomas is on medication, mood stabilisers and anti-psychotics. A lot of people put on weight."
And Mark found the time off tougher than he thought, as he also used the time to study what his character would have been experiencing, including hearing voices inside his head.
He added: "Those five weeks were really kind of lonely.
"Putting on the weight for Thomas was really challenging. I didn't expect it to be.
"I thought I was going to have a fun time doing that, but when you're force-feeding yourself, some of the romance of food sort of leaves."
The actor admitted he was "really afraid" of the role because he wanted to depict Thomas' struggles honestly and accurately so felt a lot of "responsibility" to get it right.
He said: "It means a lot to me to be honest with that, which means going into that world and getting to know it and getting comfortable with it.
"And that's challenging, and so that aspect of it was challenging...I was really afraid to play him. I think it's really an important issue, and I want to tell it as honestly as possible. The responsibility is on me."
Mark's 'Avengers: Endgame' co-star Paul Rudd recently undertook a similar task, playing two characters in 'Living With Yourself' but they didn't "compare notes" about their approaches.
Mark said: "He's amazing in that. We didn't compare notes, but he's great in that. He's great in everything, goddammit."