Ockham's Spoon

Giving a movie villain a PhD works well regardless of your audience.
 
People without a PhD: "Oh, they are showing that the villain is really smart.  Makes sense."
 
People with a PhD: "Ah, grad school and academia drove him to madness.  Makes sense."

In my mind the real question is what does it mean for characters to lose their humanity?  Do they become amoral killers? Do they start growing scales and tentacles?  Is the condition fatal or do they just become something else?  Once you nail down exactly what it means to lose their humanity, you can assign mechanical effects in gaming terms, using some of the excellent suggestions already put forth.

My wife and daughter were having a philosophical discussion as to whether the body was ruled by the head or the heart.  They asked me what I thought, and I said "Neither.  The body is ruled by the bladder, and it is a tyrant."

I was talking to this old man I know and I asked him, "After 60 years of marriage, you still call your wife sweetheart, dear, darling. What's your secret?"
 
He said, "I forgot her name 10 years ago and I'm afraid to ask."

I went to the zoo yesterday, but the only animal they had was a dog.
 
It was a shih tzu. 

Especially coming from Bones, I thought it was the He's Dead Gym.