I tried Drain or Damage of an attribute or skill, and that didn't work so well--I get the constant red throbbing screen and it doesn't really permanently work right anyhow. There are a lot of advantages I can put in, Fortifying this or that or giving Night Eye, Feather, and so on. But going through the entire list of spell effects, and testing many of them, I have found only a few disadvantages I can give a character.
Blind
Burden
Stunted Magicka
Weakness to disease, magicka, fire, etc.
That's about it. I can throw in Sun Damage on a birthsign but if I do that to, say, Dark Elves, then there's an awful lot of dead Dark Elves lying about in the game.
I would like to be able to permanently limit a given character's Intelligence, or Speechcraft, or such, and I don't know if that is even possible or if it has already been done.
I am entirely an amateur modder, having made extensive mods for myself but none that anyone else would want to bother with, so I know a bit but I haven't a clue about scripting or some of the more exotic sorts of things.