An example of this would be having the villain put Twilight under the disillusion that her friends are not so much her friends anymore, but her subjects, and that they’d treat her differently/unfairly because of it.
 
With Twilight depressed at this, the villain would have Twilight under his/her thrall, and use her magic to do villainous things.
 
The lesson of that episode (probably a 2-parter) will have the lesson of change isn’t always pleasant to go through (especially if changes happen to a friend), but they’re still friends, no matter what changes take place.