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do Custom Lights need new setup?

It really depends on each instrument, on the temperature, humidity, construction of your neck. I don't think anyone can give you a sure answer.

The question is :

Will your neck move because of the changed tension?

On most instrument I would guess that it would not make a huge difference. Anyway, if your neck moves, it's a 30 second fix with the truss rod.

I would try them without worrying too much if I were you.
 
Sorry, I have always had the same gauge strings on this instrument.. can you tell me what I should be looking out for as far as problems go? action has changed? pickups not picking up evenly across strings, harmonics/12th fret don't match the open string? all of the above?

Thanks for the help!