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In the Ocean's 12, I remember the scene of Brad Pitt asking "What's wrong with you?" of Matt Damon, who had interrupted his sleep to ask a favor.

I think the phrase "What's wrong with you?" is more often used when someone scolds/blames somebody else for their wrongdoings rather than when they want to find existing problems (if this make sense).

Given the context, can I assume that Brad Pitt said it to show that he is irritated and actually showing his unpleasant feelings to Matt Damon?

Or was he just asking what problem Matt Damon has?

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It depends on the tone it's used with but generally it's meant as a sign or irritation. Think of it as short term for "what is wrong with you mentally that is causing you to say/Do these things that are so annoying/aggravating?"

If you want to know if something is wrong in a form of concern, then you'd simply use "What's wrong?". That way you're not blaming the person you're asking :)

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Very often, when a person has been annoyed by someone, and angrily asks "What's wrong with you?", the question is (a) a rebuke (b) rhetorical (an answer is not required). The question is not an enquiry about a person's health or wellbeing.

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