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It's not that they are mentally sick (although it's funnier to say it this way) but it does alter their behavior. Basically their relation with anguish, hatred, power and chakra is a vicious circle : their anguish and pain directly translate into more power and stronger/darker chakra which in turn increase their hatred which lead to even more power, etc.
The fact that Senju DNA seems to increase all Uchiha traits could even explain an extreme case like Obito who changed from a good guy to a maniac virtually instantly.
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