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Repetitive negative thinking (RNT) about self-referential information is a transdiagnostic cognitive vulnerability factor that may account for the relationship between these two classes of symptoms. We propose a model where negative self-referential processing and cognitive inflexibility interact to increase risk for RNT, leading to internalizing problems in ASD. Examination of interactions within and between two well-characterized large-scale brain networks, the default mode network and the salience network, may provide insights into neurobiological mechanisms underlying RNT in ASD. We summarize previous literature supporting this model, emphasizing moving toward understanding RNT as a factor accounting for the high rates of internalizing problems in ASD. 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