Social interaction is ubiquitous in human society. The two-person approach-a new, powerful tool to study information exchange and social behaviors-aims to characterize the behavioral dynamics and neural mechanisms of real-time social interactions. In this review, we discuss the benefits of two-person approaches compared to those for conventional, single-person approaches. We describe measures and paradigms that model social interaction in three dimensions (3-D), including eye-to-eye,

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... y, and brain-to-brain relationships. We then discuss how these two-person measures and paradigms are used in psychiatric conditions (e.g., autism, mood disorders, schizophrenia, borderline personality disorder, and psychotherapy). Furthermore, the advantages of a two-person approach (e.g., dual brain stimulation, multi-person neurofeedback) in clinical interventions are described. Finally, we discuss the methodological and translational challenges surrounding the application of two-person approaches in psychiatry, as well as prospects for future two-/multi-person studies. We conclude that two-person approaches serve as useful additions to the range of behavioral and neuroscientific methods available to assess social interaction in psychiatric settings, for both diagnostic techniques and complementary interventions.