Oxytocin's role in anxiety: a critical appraisal.

A growing literature suggests that the oxytocin (OT) system may play a role in human anxiety states, anxiety-related traits, and moreover, that this system may be a target for the development of novel anxiolytic treatments. However, studies of OT's acute and chronic effects on various aspects of anxiety have produced mixed results. In this forward-looking review, we discuss the myriad phenomena to which the term "anxiety" is applied in the OT literature and the problem this presents developing a coherent picture of OT's role in anxiety. We then survey several different fields of research that support the role of the OT system in human anxiety, including evolutionary perspectives, translational and neuroimaging research, genetic studies, and clinical trials of intranasal OT. As an outgrowth of this data, we propose a "bowtie" model of OT's role at the interface of social attachment and anxiety. We next direct attention to understudied brain regions and neural circuits which may be important to study in OT experiments in humans anxiety disorders. Finally, we conclude by proposing questions and priorities for studying both the clinical potential of OT in anxiety, as well as mechanisms that may underlie this potential. Crucially, these priorities include targeted proof-of-concept clinical trials of IN OT in certain anxiety disorders, including investigations of individual moderators of OT's anxiolytic effects (i.e. sex, genetic factors, and early experience). This article is part of a Special Issue entitled Oxytocin and Social Behav.