Absence Makes the Mind Grow Fonder: Reconceptualizing Studies of Safety Learning in Translational Research on Anxiety.

Overgeneralized fear (OGF), or indiscriminate fear responses to signals of threat and nonthreat, is a well-studied cognitive mechanism in human anxiety. Anxiety-related OGF has been studied primarily through fear-learning paradigms and conceptualized as overly exaggerated learning of cues signaling imminent threat. However, the role of safety learning in OGF has not only received much less empirical attention but has been fundamentally conceptualized as learning about the absence of threat rather than the presence of safety. As a result, the relative contributions of exaggerated fear learning and weakened safety learning to anxiety-related OGF remain poorly understood, as do the potentially unique biological and behavioral underpinnings of safety learning. The present review outlines these gaps by, first, summarizing animal and human research on safety learning related to anxiety and OGF. Second, we outline innovations in methods to tease apart unique biological and behavioral contributions of safety learning to OGF. Lastly, we describe clinical and treatment implications of this framework for translational research relevant to human anxiety.