Fear and safety learning in anxiety- and stress-related disorders: An updated meta-analysis

Fear learning processes are believed to play a crucial role in the development and maintenance of anxiety and stress-related disorders. To integrate results across different studies, we conducted a systematic meta-analysis following PRISMA guidelines to examine differences in fear conditioning during fear acquisition, extinction, and extinction recall between individuals with anxiety-related or stress-related disorders and healthy participants. This analysis updates the work of Duits et al. (2015) while also refining distinctions between physiological and behavioral outcomes and examining extinction recall. Our meta-analysis encompasses 77 studies published from 1986 to 2022, involving 2052 patients with anxiety disorders, obsessive-compulsive disorder, or post-traumatic stress disorder, and 3258 healthy controls. The results indicate significant differences in fear acquisition, extinction, and recall between the two groups. Specifically, during acquisition patients exhibited heightened physiological and behavioral responses to the CS- and reported increased affect ratings for the CS+ . During extinction and extinction recall, patients continue to show heightened threat expectancy and negative affect ratings towards the CS- and increased affect ratings towards the CS+ . No differences were found in CS+ /CS- differentiation between groups. These findings imply that individuals with anxiety and stress-related disorders may exhibit amplified responses to safety cues and stronger reactions to threat cues during fear conditioning, lasting through extinction and extinction recall. These changes may lead to increased sensitivity in detecting fear and slower extinction process, resulting in more enduring anxiety responses. We discuss these results in the context of existing literature on fear and safety learning and consider potential underlying mechanisms.