title: From Pavlov to PTSD: the extinction of conditioned fear in rodents, humans, and anxiety disorders.
abstract: Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a neutral cue to predict a biologically relevant event: after repeated predictive pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a bell, which caused them to salivate. Like sustenance, danger is biologically relevant, and neutral cues can take on great salience when they predict a threat to survival. In anxiety disorders such as posttraumatic stress disorder (PTSD), this type of conditioned fear fails to extinguish, and reminders of traumatic events can cause pathological conditioned fear responses for decades after danger has passed. In this review, we use fear conditioning and extinction studies to draw a direct line from Pavlov to PTSD and other anxiety disorders. We explain how rodent studies have informed neuroimaging studies of healthy humans and humans with PTSD. We describe several genes that have been linked to both PTSD and fear conditioning and extinction and explain how abnormalities in fear conditioning or extinction may reflect a general biomarker of anxiety disorders. Finally, we explore drug and neuromodulation treatments that may enhance therapeutic extinction in anxiety disorders.
authors: Tufts University Psychology, 490 Boston Avenue, Medford, MA 02155, USA; Massachusetts General Hospital Psychiatry, 149 Thirteenth Street, Charlestown, MA 02129, USA. Electronic address: michael.vanelzakker@gmail.com.
authors: Michael B
authors: MB
authors: VanElzakker
authors: Tufts University Psychology, 490 Boston Avenue, Medford, MA 02155, USA; Massachusetts General Hospital Psychiatry, 149 Thirteenth Street, Charlestown, MA 02129, USA.
authors: M Kathryn
authors: MK
authors: Dahlgren
authors: Massachusetts General Hospital Psychiatry, 149 Thirteenth Street, Charlestown, MA 02129, USA.
authors: F Caroline
authors: FC
authors: Davis
authors: Tufts University Psychology, 490 Boston Avenue, Medford, MA 02155, USA.
authors: Stacey
authors: S
authors: Dubois
authors: Tufts University Psychology, 490 Boston Avenue, Medford, MA 02155, USA; Massachusetts General Hospital Psychiatry, 149 Thirteenth Street, Charlestown, MA 02129, USA.
authors: Lisa M
authors: LM
authors: Shin
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D003214:Conditioning, Classical / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D006801:Humans; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics / Q000503:physiopathology / Q000628:therapy
keywords: Amygdala; Anxiety; Fear conditioning; Fear extinction; Posttraumatic stress disorder; Prefrontal cortex; Treatment