Learning models of PTSD: Theoretical accounts and psychobiological evidence

Abstract

Learning abnormalities have long been centrally implicated in posttraumatic psychopathology. Indeed of all anxiety disorders, PTSD may be most clearly attributable to discrete, aversive learning events. In PTSD, such learning is acquired during the traumatic encounter and is expressed as both conditioned fear to stimuli associated with the event and more general over-reactivity—or failure to adapt—to intense, novel, or fear-related stimuli. The relatively straightforward link between PTSD and these basic, evolutionarily old, learning processes of conditioning, sensitization, and habituation affords models of PTSD comprised of fundamental, experimentally tractable mechanisms of learning that have been well characterized across a variety of mammalian species including humans. Though such learning mechanisms have featured prominently in explanatory models of psychological maladjustment to trauma for at least 90 years, much of the empirical testing of these models has occurred only in the past two decades. The current review delineates the variety of theories forming this longstanding tradition of learning-based models of PTSD, details empirical evidence for such models, attempts an integrative account of results from this literature, and specifies limitations of, and future directions for, studies testing learning models of PTSD.

On the Road to Translation for PTSD Treatment: Theoretical and Practical Considerations of the Use of Human Models of Conditioned Fear for Drug Development

“…Relative to healthy controls, PTSD patients as well as panic disorder and generalized anxiety disorder patients show shallow fear generalization gradients, indicating overgeneralization of conditioned fear (Lissek et al 2010(Lissek et al , 2014aLissek and van Meurs 2014). These data are in line with findings that subjects with PTSD do not show physiological discrimination between CS+ and CS− cues, even though they report contingency awareness perfectly accurately (Acheson et al 2015b;Jovanovic et al 2012).…”

“…Unsurprisingly, the disorder is associated with implicit and explicit strategies for cue avoidance, which can be disruptive to daily function and interfere with long-term recovery. Thus, PTSD may be caused at least in part by disruption in one or more elements of the learned fear process (Lissek and van Meurs 2014). Here, we will describe common laboratory-based measures of these processes, their relationship to symptom clusters and predictive validity for subsequent clinical trials if available, response to pharmacological treatment in both controls and PTSD patients, and considerations of their use in drug development studies.…”

Decreased uncinate fasciculus tract integrity in male

“…Furthermore, the uncinate fasciculus connects the (lateral) prefrontal cortices to the hippocampus, a structure important for contextualizing, including discriminating between threatening and safe contexts. 50 Posttraumatic stress disorder has been associated with dysregulations in context processing, 51 such as enhanced fear generalization 52 and impaired contextual extinction learning 3 and safety learning. 53 Notably, these processes of contextualization depend on the hippocampus and its communication with the prefrontal cortex.…”

Oxytocin Facilitates Pavlovian Fear Learning in Males

“…More specifically, we examined whether the seemingly contradictory findings were based on OXT's facilitation of two separate learning processes, namely, the learning of negative and avoidance behaviors compared with positive, prosocial behaviors. According to one model of fear conditioning and extinction as being two competing processes, the stronger of the two processes overrides and thus inhibits the other (Lissek and van Meurs, 2014). Given our previous findings that OXT prior to extinction learning increased fear extinction, we hypothesized that it could also increase fear learning if given prior to conditioning.…”