Laboratory models of post-traumatic stress disorder: The elusive bridge to translation

Abstract

Post-traumatic stress disorder (PTSD) is a debilitating mental illness composed of a heterogeneous collection of symptom clusters. The unique nature of PTSD as arising from a precipitating traumatic event helps simplify cross-species translational research modeling the neurobehavioral effects of stress and fear. However, the neurobiological progress on these complex neural circuits informed by animal models has yet to produce novel, evidence-based clinical treatment for PTSD. Here, we provide a comprehensive overview of popular laboratory models of PTSD and provide concrete ideas for improving the validity and clinical translational value of basic research efforts in humans. We detail modifications to simplified animal paradigms to account for myriad cognitive factors affected in PTSD, which may contribute to abnormalities in regulating fear. We further describe new avenues for integrating different areas of psychological research underserved by animal models of PTSD. This includes incorporating emerging trends in the cognitive neuroscience of episodic memory, emotion regulation, social-emotional processes, and PTSD subtyping to provide a more comprehensive recapitulation of the human experience to trauma in laboratory research.

Figure 1.

A schematic comparing how fear transfers to a wide variety of stimuli in a simplified laboratory-based fear learning and a real-world example aversive experience. The complex nature of how fear associations spread to idiosyncratic details associated with trauma complicates efforts to map simplified experimental protocols of direct CS-US learning to real-world manifestations of learned fear.

Figure 2.

Examples for how seemingly small changes in the presentation of conditioned and unconditioned stimuli can affect the ability to learn fear and safety. These subtle nuances are detailed in the associative learning literature, but basic research evaluating these effects in clinical populations, particularly PTSD, is lacking.