Neural Mechanisms of Impaired Fear Inhibition in Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) can develop in some individuals who are exposed to an event that causes extreme fear, horror, or helplessness (APA, 1994). PTSD is a complex and heterogeneous disorder, which is often co-morbid with depression, substance abuse, and anxiety disorders such as panic or social phobia. Given this complexity, progress in the field can be greatly enhanced by focusing on phenotypes that are more proximal to the neurobiology of the disorder. Such neurobiological intermediate phenotypes can provide investigative tools to increase our understanding of the roots of the disorder and develop better prevention or intervention programs. In the present paper, we argue that the inhibition of fear responses is an intermediate phenotype that is related to both the neurocircuitry associated with the disorder, and is linked to its clinical symptoms. An advantage of focusing on fear inhibition is that the neurobiology of fear has been well investigated in animal models providing the necessary groundwork in understanding alterations. Furthermore, because many paradigms can be tested across species, fear inhibition is an ideal translational tool. Here we review both the behavioral tests and measures of fear inhibition and the related neurocircuitry in neuroimaging studies with both healthy and clinical samples.