Understanding Human Fear Extinction: Insights from Psychophysiology.

The study of fear extinction has been driven largely by Pavlovian fear conditioning methods across the translational spectrum. The primary methods used to study these processes in humans have been recordings of skin conductance (historically termed galvanic skin response) and fear-potentiation of the acoustic startle reflex. As outlined in the following chapter, the combined corpus of this work has demonstrated the value of psychophysiology in better understanding the underlying neurobiology of extinction learning in healthy humans as well as those with psychopathologies. In addition, psychophysiological approaches, which allow for the preservation of methods between species, have shown their applicability to the assessment of wide-ranging treatment effects. The chapter concludes with potential trajectories for future study in this area.

Pituitary Adenylate Cyclase Activating Peptide and Post-traumatic Stress Disorder: From Bench to Bedside.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with isoforms consisting of either 27 or 38 amino acids. PACAP is encoded by the adenylate cyclase activating peptide gene, ADCYAP1, in humans and the highly conserved corresponding rodent gene, Adcyap1. PACAP is known to regulate cellular stress responses in mammals. PACAP is robustly expressed in both central nervous system (CNS) and peripheral tissues. The activity of PACAP and its selective receptor, PAC1-R, has been characterized within the hypothalamic-pituitary-adrenal (HPA) axis and autonomic division of the peripheral nervous system, two critical neurobiological systems mediating responses to stressors and threats. Findings from previous translational, empirical studies imply PACAP regulation in autonomic functions and high expressions of PACAP and PAC1 receptor in hypothalamic and limbic structures, underlying its critical role in learning and memory, as well as emotion and fear processing. The current review summarizes recent findings supporting a role of PACAP/PAC1-R regulation in key brain areas that mediate adaptive behavioral and neurobiological responses to environmental stressors and maladaptive reactions to stress including the development of fear and anxiety disorders.

An analysis of fear inhibition and fear extinction in a sample of veterans with obstructive sleep apnea (OSA): Implications for co-morbidity with post-traumatic stress disorder (PTSD).

Obstructive sleep apnea (OSA) is a respiratory condition characterized by interrupted sleep due to repeated, temporary collapse of the soft tissue of the upper airway that can lead to a cascade of physiological and psychological adverse health outcomes. The most common therapeutic interventions for OSA patients include the application of continuous positive airway pressure (CPAP) which acts to keep the airway open and, as such, provides less interrupted and more restorative sleep. Improved sleep has been linked to more efficacious treatments for psychiatric conditions most notably those that include cognitive-behavioral elements, new learning, and memory consolidation. In the current study, we investigated the acquisition, inhibition, and extinction of conditioned fear in OSA patients, before and after CPAP therapy, using an established fear-potentiated startle paradigm. Patients with OSA displayed an intact ability to acquire, inhibit, and extinguish fear prior to CPAP treatment and this ability was significantly enhanced following CPAP usage. In addition, those patients with more severe OSA, as measured by apnea-hypopnea index (AHI), were more likely to show improved fear inhibition and extinction. Lastly, we observed impairments in discrimination between reinforced and nonreinforced conditioned stimuli, in the inhibition of fear, and in fear extinction in a subset of patients with OSA and co-morbid posttraumatic stress disorder (PTSD). These data suggest that evolving treatment algorithms for PTSD should address disrupted sleep problems prior to initiation of inhibition/extinction-based exposure therapies.