Neuropeptide Y (NPY) and posttraumatic stress disorder (PTSD): A translational update

Posttraumatic stress disorder (PTSD) is a trauma-evoked syndrome, with variable prevalence within the human population due to individual differences in coping and resiliency. In this review, we discuss evidence supporting the relevance of neuropeptide Y (NPY), a stress regulatory transmitter in PTSD. We consolidate findings from preclinical, clinical, and translational studies of NPY that are of relevance to PTSD with an attempt to provide a current update of this area of research. NPY is abundantly expressed in forebrain limbic and brainstem areas that regulate stress and emotional behaviors. Studies in rodents demonstrate a role for NPY in stress responses, anxiety, fear, and autonomic regulation, all relevant to PTSD symptomology. Genetic studies support an association of NPY polymorphisms with stress coping and affect. Importantly, cerebrospinal fluid (CSF) measurements in combat veterans provide direct evidence of NPY association with PTSD diagnosis and symptomology. In addition, NPY involvement in pain, depression, addiction, and metabolism may be relevant to comorbidities associated with PTSD. Collectively, the literature supports the relevance of NPY to PTSD pathophysiology, although knowledge gaps remain. The NPY system is an attractive target in terms of understanding the physiological basis of PTSD as well as treatment of the disorder.