The neuropeptide Y–autonomic–cardiovascular axis in military traumatic stress: Molecular mechanisms and translational implications for brain–heart crosstalk

Abstract

Military traumatic stress provides a distinctive human model for studying brain–heart crosstalk because it combines threat exposure, operational strain, sleep disruption, autonomic activation, endocrine stress responses, and cardiovascular load. Posttraumatic stress disorder (PTSD) in military and veteran populations is increasingly recognized not only as a psychiatric consequence of trauma but also as a condition associated with elevated cardiovascular vulnerability. However, the molecular mechanisms linking traumatic stress, autonomic dysregulation, and cardiovascular risk remain insufficiently defined. Neuropeptide Y (NPY), a stress-responsive neuropeptide widely distributed throughout central and peripheral tissues, may represent a key molecular node in this process. Centrally, NPY participates in fear regulation, anxiety modulation, stress recovery, and resilience. Peripherally, NPY acts as a sympathetic co-transmitter and influences vascular tone, endothelial function, myocardial remodeling, and cardiac electrophysiology. This review summarizes evidence supporting the NPY–autonomic–cardiovascular axis as a mechanistic framework for brain–heart maladaptation in military traumatic stress. We propose a dual-role model in which acute stress-related NPY mobilization, interpreted alongside separate central-circuit evidence, may support resilience and preserve performance under extreme stress, whereas chronic NPY dysregulation or excessive peripheral sympathetic NPY signaling may contribute to autonomic imbalance, vascular dysfunction, arrhythmia susceptibility, and long-term cardiovascular burden. Translationally, NPY should not be treated as a stand-alone biomarker. Its value will depend on integration with heart rate variability, catecholamines, inflammatory markers, genetic variation, wearable monitoring, deployment exposure, PTSD trajectories, and cardiovascular endpoints. Future longitudinal military cohort studies are needed to determine whether NPY predicts risk, serves as a marker of recovery, mediates autonomic maladaptation, or identifies modifiable intervention targets in brain–heart medicine.