Post-traumatic stress disorder and cardiometabolic dysfunction: Molecular mechanisms and therapeutic targets

Post-traumatic stress disorder (PTSD) is a complex psychiatric condition affecting approximately 6.1% of the US population and is characterized by intrusive memories, trauma avoidance, emotional dysregulation, and hyperarousal. The disorder is associated with significant neurobiological changes, including structural and functional alterations in key brain regions such as the amygdala, hippocampus, corpus callosum, prefrontal cortex, and premotor cortex. Neurologically, PTSD is marked by heightened amygdala activity, reduced ventromedial prefrontal cortex activation, and significant cognitive impairments, particularly in verbal and autobiographical memory. Physiological dysregulation is evident in lowered cortisol levels, autonomic nervous system dysfunction, elevated sympathetic arousal, and systemic inflammation. Recent research has highlighted a critical, mutual relationship between PTSD and metabolic syndrome, with PTSD patients exhibiting increased susceptibility to cardiovascular disease and metabolic imbalances. These connections are mediated by complex neuroendocrine mechanisms, primarily involving activation of the sympathetic nervous system and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. This review examines emerging evidence linking PTSD with metabolic dysfunction, focusing on cardiovascular inflammation and the renin-angiotensin system. Understanding these intricate interactions is crucial for advancing comprehensive management strategies and identifying potential therapeutic interventions.