Neurobiological Mechanisms Underlying Hippocampal Dysfunction in Post-Traumatic Stress Disorder

Abstract: Post-traumatic stress disorder (PTSD) is a highly prevalent and debilitating condition that typically develops after exposure to severe trauma. Core symptoms include re-experiencing and avoidance of trauma memories, negative emotions and thoughts, and hyperarousal. The global lifetime prevalence of PTSD is approximately 6%, yet 40% of patients do not respond to traditional exposure therapies or pharmacological treatments. The unclear pathological mechanisms underlying PTSD have made it difficult to develop effective therapies. PTSD progression is often linked to impairments in fear memory formation, with the hippocampus, a key region of the limbic system, playing a crucial role in regulating this process. The hippocampus is involved in the amygdalahippocampus- medial prefrontal cortex circuit, one of the best-understood neural circuits associated with fear. Additionally, the neuroendocrine system influences and is regulated by the hippocampus, further affecting the development and progression of PTSD. In recent years, the integration of molecular genetic methods with insights into the mechanisms of hippocampal fear circuitry offers promising prospects for breakthroughs in PTSD diagnosis, treatment, and mechanism research. This review aims to systematically summarize the role of the hippocampus in PTSD, providing new ideas and strategies for advancing research and treatment approaches for this disorder.