Clinical meaning
PTSD results from a failure of normal fear extinction following exposure to a traumatic event. The amygdala becomes hyperreactive, generating exaggerated fear and threat responses to trauma-associated cues. The medial prefrontal cortex (mPFC), which normally inhibits amygdala activity during fear extinction, shows hypofunction in PTSD, resulting in impaired ability to suppress conditioned fear responses. The hippocampus, critical for contextualizing memories (distinguishing past trauma from present safety), undergoes volume reduction from chronic glucocorticoid neurotoxicity, impairing memory consolidation and producing fragmented, intrusive trauma memories. The HPA axis paradoxically shows enhanced negative feedback (low basal cortisol with exaggerated cortisol suppression on dexamethasone test) and sympathetic nervous system hyperactivation (elevated norepinephrine, exaggerated startle). Noradrenergic hyperactivation from the locus coeruleus drives hyperarousal symptoms and consolidation of traumatic memories, which is why alpha-1 adrenergic blockade with prazosin can reduce trauma-related nightmares.