Clinical meaning
Post-traumatic stress disorder (PTSD) results from maladaptive neurobiological responses to traumatic experience, involving hyperactivation of the amygdala (threat detection and fear conditioning), hypoactivation of the medial prefrontal cortex (mPFC — impaired fear extinction and emotional regulation), and hippocampal volume reduction (impaired contextual memory processing, inability to distinguish past trauma from present safety). The HPA axis is paradoxically hypoactive in PTSD (low cortisol despite elevated CRH), contrasting with the hypercortisolism of depression — this may explain enhanced fear memory consolidation. The noradrenergic system is hyperactive (elevated norepinephrine from locus coeruleus), contributing to hyperarousal, exaggerated startle, insomnia, and nightmares. Trauma memories are stored as sensory and emotional fragments rather than coherent narratives, leading to re-experiencing symptoms (flashbacks, intrusive memories, nightmares). PTSD diagnostic criteria (DSM-5-TR) require exposure to actual/threatened death, serious injury, or sexual violence, plus symptoms in four clusters persisting > 1 month: intrusion/re-experiencing, avoidance, negative cognitions/mood alterations, and arousal/reactivity changes. Evidence-based treatments include trauma-focused psychotherapies (prolonged exposure therapy, cognitive processing therapy, EMDR) as first-line, and pharmacotherapy (SSRIs — sertraline and paroxetine are FDA-approved; SNRIs — venlafaxine) as first-line medications. Prazosin (alpha-1 antagonist) specifically targets trauma-related nightmares by blocking noradrenergic activation during sleep.