Post-traumatic stress disorder is the clinical syndrome that develops after exposure to actual or threatened death, serious injury, or sexual violence. DSM-5 requires exposure plus symptoms from four clusters persisting beyond 1 month with functional impairment.
The four symptom clusters: (1) Intrusion — intrusive memories, nightmares, flashbacks, intense psychological distress to trauma cues, physiological reactivity to cues. (2) Avoidance — avoidance of trauma-related thoughts/feelings/external reminders. (3) Negative cognition and mood — inability to remember important aspects, persistent negative beliefs, persistent distorted blame, persistent negative emotional state, diminished interest, detachment, inability to experience positive emotions. (4) Hyperarousal — irritability, reckless behavior, hypervigilance, exaggerated startle response, concentration difficulty, sleep disturbance.
The circuit failure we built in Volume 1: amygdala over-active (false threat detection), hippocampus under-active (failed contextual safety updates), medial PFC under-active (reduced top-down regulation), locus coeruleus over-active (chronic hyperarousal). Each symptom cluster maps to a specific circuit failure. The four components have been characterized in functional imaging across multiple cohorts.
First-line treatments: trauma-focused psychotherapies — prolonged exposure (PE), cognitive processing therapy (CPT), eye movement desensitization and reprocessing (EMDR) — all have substantial evidence. The mechanism is reactivation of trauma memory in a safe context, allowing the hippocampus to deliver belated contextual updates to the amygdala. SSRIs (sertraline and paroxetine FDA-approved) and SNRIs reduce amygdala reactivity over weeks. Combined treatment outperforms either alone for moderate-severe cases.
Adjunctive medications for specific symptoms: Prazosin (alpha-1 antagonist) is specifically effective for nightmares — reduces noradrenergic tone from locus coeruleus during sleep. Start 1 mg at bedtime, titrate to 10-16 mg as needed. Beta-blockers for autonomic hyperarousal. Antipsychotics at low dose for severe agitation or dissociation, with caution.
Emerging treatments: MDMA-assisted psychotherapy is in late-stage trials and has shown remarkable effect sizes — appears to facilitate trauma processing by reducing fear while preserving cognitive access. Ketamine for treatment-resistant PTSD has growing evidence. Stellate ganglion block being studied for autonomic hyperarousal symptoms.
When you encounter a patient with PTSD, the treatment toolkit is broad and effective. Most patients improve substantially with structured trauma-focused therapy plus appropriate pharmacology. The neurobiology is reversible — amygdala reactivity normalizes, hippocampal function returns, top-down PFC control rebuilds. The war can end, mechanistically and clinically.