Which neurotransmitter system dysfunction is primarily implicated in the pathophysiology of panic disorder?

Explanation

## Neurobiological Basis of Panic Disorder **Key Point:** Panic disorder is fundamentally a disorder of dysregulated serotonergic and noradrenergic neurotransmission, particularly involving the amygdala, locus coeruleus, and prefrontal cortex. ### Serotonergic System - Hypofunction of 5-HT in the amygdala and prefrontal cortex leads to impaired fear extinction and threat appraisal. - SSRIs (first-line pharmacotherapy) work by increasing synaptic 5-HT, normalizing fear processing. ### Noradrenergic System - Hyperactivity of the locus coeruleus (the brain's main noradrenergic nucleus) drives the acute panic attack physiology. - Elevated NE correlates with sympathetic arousal: tachycardia, tremor, hyperventilation. - SNRIs (serotonin-norepinephrine reuptake inhibitors) address both systems. ### GABA System (Secondary Role) - While GABAergic dysfunction exists, it is not the primary pathology; benzodiazepines provide acute symptom relief but are not first-line due to dependence risk. **High-Yield:** The "fear circuit" in panic disorder involves: 1. Amygdala hyperactivity (threat detection) 2. Locus coeruleus overactivity (sympathetic drive) 3. Prefrontal cortex hypoactivity (impaired threat inhibition) **Clinical Pearl:** This is why SSRIs/SNRIs take 2–4 weeks to work—they gradually restore serotonergic tone and normalize amygdala reactivity, whereas benzodiazepines provide immediate symptom relief by enhancing GABA.