## Neurobiological Basis of Panic Disorder **Key Point:** Panic disorder is characterized by dysregulation of the serotonergic and noradrenergic systems, with evidence pointing to decreased serotonergic neurotransmission and hyperactivity of the noradrenergic locus coeruleus. ### Serotonergic System - Reduced serotonin (5-HT) availability and receptor sensitivity - Dysfunction in raphe nuclei projections to limbic structures - SSRIs and SNRIs are first-line pharmacological treatments, supporting serotonergic hypothesis ### Noradrenergic System - Hyperactivity of the locus coeruleus (LC) in the brainstem - Excessive norepinephrine release triggers panic symptoms (palpitations, tremor, anxiety) - α~2~-adrenergic agonists (clonidine) can reduce panic attacks ### GABA System (Secondary Role) - Reduced GABAergic inhibitory tone in amygdala and prefrontal cortex - Benzodiazepines enhance GABA function and provide acute relief - Not the primary pathophysiology but contributes to symptom maintenance **High-Yield:** The "fear network" model implicates amygdala hyperactivity with impaired prefrontal cortex inhibition, mediated by serotonergic and noradrenergic dysregulation. **Clinical Pearl:** SSRIs take 2–4 weeks to show efficacy because they require neuroadaptation and receptor desensitization, not just acute neurotransmitter elevation.
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