Panic attacks are not simply emotional reactions.
They represent a dysregulated neurophysiological cascade, often occurring without external threat, yet triggering the body's primal survival response.
Neuroscientific evidence highlights the amygdala as the epicenter for fear processing. In panic episodes, the amygdala becomes hyperactivated, even in the absence of identifiable danger. This hyperactivity triggers a cascade involving the hypothalamic-pituitary-adrenal (HPA) axis, resulting in the abrupt release of catecholamines, particularly adrenaline (epinephrine).
Dr. Kerry Ressler, Chief Scientific Officer, notes that "the fear circuitry in panic disorder appears hypersensitive, even to internal cues like heart rate fluctuations or respiratory changes."
<h3>Autonomic Nervous System: Sympathetic Dominance in Panic</h3>
During a panic attack, the sympathetic division of the autonomic nervous system becomes dominant, initiating the classic "fight-or-flight" pattern. This includes increased cardiac output, rapid respiration, peripheral vasoconstriction, and elevated glucose mobilization.
Physiologically, this is designed to prime the body for immediate action. However, in panic disorder, this reaction is disproportionate and often misinterpreted by the brain as a sign of imminent catastrophe, leading to a self-reinforcing feedback loop.
Recent studies using functional MRI and PET scans show heightened connectivity between the amygdala, brainstem, and insular cortex, suggesting panic episodes are partially sustained by aberrant interoceptive awareness—the brain misreading internal physiological signals.
<h3>Neurochemical Disruptions: Norepinephrine and Beyond</h3>
Central to the pathophysiology is the dysregulation of norepinephrine originating from the locus coeruleus, a brainstem nucleus involved in autonomic arousal. In patients with panic disorder, even minimal stress may trigger an exaggerated noradrenergic discharge, reinforcing both physical symptoms and subjective fear.
Gamma-aminobutyric acid (GABA), the brain's primary inhibitory neurotransmitter, also plays a significant role. Reduced GABA activity, particularly in the limbic system, diminishes the brain’s ability to regulate excitatory signals, lowering the threshold for panic induction.
Serotonin (5-HT) abnormalities, especially in the raphe nuclei—have been implicated as well. Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacologic treatments in part because of their role in modulating this overactive fear circuitry.
<h3>Respiratory Mechanisms: Hyperventilation and Carbon Dioxide Sensitivity</h3>
Patients in panic frequently hyperventilate, leading to respiratory alkalosis, which in turn causes dizziness, paresthesia, and lightheadedness. These sensations may be misinterpreted as signs of serious illness, intensifying the panic response. This suggests that a lower tolerance for rising CO₂ levels may signal the brain to initiate emergency responses, even when oxygen levels remain adequate.
<h3>Somatic Manifestations: The Visceral Experience of Alarm</h3>
Panic attacks present with a dense constellation of somatic symptoms, including chest tightness, trembling, diaphoresis, nausea, and heat surges. While none of these signs are inherently dangerous, they are perceived as life-threatening, particularly during the first experience.
These symptoms originate from systemic adrenergic activation and rapid metabolic shifts, which are not merely psychological, but rooted in definable neurophysiological processes.
<h3>Chronobiology and Circadian Triggers</h3>
Emerging evidence suggests a chronobiological dimension to panic attacks, especially nocturnal episodes. These often occur during stage 2 of non-REM sleep, when cortical arousal is low but brainstem vigilance mechanisms remain active. The precise cause remains under investigation, but dysregulated circadian modulation of the HPA axis may explain susceptibility during certain sleep phases.
Panic attacks are not imaginary threats they are real, measurable physiological events governed by complex neural interactions and biochemical imbalances. Understanding the mechanisms from amygdala hyperactivity and norepinephrine surges to CO₂ hypersensitivity enables clinicians to differentiate panic from other medical causes and tailor interventions more effectively.
By advancing our grasp of the neurophysiology behind panic, clinicians are better positioned to deliver treatments grounded in neuroscience rather than assumptions about behavior or mood.
