Possible mechanisms for lactate's induction of panic

Area of Science:

• Neuroscience
• Psychiatry
• Biochemistry

Background:

• Panic disorder and agoraphobia are characterized by recurrent panic attacks.
• Lactate infusions are known to provoke panic attacks in susceptible individuals.
• The precise physiological mechanisms underlying lactate-induced panic remain unclear.

Purpose of the Study:

• To investigate the physiological and biochemical mechanisms responsible for lactate-induced panic attacks.
• To differentiate between central and peripheral factors contributing to panic.
• To evaluate the roles of catecholamines, ionized calcium, and acid-base balance.

Main Methods:

• Single-blind intravenous infusion of 0.5 M racemic sodium lactate in patients with panic disorder/agoraphobia and healthy controls.
• Monitoring of physiological parameters (pulse, blood pressure, venous PCO2, pH, bicarbonate).
• Measurement of blood L-lactate, pyruvate, and plasma levels of ionized calcium, phosphate, prolactin, epinephrine, norepinephrine, and cortisol.

Main Results:

• 72% of patients experienced panic attacks during lactate infusion, while controls did not.
• Peripheral catecholamine surge was not identified as the primary mechanism, though elevated epinephrine may predispose.
• Heightened central noradrenergic activity was observed in many, but not all, panic attacks.
• Decreased ionized calcium or metabolic alkalosis did not appear sufficient to induce panic.

Conclusions:

• Lactate-induced panic attacks in panic disorder are not solely driven by peripheral catecholamine release.
• Central noradrenergic hyperactivity may play a significant role in lactate-induced panic.
• Existing hypotheses regarding ionized calcium depression and metabolic alkalosis as direct causes of panic are not supported by these findings.