The neurochemistry of panic

Orexin, a brain peptide best known for its link to the sleep disorder narcolepsy, participates in the pathophysiology of panic disorder, according to a report in this week’s Nature Medicine.

In people with panic disorder ― characterized by recurrent panic attacks ― there is evidence of decreased brain inhibition and marked increases in autonomic and respiratory responses after intravenous infusions of sodium lactate ― a common test for panic disorder. In rats, a brain region known as the DPH participates in anxiety-like states and is similarly vulnerable to sodium lactate.

The DPH has a large number of neurons that contain orexin ― a peptide involved in arousal and vigilance states. Philip Johnson and his colleagues therefore investigated the role of orexin in panic anxiety and found that activation of orexin neurons leads to a panic-prone state in rats. Silencing the hypothalamic orexin gene with RNA interference or with orexin-receptor blockers prevented the panic responses.

The team also found that humans with panic anxiety have elevated levels of orexin in the cerebrospinal fluid compared to subjects without panic anxiety. These results indicate that the orexin system may constitute a potential new target to treat panic disorder.