Keep calm and carry on: as long as your orexin levels are low

Scientists link the orexin system in the brain to panic disorder, paving the way for research into new treatments for severe anxiety disorder.

Panic disorder is a severe anxiety disorder characterised by recurring panic attacks. Sufferers are suddenly overcome with a feeling of terror and often have physical symptoms such as increased breathing and heart rates. Previous work has shown that individuals with a panic disorder have decreased levels of γ-aminobutyric acid (GABA) and GABAergic drugs (such as benzodiazepines), which enhance the effect of GABA in the brain, are effective treatments for sufferers.

Johnson and colleagues, from research institutes in the USA and Sweden, used a rat model that mimics the panicked state seen in humans to understand the biology behind panic. The rat panic model works by chronically inhibiting GABA synthesis in the dorsomedial-perifornical hypothalamus of rats and then challenging the rats with sodium lactate to produce an anxiety-like state. This model targets a region of the brain rich in neurons that synthesise a neuropeptide (a small molecule used by neurons to send signals to each other) called orexin (ORX). Therefore, the researchers investigated whether the orexin system in the brain is involved in inducing panic.

The study, published in Nature Medicine, showed that when ORX-synthesising neurons are activated there is an increase in panic behaviour in the rats. This panic response could be blocked by silencing the gene for ORX synthesis using RNA interference or by using antagonist drugs against the ORX-receptor on neurons. Furthermore, the researchers analysed cerebrospinal fluid from people with or without panic anxiety and found that ORX levels are higher in people with panic anxiety.

This work gives an insight into the underlying biology behind panic and highlights the potential of drugs against the ORX system as treatment for panic disorder.

Johnson, P., Truitt, W., Fitz, S., Minick, P., Dietrich, A., Sanghani, S., Träskman-Bendz, L., Goddard, A., Brundin, L., & Shekhar, A. (2009). A key role for orexin in panic anxiety Nature Medicine, 16 (1), 111-115 DOI: 10.1038/nm.2075