Vigilance Hormone Linked to Panic Attacks

A new study has linked panic disorder to a wayward hormone in a brain circuit that regulates vigilance. While too little of the hormone, called orexin, is known to underlie narcolepsy, the new finding suggests that too much of it may lead to panic attacks.

Panic disorder is an anxiety disorder that afflicts 6 million American adults. It's characterized by unexpected, repeated episodes of intense fear. These can be accompanied by physical symptoms including chest pain, heart palpitations, shortness of breath, dizziness or abdominal distress. Panic disorder is also a risk factor for suicidal behavior.

Panic attacks can be induced in susceptible people by infusing them with a normally innocuous salt called sodium lactate. The salt also triggers panic-like behaviors in susceptible rat strains. Sodium lactate was previously shown to activate brain regions associated with orexin-secreting neurons. Orexin, produced in a circuit emanating from the brain's hypothalamus, regulates arousal, wakefulness and reward.

Dr. Anantha Shekhar and colleagues at Indiana University and Lund University set out to further investigate the role of orexin in panic attacks. Their study was funded by NIH's National Institute of Mental Health (NIMH) and National Center for Research Resources (NCRR). It appeared on December 27, 2009, in the online edition of Nature Medicine.

The investigators found that sodium lactate activates orexin-secreting neurons in panic-prone rats. Increased activity in these neurons correlated with anxiety-like behavior in the rats. Using a technique called RNA interference, the researchers then prevented orexin genes from turning on. Without the ability to activate orexin, the panic-prone rats didn't develop anxiety behaviors following sodium lactate infusions. Blocking orexin receptors with a drug also blocked the anxiety-like behavior.

The scientists next measured orexin in the cerebrospinal fluid of 53 people showing suicidal behavior. Those with panic disorder had higher levels of orexin than those without panic disorder. In addition, those with only panic anxiety had significantly higher orexin levels than those with major depression accompanying their panic anxiety. This finding, the authors note, is consistent with a previous medication study showing that sertraline, a well-known antipanic and antidepressant drug, lowered orexin concentrations in cerebrospinal fluid. In contrast, bupropion, an antidepressant that is not as effective in treating panic disorder, didn't lower orexin concentrations.

The new finding suggests a critical role for an overactive orexin system in producing panic attacks. Medications that block the orexin receptor, the researchers say, may provide a new therapeutic approach for the treatment of panic disorder.

"Targeting the brain's orexin system may hold promise for a new generation of anti-anxiety treatments," says NIMH Director Dr. Thomas R. Insel. "This is a good example of how translational experiments in rats and humans can potentially yield clinical benefits."