What causes panic attacks?

If you've not had a panic attack, you can scarcely imagine what they are like. When I diagnose patients with this condition, they all nod when I describe panic as not so much a feeling of "I'm so anxious" but a frightening conviction that "I will pass out" or “I will die.” As opposed to anxiety, panic attacks are intense and episodic, occurring abruptly with or without a particular trigger. They cannot be banished with rational override. If they are not recognized as panic, they often result in expensive overuse of medical services through visits to ERs, cardiologists, or pulmonologists. Theories abound on the biological underpinnings of these show-stopping events.

Panic attacks often include a subjective feeling of not being able to get a deep breath accompanied by the need to yawn or sigh in order to improve the situation. Conscious attention to breathing overrides the automatic regularity of inhalation and exhalation, a state I've dubbed "too much minding the matter.".As a result of disordered breathing, panic victims suffer disturbances in body levels of carbon dioxide, either hypercapnia (too high) from shallow breathing or hypocapnia (too low) as a result of hyperventiliation.

Oddly, variances in either direction have been linked to the onset of panic attacks. Shallow breathing or hypoventilation produces hypercapnia which in turn induces a fear of suffocation--think buried alive or stuck in a mineshaft rebreathing air increasingly devoid of oxygen. Some researchers believe that panic patients have an overly sensitive internal suffocation alarm--any rise in carbon dioxide levels sets off a frantic 'gotta’ get outta here now' reaction. Conversely, hyperventilation produces hypocapnia which causes a constriction of airways and an unpleasant awareness that each inhaled breath is insufficient. Either way spells panic for susceptible souls. Many people with panic complaints often lose that frantic focus on breathing while exercising as aerobic activity drives a deep and regular breathing pattern.

Newer research suggests that a hormone that plays a role in wakefulness may contribute to panic attacks. Before considering how high levels of orexin (orx) turn ordinary citizens into panicky wrecks, here’s some interesting background on this hormone also known as hypocretin. Brain cells that release orexin are found in the hypothalamus and are active during waking hours and inactive during sleep. Orx receptors exist throughout the brain and are activated by orx release. A lack of orx-producing neurons causes narcolepsy—a condition associated with unpredictable and sudden attacks of sleep. Researchers have used orx-antagonists which block the effects of orx to induce sleep in lab animals and humans.

Pharmacologists at Wake Forest University administered orx as a nasal spray to a slew of sleepy monkeys to see if they could rouse sufficiently to perform complex mental tasks(1). The monkeys, like your average teenager, were kept awake with videos, music, treats, and interacting with humans ‘til all hours of the night. As you can see from the PET scans above, snorting orx changed great scads of sleepy blue brain material into red, glucose-metabolizing neurons hard at work on image-matching tasks, and the orx-treated group performed circles around their sleepy colleagues. Imagine squirting your comatose teen with orx on a school morning!

So what’s orx got to do with panic? Psychiatrists at Indiana University found that panic-prone rats were over orx-ed(2). Not hard to imagine if a little orx is good for alertness, too much orx would result in a tightly wound rat—or human—jumpy, easily startled, and prone to freak out. And the more active the orx neurons in the rats, the more their paniclike behavior increased.

Not satisfied with rat data alone, the investigators somehow persuaded humans with panic disorder to undergo spinal taps, checking for levels of orexin bathing their beleaguered brains compared to others free from fear. Sure enough, orx levels were much higher in the panic-prone. Someday, orx-antagonists that block orx receptors may be a non-sedating, non-addictive approach to panic control.

_____

1. Deadwyler, SA et al. Systemic and nasal Delivery of Orexin-A Reduces the Effects of Sleep Deprivation on Cognitive Performance in Nonhuman Primates. Journal of Neuroscience. 26 December, 2007, 27(52): 14239-14247.

2. Johnson, PL et al. A Key Role for Orexin in Panic Anxiety. Nat Med. 2009;16[1]:111-115.