Sunday, March 20, 2011

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.


Anonymous said...

Question NOT related to this post, if you don't mind.

The super 'bugs' have hit. It is reported 350 people died in a CA area alone recently from them.

Will you post what you are going to do about this personally, other doctors, and what people can do to prevent this, esp. if they have to go to the hospital.

Anonymous said...

I just saw this and I really, really, really hope that something to moderate the orx can be found. The thing that is so untenable about panic attacks is that they can come out of the blue. It's not necessarily linked to any particular stressor or event. I can't tell you how many perfectly good health care resources I wasted in EDs (dying of heart attack, was my presenting complaint)before a doc finally told me that it "could" be panic disorder and maybe I should see a shrink.

Anonymous said...

My story is the same as anonymous, above. Come out of the blue with absolutely no pattern? Yep. Wasted thousands on ED visits? Yep. I get the kind where I can't get a deep breath, heart palpitations, weird head sensations. UGH. I hope my kids don't inherit this, and if they do, I hope the orx inhibitor is around when they're older.

femail doc said...

Certainly anxiety runs in families, probably propensity to panic does too. When questioned about quality of life, patients with anxiety disorders rated their QoL lower than did persons with cancer. I look forward to the ability to manipulate orx in both directions!

Anonymous said...

1 of the pain-in-the-neck things about PA is that the cause lies in the thorny area between 2 things; 1) panic attack is a learned behavior so there is a psychological aspect and 2) It has a very real physical cause. I believe that we sufferes have literally changed our brains into this. The good news is you can take SSRIs and forget how to have them. You dont have to be on SSRIs forever plus coping (and ignoring( skills help tremendously. It is a really, really scary thing but it is very beatable. (I'm not an MD, this is my personal experience)

Mr. Edward said...

When I was at school I started hyperventilating for no apparent reason and I broke out into a sweat and started shaking so I had to sit down because my knees were shaking. My hands were also shaking and I had to clench my fists to stop them from shaking.I felt like I was going to throw up and I felt really dizzy. I didn't really think it was a big problem but then someone said their sister had a panic attack and it sounded a lot like what I had.
how long do panic attacks last