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.

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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.

Radiation from medical imaging

Plagued by shoulder pain, especially at night, Jack was not happy with his orthopedist nor improved by physical therapy. Being a tightly wound sort, he'd come to the conclusion that the pain must be from cancer. I was happy to reassure him, as I'd done many times in the past, that he did NOT have cancer. Soothing the worried well (there's actually an ICD-9 diagnostic code for 'worried well') is one of the easiest parts of my day.

But Jack came back the following week, yet again shouldering grave doubts. A second opinion from another orthopedist confirmed the original diagnosis of a torn rotator cuff. So what was on Jack's mind? He was agonizing over the fact that Dr. Two took a repeat set of shoulder films. Not the unwarranted expense that now worried Jack, however, he was near tears over the possibility that this extra radiation would significantly increase his future risk of cancer.

So what's the scoop on medical imaging and cancer risk? Radiation from any source is not only a cancer inducer, turning healthy cells into pre-malignant ones, but also a cancer promoter which can push these compromised cells into a more abnormal state. Radiation danger is compounded through a lifetime of ionizing destruction; years of exposure compounding today's CT with yesterday's tan. If you'd like an estimate on your annual irradiation, check out the interactive quiz at American Nuclear Society's website.

If you're not an internet quiz type, let me inform you that a single CT scan can deliver a radiation dose equal to dozens of shoulder films. And there's no particular standardization here; radiologists can adjust their sets to enhance detail, and the higher the dose, the crisper the image. As a result, concerned specialists have banded together in various self-policing initiatives to rein in the rads, among them Image Gently setting guidelines for testing children and Image Wisely for adults. Nevertheless, the estimated annual number of CT scans in the US rose from 3 million in 1980 to 67 million in 2006 and the numbers continue to climb. Scarcely an ER visit goes by for one of my patients without an accompanying CT procedure. And one CT begets another when "incidentalomas" are found (unexpected abnormal findings of unclear significance) that require future scans to clarify their nature.

Based on data from survivors of the atomic bombings in war-time Japan, biophysicist David Brenner estimated the lifetime risk of cancer for a child undergoing a single abdominal CT as one in 1000. While other experts take issue with both his calculations and his conclusions, all agree that rads must be reduced.

One of the most innovative approaches comes from Mass General Hospital. Docs there created a rather complex program that scores the appropriateness of the choice of a diagnostic CT as compared to other imaging techniques for any particular clinical situation. The software shares this info with the ordering physician who is then offered the opportunity to change their minds and their orders. This software replaces the aggravating insurance pre-authorization procedures that Dr. James Thrall has dubbed "1- 800- may- I- do- a scan." Once this process was in place, CT use at MGH dropped considerably.

There is no doubt that CT technology has been critical to the accuracy of diagnosis since its inception. Pre-CT scanning (back when I was a doc-lette in training), diagnosing brain tumors involved a horrendous procedure wherein air was introduced into the spaces around the brain (as demoed graphically in "The Exorcist"). CT scans are perfectly appropriate even while over-ordered. Ask your doctor, however, what your other choices might be when offered such tests.

Alpha brain waves and sleep disturbances

I stay in touch with the world in the course of a night as things that go bump in the night make me jump. Ringing phones send me into a hot flash of anxiety and insomnia even if it's just the gentle whir of a cellphone on vibrate! Last night, my husband's cell went off at 3:30 a.m. one floor and half the house away. He snoozed on while I tossed and turned.

No doubt that many--e.g. mothers, doctors, and plumbers--all need a heightened nighttime awareness of the world, but this sleep-searing sensitivity can get out of hand. "Resistance to acoustic disturbance" is a measure of sleep soundness and is known to vary during the course of a night's sleep and also from sleeper to sleeper. Scientists are hot on the trail of why.

Nocturnal observations of 13 sleepers sleeping in a Massachusetts General sleep study lab revealed certain brain wave characteristics that predicted whether or not an individual would rouse to the noise of traffic or phones(1). As we transition from wakefulness to sleep, certain patterns emerge in our brain wave patterns signaling a shutting down of external awareness and a growing hubbub of internal brain activity. Alpha waves that flow from the back of our brain decline in amplitude as we drift into sleep. However, this wakeful wave does not disappear entirely, and, in fact, the more powerful these alpha signals, the more fragile our sleep.

The scientists confirmed that increased alpha activity as seen on EEG prior to the delivery of an external sound increased the likelihood that the subject would rouse unto wakefulness in response to the noise. Thus, alpha activity in the brain not only correlates with mental alertness by day but easily disturbed snoozing by night. The researchers concluded that this information may someday allow for the over-alpha'd amongst us to be variably medicated based on read outs from sleep monitoring devices rather than bluntly sedated for hours by currently available meds.

Sounds kind of "Brave New World"ish to me. And who then will lie awake waiting for teens?
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(1) McKinney SM, Dang-Vu TT, Buxton OM, Solet JM, Ellenbogen JM (2011) Covert Waking Brain Activity Reveals Instantaneous Sleep Depth. PLoS ONE 6(3): e17351. doi:10.1371/journal.pone.0017351.