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.

Of Busyness and Chocolate

"We show in two experiments that without a justification, people choose to be idle; that even a specious justification can motivate people to be busy; and that people who are busy are happier than people who are idle.”(1)

The past few days have been stressful, so last evening I set to work on my kitchen, wiped down cabinets, sudsed up countertops, and then got down on my knees to hand scrub the floor. This was a Friday night, mind you, but I was content if more than a little sweaty, completely calmed by my whirlwind of activity. As a result, I've been thinking about busyness, and, my conclusion-- based on encounters with people both happy and un--is that humans enjoy being busy. Researchers from the University of Chicago’s Booth School of Business concur that busyness is a source of happiness.

As you know from this blog, scientists will study just about anything, and their most willing and available subjects are college students. Researchers at the University of Chicago theorized that "People dread idleness, yet they need a reason to be busy." So they grabbed a group of undergrads, hooked them up with a bogus survey, and here's what they found about idleness, chocolate, motivation, and happiness.

The students were asked to complete the survey then offered various strategies for turning it in. All involved the choice between a 15 minute sit-around-and-wait versus a 15 minute walk to another location. Without a chocolate inducement, the majority of subjects chose to wait. If offered a choice of milk chocolate on site vs. walking for dark, however, significantly more subjects opted to ambulate. The final test group was forced to walk or wait as a condition of the experiment. In every case, those who walked judged themselves happier than their lazy-bone colleagues. The researchers concluded, as stated above, that while people might choose to be idle, they’re willing to get moving for rewards as ‘specious’ as chocolate, and they’re always glad to be busy.

I talked this all over with a psychologist friend, and we agreed that this research is adrift in specious reasoning. Did the walkers, in fact, become happy due to walking or did they walk because they were happy? Or did they become happy while walking because it was such a nice break from their busy schedules to slow down and walk through the beautiful campus (if indeed the U. of Chicago campus is beautiful). Or is this the healthy person bias, meaning are people who choose to walk for chocolate on average people who are optimistic about the future and happily seeking healthy choices?

Other research confirms another obvious fact, namely that active people derive satisfaction not necessarily from busyness so much as from being valued and needed as a result of that which they accomplish in their work. And too busy, frantically busy, is a known detriment to health. Stay tuned for more busy research in upcoming posts.
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(1) Hsee, CK, et al. "Idleness aversion and the need for justifiable busyness." Psychol Sci. 2010 Jul;21(7):926-30.

Other people's motives--How do we judge?

As soon as I learned to drive, my parents instructed me to 'lock your doors' when driving at night or through 'certain neighborhoods.' When I moved to Cleveland for internship, my uncle advised me to forget locking my doors in those riskier parts of that city but rather DO NOT drive through them under any circumstance, night or day.

With such precautions drummed into me at an impressionable age, I remain ever alert to shady pedestrians at downtown intersections. To my son's dismay, I'll lock the doors if I judge a sketchy passerby likely to open the door and grab my purse or, worse yet, to hop in the passenger seat and abscond with me and/or my car (Oh like that would ever really happen Mo-om!).

Call me paranoid or over-sensitive, but never deny that I have a highly trained right temporoparietal lobe aka the temporoparietal junction (TPJ). Scientists now know that this section of our brain, seated just above the right ear, is vice president in charge of judging other people's motives. Here's how they figured this out.

Patients with brain damage to the TPJ are known to have trouble inferring moral intentions. Social scientist Liane Young and colleagues at MIT decided to test normal subjects with their TPJs intact and turned off. Now who on earth would volunteer for an experiment that involves turning off a section of their brain? Perhaps MIT undergrads feel they have neurons to spare.

Anyway, Young and company used "transcranial magnetic stimulation (TMS), a technology that uses a tightly focused magnetic field to temporarily disable individual regions of the brain." Before and after a magnetic zap to their TPJ, the volunteers read scenarios in which subject A accidentally kills subject B or narrowly misses killing the hapless B on purpose. As opposed to their righteous pre-TMS states of mind, the group post-TMS were much more forgiving of attempted murder.

So what? Well, we know that the TPJ continues to mature through adolescence and beyond, so someday my son will 1) be more forgiving of my heightened sense of other people's malevolent motives, 2) will lock his own darn doors, and 3) will make better choices in general (I hope). In addition, the MIT social scientists are now turning their attention to the TPJs of persons with autism spectrum disorders, conditions in which the ability to 'read' other people is seriously impaired.

Pain perception

Some people are stoic and some aren't. … Maybe there's a plausible biological reason for that difference.
---Dr. Geoffrey Woods, Medical geneticist, Cambridge University

My patient's face was all pinchy with pain, an expression not generally seen in a 20-something year old lady. She'd visited Walmart the previous day (an outing that always makes me pinchy with impatience as my husband meanders through every last aisle). While there, she bent over to examine some wonderful find and skewered her forehead on a metal hook.

"Ew," you're thinking, which is what I would've thought if there had been a ragged tear in her face, or any kind of mark whatsoever. Her forehead, however, was completely smooth and unblemished.

"So," I said, "where did it snag you?" And I touched the indicated spot, sending her recoiling in pain, pinchier than ever. The area wasn't red, abraded, swollen, or bruised. I told her that while I appreciated she was in a lot of pain, my examination indicated no serious injury. I then assured her that her pain should diminish greatly in the following days.

As usual, when confronted with pain reports that seem to far outstrip apparent injury, I wished I could walk a mile in her forehead. What was she really feeling in there? Real pain, real drama, a need for sympathy, worried sick, or what?

Dr. Woods and company also wondered why humans demonstrate such a wide spectrum of pain perception. They already knew from previous research that three rare mutations in the SCN9A gene are a serious problem insofar as such genetic changes can cause persons to be either too sensitive or completely oblivious to painful stimuli. In the first case, the faulty SCN9A gene allows sodium ions to flood through channels in the surface membranes of cells in the central nervous system. As a result, these neurons painfully overfire in response to minor daily occurrences such as bumping a shoulder against a wall when taking a corner too close. At the opposite extreme, SCN9A gone haywire in a different way prevents the perception of pain altogether. Affected persons, consequently, receive no signals say from a fracture or sprain and, therefore, have no cue to stop moving and get off the injured joint.

The Cambridge team went looking for subtle, more common mutations in the SCN9A gene, namely substitutions of a single nucleic protein (SNP) in the gene's sequence(1). They studied a group of subjects with osteoarthritis of comparable severity to see if these SNP variations correlated with differing levels of pain perception. One variation present in a small subset of the group was indeed associated with the highest pain perception in those who carried it. The scientists then looked in other people with other common pain syndromes such as sciatica and lumbar disk disease, again finding that "the statistical link between having the rare SNP and feeling more pain was impressively strong." In other words, those persons with lower pain thresholds were significantly more likely to have this particular SNP variant.

The researchers found that just under 20% of their subjects carried one copy of this particular SCN9A mutation, but only 2-3% had two defective copies, and these were the people most likely to react strongly to their painful conditions. Further testing suggested that this mutation renders them incapable of squeezing their sodium channels shut so wave after wave of pain news just keeps rolling in.

Obviously, this genetic test is not available for clinical use, and there's nothing to be done about it anyway. Those of us in the medical business and everyone involved in the sympathy business can now appreciate, however, that some persons are hard-wired for more pain than others; for such persons, that 'stiff upper lip' advice may be harder to follow. And my hapless Walmart shopper was back two days later, her forehead no longer tender but her head now clamped in the vise of a secondary tension type headache brought on by scrunching her brow over the original hooking.
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1) Woods, GC, et al. "Pain perception is altered by a nucleotide polymorphism in SCN9A," Proceedings of the National Academy of Sciences.

Cigarettes and cognition

I was just visiting Mauigirl's blog; she's been struggling with the declining health of her aging mom. Between a hospital stay followed by a move to a nursing home, MG's mom has been one month without a cigarette. MG notes that research suggests that nicotine has favorable effects on cognition and wonders if the notable change she's seen in her mom's mental functioning might be, in part, due to the lack of nicotine. I've often told my patients that people like to smoke for good reason, that, in fact, cigarettes are not only calming but wonderful for concentration and focus.





Cigarettes--or rather the nicotine within--may be neuroprotective. While I'm all in favor of saving the brain, I won't be prescribing cigarettes to anyone wishing to keep their marbles. But there's interesting evidence suggesting that nicotine is not without its benefits to brain.

Scientists have noted that persons who smoke have lower rates of neurodegenerative diseases such as Parkinson's and Alzheimer's. Korean rats were encouraged to smoke via an automatic smoking machine. After four weeks of 'automatic smoking' for ten minutes per day, the rodents were significantly protected against the seizure-inducing effects kainic acid. Apparently, if you want to dip your head in kainic acid (whatever that is), you might consider smoking too.

Kainic acid exposure aside, researchers have other theories why nicotine is good for the brain. The brain is full of nicotinic acetylcholine receptors; activation of these cellular switches has a number of beneficial actions. This effect of nicotine has been compared to "turning up the volume of a radio signal." As acetylcholinergic brain cells are in charge of memory and executive functioning--i.e. planning and carrying out complex tasks--turning up the volume is a good thing. No wonder people enjoy the clarity and focus of a Marlboro.

Neuroscientists at the University of Florida have discovered still another mechanism as to why nicotine might promote brain health. They found that nicotine prevents overactivation of little neuron-supporting cells called microglia. When the microglia get all hot and bothered with overactivation, they can set off events toxic to their neuronal buddies unto death. Well who wants that? Check out what Florida's Dr. Douglas Shytle has to say about that:

Microglia can be your best friend or your worst enemy depending on the signals they receive. The analogy is that you keep talking to them they will take care of you, but if you stop talking they are more likely to get aggressive and have a toxic effect on the brain.

If all this makes you want to take up smoking again, hang on. The Southern investigators realize that they must "now develop drugs that mimic the beneficial action of nicotine without its unwanted side effects."

Occipital neuralgia and Lyrica

Maureen periodically flinched while we talked as searing pain shot up the back of her head. Short but severe, these jolts of pain were diagnostic of neuralgia, a condition wherein a single nerve-- the greater occipital in this case-- seizes with pain. As a result, my patient was experiencing show-stopping discomfort from the base of her skull over the back of her head, sometimes on the left and other times on the right.

She spent her days hunched, like so many of us, over a computer and desk. On standing, she carried her head forward and her shoulders rounded reflecting the anterior thrust of her daily activities. All this was aggravated by breasts so large that her bra straps had dug permanent grooves in the top of her shoulders.

No easy fix for Maureen. I assumed that she, like many people, would not embrace the idea of medication, particularly over the long haul. I told her my plan--a short term fix to improve things quickly with a medication called Lyrica coupled with a larger plan to improve her posture, strengthen her supporting abdominal and back muscles, and perhaps consideration of breast reduction surgery.

Lyrica (pregabalin) is indicated for the treatment of seizures, diabetic neuropathy, nerve pain following seizures, and was recently approved for the treatment of fibromyalgia. Its use for occipital neuralgia, therefore, is 'off-label' but experience confirms that it soothes hypersensitive nerves no matter their location. Unfortunately, it's not without side effects, causing sedation, dizziness, and dysequilibrium, but its analgesic benefits can far outweigh these problems in patients whose daily lives are completely turned upside down by pain.

Maureen headed out with samples plus referrals to a physical therapist and a plastic surgeon and a written copy of the plan. Here's the phone message I received the next day:

Patient doesn't want to take Lyrica over a long period of time, was looking for a quicker working solution to pain. Advise.

Argh. Message back to patient:

Lyrica is a quicker working solution. Physical therapy, posture work, and possible surgery is the longer term answer.

The next message from Maureen sent the following day:

Pain free for the first time in weeks!

Fear Factor

"Get over it!"

Those who fear not are fond of telling the overwrought amongst us to face our fears and move on. If you're a hot reactor who barely copes with scary movies or prefers to watch TV's "24" through slits between your fingers, here's some interesting news. You may, in fact, be genetically wired to startle and gasp and burst into tears.

Anxiety is a good thing, an unpleasant emotion that warns us against potential danger. Anxiety run amok can be a show-stopper--ask anyone who suffers from phobias and struggles with fear of crowds, riding in cars, flying in airplanes, visiting the doctor, or other situations that most people plunge through with nary a second thought. Neuroscientists are hot on the trail of the biological bases for various behaviors and the genetic codes that determine why we act the way we do.

Investigators at Weill School of Medicine in New York noted that mice with a small change in the gene sequence for a brain chemical called brain-derived neurotrophic factor (BDNF) are wimpy little things. BDNF is an important protein in mice and humans alike that supports brain cells to thrive and multiply especially in the brain regions responsible for learning and memory. These scaredy mice have DNA coding for BDNF that is just one molecule different from that of their intrepid colleagues. The cringing rodents with genetically skewed BDNF are not only anxious but known to have difficulty overcoming their fears and are resistant to treatments such as Prozac that decrease anxiety.

Dr. Fatima Solimon and her fellow psychobiologists at Cornell brought human and mouse volunteers with both normal and variant BDNF down to their lab for a psychological workout. Fear responses are prone to 'extinction' when subjects are repeatedly exposed to the threatening stimuli without any consequences. Psychologists use such exposure therapy to help people overcome phobias. Mice freeze and humans sweat when fearful, and the researchers checked how long it took subjects to quit freezing and sweating as correlated with their genetic type. In addition, the humans underwent functional MRI scans looking for high activity in brain regions known to be associated with both fear as well as the ability to master emotions through conditioning.

Their experiments confirmed that humans with variant BDNF coding have no problem learning that which is threatening but have a terrible time unlearning the cues that first signified danger. The people kept sweating and the mice kept freezing in their tracks long after the fearless subjects with the hardy BDNF were dry, calm, or scampering about their cages. And MRI scanning confirmed that those with the anxious variety of BDNF had trouble turning off their fear centers and turning on their learning centers.

Solimon and company whose findings appeared in a January, 2010 issue of Science Magazine are hopeful that their findings may ultimately translate into better understanding and treatment of persons with anxiety disorders, phobias, and PTSD. Those who suffer so are indeed eager to get over it.

Emotion and Memory

My friend got lost years ago while on a cross-country skiing trip. The morning paper and the evening news reported search efforts in daily, discouraging detail. Time passed, and the possibility that my friend and her skiing partners lived on became less and less likely. One day, however, while driving home with the car radio on, a breaking-news bulletin announced that they had been found, alive and well if a bit frost-nipped on fingers and toes. I had to pull over and get a grip on my teary emotions.

I can tell you the exact spot I pulled over, the weather, and where I had been. This all quite remarkable as, on average, I've a big picture sort of mind while the details leak before storage in long-term brain files (no surprise this to my husband). My friend later told me that everyone invariably related the minutiae of the moment in which they'd heard of her rescue--this after I'd supplied her with my experience as if it were the most fascinating tale.

So what's with this emotional boost to memory? If you were alive at the time, you can doubtless remember where you were when Kennedy was shot or the moon landing occurred. Likewise for the World Trade Center tragedy and perhaps Princess Diana's death.

Japanese neuroscientists studied emotion and memory in patients with Alzheimer's Disease (AD) following the devastating Kobe earthquake of 1995.(1) They performed brain MRIs on all the subjects, then checked out who remembered the earthquake and who remembered the MRI. The patients were much more likely to remember the quake, suggesting that intense emotions reinforced the memory.

The researchers went on to correlate the ability to remember the temblor with the residual size of the subjects' hippocampus (the brain's memory center) and amygdala (emotional center). Victims of AD are known to suffer from brain shrinkage. Those who retained the emotional memory of waking up to a significant earthquake were much more likely to have a normal-sized amygdala no matter the size of their hippocampus, and, likewise, those with impaired emotional event memory had more intense amygdalar damage.
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1)Kazui, H. Emotion and memory. Four studies of the emotional memory in Alzheimer's disease. Japanese Journal of Neuropsychology. VOL.18;NO.3;PAGE.150-156(2002).

Too close for comfort?

I recently attended my 40th high school reunion. I talked for awhile with one old friend I hadn't seen in years. But I was distracted during the entire conversation by her preferred conversational distance which was close, darned close! Not a breath problem--hers was fine and apparently mine was too--just my problem with her 'in my face' proximity. A new study may indicate why, and it implicates my overactive amygdala.

I've mentioned before that the amygdala, an almond-sized region at the base of the brain, is nerve cell center for coordinating response to threat. If yours is on overdrive like mine, you may over-respond to horror movies, scary books, and phones ringing in the night.

Neuroscientists had the opportunity to study the biological underpinnings of personal space in a patient known as SM. She had a genetic disorder that took out her amygdala, and as a result, she could not recognize fearful facial expressions in others, and was very outgoing and far more trusting than average. And she cozied up in conversational situations such that she--Ms. Red above--let an experimenter get twice as close to her as the other Ms. Blues did without expressing any discomfort in the situation. (1)

Scientists went on to study preferred conversational distance with functional MRI scanning.(2) They socked away average persons with intact amygdalae in the machine, then got closer and closer to the subjects, measuring their brains for activity. When they invaded that person's comfort zone, the amygdala lit up with activity.

"Our findings support the idea that the amygdala functions as the brakes in social interactions, If you take away the amygdala, it seems like you are less tuned to ... social [behaviors] that can cause discomfort," says neuroscientist Richard Davidson of the University of Wisconsin.(1)
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1) ScienceNOW Daily News, August 31, 2009
2) Kennedy DP et al. Personal Space Regulation by the Human Amygdala. Nat Neurosci 2009 Aug 30.

The amygdala and PTSD

I can hardly bear to watch violent or scary movies. I walked out on The Ring the moment the dried-up little girl was found in the closet (thankfully, the movie was 'showing' at the time in our living room). And the opening scene of The Exorcist in which Father Merrin finds the creepy little statue, the wind blows, and a couple of dogs fight still can interfere with a good night's sleep for me.

Research suggests that an overactive amygdala (the brain's VP in charge of processing emotional experiences and fear) may predict how an individual handles stress, be it in pictures or for real. Israeli scientists used functional magnetic resonance imaging (fMRI) to scan the brains of 18 year old subjects undertaking training as paramedics(1). They scanned the trainee's brains while showing them photographs of graphic medical scenes specifically looking for activation in the amygdala region. They also screened the recruits for stress symptoms including anxiety and insomnia.

After 18 months and a grisly load of combat experience, the researchers found that those paramedics with the largest increases in stress symptoms were the ones with the greatest amygdaloid activity on the initial scan. Study co-author Talma Hendler says that the amygdala may be an "a priori biological marker" for individual susceptibility to post-traumatic stress disorder.

Rather than use a fancy, expensive fMRI as a screening test for fitness under fire, I suggest a less expensive showing of Inglorious Basterds. Check the subjects' heart rate and blood pressure by the movie's end, and you'll know who's ready for the field and who should stick to the office.
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1. Proc Natl Acad Sci USA. 2009 Aug 18;106(33):14120-5.

Bystolic testimonial

I wrote some time ago about a medication called Bystolic, a beta-blocker used for hypertension and irregularities in heart rhythm. Beta-blockers also have been used for years to calm the body manifestations of anxiety such as a racing heart, and they are, therefore, useful for stage fright. I have several lawyer/patients who use beta-blockers when they must speak in court. Another patient was having panic attacks that were difficult to diagnose as they manifested with symptoms quite similar to TIAs. After completing a detailed cardiac work-up, I put her on a small dose of Bystolic (2.5 mg. or 1/2 of the smallest available tablet) which controlled both her attacks and her blood pressure.

Here is an e-mail I received from Cheryl on her experience:

I have been using Bystolic for over a month. I love it. Not only is it controlling my anxiety and fast heart rate, my blood pressure is down and I have a generalized good feeling. Things don’t get me worked up like before. And, I’m breaking the 5mg in half. I did have to stop taking it in the evening because my sleep was restless. But, I start my day with a cup of coffee and half a Bystolic and it’s a good thing. I was reluctant after trying samples of Diovan that almost killed me. (Yuk on that one….Poison*).

If I had known how great I would feel on Bystolic, I would have taken it a long time ago. I’m not a pill-popper and dodge it, but this works! I am a health freak and have fought taking meds, but my doctor prescribed it for my racing heart. The benefits make my life happier and healthier.

*This is Cheryl's reaction to Diovan. It often works well for others, and is a good drug for hypertension.

Abilify testimonial

I wrote recently about a patient whose 'delusional parisitosis' was ruining her life. She felt that bird mites had invaded her home, her car, and her siblings' homes, making her too anxious and distracted to work or carry on any semblance of normalcy. A psychiatrist started her on Abilify last month during a brief involuntary hospitalization orchestrated by her frantic family.

She came in today, 5 weeks into her Abilify treatment. She looked well--rested and tear-free. She declared that things were 'almost back to normal'; she was back in her home, no longer experienced abnormal skin sensations, and had returned to work. I didn't ask her if the mites were gone, nor did she volunteer anything along the lines of 'what do you suppose that crazy business was all about?' I didn't feel like she needed to acknowledge whether or not the mites were real or imagined; it was more than sufficient that they were no longer front and center in her mind and her life.

I hope her insurance pays for this medication. It's four-plus expensive, but what an amazing difference it's made for her.

Brain centers in charge of voice recognition

In everday life, we automatically and effortlessly decode speech into language independently of who speaks. Similarly, we recognize a speaker's voice independently of what she or he says.(1)

My first call of this holiday weekend was a real jaw-dropper. The youngish man was most put out; he'd been assured that his prescription was called in and, on arriving at the pharmacy, found that they had no record of it. In language worthy of a drunken sailor, he anonymously expressed his deep unhappiness, and concluded that my staff and I were copulating pieces of excrement but in different words.

Now I certainly appreciate his aggravation--been there (at the pharmacy as a customer) done that (felt my blood pressure rising that the pharmacy staff had no knowledge of any script) myself. As often as not, it's an oversight or delay at the pharmacy, but I do know (as do you my patients) that we also have system failures at the office. That said, this tirade was inappropriate done anywhere but in the privacy of one's own brain or car, and I would like to know the identity of the caller so we can discuss whether or not he should continue as our patient if he even cares to do so.

So now we're on the topic du post: voice recognition. I remember a much more pleasant call nearly two decades ago when my front desk assistant announced I had a personal call on line 6. I didn't recognize the name she gave me (remember--we do admit to system failures) but I instantly knew the voice of my freshman college best buddy whom I'd lost track of for 17 years. Now scientists have identified the bit of gray matter that lights up with delight or dismay at the sound of a familiar voice.

Using functional MRI scanning, researchers from the Department of Cognitive Neuroscience at the University of Maastricht located an area of the auditory cortex that hums with activity as test subjects decipher the message and the messenger of spoken stimuli. In order to establish the identity of my anonymous caller, I need to find a staff member whose right anterior superior temporal sulcus (this STS is a brain bit located roughly behind and slightly above the right ear) along with the nearby Heschl's gyrus roars with recognition (and righteous indignation) when the message is replayed.

And Mr. No-Impulse-Control, get this, Pat at the front desk has a highly developed STS, and we will smoke you out. And know that a plainly worded message, even one expressing anger appropriately over lost time and effort, would've resulted in a prompt call by me to your pharmacy!
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Formisano et al. "Who" is saying "What"? Brain-based decoding of human voice and speech. Science. 7 November 2008, Vol 322, pps. 970-973.

Delusional parasitosis

The ones that crawl in are lean and thin
The ones that crawl out are fat and stout
Your eyes fall in and your teeth fall out
Your brains come tumbling down your snout

No lighthearted matter, these creeping mites, for two of my patients. The first middle-aged lady came in last summer toting a small aquarium full of water. Floating within were numerous diaphanous strands that trembled and tumbled as she heaved the case onto the table.

"Bugs," she declared, "the things that are crawling into my nose and making me crazy."

She was not kidding; she was in tears. She didn't say I think I'm going crazy because I imagine bugs, she said these are bugs.

The second lady came with her brother and sister in tow. He was carrying a crystal wine glass filled with alcohol and covered with saran wrap. Within floated three 'mites' captured as they scurried up someone's arm; I can't remember which one of the sibs caught the little buggers. I carefully poured off the alcohol and managed to snag the tiny particles onto a slide.

"Two clumps of fiber and pile of skin cells," I declared on returning to the exam room. "C'mon back and have a look."

Did they say "Oh my goodness, how foolish we feel now?" Nope, they just shrugged and said "we must've missed them which is amazing as they swarm by the thousands up our arms and legs." Lady #1 didn't go so far as to pin down the species of her infestation, Lady #2 was quite clear the pests were bird mites.

This is not only a psychotic syndrome, but the ability to pass the delusion along to others is a known phenomenon dubbed Shared Psychotic Disorder (SPD) which occurs in as many as 15% of cases of Delusional Parasitosis (DP). Must be a huge delusional exaggeration of the way one starts to itch when someone near by starts to scratch.

Per Wolfgang Trabert(1), when SPD patients are separated from the 'inducer,' a significant number of them undergo a spontaneous remission. Indeed, the brother and sister of this patient pulled back from their personal mitey troubles and had Lady #2 involuntarily admitted for psychiatric evaluation. She emerged slightly less upset due to the use of anti-psychotic meds, but still convinced that her house (that she's abandoned), her car (which she still drives but coats herself before doing so in olive oil as mites don't care for the taste), and her new apartment all continue infested.

Helping Lady #2 try to regain some semblance of a normal life is the hardest thing I've ever attempted in 28 years of practice. Her major source of information is birdmites.org. Check it out; is this fact or a web-site run by a bunch of SPD patients?
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1. Trabert, W. Shared Psychotic Disorder in Delusional Parasitosis. Psychopathology 1999;32:30-34.

Screening for post-partum depression

For those of us who have abruptly run out of estrogen--before a period, after delivering a child or miscarrying, and entering menopause--it is no news that sudden declines in this hormone can precipitate anxiety and depression. Pediatricians at the University of Colorado have devised a quick and easy 3 question screen to identify women at risk for significant post-partum mood disorders.

Women are instructed to answer 'most of the time,' 'some of the time,' 'not very often,' and 'never' to the following statements:

1. I have blamed myself unnecessarily when things went wrong.
2. I have felt scared or panicky for not very good reason.
3. I have been anxious or worried for not very good reason.

Dr. Stephen Stahl has pointed out a phenomenon he calls 'kindling' with respect to hormone-related mood swings, namely that a history of responding to hormone changes in a sad or anxious sort of way makes it more likely that a woman will have a similar response to such episodes in the future. I think this 3 question tool would be useful in identifying women having a rough go of it mood-wise through the other biggest hormonal challenge of a woman's life, namely menopause.

Social anxiety disorder

(aka generalized social phobia or GSP)

No one likes to be criticized, but criticism affects some more than others. I believe, for instance, that women who are unable to extract themselves from abusive relationships are more likely to react strongly and fearfully to criticism which further traps them in a toxic bond. Psychiatrists at the National Institute of Mental Health theorized that individuals with GSP who are fearful of social situations may demonstrate a stronger brain reaction to criticism than persons free of such anxieties.

They performed functional magnetic resonance imaging scans on subjects with GSP and controls. While under observation, the scanees read comments such as "You are ugly" "You are quite the looker" or "He'd look better with a paper bag over his head."

The GSP victims got all hot and oxygenated in their medial frontal cortices (brain area in charge of representation of self) and their amygdalae (brain area responsible for fear reactions) when they were slipped a slip with a personal insult. They had no such reaction to praise, nor did negative comments about others raise their amygdaloid activity.

Comments such as 'buck up honey, all those people are human just like you and they all go to the bathroom just like you' are unlikely, therefore to change the neural activity of those with GSP. Anti-anxiety agents that tone down the amygdala are helpful, and further research into changing neural circuitry is anticipated.

"Happiness is a Serious Problem"

Current events make the pursuit of happiness even more of a challenge than usual. One of several books I'm juggling now is Dennis Prager's 1998 bestseller "Happiness is a Serious Problem." Perhaps we are missing some opportunities to increase our satisfaction with our personal situation. Here's Prager's take on health:

Take the expectation of health. For most people, the only time good health brings them happiness is when they do not expect to be healthy and then find out that they are. Imagine that you discover a strange new lump on your body. You go to the doctor, who tells you that it looks suspicious and that you should have a biopsy. After waiting a week for the results, you learn that the lump is benign. That day will be one of the happiest days of your life.

Now this is remarkable because the day before you discovered the lump you were not one bit healthier than you were on the supremely happy day you learned that your lump was benign. Nothing in the state of your health has changed, yet you are now profoundly happy. Why? Because on this day, you did not expect to be healthy.

...[I]deally, we should awaken every day and be as happy about our good health as if we had just received the wonderful news that a lump was diagnosed as benign.

Beta blockers and post-traumatic stress disorder

One of my family members watched another person die suddenly, violently, and unexpectedly this weekend. I think I'm more freaked than my near and dear one is, but here's my doctorly thought processes after I was done flipping out.

Norepinephrine (NE, aka noradrenaline) is a neurotransmitter integral to the stress response and the formation of emotional memories. The beta-sympathetic nervous system (the automatic 'fight or flight' response that occurs without conscious activation) is mediated by NE which enhances the vivid but not necessarily accurate memories associated with highly emotional experiences. Think of a moment that was a charged one for you, say where you were when President Kennedy was shot (if you're old enough) or when you first heard about the World Trade Centers, and notice the details of that memory compared with other, blander recollections.

Experts call the development of post-traumatic stress disorder (PTSD) a 'derailment of memory process.' Not everyone is prone to an exaggerated or detrimental response to strongly charged experiences, but those who are can develop stubborn and destructive behavior patterns that ripple way beyond the actual trauma over time. While bioethicists argue over the morality of supressing intense and unpleasant memories, for better or worse it is possible to attenuate these memories through the use of beta-blockers. Amazingly, not only do the benefits of such therapy accrue when the medication is used shortly after the traumatic even, but also when the event is re-enacted through scripted imagery after some time has passed.

Should I offer beta-blockers (such as propranolol or metoprolol) to my family member? Perhaps I should just take a deep breath and take some myself.

The amygdala and the social conservative

I've mentioned before that I have an overactive amygdala. Through a series of genetically determined events that I've explained before here, I get an intense second-hand fear response that renders me unable to watch scary movies. Just can't take it when the actress hears a noise and heads right down to the cellar to investigate when I know full well she should run even as I also know it's only a movie.

Now anxiety is a good thing when it sets off an appropriate 'fight or flight' response that allows us to recognize danger and either run or creep down those stairs provided we're fully certified in the martial arts (of course, karate is no use at all against the supernatural...). And it's a bad thing when it renders us unable to leave the house or apply for a job (met a patient like that just yesterday). But who'd have thought that an overactive--or indifferent--amygdala might affect our political beliefs? Well, color me conservative as I read the following from Science Magazine.(1)

Political scientists teamed up with psychologists in Texas and Nebraska to find out if our political beliefs might have a biological basis. In their own words:

In a group of 46 adult participants with strong political beliefs, individuals with measurably lower physical sensitivities to sudden noises and threatening visual images were more likely to support foreign aid, liberal immigration policies, pacifism, and gun control, whereas individuals displaying measurably higher physiological reactions to those same stimuli were more likely to favor defense spending, capital punishment, patriotism, and the Iraq War.

During session one, the scientists quizzed the group--preselected for the strength of their political convictions no matter what the content of their attitudes-- on their political beliefs, demographics, and personality traits. When the subjects next came down to the lab, they were hooked up to physiological equipment that measured change in skin conductance as well as the strength of their blink or startle response. They were then shown three threatening images (a very large spider on the face of a frightened person, a dazed individual with a bloody face, and an open wound with maggots in it) or three sweet little pictures (a bunny, a bowl of fruit, and a happy child) interspersed amongst non-charged visuals.

Arousal causes increased moisture on the skin which increases conductance and fear causes a hard flinch or blink response of the muscles around the eye. Well I don't think I'd have a problem with a maggot show, but I know my heart rate would rise and I'd shut my eyes in moment to a large spider crawling on someone's face. The investigators found that an exaggerated response to the threatening pictures did correlate with a more conservative or socially protective attitude.

While the researchers were reluctant to conclude just what cause and effect processes were at work, they conjectured that "political attitudes and varying physiological responses to threat may both derive from neural activity patterns, perhaps those surrounding the amygdala. Amygdala activity is crucial in shaping responses to socially threatening images and may be connected to political predispositions."

Please note that in no way do I imply that all social conservatives have an exaggerated fear response. Nor do I think that close vigilance on the part of our society with respect to external danger is a bad thing.
_____
Oxley, DR, et al. Political Attitudes Vary with Physiological Traits. Science19 September 2008: Vol. 321. no. 5896, pp. 1667 - 1670.

Viagra, women, and antidepressants

Depression is a surefire way to kill your libido. Treating depression with antidepressants is also a surefire way to kill your libido. Initially, patients may be so relieved to no longer be depressed that they are willing to give up their sexual interests for the medication benefits. After awhile, however, the increased pleasure in life and relationships makes intimacy issues unacceptable.

Doctors at the University of New Mexico wondered if phosphodiesterase type 5 inhibitors (aka Viagra, Cialis, or Levitra) might improve the sexual outlook for women whose spirits have risen on antidepressants even as their libidos have fallen. Viagra and company are known to lift certain parts in men on depression meds.

Over a period of 4 years, they randomized 98 women whose depressions AND sexual interests were completely squashed on serotonin reuptake inhibitor type medications. Taking no one's word for granted, they not only followed up the women's sexual activity event log, but also administered the Clinical Global Impression function scale, the Female Sexual Function Questionnaire, the University of New Mexico Sexual Function Inventory (female version of course), AND the Hamilton Depression Rating scale (just to make sure no depression was creeping back in the picture).

The women on the real deal Viagra sent their Clinical Global Impression sexual function scale soaring to nearly double the levels of their pre-treatment activity. They also improved their scores on their Sexual Function quizzes. The investigators do note that this study selected for a group of women motivated to improve their sexual functioning and relationships, and therefore the findings might not be generalizable to all women experiencing such troubles while on antidepressants. It's also possible that filling out forms and quizzes on sexual functioning might enhance sexual interest.

I find this study particularly interesting as Viagra-like drugs work particularly well in men through the promotion of blood flow into certain parts that must be engorged with blood for proper sexual functioning. It is encouraging to find that the medications can increase interest and activity in women whose sexual response is less dependent on the localized pooling of blood.