Fear itself

Past experiences in my life have instilled into me a deep dislike of being the center of attention.  Talking about what you love, what you're interested in, is arrogance and conceit -- I learned that lesson early.  Also, protect what you care about, or it'll be ridiculed, demeaned, or taken away.  The result was that even in safe situations, I have always been afraid to open up, and even people I've known for years really hardly know me at all.

The fact that I no longer have to spend my life in a protective crouch has not eradicated that fear.  It's a significant part of why I'm as shy and socially awkward as I am, and why I'm the guy at parties (if I get invited in the first place) who's standing there with a glass of scotch, looking around frantically for a dog to socialize with.  I've tried for years to be okay with graciously accepting compliments when they come, and to open up to others about my interests, but to say it doesn't come naturally to me is a wild understatement.

This all comes up because of some research released last month from scientists at the RIKEN Center for Brain Science in Saitama, Japan.  A team consisting of Ray Luo, Akira Uematsu, Adam Weitemier, Luca Aquili, Jenny Koivumaa, Thomas J.McHugh, and Joshua P. Johansen published a paper in Nature: Communications called "A Dopaminergic Switch for Fear to Safety Transitions," wherein we find out that a single neurotransmitter (dopamine) acting in a single part of the brain (the ventral tegmental area) is apparently responsible for unlearning fear responses.

The authors write:

Exposure therapy, a form of extinction learning, is an important psychological treatment for anxiety disorders such as post-traumatic stress disorder (PTSD).  Extinction of classically conditioned fear responses is a model of exposure therapy.  In the laboratory, animals learn that a sensory stimulus predicts the occurrence of an aversive outcome through fear conditioning.  During extinction, the omission of an expected aversive event signals a transition from fear responding to safety.  To switch from fear responding to extinction learning, a brain system that recognizes when an expected aversive event does not occur is required.  While molecular changes occurring in the ventromedial prefrontal cortex (vmPFC) and amygdala are known to be important for storing and consolidating extinction memories, the brain mechanisms for detecting when an expected aversive event did not occur and fear responses are no longer appropriate are less well understood... 

[Our] findings show that activation of VTA-dopamine neurons during the expected shock omission time period is necessary for normal extinction learning and the upregulation of extinction-related plasticity markers in the vmPFC and amygdala.  Notably, inhibition of VTA-dopamine neurons during the shock period of fear conditioning facilitates learning, suggesting that activity in VTA-dopamine neurons is not simply important for learning in response to any salient event.  These results also reveal that distinct populations of VTA-dopamine neurons... are important for the formation of stable, long-term extinction memories.

Team leader Joshua Johansen was unequivocal about the potential for this research in treating long-term anxiety and PTSD.  "Pharmacologically targeting the dopamine system will likely be an effective therapy for psychiatric conditions such as anxiety disorders when combined with clinically proven behavioral treatments such as exposure therapy," he said in a press release from RIKEN.  "In order to provide effective, mechanism-based treatments for these conditions, future pre-clinical work will need to use molecular strategies that can separately target these distinct dopamine cell populations."

Illustration from Charles Darwin's Expression of the Emotions in Man and Animals (1872), captioned, "Terror, from a photograph by Dr. Duchenne."  [Image is in the Public Domain]

I have suffered from serious anxiety most of my life, and I have a dear friend who has PTSD, and believe me -- this is welcome news.  My one attempt to use an anxiolytic medication was a failure (it killed my appetite, which someone with as fast a metabolism as I have definitely doesn't need), and "exposure therapy" has, all in all, been a failure.  The idea that there could be a way to approach these debilitating conditions by targeting a specific molecule in a specific part of the brain is pretty earthshattering.

I know it's a long way between identifying the brain pathway involved in a disorder and finding a way to alter what it's doing, but this is a significant first step.  The idea that I might one day be able to go to social gatherings without feeling a sense of dread, and to talk to people rather than just dogs, is kind of amazing.  Until that happens, I'm probably still going to have to deal with my anxiety, but it's nice to know someone is working on the problem.

************************************

This week's book recommendation is especially for people who are fond of historical whodunnits; The Ghost Map by Steven Johnson.  It chronicles the attempts by Dr. John Snow to find the cause of, and stop, the horrifying cholera epidemic in London in 1854.

London of the mid-nineteenth century was an awful place.  It was filled with crashing poverty, and the lack of any kind of sanitation made it reeking, filthy, and disease-ridden.  Then, in the summer of 1854, people in the Broad Street area started coming down with the horrible intestinal disease cholera (if you don't know what cholera does to you, think of a bout of stomach flu bad enough to dehydrate you to death in 24 hours).  And one man thought he knew what was causing it -- and how to put an end to it.

How he did this is nothing short of fascinating, and the way he worked through to a solution a triumph of logic and rationality.  It's a brilliant read for anyone interested in history, medicine, or epidemiology -- or who just want to learn a little bit more about how people lived back in the day.

[If you purchase the book from Amazon using the image/link below, part of the proceeds goes to supporting Skeptophilia!]

Dentophobia

I only have one real phobia, and that is: dentists.

I know where this phobia came from.  My childhood dentist, Dr. Webre, was not of the kind, gentle, "you seem to be uncomfortable, do you need more Novocaine?" variety.  Dr. Webre graduated from the Josef Mengele School of Dentistry.  Once, when I was about nine years old, he was filling a small cavity, and I could still feel the drill.  I tried to man up, and was doing my best not to scream, but evidently I flinched a little.  Dr. Webre's response?

"Stop that jerkin' around, or this drill is going to go right through your face."

He said this to a nine-year-old child.

I know, as an atheist, that I don't believe in hell, but I'd almost be willing to revise my belief system if somehow it would mean that Dr. Webre was there.

Oh, and I haven't mentioned that when he removed my wisdom teeth, he broke one of them.  Into three pieces.

So, like I said, it's kind of understandable that I have an absurdly powerful fear of dentists.  I start feeling nauseated about a week before an appointment, and it doesn't go away until I'm in the car driving home afterwards.

[image courtesy of the Wikimedia Commons]

Doctors have made great strides in treating deep-seated phobias.  The trick is disconnecting the limbic system fear-response from whatever the stimulus is, and is often accomplished through a combination of medications and exposure therapy.  The problem is, exposure therapy means... exposing yourself to the cause of the phobia.  In my case, it was much easier just to avoid the whole thing and hope that my teeth wouldn't fall out.

Now, let me say up front that my current dentist is awesome.  He has this wonderful thing called "sedation dentistry" in cases where you need something major done.  You not only more or less sleep through the entire procedure, you don't remember anything afterwards.  I saw this work wonderfully when my younger son, Nathan, had his wisdom teeth extracted.  Nathan was given a combination of diazepam and triazolam prior to going in.  You might be wondering what these two drugs are, so allow me to explain that the difference is that diazepam has two azepams, while triazolam has three azolams.

Okay, I admit, I have no idea what those drugs are.  But they were amazing.  When Nathan came out of the dentist's office after the extractions, he was showing the level of agitation normally associated with lobotomy victims.  On the way home, he had to exert all of his effort to avoid drooling on the upholstery.  He went right to bed, woke up five hours later, and had no memory of any of it, then or since.

So I'd seen the whole thing work splendidly, but I still couldn't bring myself to go in.  My feeling was that I'd have needed some diazepam and triazolam just to be able to make the phone call and make an appointment without fainting or throwing up.  But last month, I realized I had to do something, because one of my teeth was kind of sensitive, and I was worried that if I didn't get it checked I was probably going to regret it.

So I called and made an appointment.  The only way I was able to do it was that I kept telling myself that (1) I could cancel it if I freaked out too badly, and (2) Dr. Webre wasn't going to be there, cackling and rubbing his hands together maniacally, when I got to the dentist's office.

I made it through the following month, barely.  The nightmares started about a week before the appointment.  I couldn't concentrate on anything but the thought of OH DEAR GOD I HAVE A DENTAL APPOINTMENT IN A WEEK.  Then it was the day before, and the day of, and a sort of gallows-hilarity descended upon me.  Yesterday, during my classes, I had this frenetic, hysterical energy.  "Ha ha!" my brain seemed to be saying.  "May as well laugh, given that you're going to die in five hours!"

I know that this may all seem ridiculous to my readers who aren't phobic about anything.  But I am not exaggerating when I say that anyone who has a phobia about something they have to deal with on a daily basis -- like going outside, or the dark, or insects -- must truly exist in perpetual agony.

Anyway, I drove to the dentist's office, was welcomed warmly by first the secretary and then the hygienist, and taken into the examining room.  And...

... everything went fine.

My sensitive tooth turned out to be a little bit of root exposure from receding gums.  The hygienist and the dentist both said that it was nothing to worry about, that it could be treated with a sensitive-teeth toothpaste and a fluoride rinse, and failing that, the spot could be sealed with a simple procedure that takes about 45 minutes and doesn't even require Novocaine.  Everything else about my mouth was fine, which shocked everyone given that the last time I'd been in the chair was fifteen years ago.

Dumb luck, sometimes, is a wonderful thing.

So they made me promise to come back in a year for a cleaning.  I said I would, and I think I was being honest.  As exposure therapy goes, this one may have been fairly successful.  I can only hope that next year, I won't go through the agonizing four weeks between phone call and appointment, picturing every possible worst-case scenario my limbic system can dredge up.  I think, actually, that I won't worry very much at all.

Take that, Dr. Webre.