Bernards Voices

Nature’s Eric Olson interviews Kerry Ressler’s on his research published in Nature 470, February 24, 2011:

Why do some people develop post-traumatic stress disorder, but others emerge from a horrific event relatively unscathed? A molecule involved in orchestrating the brain’s response to stress may hold the key to this difference.

Women are 30 to 50 per cent more likely to develop PTSD than men. (The interview doesn’t address the episodic nature of PTSD. I don’t believe this research tell us anything about an episode’s frequency or intensity–for example, a flashback triggered by a car back fire. Nor does it address the extent with which anxiety episodes are chronic and worsen over time. I have my own personal obsession, I guess would be the word, about whether levels of estrogen and how they change over a woman’s lifetime, impact the intensity of her anxiety or depression.)

During the interview, PTSD is mentioned often by the interviewer, but the researcher, Kerry Ressler, doesn’t seem to differentiate between PTSD, panic and generalized anxiety disorders, as well as depression. The biological factors (the protein: Pituitary adenylate cyclase-activating polypeptide (PACAP), and its modulation by estrogen) impact fear inhibitors and stress responses independent of which anxiety disorder is being discussed. But it does appear that research was conducted on “heavily traumatized subjects,” rats, mice? Why? Because the symptoms were easier to induce and observe? Because the name PTSD is more eye-catching in headlines and grant applications?

Fast forward to minute 6:38 of the podcast:

Related transcript.
Research article abstract.

Dr. Ressler:

I don’t necessarily think that the symptoms at the final common pathway of symptoms level, there is necessarily a difference between men and women, but what we are increasingly learning about complex brain disorders is that there is probably many different ways to get to that disorder.

Mental disorders affect more than 160 million Europeans — 38% of the population — each year, says a report1 issued today by the European Brain Council and the European College of Neuropsychopharmacology. Yet, fewer than a third of those affected receive treatment.

This number is higher than the “1 in 4″ that we in Healthy Outcomes Partnership quote. It is higher because this study includes elderly and children, and also because it includes disorders like insomnia.

Led by Hans-Ullrich Wittchen, a psychologist at the Technical University of Dresden in Germany, the three-year study covered the 27 countries in the European Union (EU) as well as Switzerland, Norway and Iceland. The researchers found that the most common disorders are anxiety, insomnia and depression, which account for 14%, 7% and 6.9% of the total, respectively.

In a previous report also led by Wittchen, health-care costs to the EU for mental disorders were estimated at around €277 billion (US$394 billion). In October, Wittchen and his colleagues will publish a report estimating the present cost of these diseases to governments. Wittchen hints that the true figure, with the addition of new conditions, age ranges and countries, could be more than double the 2005 estimates.

“It’s very rare that you get treatment in the year after onset,” said Wittchen.

The higher figure resulted from the addition of 14 previously excluded disorders, many of which affect children and the elderly. But the frequency of mental disorders has probably not gone up substantially, Wittchen says. “There’s no evidence for changing rates.”

Or listen to the podcast (fast forward to time 6:37).

Kerri Smith reports in Mental disorders affect more than a third of Europeans: Nature News.

Prof. Murray B Stein MD and Prof. Dan J Stein MD, in The Lancet, Volume 371, Issue 9618, Pages 1115 – 1125, 29 March 2008.

Abstract:

Our understanding of social anxiety disorder (also known as social phobia) has moved from rudimentary awareness that it is not merely shyness to a much more sophisticated appreciation of its prevalence, its chronic and pernicious nature, and its neurobiological underpinnings. Social anxiety disorder is the most common anxiety disorder; it has an early age of onset—by age 11 years in about 50% and by age 20 years in about 80% of individuals—and it is a risk factor for subsequent depressive illness and substance abuse. Functional neuroimaging studies point to increased activity in amygdala and insula in patients with social anxiety disorder, and genetic studies are increasingly focusing on this and other (eg, personality trait neuroticism) core phenotypes to identify risk loci. A range of effective cognitive behavioural and pharmacological treatments [SSRIs] for children and adults now exists; the challenges lie in optimum integration and dissemination of these treatments, and learning how to help the 30—40% of patients for whom treatment does not work.

Listen to the podcast (interview starts at minute 6:00).

My notes from the podcast–bolded items in abstract plus:

• like sadness vs depression, shyness vs social anxiety exist on a spectrum, and it is the “most shy person you know” where this disorder may interfere with their life, and is worth treatment.
• diagnosable in 5% of the population
• easy to diagnosis.  physician/therapists asks: “Does you shyness interfere with your life?”  A yes answer is a strong predictor.
• stigma:  eg. General Physicians often themselves consider it trivial

Also in the issue Simon Wessely provides a dissenting view, reviewing How shyness became social phobia by Christopher Lane.

Pathologising shyness, eccentricity, or sadness does few any favours—neither those who receive unhelpful labels, nor those with major mental disorders who need all the resources and research we can muster.

Slate’s Hang Up and Listen podcast, April 18th, covers 3 topics, including Justin Duchscherer’s depression. Fast forward to minute 33:30–although I enjoy the whole podcast–but it is the last segment which deals with Baltimore Orioles pitcher Justin Duchscherer’s battle with depression. They spend a lot of time talking Joe Posnanski’s article in 2009 Sports Illustrated on Zach Grienke who suffered from anxiety disorder.

An excerpt from Pat Jordan’s Men’s Journal article on Justin Duchscherer.
Jordan’s 2001 New York Times Magazine article on Rick Ankiel.
A 2010 Sports Illustrated feature on baseball players with depression.
The Reds’ Joey Votto missed part of the 2009 season with anxiety problems.
Dontrelle Willis and Khalil Greene have also suffered from social anxiety disorder.

These topics are covered in other HUAL podcasts. They do the best job–i.e. in the context of entertaining discussion about sports–covering mental illness in sports, and sports psychology–dealing with pressure on the soccer or hockey goalie, the pitcher, the field goal kicker.

Another example from Slate, in the HUAL October 25, 2010, podcast, Brandon Roy went to see a sports psychologist this summer.

The Dec 16, 2006 Lancet podcast on Generalized Anxiety Disorder addresses the question: how should our medical system detect and treat anxiety?

GAD is defined by exclusion.   It is not a panic disorder—which is a sudden, severe, episode or attack, of anxiety.   GAD is not post traumatic stress disorder—which also has clearly defined source.  GAD, Professor Peter Tyrer says, effects 10 to 12% of the population at any one time.   It is chronic.  It persists.  It is described as free floating.  Everything a person does or thinks is tinged with anxiety.   Psychological symptoms include: tension, worry, inability to concentrate. The physical symptoms are a consequence of continuous autonomic arousal: palpitations, trouble breathing, chest pains, tingling, and feelings of unreality, depersonalization.

Depression and anxiety often overlap—in fact that combination is the most common mental illness a primary care physician would see.   And it isn’t that a primary care physical would be blind to anxiety—it is so common that they know it when they see it—but what is more rare is the decision to treat it, because they, like the general public, see it as a symptom and they look past it, wanting to get to the underlying problem.

But GAD treatment exists.   Not only are there drugs (sedatives, tranquilizers, anti-depressants) but also cognitive behavioral therapies that help the patient identify their distorted cognitions and conclusions they have about their symptoms.

Since anxiety is such a common ailment, economic and social concerns demand it be dealt with in primary care.  The big challenge facing the UK national health service is to:

… make the psychological treatments available, because these are the ones that are wanted by patients, and the evidence base suggests, because of the dependence problems with drug treatments, and these occur with all types of psychiatric drugs for treatment of anxieties, nothing really which is effective in treating anxiety has no problems at all when you stop taking it, but this doesn’t apply to the psychological treatments …

The psychological treatments are successful and their effects persist.   The drugs stop being effective when the patient stops taking them.

On NPR’s Science Friday, December 11th, 2009, Ira Flatow interviews Elizabeth Phelps, Professor, Department of Psychology New York University. The podcast is short, only 12 minutes, and it is remarkably clear and informative.

To listen to the podcast, go to http://www.sciencefriday.com/program/archives/200912116, and clik the play button in the upper left hand corner under Listen.

Researchers report a non-invasive, drug-free technique to erase a bad memory in the human brain. Writing this week in the journal Nature, the researchers describe using a behavioral modification technique to remove a simple fear memory in people. The key appears to lie in when the technique is applied. Reactivating a memory, the team found, appears to open a “reconsolidation window,” a time-limited period during which the memory can be changed. We’ll talk with one of the team members about the finding, and how it may aid victims of trauma.

The current conventional talk-therapy for dealing with phobias and Post Traumatic Stress Disorder (PTSD) is called Systematic Desensitization therapy or Extinguishment. This is the old get back up on the horse that threw you therapy. Dr Phelps says that the problem with this therapy is that it creates two memories–the original fear memory and a new one that is safe–and when faced with the stimulus (you see the horse) the two memories compete with each other causing further anxiety and tilting your brain towards choosing the fear memory.

The current consensus of memory is that each time you recall a memory you change it slightly. There is a window of time, called consolidation, where the new, revised memory is processed–tagged, sorted, labeled stored in the right place in the brain. When you recall the fear memory, and then create a new version of that memory during that consolidation window, this research shows that you can replace the original fear memory, instead of creating an extra, competing version of it. (That consolidation window opened, in this study, 10 minutes after recalling the original fear memory.

We can imagine therapies (versus meds) that could be created to do this. This is an example we can understand of how drug-free, non-invasive therapy might work.

Phobias and PTSD involve fear and trauma memories.

At HOP’s (Healthy Outcome Partnership) upcoming Mental Health Week (May 10th – 15th), we will have two or three speakers on PTSD. Listening to this podcast is a nice introduction to potential PTSD therapies.

I highly encourage you to listen to this short podcast.

I finally got around to reading Louis Menand’s article on psychiatry in the March 1, 2010, The New Yorker. The article covers the same ground, though much more comprehensibly, that many of my recent posts (also Jan. 13, Jan. 6 ) have–kicking off with a review of Gary Greenberg’s Manufacturing Depression (2010).  It is a worthwhile read.  Menand asks all the questions we’ve been asking, and if he leaves us with any point of view it is that “science will never answer them.”

Do not read the psychiatric literature. Everything in it, from the science (do the meds really work?) to the metaphysics (is depression really a disease?), will confuse you. There is little agreement about what causes depression and no consensus about what cures it. Virtually no scientist subscribes to the man-in-the-waiting-room theory, which is that depression is caused by a lack of serotonin, but many people report that they feel better when they take drugs that affect serotonin and other brain chemicals.

Other books covered in the article:

• Irving Kirsch’s The Emperor’s New Drugs (2010)
• Christopher Lane’s Shyness (2007)
• David Healy’s The Antidepressant Era (1997)
• Andrea Tone’s The Age of Anxiety (2009)
• David Herzberg’s Happy Pills in America (2008)
• Jerome Wakefiled and Allan Horwitz’s The Loss of Sadness (2007)
• Peter Kramer’s Against Depression (2005) and Listening to Prozac (1994)
• and older books from the 50s and 60s.

As I read my way through the article, I found myself often agreeing with the skeptical point of view, but I had to kick myself back awake.  Mental illness is real.  Bad things can happen.  People’s lives get destroyed.  The fact that there is energetic debate within and outside the industry shouldn’t lead people to the conclusion that these diseases are not real and shouldn’t be treated with the best tools available.

As a branch of medicine, depression seems to be a mess. Business, however, is extremely good. Between 1988, the year after Prozac was approved by the F.D.A., and 2000, adult use of antidepressants almost tripled. By 2005, one out of every ten Americans had a prescription for an antidepressant. IMS Health, a company that gathers data on health care, reports that in the United States in 2008 a hundred and sixty-four million prescriptions were written for antidepressants, and sales totalled $9.6 billion.

What a successful [drug trial] typically shows is a small but statistically significant superiority (that is, greater than could be due to chance) of the drug to the placebo.  So how can Kirsch [in The Emperor's New Drugs] that the drugs have zero medicinal value?

His answer is that the statistical edge, when it turns up, is a placebo effect.  Drug trials are double-blind: neither the patients (paid volunteers) nor the doctors (also paid) are told which group is getting the drug and which is getting the placebo.  But antidepressants have side effects, and sugar pills don’t.  Commonly, side effects of antidepressants are tolerable things like nausea, restlessness, dry mouth, and so on.  (Uncommonly, there is, for example, hepatitis; but patients who develop hepatitis don’t complete the trial.)  This means that a patient who experiences minor side effects can conclude that he is taking the drug, and start to feel better, and a patient who doesn’t experience side effects can conclude that she’s taking the placebo, and feel worse.  On Kirsch’s calculation, the placebo effect—you believe that you are taking a pill that will make you feel better; therefore, you feel better—wipes out the statistical difference.

One objection to Kirsch’s argument is that response to antidepressants is extremely variable. It can take several different prescriptions to find a medication that works. Measuring a single antidepressant against a placebo is not a test of the effectiveness of antidepressants as a category. And there is a well-known study, called the Sequenced Treatment Alternatives to Relieve Depression, or STAR*D trial, in which patients were given a series of different antidepressants. Though only thirty-seven per cent recovered on the first drug, another nineteen per cent recovered on the second drug, six per cent on the third, and five per cent after the fourth—a sixty-seven-per-cent effectiveness rate for antidepressant medication, far better than the rate achieved by a placebo.

Kirsch suggests that the result in STAR*D may be one big placebo effect. He cites a 1957 study at the University of Oklahoma in which subjects were given a drug that induced nausea and vomiting, and then another drug, which they were told prevents nausea and vomiting. After the first anti-nausea drug, the subjects were switched to a different anti-nausea drug, then a third, and so on. By the sixth switch, a hundred per cent of the subjects reported that they no longer felt nauseous—even though every one of the anti-nausea drugs was a placebo.

Later studies have shown that patients suffering from depression and anxiety do equally well when treated by psychoanalysts and by behavioral therapists; that there is no difference in effectiveness between C.B.T., which focusses on the way patients reason, and interpersonal therapy, which focusses on their relations with other people; and that patients who are treated by psychotherapists do no better than patients who meet with sympathetic professors with no psychiatric training. Depressed patients in psychotherapy do no better or worse than depressed patients on medication. There is little evidence to support the assumption that supplementing antidepressant medication with talk therapy improves outcomes. What a load of evidence does seem to suggest is that care works for some of the people some of the time, and it doesn’t much matter what sort of care it is. Patients believe that they are being cared for by someone who will make them feel better; therefore, they feel better.

In 1980, the F.D.A. required that anxiety medications carry a warning stating that “anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.” The anxiety era was over. This is one of the reasons that when the SSRIs, such as Prozac, came on the market they were promoted as antidepressants—even though they are commonly prescribed for anxiety. Anxiety drugs had acquired a bad name.

The position behind much of the skepticism about the state of psychiatry is that it’s not really science. “Cultural, political, and economic factors, not scientific progress, underlie the triumph of diagnostic psychiatry and the current ‘scientific’ classification of mental illness entities,” Horwitz complained in an earlier book, Creating Mental Illness (2002), and many people echo his charge. But is this in fact the problem? The critics who say that psychiatry is not really science are not anti-science themselves. On the contrary: they hold an exaggerated view of what science, certainly medical science, and especially the science of mental health, can be.

Progress in medical science is made by lurching around. The best that can be hoped is that we are lurching in an over-all good direction.

The DSM lists only disorders—clusters of symptoms, drawn from clinical experience—not diseases. Since people manifest symptoms in an enormous variety of combinations, we get a large number of disorders for what may be a single disease.

Depression is a good example of the problem this makes.  A fever is not a disease; it’s a symptom of disease, and the disease, not the symptom, is what medicine seeks to cure.  Is depression—insomnia, irritability, lack of energy, loss of libido, and so on—like a fever or like a disease?  Do patients complain of these symptoms because they have contracted the neurological equivalent of an infection?  Or do the accompanying mental states (thoughts that my existence is pointless, nobody loves me, etc.) have real meaning?  If people feel depressed because they have a disease in their brains, then there is no reason to pay much attention to their tales of woe, and medication is the most sensible way to cure them.  Peter Kramer, in Against Depression (2005), describes a patient who, after she recovered from depression, accused him of taking what she had said in therapy too seriously.  It was the depression talking, she told him, not her.

Depression often remits spontaneously, perhaps in as many as fifty per cent of cases; but that doesn’t mean that there isn’t something wrong in the brain of depressed people.

Depression is episodic. It starts and stops. Then starts again. Kramer argues that is progressive, and episodes worsen (deepen) over time.

In the case of mood disorders, it is difficult to find a test to distinguish mental illness from normal mood changes. The brains of people who are suffering from mild depression look the same on a scan as the brains of people whose football team has just lost the Super Bowl.

Given the current scanning technology, and where and how we choose to look.

Science, particularly medical science, is not a skyscraper made of Lucite. It is a field strewn with black boxes. There have been many medical treatments that worked even though, for a long time, we didn’t know why they worked—aspirin, for example. And drugs have often been used to carve out diseases. Malaria was “discovered” when it was learned that it responded to quinine. Someone was listening to quinine. As Nicholas Christakis, a medical sociologist, has pointed out, many commonly used remedies, such as Viagra, work less than half the time, and there are conditions, such as cardiovascular disease, that respond to placebos for which we would never contemplate not using medication, even though it proves only marginally more effective in trials. Some patients with Parkinson’s respond to sham surgery. The ostensibly shaky track record of antidepressants does not place them outside the pharmacological pale.

At the bottom of column 15, in a 18 column article, we have arrived at the most important part of the article for me. I hope everyone reads this far.

Many people today are infatuated with the biological determinants of things. They find compelling the idea that moods, tastes, preferences, and behaviors can be explained by genes, or by natural selection, or by brain amines (even though these explanations are almost always circular: if we do x, it must be because we have been selected to do x). People like to be able to say, I’m just an organism, and my depression is just a chemical thing, so, of the three ways of considering my condition, I choose the biological. People do say this. The question to ask them is, Who is the “I” that is making this choice? Is that your biology talking, too?

Yes, your biology, and your psychology, and your philosophy talking.

The decision to handle mental conditions biologically is as moral a decision as any other.

The recommendation from people who have written about their own depression is, overwhelmingly, Take the meds! It’s the position of Andrew Solomon, in The Noonday Demon (2001), a wise and humane book. It’s the position of many of the contributors to Unholy Ghost (2001) and Poets on Prozac (2008), anthologies of essays by writers about depression. The ones who took medication say that they write much better than they did when they were depressed. William Styron, in his widely read memoir Darkness Visible (1990), says that his experience in talk therapy was a damaging waste of time, and that he wishes he had gone straight to the hospital when his depression became severe.

Don’t hesitate to ask someone for help.

March 19th, The New York Times Deborah Sontag reports on Haiti’s mental health system after the earthquake.

The foreign psychiatrists emphasize that they have found Haitians to be impressively resilient, but the disaster has nonetheless set off reactions ranging from anxiety through psychosis. Most worrisome are cases like that of Guerda Joseph, a 41-year-old woman who tumbled into a catatonic depression shortly after she was pulled from the rubble of her home. Mute and nearly immobilized ever since, she lies on floral sheets at the General Hospital, her Bible tucked beside her pillow, her 25-year-old adopted son by her side day and night.

More common, though, is what Dr. Lynne Jones, a child psychiatrist and disaster expert with the International Medical Corps, calls “earthquake shock,” a persistent sensation that the earth is still shaking, which makes the heart race and causes chest pain.

“This is an understandable response, and it’s important to let people know, ‘You are not crazy,’ ” Dr. Jones said. “I use a kind of metaphor: ‘Your body has a very effective fire alarm. One of the reasons you’re alive today is that it went off during the earthquake. You ran out of that building. Great, you survived. Unfortunately, the fire alarm is now sensitive and goes off when you don’t want it to, or maybe it never shut off.’ ”

An earthquake offers extreme examples of how mental illness takes hold and progresses. This analogy of a fire alarm, that doesn’t shut off, is a useful way to think about anxiety and panic in our lives.