Anxiety, PTSD and Propanolol

A recent study, Beyond extinction: erasing human fear responses and preventing the return of fear, is making a lot of headlines.

I will go through the study in a moment. But first I want to make an observation from my clinical experience.

A number of persons that I treated for anxiety disorders were on propanolol. Some used it for cardiac health, some took it to help with their anxiety problems. Their anxiety disorders ranged from uncomplicated phobias to severe, chronic PTSD stemming from service in the Viet Nam war.

For better or worse, I cannot confirm the results claimed in the new study. I did not, then or in retrospect now, find that the exposure trials or treatment in general went any smoother or quicker for the persons on propanolol. Nor did I find that the medication extinquished the fear associated with memories of the war.

Admittedly, my sample size is not as statistically significant as the one in the study. My treatment approach did not incorporate the fact, one way or another, that the patient was on propanolol. In fact, for all intents and purposes, I ignored whether or not they were on that medication.

But I think I would have noticed something if propanolol had such beneficial effects. At least I would recall those patients as being easy cases. In fact, two of them are among the most memorable for the tenacity and duration of their symptoms.

With that caveat, let me summarize the recent research.

When we bring a memory to consciousness, there is the potential to change parts of that memory and the emotions assoicated with it. This, itself, is not a new concept. It goes back to at least Freud. The process of recalling and changing aspects of a memory is termed "reconsolidation" in this and other studies.

The authors "repeatedly showed healthy volunteers pictures of spiders, one image of which was followed by an electrical shock." (Aren’t you glad you did not volunteer for that study?)

The volunteers learned to associate the image of the spider with fear. The degree of fear was measured by the "startle response" exhibited by the subjects.

Afterwards, some of the volunteers received propanolol and others got a placebo. They were then tested for how much of a startle response was elicited by the the image of the spider.

The authors found that for persons given the propanolol "the conditioned fear response was not only reduced but even eliminated…"

In contrast, those who got the placebo, their "startle response remained significant."

Simply put, after receiving propanolol, “The people did not forget seeing the photograph of the spider,” Kindt says. ”But the fear associated with the image was erased."

How does that work in the brain? The authors suggest that "(i)t may be hypothesized that beta-adrenergic blockade during reconsolidation may selectively disrupt the protein synthesis of the amygdalar fear memory, resulting in deconsolidation of the fear memory trace while leaving the declarative memory in the hippocampus untouched."

Furthermore, “Beta-blockers wouldn’t stop reconsolidation of only frightening memories, the researchers say. ‘It’s likely that any emotional memory, happy or sad, recalled after taking the drug would be dulled,’ Kindt speculates.”

On the clinical side, these findings would suggest using propanolol in conjunction with procedures like Breur’s abreaction, Freud’s cathartic method, some Gestalt therapy procedures, NLP’s dissociating and reframing, venting, exposure and other methods.

The question remains about how to square this study’s findings with my clinical experience. Here are a few guesses. It may be that there was something peculiar to the patients I treated that made them resistant to the benefits of propanolol. That, I suppose, is possible but I do not think it is likely. Alternatively, it may be that propanolol is useful in treating newly acquired fears or phobias. Or it may have a prophylactic benefit for people soon to be exposed to a trauma (think of a firefighter going to his/her first apartment building fire, a sniper fresh from boot camp about to be deployed to an Afghan hilltop).

In the end, I agree with the Guardian’s conclusion: "we don’t know whether the results would apply outside of this artificial situation. We need to see good-quality studies among people who have suffered a genuinely painful or upsetting event, to see whether this type of treatment can help them in a meaningful way."

And then there are some ethics questions to be addressed.

Kerri Smith hints at this by recalling the movie “Eternal Sunshine of the Spotless Mind.” Do we use drugs to extinguish affective memories of unhappy relationships?

If propanolol is effective in negating or dulling the emotional aspect of an event, what impact would that have on the decision-making of, say, a sniper determining whether or not to take a shot if the pathway to the target was through the body of a civilian? Would it embolden persons considering a heroic act? What would it do for persons about to commit a violent crime?

This study, for me, raises as many questions as it answers.

Recent Anxiety Research and News

  • Washington University’s newspaper reports on a study of social phobia among college students. One of its findings is that unstructured discussion of past upsetting events raises the distress level for some people. On the other hand, when the interview was structured, the “subjects’ moods did not worsen.”
  • The NIH is promoting meditation, yoga, tai chi and Pilates as means to improving physical and mental health. There is also discussion of the interconnection between physical and mental well-being. You can read the Washington Post’s article here.
  • reports on a study of the long-term relationship between childhood separation anxiety disorder and adult panic disorder. “Genetic determinants appear to be the major, underlying cause…” However, “childhood parental loss is a truly environmental risk factor uninfluenced by genetic factors, it can further affect susceptibility to panic disorder and perhaps alter an individual’s respiratory physiology for a long time.” Read more about this interesting article here.
  • The Capital Times” writes about the effect of the current economy on persons’ mental health. Some of the conclusions are “As people lose jobs or watch their retirement savings dry up, some local psychiatrists say they are seeing an increasing number of new patients with depression or anxiety, and that the symptoms of some current patients have worsened.Beyond that, these doctors say, many who need treatment aren’t receiving it because they cannot pay, having lost their jobs or their insurance.”
  • A study on “unexplained chest pain” finds that there are “several common factors among those affected, including stress at work, anxiety, depression and a sedentary lifestyle.”
    Which reinforces the benefits of stress reduction and an active lifestyle, as mentioned above in the reference to the NIH’s recent efforts.

No One Knowingly Errs

In the very first post on this blog, I wrote: "Actions based on anxiety are often regrettable."

That may be true, but someone experiencing intense anxiety or a panic attack feels under great pressure to do something, anything to relieve the anxiety and improve their situation.

Nevertheless, actions born from anxiety often have poor or unintended outcomes.

Those negative outcomes reinforce one’s feeling of being out of control, or of being inept, flawed. There is no sense of having a certain mastery or competence in the situation. In turn, those thoughts and emotions fuel further anxiety. There is now "objective" proof that the situation is overwhelming and threatening. The anxiety and panic is now grounded in hard evidence. This is the same situation I wrote about in "Anxiety, Self-Esteem and Self-Soothing."

Some recent studies shed a bit more light on this self-fulfilling prophecy.

The Rockefeller University posted "Stress disrupts human thinking, but the brain can bounce back" on January 27, 2009. In sum, they found that:

  • "A new neuroimaging study on stressed-out students suggests that male humans…don’t do their most agile thinking under stress."
  • "[stressed persons] had a harder time shifting their attention from one task to another than other healthy young men who were not under the gun."
  • In research on rats, the workers found further biological basis for poor performance under stress:
    "repeated stress on rats shriveled nerve cells of the medial prefrontal cortex, and that a shrunken prefrontal cortex is linked to slower performance on attention-shifting tasks."
  • However, there is good news as well. Within a month after the stress ends, the brain bounces back to its normal state and attention and performance returns to a person’s baseline level.

These findings are generally verified in another recent study: "Driving Under the Influence (of Stress): Regional Effects of 9/11 Attacks on Driving." "The authors found that there was an increase in the rate of traffic fatalities in the three months following the 9/11 attacks, but only in the Northeast, the region closest to the terrorist attack…" Further, there was "a 100 percentage point increase in the rate of drug- and alcohol-related fatal traffic accidents in the Northeast."

The authors theorize that "being close to the location of a traumatic event, such as the 9/11 attacks, may increase psychological stress, which may, in turn, impair one’s driving ability and thus lead to an increase in fatal traffic accidents."

Being under stress, whether from an upcoming test or a nearby terrorist attack, impairs a person’s ability to think, plan, perform. The consequences of choosing a course of action under stress and anxiety (for example, is it a good idea to drink alcohol if I know that I will have to drive later), can be severe. Doing poorly on a test or getting into a car crash can provide the illusory conclusions that I am not smart or I am a really bad person. With those beliefs, one is even more likely to become unduly anxious and underperform in the future.

But again notice the silver lining in the second study-traffic fatalities declined again three months after the stress of the 9/11 attack.

However, the effects of long-term stress or life-threatening events may not be so quickly reversed.

A study from the University of Wisconsin, published in the January 26, 2009 Proceedings of the National Academy of Sciences, looked at the immune systems of children who had lived in orphanages in Romania, Russia or China and were later adopted by American families. They found that, even after ten years of life in "stable, affluent, loving environments…their immune systems are compromised as well. In fact, they look just like the [more recently] physically abused kids."

"’Even though these children’s environments have changed, physiologically they’re still responding to stress. That can affect their learning and their behavior, and having a compromised immune system is going to affect these children’s health,’ says senior author Seth Pollak, a professor of psychology and pediatrics at UW-Madison."

Imagine, if you will, how easy then it would be for those children to form negative opinions about themselves and their abilities. They are ill more frequently than the children around them, have more difficulty making correct judgements. Their behaviors are not as well controlled as their peers’. They have more difficulty learning and in school. All this despite the apparent advantage of now living in "stable, affluent, loving environments." Who else to blame but themselves?

Let’s look at the sheerly biological side of this matter. In 2006, the Department of Neuroscience, Mount Sinai School of Medicine studied rats exposed to 21 days of restraint stress. [Readers interested in the effects of restraint stress on animals, in simpler language, are recommended to read Restraint and Handling of Wild and Domestic Animals By Murray E. Fowler] Mount Sinai’s study found significant impairment of the medial prefrontal cortex. "[N]early one-third of all axospinous synapses on apical dendrites of pyramidal neurons in medial PFC are lost following repeated stress…Dendritic atrophy and spine loss may be important cellular features of stress-related psychiatric disorders where the PFC is functionally impaired."

That’s a dense packet of jargon. Let’s break down those last two sentences a bit.

Click here for a look at the medial prefrontal cortex.

Now, why is the medial pre-frontal cortex important?

Here’s what Wikipedia says about that area of the brain:

"The most typical psychological term for functions carried out by the pre-frontal cortex area is executive function. Executive function relates to abilities to differentiate among conflicting thoughts, determine good and bad, better and best, same and different, future consequences of current activities, working toward a defined goal, prediction of outcomes, expectation based on actions, and social ‘control’ (the ability to suppress urges that, if not suppressed, could lead to socially-unacceptable outcomes)."

So the pre-frontal cortex assists in judgement, planning, decision-making (e.g., should I drink if I am going to have to drive home).

The dendrites bring information into the cells of the medial pre-frontal cortex. A loss of "nearly one-third" of these information carriers would have significant and negative impact on the ability to make judgements, plans, etc.

This same area of the brain has been implicated in Post-Traumatic Stress Disorder. In "Amygdala, Medial Prefrontal Cortex, and Hippocampal Function in PTSD", the authors find that the "medial prefrontal cortex appears to be volumetrically smaller and is hyporesponsive during [PTSD] symptomatic states and the performance of emotional cognitive tasks in PTSD. Medial prefrontal cortex responsivity is inversely associated with PTSD symptom severity."

So, in both PTSD and situations of significant, chronic stress, there is long-term impairment of the medial prefrontal cortex. In turn, the afflicted person’s executive functioning (judgement, planning, decision-making, etc.) is worsened for lengthy periods of time.

It appears that shorter periods of lower grade stresses (e.g., an upcoming important test) produce briefer periods of poor executive functioning and less extensive impairment of the medial prefrontal cortex.

These studies can be used to make another point. We have seen that a stressed person has impaired executive functioning that stems at least in part from damage to the medial prefrontal cortex. Consequently, a stressed person will be cognitively, emotionally and behaviorally functioning at a lower level than their best capabilities. Therefore, these persons should be especially cautious before making and carrying out plans (even one as simple as whether or not to drive to a keg party). Equally important, their choices and behaviors have to be viewed in the context of being stressed and having a damaged prefrontal cortex.

With this knowledge in hand, a stressed, anxious or panic-stricken person can revise their opinions of themselves in a more objective fashion.

We would not judge how good a runner one was if the judgement was based on a 100 yard dash done when the person had the flu. All that can tell us is how they perform when significantly ill and impaired.

Forming your self-image and self-esteem on the evidence of beliefs, judgements and actions while stressed or suffering its after-effects is equally absurd.

Unfortunately, many people with anxiety, panic and other psychiatric disorders do exactly that. The net result is to generate further stress because of the internal self-criticisms and anxiety about their ability to function in the world. That, in turn, yields more impairment of the prefrontal cortex and consequently worsening executive functioning. A person’s self-image and self-esteem will then be in a graveyard spiral.

I will return to these studies and their implications in a later post about anxiety and self-image. For now I will leave you to ponder Socrates’ claim that "No one knowingly errs." Especially as it might apply to persons who are anxious, panicky, stressed and make invalid assumptions, poor judgements and mistakes in their actions.