Anatomy Lesson 2008: Living in Fear

You may want to play this music while reading this post: Bach: Gottes Zeit ist die allerbeste Zeit (BWV 106)

The “Anatomy Lesson” has several meanings:

1. A lesson in Anatomy
2. A famous painting of Rembrandt van Rijn (of Nicolaes Tulp) (1632).
3. The homepage of the AMC, the Academic Medical Center in Amsterdam, inspired on the painting of Rembrandt.
4. A yearly symposium at the intersecting plane of medicine, art and society, organized by the AMC and the Volkskrant, a Dutch newspaper.
   

This year I was invited to the yearly “Anatomische Les” in the concertgebouw, Amsterdam’s beautiful concert hall (see Wikipedia). It is a very official happening. The audience had to take their seats long before the start. It took more than 2 hours without any break.

Anatomy Lesson 2008 in the Concertgebouw

This year’s theme was FEAR. The program was as follows:

• Welcome – Rinnooy Kan
• Presentation of new work of art of Albert van Westing (1960), recently bought by the AMC – Wim Pybes, director of the “RijksMuseum”
• “Mit Freud und Freud ich fahr dahin”- Johan Sebastian Bach. 1.”O Jesu Christ, mein’s Lebens Licht” 2. Gottes zeit ist die allerbeste Zeit – Baroque Ensemble “Follia d’ Amsterdam” together with the choir “Nuovo Musico” , conducted by Gustav Leonhardt (above is another version). The cantatas express both fear for death and faith in God.
• Audiovisual presentation of the assay ” de vertrouwenscrisis” (what went wrong with the fundamental trust in the Dutch society?), written by 19 different publicists.
• Audiovisual impression of pupils of Amsterdam High Schools attending lectures in psychiatry: funny and disarming.
• And the climax: a 50 min lecture of Prof. Arieh Y. Shalev, M.D. (Head Department of Psychiatry at the Hadassah University Hospital of Jerusalem, Israel) about living with fear.

I will try to summarize the main points of Shalev’s lecture as I remember them (no notes).

There are several factors that may influence how people react to fear:

1. DNA (fixed), inherited differences – (written composition in musical notation)
2. Epigenetic Mechanisms (mostly but not exclusively determined postnatally). (tuning of the piano, quenching the middle register)
3. (Gene) Expression (Accordion register determining ranks and timbres, determined by the accordionist)
   
4. Exogenous factors (i.e. empathy and affection) (the people singing, the acoustics)

Fear is an emotional response to threats and danger, meant to protect against a threat (fright-fight-or-flight). It is a basic survival mechanism occurring in response to a specific stimulus, such as pain or the threat of pain. Recognizing a person in agony is easy. The facial expression of fear includes the widening of the eyes (out of anticipation for what will happen next); the pupils dilate (to take in more light); the upper lip rises, the brows draw together, and the lips stretch horizontally. Muscles used for physical movement are tightened and primed with oxygen, in preparation for a physical fight-or-flight response. When the stimulus is shocking or abrupt, a common reaction is to protect vulnerable parts of the anatomy, particularly the face and head. When a fear stimulus occurs unexpectedly, the victim of the fear response could possibly jump or give a small start. The person’s heart-rate and heartbeat may quicken (from Wikipedia).

The amygdala, an almond shaped complex of related nuclei, located in the middle of the brain, is a critical processor area for fear. Connected to the hippocampus, it plays a role in emotionally laden memories. It is part of the limbic system.

Fear, begins with arousal. For instance:

1. You hear a sound. The amygdala is alerted.
2. You see a face, the amygdala is alerted to a greater extent. Your pupils enlarge, your breathing and hartbeat quicken.
3. You recognize the face; it is nobody to be afraid of: the fear response is dampened. The heartbeat drops to normal levels, because you are reassured that there was no danger.

But suppose (1) you’re walking in a dark alley and (2) you see a gun. (3) Next you see a man holding that gun. (4) He shouts something threatening. There are no breaks anymore (by prefrontal cortex/hippocampus on the amygdala) and the fear machine starts running at full speed. Thus, in case of a major threat, in a split second all alarm bells ring: the abovementioned reflexes occur immediately and with no point of return.

One’s memory of what happens consists of separate “pictures”: (1) the alley, (2) the gun, (3) the man, (4) a loud voice (and perhaps smell). Normally, moments of fear will takes it’s place along other memories, although this may take some time.

However, depending on the kind of fear, your personality and external factors, memories to the incident causing fear may stay at the foreground. It may become a memory that comes to the mind frequently and spontaneously or evoked by one of the remembered associations. For instance any alley may cause the full blown fear response again in the abovementioned example.

Shalev telling this, I suddenly understood my reactions to a car accident. While driving on the highway, the driver lost control of the vehicle, causing it to skid and finally ending against a huge concrete wall. I was sitting in the back and while the car was turning I saw “the wall hitting us”. My “last thought” was “that was it”. The car was total loss, but luckily all 5 (members of a dancing group) survived. Apparently because of the “fear of death”, the impression of that very moment staid long with me. For almost a year I felt frightened not only in a car, but also when I saw a car or motor turning fast around the corner or when moving sideways in an airplane during landing. It must have been a similar feeling as when the car turned and hit the wall. The resemblance of that moment brought the memory and the fear back in quite un uncontrollable way. But as time passed by, so did this emotional reaction. The memory itself was still there, but at the background and slowly all intense associations with that frightful moment faded.

This is what normally happens with frigtening experiences. Fear can be retriggered by a memory (smell, picture, situation) linked to what happened, but can extinguish over time. Thus responding to a conditioned stimulus (CS) spontaneously recovers with the passage of time indicated that extinction does not erase the conditioned memory, but is a form of (active) inhibition. The brain (prefrontal cortex/hippocampus) learns how to coop with it and suppress the emotional fear reflex (amygdala).

However, some fears don’t extinguish and have a lifelong impact. For instance in post-traumatic stress disorder (PTSD), which is a severe and ongoing emotional reaction to extreme physical or psychological trauma.

Shalev gave several examples of people with PTSD other than PTSD in war veterans . For instance, a mother who lost her daughter on the complications of a simple (and unnecesary) intervention. The daughter died of sepsis and from that moment on the mother continued to live in the past, persistently reexperiencing the traumatic event.

This was what the mother remembers as the most frightful moment:

I entered the door, my hand still holding the knob. There she lied staring with pupils so dilatated that her irisses were no longer visible. Death was inevitably approaching. I wanted to scream for help, but there were no doctors present and nurses were all running around. I could do nothing about it.

That was a recurrent theme in all examples: feeling desparate and helpless while facing the inevitable.

In PTSD patients the normal extinction mechanisms don’t work. PTSD patients remain in a state of arousal.

In a longitudinal MRI study Shalev showed that a smaller hippocampal volume is not a necessary risk factor for developing PTSD and does not occur within 6 months of expressing the disorder, thereby dismissing the widely held belief that the volume of the hippocampus is reduced in PTSD patients . (Bonne O et al. Am J Psychiatry. 2001 Aug;158(8):1248-51. Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD.)

Shalev also emphasized that the mere reiteratation of the traumatic event doesn’t help the patient. If the patient is in fear it doesn’t help to bring him to an alley all over again, and to leave the alley again as soon as the patient gets frightened. This only reinforces fear. What should be done is to learn the patient to associate the alley with positive events through psychotherapy. Trust, empathy, friendship can all help as well.

Because extinction is a form of learning some medical treatments given soon after the trauma will not help to reduce the PTSD. In a Randomized Controlled Trial presented at the American College of Neuropsychopharmacology 46th Annual Meeting (December 8-12, 2007), Shalev and coworkers showed that cognitive therapy or prolonged exposure therapy (a type of cognitive behavioral therapy) within 1 month had a reduced prevalence and severity of PTSD at 5 months to 20%, whereas early treatment with a selective serotonin reuptake inhibitor (SSRI) fared no better than individuals randomized to placebo or spontaneous recovery (wait-list) groups (60%). According to Shalev this is a phantastic effect. (Source: Medscape ).

Still, although cognitive therapy is effective, many PTSD patients remain symptomatic despite initial treatment.
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This post was (also) written for next Grand Round hosted by Mexican Medical Student. Enrico had a tentative theme in mind (with some flexibility to change it ) but these words should be applicable: renewal, metamorphosis, change, transformation. Well, this story was about how extreme fear can transform you in another person. Furthermore death, referred to in the Bach cantate, is our ultimate transformation.
Finally I hope that Enrico, being both a medical student and a classical pianist likes Bach.