Sunday, May 5, 2013

Relief From Death Anxiety: In Your Medicine Cabinet Already?

The radio show Wait, Wait....Don't Tell Me! has a weekly segment called "Bluff the Listener" during which a caller listens to three unbelievable stories and then guess which one of the three is actually true.  Much to my surprise, this week's "true" (yet unbelievable) story is about evidence that acetaminophen might relieve existential angst. (Here's a direct link to the audio segment.)

Julius Axelrod (Source: National Institutes of Health)


Really?  Good ole' Tylenol might relieve bothersome thoughts about the ultimate threat to our existence?  How could I not investigate this further, if only because the report threatens any conception I have of this meek anti-pyretic/analgesic. The title of the study from Psychological Science piqued my intrigue: "The Common Pain of Surrealism and Death: Acetaminophen Reduces Compensatory Affirmation Following Meaning Threat."  

The journal article describes two separate studies, but has a background section with some familiar sounding concepts to palliative care clinicians and others which are likely foreign.  The authors describe evidence which suggests both physical and social pain may activate the dorsal anterior cingulate cortex (dACC).  This area of the brain may serve as a "cortical alarm system" which is sensitive to any discrepancy in the environment (such as a new severe pain stimulus or perceived social slight).  The dACC has thus "been theorized to be the source of the unpleasant arousal associated with uncertainty and violations of expectations."  Indeed, the authors cite evidence suggesting acetaminophen may reduce activation of the dACC.

What about fear of death?  We'll get there, but first, the "Meaning Maintenance Model" which is useful for understanding the study:
""The Meaning Maintenance Model" focuses on people’s compensatory responses to violations of expectations, termed meaning threats. The model posits that any perceived meaning threat produces unpleasant arousal that often lies outside of awareness, and is nonspecific to the causal stimulus. This arousal arguably serves to prompt people to identify the source of the perceived discrepancy and, if time and cognitive resources are sufficiently available, to accommodate to the unexpected event....In many cases, however, it is not possible to resolve the violation, either because the problem is too complex or because the source of the arousal has not been identified correctly. When this occurs, people may respond to the arousal by affirming any available unrelated schema to which they are committed. These affirmations of intact meaning frameworks serve to dispel the unpleasant sense that something is wrong."
In other words, if there's a violation to meaning which is challenging to resolve (e.g. thinking about one's own death), a person might compensate by using cognitive resources to resolve an unrelated but easier to resolve challenge. At the heart of the hypothesis, the presence of a violation of meaning may influence how the person resolves the easier challenge.  The person may overcompensate in resolving the "easier" challenge if already presented with a violation to meaning that cannot be readily resolved.   How did the researchers test this hypothesis?


In one of the double-blind, randomized controlled studies, the participants received either Acetaminophen 1000 mg or a placebo pill orally.  After completing some filler tasks to allow time for the drug to reach peak effect, all participants were randomized to complete an essay on one of two topics: 1. What will happen to their body after they die and how they feel about it or 2. The experience of dental pain.  Dental pain was chosen because it's an aversive event but likely doesn't create an experience of "violated expectations" like imagining death might.

Subsequently, subjects read about a hypothetical arrest of a person accused of prostitution and were asked to set a bail amount (a "social judgment survey"),  an arbitrary task for most of us but one which isn't too challenging to think about.

The researchers found that of all the participants, the group which was asked to write about their own death after taking a placebo pill set the highest bail.  The difference between this group and the other groups was statistically significant whereas the difference between the other groups (including the death-writing/Tylenol-taking group) was not significant.  In other words, the death-writing/placebo-taking group "compensated" by punishing the accused person more harshly yet this effect appeared to be mitigated by acetaminophen.

Self-reported positive and negative affect did not differ between any of the study conditions, suggesting to the researchers that compensation/"meaning maintenance" is largely not a conscious process.

Included in the paper is another study using similar methods to test the same hypothesis but with different conditions.  They found similar results.  The authors point out that while Acetaminophen acts at the dACC, it also acts elsewhere, so no conclusion can be made about the neurophysiological basis of any effect.  

So, after being asked to reflect on death, participants in this study (who were students at the  University of British Columbia where the studies were conducted) inflicted a harsher penalty than normal, perhaps to compensate subconsciously for their inability to resolve the "violation" of thinking about their own death. Should your electronic medical record system now add "existential angst" as an indication for Tylenol?  Keep prescribing it for mild pain and fever, but there's nothing in this study which suggests added value of Tylenol for a patient facing a serious, potentially life-threatening illness. There's probably more relevance to defense attorneys who might consider asking potential jurors during voir dire if they have recently been diagnosed with a life-threatening illness (I suspect that's a stretch, too). 

What is the relevance of this study, then, to you, the curious Pallimed reader?

Cicely Saunders' concept of total pain and Eric Cassell's deconstruction of suffering are frequently cited in palliative care literature.  Both suggest a common pathway by which changes in a person's physical, social, psychological, and spiritual states might inflict the person.  I cannot remember coming across a proposed neurophysiological explanation of the phenomena- if one exists, I'd love to see it. The theoretical "meaning maintenance model" described in the article seems to resonate well with total pain/suffering as well as our attempt to intervene through palliation.

If the "meaning maintenance model" is real, what adaptive and maladaptive ways do people use in a subconscious attempt to compensate?  For instance, people cannot control the fact that they will die, but can exert some control over decisions about their healthcare.  What subconscious processes are at play as patients and their physicians navigate these decisions?

What palliative care interventions provide an avenue for people to compensate when faced with the "unpleasant violation of expectation" which can be associated with the imminent threat of death?  Of many possibilities, dignity therapy comes immediately to mind as a therapy which fits the model of "affirming an intact meaning framework" in a constructive manner.  What are the neurophysiological effects of dignity therapy?

In the context of this study, it's also interesting to reflect on the variation amongst people with respect to death anxiety.  Might this be explainable by differences in neurophysiology?  For instance, when faced with death, might a region of the brain (such as the dACC) become less activated in some people than others?  What affect could age have on the response of this region of the brain (e.g. does it become less responsive as we grow older, on average).  What about over the course of a chronic disease?

What about spiritual practices?  Might mindfulness or reflecting on a religious verse about death influence the reactiveness of the dACC? In a very brief search, I did find a few references to the dACC being thicker on average in those who meditate, and a growing body of evidence suggests the value of mindfulness for various physical and psychological symptoms. (My hypothesis: Look at the mirror on your medicine cabinet rather than inside the cabinet for a possible source of relief for death anxiety.)

Lots of questions.  Maybe, unbeknownst to me, some answers exist, though I suspect future career(s) could be formed around some of them at the intersection of neurophysiology, psychology, and medicine .  

@lfettig

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