Drugs and Trauma.
Attempts to reduce the intensity of fear-memory encoding through the disruption of protein synthesis… Continue.
If you suffer from a fear-related mental illness (or know someone who does) and have noticed that your decision-making Kung Fu (i.e. your ability to make sound and timely decisions, electing optimal options regularly) is less sharp than it once was, know that Neuroeconomists around the world are… still working on it.
The link between fear and decision-making proficiency is well established (Hartley and Phelps, 2012); one might cringe when imaging the decision-making cycle of a person who is chronically distracted by fear memories, such as someone with Post Traumatic Stress Disorder (PTSD). It is reasonable, therefore, to consider that the aggregate decision-making proficiency of a large population could be improved through the general reduction of chronic fear-related mental illness.
Hoffman et. al. (2015) explored whether the intensity of the impact of traumatic memories could be reduced through the early disruption of their encoding. They thought that if you could take a drug (in this case, Rapamycin) before a traumatic event was encoded in your memory, the encoding process (the moments after an event occurs when your brain is figuring out where to put the stuff it just experienced) would be altered, extreme memories would be absorbed less aggressively, and their longer term effects on individuals would be reduced. Sadly, they found that whilst Rapamycin does influence the coding of normal memory (and even some fear memories), it had little impact on fear memory encoding in chronically stressed groups.
Their logic was straightforward; whereas you might draw all kinds of romantic, poetic, or existential conclusions about how your memory works (or doesn’t), the encoding of new memories is characterized by a number of steps, one of which (critical to later retrieval), is protein synthesis — explicitly, a protein called zif268. Disrupting that synthesis can directly alter the way your brain takes in new information, thereby affecting its accessibility, or the process through which you call upon that particular information in the future. As anxiety disorders are characterized by persistent, unwavering, and excessively strong memories in the case of someone suffering from PTSD, memory retrieval is not always voluntary, and can lead to maladaptive behaviour (Pittman, 1989). If you could use a drug to make a person less vulnerable to the formation of chronic fear memories, this could have huge implications for public and private sector organizations that experience above-average PTSD occurrence within their populations (military, emergency services, etc).
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To test their theory, Hoffman et. al. administered Rapamycin (a drug linked with anti-ageing, but whose other effects are still being explored) to rats and then exposed them to novel fear-related stimuli using fear chambers (also called light and sound attenuating chambers, this simply describes a small box that either shows a light and/or plays a sound and then delivers an electric shock to the animal inside it, see figure 1). They induced chronic stress in one group of rats (stressed condition) and retained a naïve control group. They subsequently euthanized the rats, dissected their brains, and observed the differences in protein synthesis for memories in the context of rats who had not experienced chronic stress. The rats were housed in relatively comfortable accommodation with their cohort, including access to food and water at their discretion. Chronic stress was induced in the experimental group of rats by putting them in wire mesh restraints for six hours a day for 21 days (no food or water either). The control group was nurtured under identical conditions (minus time spent in a wire-mesh restraint) for comparison; during the six hour period where the rats in the stressed condition, the control group was denied access to food and water (Hoffman et. al., 2015).
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They confirmed that chronic stress increases the intensity of new fear memories (this is not new); of far more interest was that they observed that the stress-enhanced “freezing” of new memories was associated with increased activity in the Amygdala, specifically in the lateral and basal areas (LA and BA); these areas have been shown to be critical in the integration of new stimuli (conditioned or unconditioned) in the formation of fear memory, and active during its retrieval. Hoffman et. al (2015) confirmed a significant main effect of conditioning for the LA (F1,28 = 39.244, p < 0.001), and BA (F1,28 = 12.10, p < 0.005), suggesting that fear conditioning was exacerbated by chronic stress. They also discovered that the stressed group had greater zif268 mRNA expression compared to the control group (t14 = 2.357, p < 0.05).
We know that that anxiety increases our focus on negative choice options, the likelihood that we will interpret ambiguous options negatively, and our overall risk aversion, (Hartley and Phelps, 2012). In this context, any initiative that can reduce the impact of new traumatic memories holds the potential to stabilize the lives of countless people whose fear/chronic stress-related condition directly impacts their judgement on a daily basis. Whereas Rapamycin was effective at reducing the intensity of fear memories in the naïve group, it did not significantly affect fear memory retention or recall in the stressed group (based on comparisons of zif268 levels). Despite the bad news, Hoffman et. al (2015) advocate the continuation of research aiming to block the reconsolidation of fear memories, on the strength that inhibiting protein synthesis and/or protein translation has been shown to produce persistent amnesia for the original memory (Nader & Einarsson, 2010). The role of the Amygdala in the interpretation of new stimuli, and its heightened sensitivity in participants exposed to chronic stress might also present an interesting path to explore. The Canadian Mental Health Association (CMHA) predicts that about eight percent of Canadians will suffer from PTSD in their life (CMHA, 2013).
References
Hartley, C. A., & Phelps, E. A. (2012). Anxiety and decision-making. Biological psychiatry, 72(2), 113–118.
Hoffman, A. N., Parga, A., Paode, P. R., Watterson, L. R., Nikulina, E. M., Hammer, R. P., & Conrad, C. D. (2015). Chronic stress enhanced fear memories are associated with increased amygdala zif268 mRNA expression and are resistant to reconsolidation. Neurobiology of learning and memory, 120, 61–68.
Johansen, J. P., Cain, C. K., Ostroff, L. E., & LeDoux, J. E. (2011). Molecular mechanisms of fear learning and memory. Cell, 147(3), 509–524.
Canadian Mental Health Association. (2013). Post-Traumatic Stress Disorder. Retrieved on April 15, 2015 from URL http://www.cmha.bc.ca/get-informed/mental-health-information/ptsd
LeDoux, J. (2000). Emotion circuits in the brain. Annual Review of Neuroscience, 23, 155–184.
McLaughlin, K. J., Gomez, J. L., Baran, S. E., & Conrad, C. D. (2007). The effects of chronic stress on hippocampal morphology and function: an evaluation of chronic restraint paradigms. Brain Research, 1161, 56–64.
Pitman, R. K. (1989). Post-traumatic stress disorder, hormones, and memory. Biological Psychiatry, 26(3), 221–223.
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