In his NY Times article “A Drug to Cure Fear,” Richard Friedman noted: “It has been an article of faith in neuroscience and psychiatry that, once formed, emotional memories are permanent.” This has not been a principle of these disciplines, including clinical psychology, for many years. Consolidation-reconsolidation-extinction models have been around for some time now, applied in particular to persons suffering from traumatic memories; e.g., Holocaust survivors, war and genocide survivors, etc. “Extinction” of memories creates room for new memories, that then inhibit overwhelming threat memories.
According to this thinking, retrieval of memories can render them labile and “disruptable,” because order for a memory to persist after retrieval it has to be re-consolidated – a point at which new experiences and information can – and will – be combined with the old memory and made into a new one.
I am currently working with Joe LeDoux, a prominent New York University neuroscientist who studies defensive survival neural circuits in mammals. Joe will quickly point out that he and his colleagues do not study fear or anxiety, since these are more complex emotions, involving autonoetic consciousness and working memory, etc. Joe sees anxiety as “the price humans pay for autonoetic consciousness.” He places conscious experience at the center of the science of anxiety. (Joe and I will be having a dialogue on the neuroscience and subjective phenomenology of severe fear and anxiety and their alleviation through psychotherapeutic approaches on Friday evening March 18th at NYU – if interested, contact me at [email protected] for further details of the meeting.)
Friedman refers to a popular psychotherapeutic approach to alleviating the intensity of trauma memories: exposure, and the problem of relapse upon re-exposure to trauma memories. In fact, in Joe’s lab, some researchers have advanced the efficacy of exposure therapy; e.g., when a researcher accidentally delayed the exposure trials (putting a longer delay between the first and second trial) they discovered an increased resilience to re-exposures.
In terms of avoidance, which many psychotherapists try to reduce so the person has a chance of disconfirming their fears, Joe’s lab actually found therapeutic value in what they termed “proactive avoidance.” This term describes “…behaviors and thoughts that directly engage with anxiety triggers in order to change, through learning, their impact and thereby help the organism exert control…This kind of strategy combines self-exposure to anxiety-provoking situations with strategies for gaining control over the trigger cues” (LeDoux 2015, p. 311).
In regard to Friedman’s reference to propranolol (a general beta-adrenergic blocker which can block the Beta-receptors in the heart, reducing the heart’s contractile force) used to enhance the efficacy of exposure therapy, LeDoux’s lab at NYU back in the 1990s (and at other labs) found that the synaptic plasticity underlying acquisition of the CS-UCS (conditioned stimulus-unconditioned stimulus) association by the amygdala in threat learning depends on a subtype of glutamate receptors, i.e., NMDA receptors. Glutamate is an excitatory amino acid. The most plentiful neurotransmitter in our brains, it involves what’s called the ionotropic signal transduction system and it has a much faster transmission velocity than dopamine, serotonin, etc. (metabotropic systems).
Glutamate is involved with learning, synaptic plasticity, etc., and Joe and his colleagues found that if you antagonized (block) these NMDA receptors in the lateral amygdala, threat conditioning is disrupted. Conversely, the use of a glutamatergic agonist (facilitator of the receptor activity), e.g., d-cycloserine (DCS) increased the intensity of the memory created by threat learning. In brief, DCS can facilitate in humans and mammals the process of extinction and exposure.
Cortisol, a stress hormone released by our adrenal cortex, given prior to exposure therapy, reduced subjective reports of anxiety. Cortisol seems to affect both explicit and implicit processing systems, consistent with the extent of its receptors in the neocortex as well as “limbic” subcortical (emotional brain processes, “under the hood”) structures.
Joe’s lab also found that blocking the neuromodulator orexin disrupted fear conditioning. Orexin in the locus coeruleus (a center for norepinephrine) facilitates the release of norepinephrine in the amygdala. Orexins are involved with anxiety, including panic disorder. Joe’s lab is also investigating other agents which can facilitate the extinction of overwhelming fear.
Friedman cogently notes that the use of stimulants, as is occurring in the military, can actually increase the intensity of the consolidation of trauma memories. He noted that they increase norepinephrine. He left out that these medications can, and do, reverse the action of the dopamine transporter (by activation of protein kinase C and calcium calmodulin kinase II resulting in phosphorylation of the dopamine transporter, DAT-these protein kinases are specifically linked to what are called “second chemical messenger systems” in our brain) leading to an excessive amount of dopamine in the synapse. They also are potent sympathomimetic agents (effects occurring not just in the brain, but in the sympathetic nervous system), similar to cocaine.
The dialogue between whether to use medications and other “biological” treatments or psychotherapy to alleviate severe anxieties has a very long history. Scott Stossel (2013) in his national bestselling book “My Age of Anxiety: Fear, Hope, Dread, and the Search for Peace of Mind,” in a chapter entitled “Medication and the Meaning of Anxiety,” gives a very good account of the pros and cons of both approaches. He uses Walker Percy as an example of someone who eschews the use of drugs to treat human anxieties. In speaking of anxiety, Percy noted: “under one frame of reference a symptom to be gotten rid of, under the other, it may be a summons to an authentic existence, to be heeded at any cost” (p. 223, quoted in Stossel’s My Age of Anxiety).
Friedman is aware of the controversy surrounding the use of medications in the treatment of trauma. Do we really want to forget the memories of a genocide or collective trauma like 9/11 for example? Friedman noted that it’s not about erasure of memories, but more about reducing the intensity and overwhelm of trauma memories. From an evolutionary perspective, for example, anxiety as a signal could be life-saving.
Friedman concludes that these (and other objections to the use of medications for existential anxieties, and what Freud called the normal misery of everyday life, as opposed to the concept of “cosmetic psychopharmacology”) are good points, but so is the point of alleviating intense terror, panic and severe anxiety if it makes someone’s life better and reduces intense suffering. The question Joe LeDoux and I will be addressing, among other questions, will be how to increase the efficacy of psychotherapeutic approaches to the alleviation of these painful and overwhelming states of anxiety and panic.
Reconsolidation and extinction of the intensity of traumatic memories can be accomplished without the use of drugs. As previously noted, Joe’s lab found proactive avoidance to be particularly helpful. This can be usefully applied to people not just with PTSD, but also with severe social anxieties, etc. Just as the brain (or what I would say the MindBrain, a term used by neuroscientist Jaak Panksepp) can learn to be anxious, it can learn to reduce panic and anxiety.
Joe and I will be discussing ways of improving psychotherapy to facilitate the reduction of overwhelming fear and anxiety at our March 18th colloquium at NYU. Parenthetically, I think some of what Christopher (Kit) Bollas (2013) mentions in his book “Catch Them Before They Fall: The Psychoanalysis of Breakdown” fits in very nicely with current affective neuroscience and developmental psychobiology research on psychotherapeutic approaches to fear and anxiety.
For those interested in a recent update on what LeDoux’s lab has been discovering about anxiety, see the following youtube video:
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Bolas, Christopher (2013) “Catch Them Before They Fall: The Psychoanalysis of Breakdown. Routledge
Friedman, Richard, “A Drug to Cure Fear,” January 22, 2016; New York Times
Ledoux, Joseph (2015) “Anxious: Using the Brain to Understand and Treat Fear and Anxiety.” Viking
Stossel, Scott (2013) “My Age of Anxiety: Fear, Hope, Dread, and the Search for Peace of Mind.” Vintage
Zarmbo, Alan “Pentagon study links prescription stimulants to military PTSD risk.” November 19, 2015, Los Angeles Times