Building Bridges: Connecting Post-Disaster Responses to Molecular Processes

 

Raquel E. Cohen, M.D., M.P.H.

 

                                                                                                                                                                                    November 30, 2006

 

           

            After reading Nobel Laureate (2000) Dr. Eric R, Kandel’s In Search of Memory[1] and after reviewing over more than 30 years of assisting in catastrophic events in which I have participated (www.raquelcohendisaster.com), I became aware that “remembering” was a constant expression associated with painful emotions in the vast majority of survivors.  The intensity of the emotions varied from muted to histrionic in the first days post-disaster, but they kept changing in a variety of ebb and flow, with some individuals regaining their composure while others seem to ruminate and remember for long periods of time.  I was concerned about some individuals who seemed to forget how to return to function in a helpful manner.  I wondered if their repression might not lead to emotional disorders later on but, meeting them a year or two later, they seemed to have recovered from the trauma.  This stimulated the impetus to conceptualize a link between Dr Kandel’s research findings and my observations in the field.

            Although there are many unknowns in the interplay of neurotransmitters, hormones, and electrical potentiation in neural functions and configurations for the “formation of memory consolidation, extinguishing and post-trauma events” puzzle, I believe that the research findings of memory component documented by Dr. Kandel will emerge as key to signs/symptoms of post-trauma behavior.

            The goal of this paper is to apply the research of Dr. Kandel on memory to the molecular process of behavior disaster response, and to share these emerging and hypothesis-based concepts in language that is familiar to mental health professionals who are active and participate in assisting survivors after a disaster

METHODOLOGY USED
            I have attempted to select and document key research findings of Dr. Kandel’s research involving learning and memory as building blocks to support the mental health concepts in this paper, the most important of which is that stored memory of traumatic experiences post-disaster are biologically linked to responses, reactions and behavior after the disaster. All the names of the biologic compounds and proteins for the experiments and investigations are not identified so as to simplify and facilitate the mental health concepts, but the complete documentation can be found in the published research of the included authors.

            My objectives are to describe basic molecular processes involved in learning and memory as documented by Dr. Kandel, to design a construct that links learning experiences to long and short term memory production during a traumatic event, and to posit the question as to whether the post-trauma reactions rely on memory and learning?  Linking molecular processes to traumatic memories learned through sensitization and conditioning during the experience and impact of a disaster may help us understand the biologic component of post trauma response.

            Given the hypothesis of this paper, a future research question must be asked: “If long term memory encoding and storage can be interrupted, facilitating extinction, then could traumatic post disaster reactions be ameliorated, i.e. is trauma memory associated to behavior responses after traumatic events or does it rely on other mechanisms?”
HOW DOES A PERSON LEARN?
            An individual that has experienced the impact of an earthquake, tsunami, volcanic eruption, or other natural disaster will “learn” many new lessons written in the language of shock, terror, panic and fear.  They will also learn how their familiar, safe environment will not be the same for a length of time, and will need to develop new modalities of daily life, some adding to the stress.  Research findings illustrate individual molecular findings that point to changes in synaptic strength brought about by increased rate of stimulation to neurons.  These neurons will develop a molecular signaling pathway that includes several specific proteins. They will produce long-term potentiation for learning, (daily new post-disaster experiences and accommodations) resulting in short term or long-term memory according to certain conditions.

            The process of learning includes the following mechanisms:
            Habituation
: After a sensory stimulus increases synaptic strength, a learned behavior will be initiated by reconfiguring a neural network and storing information in the brain. Habituation eventually weakens the synaptic connections after safety/repetition is recognized and the organism adapts to the stimuli.  This may happen after the survivor enters a shelter and is attended by the emergency personnel who will offer support and guidance.

            Sensitization: Increased strength of activating a noxious sensory stimulus produces a neural communication between the information transmitted and the motor neuron whose action potential causes the behavior.  Mediating circuits linked
in different configurations to the motor neuron reinforce/assist the storage of the memory.  This could be the outcome in survivors who needed amputation of their legs after remaining in the boiling “muck” engulfing the town of
Armero during the eruption of the Nevada Volcano in Colombia (1985).

            Conditioning: Denotes the process by which stimuli, not linked with a reflex or usual response, come to be so linked. It can denote a noxious stimulus specifically pairing the memory to the associative learning of a new experience. Conditioning can be referred to repeated neutral, habitual situations, associated or paired with noxious painful experiences.  The future response to similar neutral stimuli will influence defensive behavior, a response I often saw demonstrated in the years following years Hurricane Andrew (South Florida 1992) whenever there was a strong rainstorm, when children in classrooms would become agitated, peer out of the schoolroom window, and express fear.

CONSOLIDATION OF MEMORY           

            Once the learning neural pathway has been established, the consolidation of memory can be categorized into short and long-term memory.

            Short Term Memory (STM): The duration of STM storage depends on the length of time a synapse is stimulated.  Activation of the sensory pathway sets up the processing capacity of mediating and modulating the stimulus to be stored for short time duration.

            Long Term Memory (LTM): Strong and long lasting neuron stimulation will proceed to link messages to neural cells. Signals from a cell environment activate genes’ regulatory proteins that switch “on” other specific genes, encoding and storing particular proteins to develop LTM.   Stronger stimuli send signals to the nucleus of the cell (gene storage) telling it to activate genes that encode proteins, producing “switch on” effector genes, forming new synaptic connections. Growth and maintenance of new synaptic terminals makes memory persistent through the capacity for plasticity.  The question of what components we keep in each type of memory post-disaster is an important research quest for investigators and mental health professionals because it may explain the variety of responses, symptoms and disorders following a disaster.  Another area in need of further inquiry is the fact that the developing brain systems in children may function differently than in adults or the elderly.
            The brain can be changed by new synaptic connections as a result of experience (post-disaster sensory external stimulus) by altering the strength and structure of pre-existing connections. If we analyze the characteristics of the disasters that have occurred in the past decade and study the impact and recovery pathways affecting populations with different cultures, ethnicity, religion and resources to modify the learning and impact of those disasters, it becomes evident that to understand the problems of the survivors, we need to study the biologic variability of what they have learned and remembered.  Memory storage may result from changes in synaptic strength brought about by different patterns of sensory stimulation which promote increased connections and expansion due to the potential for plastic conditioned property and structural changes of the neurons.
ROLE OF MOLECULES IN LONG TERM MEMORY STORAGE
            Protein synthesis is required to develop persistent synaptic changes, based on alterations in gene expression. Memory storage depends on the coordinated expression of specific genes. These genes code for proteins that alter the structural elements connecting different pathways of the brain and establishing persistency.  The future role of genetic, familiar resiliency may assist us in understanding and finding methods to better assist survivors.

GENE EFFECT ON MEMORY
            By blocking the synthesis of new proteins during learning (sensory stimulus), no growth of synapse connection can be formed, blocking the consolidation of memory and storage. The function and structure of the cell will be modified due to the interplay of proteins. During the process of activating the cell genetic regulatory mechanism, two types of proteins balance both the stimulus and the extinction process by blocking the synthesis of new proteins. Stimulated by learning and impeding the growth of synapse connections, the possibility of interfering with the consolidation of memory is probable.

Is this the underlying property of forgetting traumatic events post-disaster?

            These opposing regulatory actions provide a threshold for memory storage. At the synaptic terminal there can be formation of new connections producing inhibition or maintenance of new growth. Dr. Kandel’s research assists in conceptualizing the variety of remembrances exhibited by the varied populations with which I have dealt in the 30 years of my post disaster experiences as well as explaining the manner in which survivors recounted their memories.

STORAGE OF EXPERIENCES

            Listening to the variation of emotional tonality when survivors were sharing their memories, it was evident that some events left strong reactions while others were muted.   Dr. Kandel’s research offers evidence of the molecular processes that accompany these reactions.
            The production of the protein that stimulates the permanent connections is balanced by the increasing protein suppressing them (extinction). The result is that the process of the memory enhancing capacity diminishes, inactivating the encoding for memory. By removing this biologic constraint, the capacity that triggers the switch to LTM will be strengthened. A strong emotional trauma (individual threshold reaction to anxiety and fear) could bypass the control of the specific suppressing protein and increase the strength of the stimulating protein, putting the trauma in long term memory storage.  This will store individual, meaningful components of post-trauma memory, sensitizing the survivor for a long period of time.  This supports disaster research, which verifies that a small percentage of survivors will exhibit pathological syndromes for a long period of their lives.

EXPLICIT AND IMPLICIT CATEGORIES OF MEMORY STORAGE AND RETRIAVAL

            Survivors of traumatic events are able to retrieve memories at will, but may also have memories that appear spontaneously, some frightening, others more neutral. These two memory categories have been labeled implicit and explicit.
            Explicit memory can be categorized as conscious or declarative recall of events, people, facts, stories, skills, and capacities. Some of these capacities may be blocked during the early stages of the post-trauma following a disaster, but will be recovered by most survivors.

            Implicit memory is unconscious automatic performance of learned experiences.  It demands the communication and collection of processes involving different, currently unknown brain systems which are being identified by ongoing research. Some efforts to blunt traumatic, handicapping memories using medication to block the expression of painful remembrances are being researched, although the mechanisms are still unknown.
Associations of fear with trauma:

            Constant repetition can transform explicit into implicit memory. Experiences are recorded and recalled as conscious and unconscious, exerting a powerful effect on behavior and feelings. Depending on a variety of sequential stimulations, these memories can be extinguished or reinforced. They can be distorted, associated with components of other memories, or further conditioned with neutral stimuli. Bridging provides the links between molecular processes and the fear and anxiety produced by traumatic events. We can envision how personal reactions to traumatic events will differ depending on multiple variables, among which are resiliency, past traumatic experiences, and personality traits.

EMOTIONAL TRAUMA
            Anxiety as a signal to potential trauma is universal as an instinctive response to body integrity and status territoriality. Learned anxiety acquired through experience (impact of traumatic post disaster events) can be associated with mental stimulus, both neutral and dangerous, linked to LTM.  Most survivors of catastrophic disasters will have an “imprint” of the many experiences during and after the disaster. What is unknown is  why these events affect the long-term memory and behavior of some survivors more than others. Fear triggers body signs to mobilize mechanisms for defense or escape, while stress reactions trigger the biologic systems necessary to perceive, evaluate, and act to preserve survival of self. Animal studies indicate that conditioned fear (pairing a stimulus with a shock) provides a model system to analyze traumatic fear conditioning. These studies show that extinction (repeated presentation of a stimulus in the absence of shock) models processes involved in exposure therapy in humans. Extinction does not erase fear memories, but instead is an active learning process leading to associations that compete with or suppress fear memories. Extinction is a fragile process that depends on the place where extinction and fear assessment take place, and can be disrupted by stress or the passage of time. Other animal studies show that extinction requires activation of a particular brain protein receptor in the amygdala, a brain area critically involved in fear and anxiety. Compounds that block this receptor block the development of extinction. Specific receptor function can be enhanced by a compound called D-cycloserine. In rats, systemic administration or local infusion into the amygdala of dose-dependent D-cycloserine facilitates the rate of extinction of conditioned fear. This requires concomitant exposure to the conditioned stimulus and involves specific receptors. Some compounds and proteins that have been used in humans for other purposes and have been well tolerated with no serious side effects are being tried to diminish the effect of traumatic memories. Clinical trials are underway to evaluate whether D-cycloserine will provide an effective pharmacological adjunct to exposure therapy in patients with PTSD.[2]
            Pawlak commented, “Understanding neural bases of stress, fear and anxiety is of immense importance to modern society. The most dramatic form, post-traumatic stress disorder (PTSD) is characterized by cognitive impairment, fear, anxiety, depression and may eventually lead to suicide. Understanding the neural mechanisms of PTSD, depression and anxiety disorders could reduce the personal and societal impact through development of more efficient therapies. This project looks at cellular mechanisms involved in experience-induced neuronal plasticity underlying learning, anxiety and fear.”

            Pawlak and colleagues determined that fear memories are encoded as changes in neuronal connections called synapses in a process known as plasticity, and have recently shown that proteases (proteins that cut other proteins) play an important role in the process, significantly contributing to fear and anxiety related to stress. The survival system of neural/hormonal responses to acute threats can become dysfunctional when memories and persistent thoughts trigger them continuously.[3]

LEARNED FEAR
            Fear can be associated to neutral stimuli through learning, which in turn can trigger emotional memories. Memory of trauma remains powerful and can be reactivated by random events. It can trigger fearful memories stored in the amygdala. Neural circuits initiate the fear response during a disaster, producing the various reactions noted in most survivors.

HYPOTHESIS OF THE PROCESS

1.      Unconscious, implicit rapid evaluation of stimulus during trauma found in all disaster experiences

2.      Physiologic response (instinctive) experienced by all survivors according to their  individual characteristics (personality, genetics, experience, resiliency)

3.      Conscious experience of sensations, body responses, thoughts, and actions (perception/evaluation/reactions) may persist or disappear. These are the memories that will be implicated in the post disaster response, behavior and adaptation of the survivors.

            The systems implicated in the sequence of these processes starts with the autonomic nervous system and the regions of the brain (hippocampus, amygdala) followed by cognitive mechanisms of the cortex. Unconscious recall of emotional memory involves implicit memory storage in the amygdala. Conscious memory of feelings involves implicit memory storage in the hippocampus.

INTERFERENCE WITH THE PROCESS
            Damage to the Amygdala: Results in intense memory of learned fear disrupting the ability of emotionally charged stimulus to elicit a response.

            Damage to Hypocampus (conscious memory): Results in intense learned fear disrupting the ability to remember the context in which the stimulus occurred.
            The cognitive system, if impaired, prevents choice of action. Unconscious appraisal mechanisms limit action.

TENTATIVE HYPOTHESIS
            We can start to assume that the molecular processes associated with learning -traumatic memory and post-disaster reactions - proceed according to and defined by biologic(genetically driven) and social components (experientially modified) specific for each individual. The interplay between these important systems will define the expression of responses after a traumatic event. The duration of these responses will vary according to many interactive individual characteristics. All of these factors may explain the different statistical findings in research published after a disaster. These factors may also clarify the questionable results obtained eliciting memories of the trauma a few hours or days post-trauma which may in fact reinforce long term memory process consolidation, thereby strengthening traumatic memories.

            The biological and social systems underlying the reactions post-trauma that are beginning to be identified and their relations to each other are presented to suggest development of a hypothesis “in progress”, which may begin to clarify and explain the difficulty of evaluating the length of the mourning process, healing, depression, and return to function following the traumatic event and the associated loss after a disaster.

Follow Up Note: The following article appeared in August 2007 in The Miami Herald:

 

TRAUMA RESEARCH AT EMORY UNIVERSITY

 

An Emory Univ. study is designed to help find a new way to reduce or eliminate symptoms of post-traumatic stress disorder, a condition that plagues up one-third of Iraq War veterans.

The Emory study of 150 soldiers with PTSD is trying to prove that virtual reality can work better and faster when subjects take a drug once widely used to treat tuberculosis. The drug, d-Cycloserine or DCS , affects a region of the brain called the amygdala that process memories and emotional reactions like fear. Research shows that the drug can also decrease fear.


[1] Eric R. Kandel  W.W. Norton & Co. NY (2006)

[2] Michael Davis Phd, Professor pf Psychiatry at Emory Univ. School of Medicine (2000)

 

[3] . Robert Pawlack,, Dept. of ell physiology and Pharmacology, Univ of Leicester UK (received the Marie Curie Excellence Grant-2005