In addition, a corollary would be that this "unlearning" happens very fast; it comes as a radical change, and the "relearning" stage, the trauma/grief resolution, occurs slowly. Dr. Olders' explanation was not too detailed, however, as the available technology of the time may not have allowed for great specificity. Subsequently, the technology has changed and greater understandings through increasingly accurate analyses of neurology have become available; we set out to investigate this additional information with the aim to provide support for an etiotropic perspective of the biology of psychological trauma and its resolution.
We should add that during this investigation, we discovered that the relationship of psychological trauma to all neurological and other biological activity, that is, not just to neuronal learning, is multifaceted and complex beyond virtually anyone's total comprehension. Moreover, these myriad activities don't always appear to mesh into sequitur systems of logic. We say "appear" because obviously the systems have to so mesh, as the brain does operate, but such integration is not yet understood, as many current understandings are limited by the realities that different systems operate differently in different parts of the brain and to the degree that the operations sometimes serve completely opposite brain functions.
Where all of this information, not to mention the various paradigms for presenting it, is overwhelming, we did find a number of consistencies that we can present that provide a picture of etiotropically-oriented biological support. We also found conflict; information that contrasted with our view. When support and conflict are taken together, however, we believe that a fairly factual underpinning is provided for our hypothesis of the biology of psychological trauma and its resolution with TRT. "Fairly" qualifies this description because, as the reader may or may not know, almost all neurological research is conducted under ethical codes that preclude absolute understandings of neurology -- neurological study is often restricted to non human central nervous systems. Although there are methods for, and increasing technologies that allow, extrapolation of the various findings to humans, they nonetheless still are extrapolations.
To present this biological picture of the etiology of psychological trauma, we consider:
In contrast to this accepted norm, we have never seen a case of pathological grief. We have seen, however, many cases where the grief response had been interfered with by the application of inappropriate social management models or psychoactive substances. In fact our model was developed to, in part, prevent such interferences (see the Text, Parts One and Three). When successful at overturning these interferences, that is, successful at stopping the application of performance based admonitions to the trauma victim and ending all drug use during the administration of the therapy, all examples of pathological grief disappeared, the loss was resolved, leading us to the conclusion that the locus of so called pathological grief is the failure of those surrounding the trauma victim or bereaved, or the victim's parallel use of drug therapy, excluding the comorbity with grief of biologically initiated mental illnesses like borderline personality disorder, manic depression, and schizophrenia (my separation of these illnesses is necessary, not because these people can't be treated properly for loss, but because these illnesses were not my specialty; people affected by biogenetic mental illness were referred to proper clinical care -- see About/ Development/ History). In other words, grief was shown to us to be a natural process for all people absent interfering variables and the comorbity with biogenetic based mental illness.
There are different ways that we can support this hypothesis through literature reviews. With regards to the problems caused by making performance demands on trauma victims, the investigator only needs to read Lindeman (1944), Bowlby (1969, 1980) and Parkes (1987) to grasp the idea that telling trauma victims or other people experiencing the bereavement cycle that they need to be stronger and so forth is the worse thing that can happen for the trauma victim -- such admonishments only exacerbate the condition. With regard to that part of our thesis that states that social drug use is an interfering variable, we can show that basic psychological research models which have the burden of proof, the responsibility, to establish a pathological condition, are, as a rule, prejudiced to the view that social alcohol use by subjects during studies of psychopathology is a non factor, thus missing the influence of the use on the so called pathological condition.
To provide one apparent example, in lieu of a literature review, van der Kolk (1987) explains the application of lithium to combat veterans affected by PTSD and the use of the lithium to reduce arousal states. A product of this application includes the subjects' reports that alcohol consumptions were lessened -- the participants say that they drank less during the week. Although there is a reference by van der Kolk to Lacoursier's (1980) hypothesis that alcohol serves as a medicator of psychological trauma (and an acknowledgement that people who are recognized to be chemically dependent can't use drugs, including some medications), there is no apparent consideration that this study of the PTSD condition in response to the application of lithium is being conducted under the extra (alcohol) medications' influences -- I found no report of the measurement of the specific amounts of the additional variable of alcohol as a medicating factor, but only reflections of generally reduced intake, seemingly without understanding of the variabilities that can result from self reports of drug consumptions. The significance of this one example is that no one appears to give a thought to the influence of an exogenous variable, in this case the administration of alcohol, on the continuance of the PTS condition; this variable (alcohol) may be interfering with the phylogenetic derived capacities to adapt, in the process interfering with the central nervous system's biological capacity to adapt out of, end, the PTS condition. This prospective failure occurs despite the unequivocal evidence that the PTSD sufferers are drinking alcohol socially during their evaluations and treatments.
To show by contrasting methods, we would never expect a trauma (affected by grief) victim to progress within the clinical process without the CNS being removed from the exogenous influences, in this instance the apparent social use of alcohol (see About/ Theory/ Drug Use). Although the example presented is only a small one, a sample, we propose that if a literature review were conducted on the subject that this brief reference would epitomize the attitudes of those who are trying to evaluate for psychopathology in either psychological trauma or bereavement; the investigators believe that social drug use is practically an irrelevant variable. The burden of responsibility for the proof of psychopathology is on those making such a claim and no such proof is available as our informal review shows that the literature does not, as a rule (recently, some biological studies are screening out alcohol users so that certain lab experiments on endocrine systems are not tainted), account for exogenous influences like social drug use when measuring for psychopathology during the trauma resolution (grieving) phase of care. For an explanation of the influences of drinking alcohol on neurosystems, and especially an explanation of the influences of alcohol consumption on chemically dependent people, see the next section (3); this information shows unequivocally that ignoring alcohol as a parallel influence is recurring phenomenon in PTS research methodologies.
Hirch's idea is that an external stimulus, such as loss, influences the central nervous system. Effector arms to this system include initiating and feedbacking responses existing between the CNS (central nervous system) and endocrine and immune systems, and between the endocrine and immune systems themselves. One chemical instrumental in activating this system is thought to be a peptide, which is synthesized in the pituitary, and is called pro-opio-melanocortin (POMC). POMC is the neurochemical (described as a coreleasing process by Kosten in a later subsection) to be responsible for not only corticotropin releasing factor (ACTH), but also beta-endorphin and other unnamed peptides. Hirch suggest that these peptides probably play a part (not clarified) in emotional and cognitive functionings.
POMC is also speculated to activate adrenal and immune systems as metabolic protections against threat or injury. The beta-endorphin and other peptide activations are thought to provide for analgesia effects during the same threat or injury. Neurophones (definition follows) produced by this process support the necessary denial that protects the person from the reality of the radical change and allows the individual to address the degrees of the change over a more protracted period -- facilitation of the integration of the loss. A "neurophone" is a neurosubstance closely related to a neurotransmitter and not always distinguishable from such.
At the end of this description, Hirch says that this system may become activated inappropriately. "Inappropriately" apparently refers to the concept of pathological grief. He also says
Perhaps certain genetic characteristics, the use of culturally learned practices, the intervention of key figures in the social network, or other such factors can reduce a person's "need" to utilize this system in the solution of the problem of grief. pg. 162.
We can synthesize our comparison of the psychoneuroimmunoendocrine system to the TRT concept of a phylogenetic-derived bereavement response by saying:
Although there are several hypothesis about long term memory and learning (Ng, 1991, Lester, 1991; Messier, 1991, and Kandel -- summary provided in chapters 64 - 65, 1991), long-term potentiation predominates as the central explanation for both. Consequently, LTP also becomes a focus in unlearning -- extinction. In this subsection, we consider all (that we could find) neurobiological learning/memory theories, but emphasize long-term potentiation and its reduction (reduction = long-term depression: LTD) during and as a response to the traumatic event.
Malenka (1989) has explained calmodulin and protein kinase activity in relationship to LTP. Malinow (1989) has described the role of PKC and calmodulin in the induction (initiates the storage in memory) of LTP. Malenka (1991), also showed that calcium released in the post-synaptic membrane, at least in certain receptors where LTP is known to occur (NMDA or N-Methyl-D-aspartate receptors -- see next section), is required to induce LTP. Muller (1991) showed that protein Kinase C (PKC) is involved in the induction of LTP, but not in the maintenance or expression of it, meaning that PKC is needed to store the first information but not necessary for keeping it in memory or otherwise acting on it. Schulman (1989) explains how the multifaceted calmodulin dependent protein kinase serves to autophosphorylate cellular proteins. "Autophosphorylation" provides for the process through which memory tends toward maintaining itself through a series of chemical actions that once started continue themselves, leading to the increase in probabilities that charges between neurons will increase. Watanabe (1992) provided evidence through behavioral studies that endogenous glycine is a fundamental component of memory storage; glycine modulates NMDA receptor activity during spatial learning (learning related to analysis, evaluation and retention of information and knowledge about distances, locations, and the achievement of tasks requiring recollections of both). In the process of this proof, the author(s) also help to establish more conclusively that LTP is the primary source of memory. O'Dell (1991) showed that tyrosine kinases play a role in LTP; O'Dell also helps to establish LTP as a source of memory. Madison asserts that two experiments by Silva, Stevens, Tonegawa and Wang (1992) and Silva, Paylor, Wehner, and Tonegawa (1992) provide advanced evidenced-based understandings of LTP. Through gene targeting, the researchers preclude calcium calmodulin kinase II from the hippocampus. There is corresponding deficiency in the ability to complete spatial learning task, also demonstrating that LTP is deficient. The difference between this and other such experiments is that the others have relied on blocking NMDA receptors (primary receptors involved in LTP; they are described in the next subsection) with certain drugs; the blocking could have the effect of altering the conclusions about the relationship of LTP to learning. Thus, through the gene targeting method, the experiments validating the role of the kinases in memory storage are validated, and LTP as a substrate of memory is validated.
I also want to thank Dr. Stevens for pointing me in the direction of additional research being done by Dr. Michael Davis at Yale University who, with a group of scientist (Charney, 1993 and described later) from that program, have studied the relationship of extinction and long term potentiation with regards to the recollection of the event. Because that is a major work on this subject, it is provided its own heading later in this chapter. Dr. Davis was also very helpful to me. It was personally gratifying to be able to speak with him and Dr. Stevens.
Hebb, DO (1949) produced the classic work on neuronal plasticity, hypothesizing the idea that synapses change in response to learning. The work of Graham Goddard in the 1960's -1980's continued the leadership. "Long-term Facilitation in Aplysia: Persistent Phosphorylation and Structural Changes" by Schacher, Glanzman, Barzilai, Dash, Grant Keller Mayford, and Kandell (1990), shows, among other things, the importance of the messenger, cAMP, and the facilitative aspects of the neurotransmitter serotonin in development of long-term synaptic plasticity. These messengers are shown to facilitate protein synthesis required for the development or changes undergone as a result of neuronal learning. There is also shown to be an increase in synapses, which increase is reflected as a strengthening of long-term memory. Rose (1991) overviews the relationship of all memory processes, long and short-term, to the requirement of neurons to restructure themselves to accommodate the retention of the information. Geinisman (1991) provides a great deal of research into the phenomenon of cell plasticity in his article "Structural Synaptic Substrates of Kindling and Long-Term Potentiation" and found in Frank Morrell's Kindling and Synaptic Plasticity (1991). This review considers increases in both quantity and size of synapses and the relationships of these changes to learning; the more learning the more synaptic quantity, size and functional capacity. One of the easiest to understand presentations of the relationship of cell plasticity to learning, memory, and mental health issues, but not necessarily psychological trauma, is provided in chapters 64 and 65 of Eric Kandel's classic Principles of Neural Science (1991).
In the article "Memory Traces: How to Increase and Decrease Their Strengths" (1987-1988), Joe L. Martinez, Jr. and Susan B. Weinberger focus on the neuromodulatory activity, associative to synaptic transmission, that strengthens the likelihood that the synapse will retain the learning expressed in it. To begin, they show that the two great neuroscientists (quote) Hebb (1949) and Cajal (1937) explained learning as a repetitive exercising of the neurons to eventually strengthen the synapses; however, some synapses are strengthened through a modulating process (quote) Brown and Kulik (1977) call the "flashbulb" memory effect: an instantaneous experience can be remembered forever and without introducing it through repetition. Martinez goes on to show that this modulation may have ties to the opioid system through the actions of enkephalin and that the degree of associative modulation (strengthening or otherwise) of the synapses involved will be a function of the importance of that which is being learned to that which has already been retained.
The work of Panksepp, Siviy and Normansell (1985 -- from now on "Panksepp" are addressed again in the next section on extinction because their work was preoccupied with showing the relationship of emotional pain to loss. However, in the interim they were also able to show the correlate, that good feelings come from the opposite of loss, gain. In this case that opposite was represented in the study of increasing social relationships and opioid interaction; a function of endogenous opioid addiction.
We extrapolated from this work (Panksepp) that abstractions retained in synapses are extensions and variations of relationships, which abstractions are apparently modulated in their retention through connections and subsequent interactions/stimulations of opioid bindings. These bindings are most probably enkephalin and, according to Panksepp, are modulated by endorphin. The abstractions are equivalent in our theory to values, beliefs, images, and realities, which aspects of existential identity can include a host of relationship variables like projection, love, and merger, variables that are sundered when confronted with their opposites during extraordinary events. A description of the molecular transaction that is sustained/interrupted during this sundrance is provided by Panksepp and reported in the next section.
The behavioral theory of extinction is that the information is lost entirely, or the information is lost only partially and through stimulation the response can be reinitiated quickly. Some of the leaders explaining the behavioral aspects of extinction include Mark E. Bouton and David E. King (1986), (1983), Mark E. Bouton and Robert C. Bolles (1979), and Robert A. Rescorla and C. Donald Heth (1975).
The molecular perspective has not been as well understood, but the understanding is increasing regularly now. Dr. Michael Davis whose apparent specialty is the address of neurobiological mechanisms underlying the retention of fear (find under the articles "Campeau, 1992, Kim, 1993 and Falls, 1992"), is also the lead writer on the molecular basis of extinction; he is one of the few people who describes in the literature the various theories related to the molecular underpinnings of extinction (Fall, 1992, pgs 861-862).
The first of these theories (Davis quotes Kornorski, 1948) posits that when something new is learned, this newness is represented by an increase in the efficacy of the transmission in one set of neurons that have a consequential effect of inhibiting another set -- the neurons formerly retaining the previously learned but now "forgotten" experience.
Another theory is that the loss of knowledge is a function of a reduction in the long-term potentiation underpinning the previous retention of the knowledge. This reduction is called long-term depression (LTD) of the synapse.
The investigations of LTD are accelerating at the time of this writing; some of the investigations are overviewed here. One of the ideas behind LTD is that it serves the purpose of keeping the informational retaining system from filling up (Abraham, 1991). "Learning and forgetting" are functions of increases (LTP) and decreases (LTD) in synaptic efficacy (Goldman, 1990, pg. 165).
Thus, the mechanisms of LTD serve as an appraiser that determines which information is the most important, a part of the CNS's attempts to integrate itself with its environment. Some of the mechanisms of LTD are explained in Levy (1983), Abraham (1983), Stanton (1989), Desmond (1991), Bidzseranova (1992) and Mulkey (1993).
Stevens shows that inhibitory activity interferes with the induction of LTP. Stanton (1991) shows long term depression as a reversal of LTP. Artola (pg. 72, 1990) explains that LTD operates inverse to LTP mechanisms and consequently "is involved in learning processes which lead to weakening of stimulus response relations such as habituation, reversal learning, and extinction."
The literature has shown for years that there are links between endocrine activity, especially the hypothalamic-pituitary-adrenal cortical axis (abbreviated in this subsection as "HPA"), and stress. Moreover, the production of cortisol, a hormone produced by the adrenal cortical gland and involved in cell metabolism, is a central, but not always consistent, factor in that linkage.
"Endocrine activity" refers to the functionings of the endocrine glands.Hypothalamic - pituitary - adrenal cortical axis" refers to the chain of events that start with the locus ceruleus's (center of brain stem) activation of norepinephrine which stimulates the hypothalamus to stimulate the pituitary gland to secret corticotropin-releasing-factor (ACTH), which then stimulates the adrenal cortical gland to produce hormones, to include cortisol and other chemicals described in this subsection. "Stress" is assumed to be a response to various factors, including loss, bereavement and psychological trauma. "Cortisol" is referenced to denote survival function as the body produces cortisol as a cell repairing agent during attacks on cellular systems.
Because the relationship of stress to HPA functionings has been well documented in many books on psychology and neurology, in this subsection we do not readdress those general issues, but concentrate instead on those studies and literature reviews that primarily pertain to HPA functionings and bereavement/psychological trauma (PTS).
The first study considered was conducted by Wolff C, Friedman S, and Hofer M, et al: (1964 and 1972). The subject was the relationship of ego defenses to endocrine activity preceding (expected death) and during bereavement. The people studied were parents of leukemia patients (children). The study concluded that preceding the death the style and effectiveness of the parents' psychologies (called ego defenses) influenced the amount of 17-hydroxicorticosteroid (for simplicity purposes = cortisol [see Taber, 1993, for further clarification]). Following the death, the output with regard to psychological defenses remained within normal levels; defenses did not alter the output during bereavement.
The second study by Jacobs S., Mason J., Kosten T., et al., (1986), and hereafter also referred to as the "second study," was of endocrine effects on bereaved spouses (measured before and after the death causing the bereavement). The second study results are being reported for the first time in this Jacobs article (1987). Jacobs states (pg. 144) that the evaluation of endocrine effects on grieving spouses did not confirm the first study's conclusions that ego defenses altered endocrine responses. Moreover, despite other studies (quote Katz, J., 1970, Bourne P., 1968, and Rose R., 1968) supporting the notion that ego defenses alter endocrine responses, Jacobs believes such studies are flawed and concludes: "It is difficult to find evidence that ego defenses determine the level of adrenal cortical activity." With regard to other neuroendocrine influences, ego defenses (in the spouse study) also showed no correlation with catecholamine, growth hormone, and prolactin.
Cortisol was found in the second study to be elevated to higher levels during high separation anxiety periods and lower levels during diminishing anxiety periods. This information corroborated the first study's similar findings and the information provided in other endocrine/stress studies (quote Bliss, E, 1956; Fox, H., 1961; Price, D., 1957; and Mason, J., 1959). Jacobs concludes (pg 145) that bereavement as a stress is "not unique" in terms of effects ("quality or quantity") on adrenal cortical activity.
Catecholamine activity, especially the production and utilization of epinephrine and norepinephrine, is well documented. Jacobs points out that cortisol is more adaptive to chronic stress than norepinephrine. This means that production of cortisol will occur as an immediate response to stress or during high anxiety periods (as described in the preceding paragraph) and then shut down the production over the protracted period of the stress response, while norepinephrine can continue to be produced throughout the entire stress period without turning off such production. The second study (Jacobs, et al., 1987) showed that adrenal medulla activity (the medulla being that part of the adrenal gland responsible for the production of blood, as opposed to brain, norepinephrine and epinephrine) is high during the acute phase of bereavement and that such levels are different from those associated with depression and that norepinephrine and epinephrine returns-to-normalcy are more rapid in younger adult as opposed to older humans and animals.
The influence of bereavement/stress were also measured on growth hormone and prolactin. The study of spouses showed that growth hormone output paralleled cortisol output -- increased during high anxiety (acute grief) periods. These findings are supportive of previous studies of the relationship between stress and growth hormone. Prolactin, which is correlated in the literature to "depressed and irritable mood," (quote De la Fuente, 1981), was shown in the second study to be correlated to separation anxiety and depression. This measurement was positive when overlap occurred at the higher ends of the statistical correlation -- the simultaneous occurrence of greater degrees of both anxiety separation and depression.
In Bereavement; Reactions, Consequences and Care, edited by Osterweis, Solomon and Green, 1984, an article (chapter 6, "Toward a Biology of Grieving," pg. 145 - 175 by Hirch, J., Hofer, M., Holland, J., and Solomon, F.,) reviews the literature on endocrine effects of bereavement and other important life events (pgs. 155-158). Before considering the endocrine effects listed here, it is important to note that this article's primary contribution to the TRT theory of psychological trauma is the "psychoneuroimmunoendocrine system" concept, which has been described in a preceding subsection. In this subsection, the discussion is limited to Hirch et al.'s (from now on referenced as "Hirch") consideration of the effects of bereavement (and psychological trauma) on endocrine processes.
Hirch reviews much of the same literature (and other work) considered by Jacobs (1987) showing that there is a correlation between the initial (acute) phase of stress or grief, the more protracted phase, and HPA and adrenal medulla initiated increases in, respectively, hormonal activity and blood norepinephrine and epinephrine. The hormonal links described are generally to increased cortisol, growth hormone and prolactin during the acute phase and returns to baseline levels during the protracted phase.
There is a high correlation between people in sad and hopeless states and the existence of 17-hydroxicorticoid (pg 157 - quote von Euler, U.S., 1959). Hirch refers to Coe's and Levine's (1983) work on endocrine effects during separation of rhesus and squirrel monkeys. Again, cortisol is shown to be increased to high levels during the protest phase (initial crying/calling phase). This increase invariably last for approximately 24 hours and then cortisol levels return to baseline norms. Adrenaline activity is, however, shown to be continuing for at least 2 weeks after the separation and is apparently correlated to adrenaline producing activity. Hirch emphasizes (pg 158) the literature demonstrating a difference between HPA activity and grief related behavior: where cortisol is elevated in the first 24 hours of the protest phase and then returned to norms, protest behavior can and does continue for as long as 11 days after separation.
Kosten makes 3 points. They are related to neurochemical (adrenal medulla production of catecholamines as regulated by enzymic activity) and HPA issues.
First, Kosten addresses an important non HPA related activity -- blood norepinephrine and epinephrine levels as influenced by enzymic activity. Kosten shows a high correlation between low levels of the enzyme monomine oxidase (MAO) and PTSD by reviewing the Davidson, J., et. al. (1985) study of 23 Vietnam veterans affected by PTSD. Kosten explains (pg. 53) that MAO is an enzyme necessary for breaking down active catecholamines into inactive metabolites, and that although high levels of MAO are usually associated with anxiety disorders, in which group PTSD is classified, the Davidson study demonstrates the opposite -- low levels of MAO are associated with PTSD.
These low levels of MAO are posited to be responsible for reductions in the breakdowns of catecholomines: fewer MAOs means fewer breakdowns and subsequent higher levels of epinephrine and norepinephrine. Moreover, there is also a correlation between the lowest levels of MAO and the occurrence of comorbity -- PTSD and alcoholism, and even when the alcoholic has been sober for almost 1 year.
Kosten see this information as significant. It is believed to provide a biological link between alcoholism and PTSD -- apparently meaning that the combat related trauma produced and continues to produce low levels of MAO, absent the low MAO levels that normally accompany active ethanol intake and detoxification. Thus, the low MAO correlation between alcoholism and PTSD establishes a biological relationship between the two processes. We will consider this subject again in the literature review related to chemical dependency (About/ Comparison - Contrast/ Multiple Sources), but will say briefly now that Kosten does not consider the ramifications of psychological trauma resulting from the biological effects of the use on the physiology of the person or the prospective psychological trauma resulting from toxic behaviors that operate contrary to previously established aspects of existential identity.
Thus the extra low MAO could be related to the extra amount of trauma that has bombarded the neurophysiology and enzyme response system. Kosten's work shows that the research supports the conclusion that psychological trauma reduces MAO levels which then results in increases in norepinephrine and epinephrine (intended to emphasize the next section on the relationship of norepinephrine on neuronal learning). I believe the real value of Davidson's work, rather than the demonstration of a cause/effect linkage between low MAO and PTS, actually supports the simpler idea that multiple psychological traumas (in this example -- combat caused and chemical dependency-caused trauma) have more profound biological influences (seeAbout/ Comparison - Contrast/ Multiple Sources).
Second, Kosten explains the dissociation between chronic noradrenergic stimulation in PTSD and returns-to-baseline levels of cortisol immediately after the crisis (as indicated in the previous discussions -- within 24 hours) as possibly a function of the desensitization of beta- receptors on the pituitary gland. This apparently means that when the traumatic event occurs, the locus ceruleus will stimulate the high levels of noradrenaline which then stimulate the hypothalamus to influence the adrenal pituitary gland to produce corticotropin-releasing-factor in large amounts, which then stimulates the adrenal cortical gland to produce large amounts of cortisol, all of this occurring within 24 hours following the event. After the 24 hour stimulative period, the noradrenaline is still being produced, but does not bind on the receptors of the pituitary because they have been desensitized by the overwhelming noradrenergic demand. "Desensitized" means that the receptors no longer accept the norepinephrine neurotransmitter. Failure to accept the neurotransmitter results in an ending of the stimulation of the corticotropin releasing factor and the return to normal levels of cortisol production by the adrenal cortex. Kosten quotes investigations of beta adrenergic receptors related to adrenal cortical activity by Reisine, et al (1983).
Third, Kosten explains that opioid activity is linked by the corelease of beta endorphin and corticotropin releasing factor from the pituitary. The speculation is that with reductions in cortisol come reductions in beta endorphin, which then leads to opioid deficiency that is medicated by exogenous opioids like heroin, etc. -- again, the argument by Kosten, which is the thesis of the article, is that PTSD causes drug addiction, in this case addiction to opioids. We think this information is important, but for different reasons. The beta endorphin reduction could be just a function of receptor blockade (Panksepp, 1985) as a phylogenetic response to loss -- the introduction of distress vocalizations warning the organism that dramatic change is in the offing and that corrective behavior is warranted. The exogenous opioid addiction could be a function of other factors, like genetic deficiencies in opioid receptor capacities as argued by Blum (1990, 1993). As indicated, we consider this issue as well as other Kosten thoughts on the subject of the relationship of PTSD to drug use in About/ Comparison - Contrast/ Multiple Sources.
Charney (1993) and van der Kolk (1987) also consider the production of cortisol and other hormones as a response to psychological trauma. However, only Olders (1987) hypothesizes that the cortisol plays a role in neuronal learning (quote Coe's work with cortisol and squirrel monkeys during separation, 1983). Otherwise, we could not find a conclusive relationship between cortisol and CNS cellular activity (we do not believe Coe's work is conclusive).
We found the most extensive work on the relationship of NE to learning/relearning to be provided in the article "Noradrenergic Enhancement of Long-Term Synaptic Potentiation" by Daniel Johnston, William F. Hopkins and Richard Gray (printed in Long-Term Potentiation: From Biophysics to Behavior, by Liss. This work shows NE to be a direct player in LTP -- NE has a role in the functioning of LTP as opposed to just the development of the synaptic structure as described by Routtenburg. In this use (Johnston's work), NE is shown in the area of the brain referenced as the "mossy fibers" to affect post-synaptic cells directly by influencing the post-synaptic calcium flows; the increase affects LTP. Through these effects, NE provides a modulating influence on LTP/learning.
There is an indisputable statistical/behavioral relationship between induction of epinephrine (adrenaline) and enhanced retention. McGaugh (1987-1988) quotes Gold and van Buskirk, 1976; Borrell, de Kloet, Versteeg, and Bohus, 1983; Gold and McCarty, 1981 and Gold and McGaugh, 1975, as having demonstrated that inductions of epinephrine have direct effects on learning retention. McGaugh then goes on to explain that epinephrine's interactions with the opioid system provides for the release of NE (pg 60). The relationship of adrenaline and noradrenaline is well known and the effects of both statistically on learning (retention) are not questioned.
NE also affects LTP by reducing the afterhyperpolarizing effect used to decrease the number of firings in otherwise usually excited neurons. Disterhoft (1987) explains that some neurons are usually excited (firing) and this excitation is prevented or reduced by an afterhyperpolarizing effect in the neuron receiving the charge -- the hyperpolarizing effect prevents the passage of action potentials. Disterhoft quotes (pg 176) Hopkins and Johnston (1984) as showing that "Noradrenaline was found to enhance the magnitude of LTP as well as its duration" and that "noradrenaline also reduces the late AHP." (Disterhoft also quotes Madison and Nicoll, 1982; and Haas and Konnerth, 1983.)
Kolb postulates that, in certain groups of combat veterans suffering a chronic form of PTSD:
"there exists not only an ongoing perceptual abnormality (impairment of the ability to discriminate specific sensory inputs associated with the traumatic event) but also excessive autonomic arousal of central adrenergic origin" (pg. 991)."Adrenergic" refers to the biological process through which epinephrine (adrenaline) and norepinephrine (noradrenaline) are released in conjunction with sympathetic system activities; the release starts with the locus ceruleus (center of the brain stem) and continues throughout that system. Noradrenergic, which refers primarily to the norepinephrine releasing processes, is sometimes used interchangeably with adrenergic within the literature, depending on whether the writer is British, American, or some other nationality (different nomenclatures).
Such stimulations are significant for autonomous system arousal -- increased respiratory and cardiovascular functionings. Kolb also considers thought/emotional/behavioral symptomalogies of PTSD, Kandel's (1982) contribution as an explanation for learning, and the neuronal effects of high intensity stimulation before presenting his neuropsychological hypothesis of chronic PTSD.
At the center of Kolb's investigations and thesis is his hypothesis that neurons undergo physical, functional and possibly structural, change and that this physical change precipitates other and usually cyclically reciprocal CNS (central nervous system) and psychic destructive processes. In this regard, Kolb argues (pg. 993) that the traumatic event begins to have its first CNS effects when the event overloads the neuronal cortical barrier, the part of the brain responsible for management of sensory input and processing to motor response -- evaluation, action and survival. "Overloaded" apparently means that the threat to the organism is so great that it is beyond the capacity of the cortical barrier to assimilate sensory input and organize an effective motor/action/survival response, at least immediately. This overloaded condition then fosters apparent functional and structural neuronal changes -- alterations to the molecular learning processes of sensitization and habituation as described by Kandel. Kolb places the locus of this cellular damage in the temporal-amygdaloid complex.
The significance of this placement is that this complex is known to be responsible for initiating integration of other brain functionings to provide for primary brain response. He also says that the damage can sometimes be so great that it prospectively causes neuronal death (quote Sapolsky, 1984). I was unable to find that neuronal death information when reading Sapolsky; I may have missed it or the proper reference. I would like to have understood it, as neuronal death caused by psychological trauma is an important issue; one about which I and all good students of psychological trauma would no doubt like to be apprised.
From this original damage, Kolb explains that cyclical and self perpetuating neurological processes continue to adversely influence learning, habituation, and sensitization. These prosesses are expressed behaviorally (as symptoms) and can include recurrent intensive arousal, which further influences cortical functioning. This influence is such that lower brain structures responsible for stimulation of noradrenergic activity are controlled less, which inhibition results in increased noradrenergic activity -- autonomous, sympathetic system, arousal; stress is created.
This process is biologically cyclical as over time the stimulation of noradrenergic activity can stimulate emotions connected to the memory of the event, which stimulation interferes with cognitive controls and functioning and "produces dissociative behaviors" (pg. 994). Of course a loss of control and dissociative states, although defensive - protective, create additional damage. Kolb recognizes primary and secondary behavioral symptoms some of which are standard PTSD symptomatology and others that are slightly different.
The neurobiological aspects of Kolb's hypothesis (related to memory and learning) is similar to TRT theory to the degree that both recognize alterations in neuronal functioning (and structure) as key to the initiation of the neurobiological manifestation of the effects of psychological trauma. Both also recognize the role of the trauma's retention in memory as an ongoing source of restimulation of neurobiological processes.
A primary difference is that TRT theory emphasizes the unlearning of memory retaining the previous psychological management system. This unlearning is represented as extinction of the neurons underpinning that system. Extinction is noted as the molecular expression of loss, which is eventually integrated by the brain through a series of relationships between adaptive memory systems; all of these adaptations are supported by PSR (protection, signalling and remedy).
Moreover, PSR, in the main the response of the noradrenergic and opioid systems, is viewed in TRT theory as an element of the integrative process. The systems are viewed by Kolb and others (discussed under stress) as systems that are functioning out of control -- they are the new problem.
From this perspective, although there is accordance with Kolb's view that the trauma's effects are principally to the neuronal cortical barrier as an overload of that system's ability to manage sensory, motor and behavioral response (survival), an additional principal alteration to synapses is to those representing the previous system of psychological reality and management, that is, those neurons (memory traces) comprising values, beliefs, images and realities.
Furthermore, the ETM hypothesis is that the underpinning of the emotional response to the trauma to which Kolb refers, is not just a consequence of the retention of the event in memory as an ongoing pain producing experience, but as a consequence of the unlearning of those values, beliefs, images and realities that comprised the neurophysiology before the trauma occurred. This unlearning is integrated by measurement (memory system two) of the depreciation (change from what was to what is following the trauma). When such measurement is coupled with opioid receptor blockade, it provides the emotional component of loss -- sadness, mourning, and so forth.
The symptoms of hyperreactivity (i.e., startle responses, explosive outbursts, nightmares, and intrusive recollections) in humans resemble those produced by chronic noradrenergic hypersensitivity following transient catecholamine depletion after acute trauma in animals." pg. 68 (our emphasis)."Catecholamine" refers to the neurotransmitters norepinephrine, dopamine and epinephrine.
central noradrenergic hyperactivity is associated with a relative decrease in brain opioid receptor binding. pg. 73.Decreases in such bindings would be thought to lead to opiate withdrawal, which is then hypothetically thought to require the addiction to the occurrence of other traumatic events so that new opioid release can fill the void and blunt or numb the withdrawal pain resulting from the initial and subsequently cyclical opioid binding deficit process.
In this section the review of the Kosten - Krystal investigations is limited to their investigations into and hypothesis of the effects of psychological trauma on the autonomous (sympathetic) system and the relationship of those effects to learned behavior. In addition, this article blends considerations of sympathetic system effects with endocrine system effects (already considered in the preceding sections on the endocrine system) in determining the biological basis of PTSD. Kosten and Krystal (1988) (also referenced in this subsection as "Kosten" and "the authors") indicate that the locus ceruleus, through stimulation of central noradrenergic activity, is important for providing alarm behaviors to the traumatic event (pg. 54).
Because the locus ceruleus is replete with neurons that have receptors that bind with endogenous and exogenous drugs, from peptides (opioids) to ethanol (although alcohol is not thought to bind in receptors, it still reduces noradrenergic response), it is inferred that uses of such drugs, which are shown to mitigate alarm responses initiated in the locus ceruleus, validate the view that the locus ceruleus's initiation of central noradrenergic activity is the source of the alarm response to the traumatic stimuli. The authors correlate the alarm behaviors of noradrenergic activity to signs and symptoms of PTSD (pgs. 56 and 57). Some of those correlations include "restlessness, irritability, sleep disturbance, exaggerated startle response, and general autonomic arousal" (quote Redmond, 1984 and Leahy, 1980).
Pharmacological and electrical interactions with central noradrenergic systems appear to validate Kosten's conclusions that noradrenergic stimulated alarm behaviors and PTSD symptoms are similar to the point that they are the same. The model presented by the authors is continued through their extrapolation of noradrenergic activity, alarm behaviors and PTSD symptoms to behavioral models.
For example, an unconditioned stimulus (an ambush) produces unconditioned response (including noradrenergic stimulated alarm behaviors) which when returned to a neutral environment (a non combat area like home) become restimulated by other experiences (in the authors' examples automobile backfires - mimicking gunfire and unmowed fields - representing tall grass from which the original ambush may have been initiated). Other behavioral correlates (pg. 58) include "fear acoustic startle response," which refers to the pairing of sound and light with shock and then withdrawing the shock later and still having the same results with only the light and sound, and "inescapable shock: the learned helplessness model," which has been referenced in the previous subsection. Both of these processes are linked to extensive noradrenergic activation.
Moreover, the inescapable shock model has demonstrated effects on other neurotransmitters systems: GABA, serotonergic, dopaminergic, and opioid systems. Serotonergic systems reverse the inescapable shock condition (quote Sherman, 1980, Edwards, 1984) and dopaminergic antagonists both reverse and prevent the condition (quote Anisman, 1981, Anisman, 1980).
There are also discussions in this article about the concurrent uses of exogenously introduced drugs as medicators of the traumatic stress response. Much of the drug information parallels that which has been provided in Kosten's article. Notably, Kosten's coauthor Dr. John Krystal is also a coauthor of this work (both groups work out of Yale University). The general idea of treatment for this condition appears to be pharmacological: "Thus, the proposed relationships among dysfunction of specific brain structures and neurochemical systems and clinical symptoms raise the possibility of discovering a rational, targeted pharmacotherapy for PTSD." See page 302 in "Charney."
As indicated in previous discussions, where the focus is on the stress response, there is no explanation for the neurological factors that are disrupted that may create or contribute to the fear, nor explanation for the emphasized memory (the repeating recollection of the event) that does not become extinct relative to other memories (there is a proposition that the failure to become extinct is an important function of genetic influence), nor is there a description of the condition that the sensitization is opposing, or to which the stress response is initiated against as Kolb has endeavored to explain in his "cortical overload" theory. Neither is there any support in this work for our theory that the locus of the reaction is in the alterations to the neuronal substrates of memory existing before the traumatic event.
We believe this focus on stress as opposed to loss is influenced in part by categorization; for example, the term "post-traumatic stress disorder" promulgated in the DSM is itself a parameter-setting mechanism for the study of psychological trauma. The words "stress disorder" focus the delineation of the problem on the stress reaction to the traumatic event, as opposed to focusing on the retention in memory of the contradictions to existential identity and subsequent loss resulting from the event. There is no term in the DSM entitled post-traumatic loss disorder to focus everyone's attention on the biological aspects of loss's retention in memory as TRT theory endeavors to effect such focus.
The problems that people surrounding trauma victims have with PTS symptoms also influence the focus. For example, in the stress focused approach, the problem of psychological trauma does not become apparent until symptoms are manifested. These symptoms can occur as a result of internal damage, as explained by Kolb in the previous subsections on memory (damage = synaptic change resulting from neuronal cortical barrier overload), or as a result of external stimulation of the memory of the event, which stimulation evokes an emotional/actional response greater than outside observers (people other than the trauma victim being observed) believe is warranted, given how non trauma-affected people would probably respond to the same stimulus.
For trauma victims, any emotional experience (even one that is unrelated to the past traumatic event) can affect the biological apparatus responsible for producing stress responses and in the process produce, again, an other-than-normal stress related activity by the trauma victim. These "other-than-normal activities" are referenced as symptoms of the post-traumatic stress disorder. Consequently, when people study psychological trauma, there is a tendency, in our view, to focus on the stress response, the nosotropic perspective of trauma.
This focus is carried into the study of the biological variants of the response, which usually means that such studies are about the effects of the trauma on the autonomous system, particularly the sympathetic (noradrenaline producing) system, and the symptoms like hyperarousal and so forth that stem from that system. As indicated, many neuroscience investigators propose that the effects on these systems is the central biological aspect of psychological trauma to solve.
In contrast, we only view the stress factor as one component of the cascade of psychobiological sequelae -- the true problem locus is the neurological retention of the contradicted existential identity and subsequent loss in memory; an event which, because of its paradoxical-based constitution, fuels the ongoing biological stress response. This stress response, which we have referred to as PSR, is seen from the ETM perspective as an attempt to remedy the changes ongoing in memory.
We have never seen anyone for whom there is no cure for the effects of psychological trauma. Moreover, long lasting consequences of psychological trauma are always, from our perspective, the responsibility of the management system surrounding the veteran (or the social response surrounding other trauma victims) and not a function of endogenous activity. Consequently, when the evidentiary biological data supporting ever continuing noradrenergic effects in combat veterans was presented (see the previous subsection), and implying that the conditions had been continued for these people, and were thought to probably continue (absent medication interventions), we had to evaluate why we saw no such people (similarly chronically affected). Possibly, these differences can be explained through consideration of populations seen, alternative treatment approaches, or the influence of drug use on the populations studied, including the possibilities of comorbity with chemical dependency.
With regards to population, the evidentiary studies may represent people more severely affected by combat trauma than patients affected by combat trauma that we saw. After all, our program was primarily outpatient and most such patients presented, not initially because of combat trauma, but either for chemical dependency or for the effects of involvement with a chemically dependent person. VA centers were known for treating combat trauma and we were not, thus they assuredly would have been considered the experts and received the most difficult cases, not to mention the mitigation of combat trauma is the responsibility of those ordering the combat in which the trauma occurred.
Moreover, although we treated such patients whose combat descriptions of carnage and death were so severe that some of our newly training (before development of the ETM Professional Training and Certification Program) counselors could not listen to descriptions of the events, none of our patients were affected to the degee that they had become completely incapacitated by the trauma, as many VA programs represent such incapacitated (or nearly incapacitated) people and is referenced by Kolb. In addition, the resolution of the trauma resulting from these other issues led to the resolution of the combat related trauma -- combat trauma cases (veterans) were rarely referred to us because of combat trauma issues.
We did see some non combat related trauma cases, however, where the effects of the trauma, were in my opinion, more severe than in any other group, including combat, and despite studies to the contrary (discussed in the next bibliography chapter). These effects included incapacitation similar to that described in scenarios where the trauma victim is being affected by inescapable shock.
This group was comprised of battered spouses of chemically dependent people and often to include experiences where the children were also physically or sexually assaulted, and where the experience of the trauma was repetitive, cyclical, and extended over long periods, for example, 25 to 35 years. Although this latter group was the most psychologically and obviously neurophysiologically devastated group to whom we provided care, they were treatable like other patients. Moreover, the obvious neurological stress related issues were as addressable as the other issues.
Treatment methods may have contributed to the continuation of the stress activity. For example, hyperarousal is a common presenting symptom, but one that is overcome by the use of the structure provided through the application of TRT. When the structure is administered, the stress symptoms are expected to become less a factor in appraising (and addressing) the psychological condition. Also, application of the TRT model showed that stress responses would continue despite the application of the structure if patients continued to use drugs socially (chemically dependent people obviously did not use drugs in our programs). In only one of the evidentiary studies addressing autonomous system effects of PTSD was it required that subjects refrain from engaging in the use of drugs (socially) as we required such abstention (see About/ Theory/ Drug Use).
With some exception, the autonomous system studies (Blanchard, 1983, Dobbs and Wilson, 1960, Malloy et. al., 1983, or Wenger) did not report screening for chemical dependency as a comorbity issue -- an issue that requires consideration because the autonomous nervous system biological effects are similar if not the same; moreover, the behavioral manifestations, that is, symptoms of noradrenergic response for PTSD and chemical dependency are identical. Since these studies were conducted (primarily on combat veterans being accorded treatment for PTSD at VA centers), other studies have determined that of all such patients comprising the presenting populations, 60 to 80 percent were suffering chemical dependency (see About/ Comparison - Contrast/ Multiple Sources).
Also, later studies are determining that chemical dependency in PTSD cases may have been developing prior to the traumatic event. Possibly, the apparent chronic form of PTSD referenced by Kolb, and not seen by us, is a product of the traumatic event occurring during the development of chemical dependency, and the failure of the various treatment efforts administered prior to the studies to have identified the comorbity issues and address the chemical dependency and its physiological concomitants and then the PTS, as we would have addressed it. This possibility would fit with our experience in working with comorbity of chemical dependency and other kinds of trauma, for example, rape, repeated physical assaults by a spouse, and assault during, say, an armed robbery where a homicide occurred, but where we documented the onset of the chemical dependency as occurring prior to the traumatic event.
In all of these cases the stress responses (inability to control hyperarousal and etc.) were substantial. Invariably, when such cases involving extraordinary hyperarousal presented, it was a result of such comorbity. For this possibility, comorbity -- chemical dependency and PTSD occurring together and the dependency to have been developing prior to the traumatic event, to have escaped the researchers views, including the views of the investigators Kolb, van der Kolk, Kosten/Krystal and Charney, their basic premises must have been that chemical dependency, rather than being considered a problem prospectively having a biogenetic basis and thus a cause of psychological trauma, is predominantly a symptom of the stress response. That is the apparent position of all 4 authors providing the industry's best analysis of the PTSD condition as it relates to autonomous system processes. As indicated, the literature addressing the issue of comorbity of pathological chemical use and PTS is provided in About/ Theory/ Drug Use.
We hope that this happens for this profession and the populations it serves. In the mean time, that is, until such discoveries are made, we believe the new technological understandings provided by molecular biology show that endogenous neurochemicals are already being produced that solve the problem of psychological trauma -- reverse the etiology of the trauma <197> as long as they are properly facilitated and they are not interfered with in their missions to accomplish the reversal.
If we were to elaborate here on the effects of psychological trauma on the immune system, the inference would be that our model, which we posit resolves trauma completely, could possibly alter the course of physiological disease -- we make no such claim. This issue is addressed again in the first section in this appendix under grief resolution as a modality for people suffering terminal cancer.
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