PERSISTING PSYCHOPHYSIOLOGICAL EFFECTS OF TRAUMATIC STRESS:
THE MEMORY OF 'STATES'

Official citation:  Perry, BD, Conroy, L and Ravitz, A Persisting psychophysiological effects of traumatic stress: The memory of "states". Violence Update 1:(8), 1-11, 1991.

One of the amazing and powerful features of the human brain is the capacity for 'memory' -- storage and recall of information. The molecular mechanisms by which the nerve cells (neurons) involved in memory store information are only partly characterized but in appears that, in response to new 'signals', neurons change neurochemical and structural properties to reach a new homeostatic 'set point' which contains 'information'. We generally think of memory as the storage and recall of cognitive information --- names, faces, phone numbers, arithmetic -- yet the same neurophysiological mechanisms involved in storing and recalling cognitive information are involved in making complex memories of a psychophysiological state which involves non-cognitive domains. The human brain can store and recall all, or a portion, of the emotional (e.g., intense anxiety) and physiological concomitants (e.g., increased heart rate) of certain life events. In this review psychophysiological aspects of exposure to traumatic and stressful life events such as rape, sexual abuse, combat or physical harm will be considered. Understanding the mechanisms by which psychophysiological 'memories' of fear and arousal result from traumatic stress has significant public health implications, each year over 2.5 million American children and adults are victimized by physical, sexual or severe psychological abuse. The psychophysiological sequelae of these traumatic events appear to make an individual vulnerable to the development of various psychiatric disorders and, further, these 'state' memories appear to play an major role in the etiology of post-traumatic stress disorders (PTSD).

POST-TRAUMATIC STRESS DISORDERS

Many individuals who experience traumatic events develop a distinct set of physical signs and symptoms. These symptoms tend to fall into three clusters; 1) recurring intrusive recollection of the traumatic event such as dreams and 'flashbacks' 2) persistent avoidance of stimuli associated with the trauma or numbing of general responsiveness and 3) persistent symptoms of increased arousal characterized by hypervigilance, increased startle response, sleep difficulties, irritability, anxiety and physiological hyperreactivity. These symptoms are exacerbated by exposure to stimuli associated with the original event.

Long recognized in combat veterans -- the 'irritable heart of soldiers' was described in Civil War veterans-- this syndrome has been described in survivors of concentration camps, Hiroshima, natural disasters, airline crashes, and in victims of rape, violent crimes, accidents, sexual abuse, physical abuse, serious medical illnesses and other traumatic events (see Krystal et al., 1989). Despite wide prevalence and serious morbidity, PTSD has not been the focus of intensive research until the last few years; indeed, it was first included in the Diagnostic and Statistical Manual of Mental Disorders in 1980 (DSM-III: American Psychiatric Association Press, Third Edition, 1980). Due to this relative clinical and research neglect, many important features of the disorder remain unexplored. The development of PTSD, however, is related to an individual's initial, presumably 'normal', adaptive physiological responses to the original traumatic event (see Perry et al. 1990, Perry 1991). Indeed many of the symptoms of PTSD are, in effect, persistence of this originally adaptive response to danger.

THE 'ALARM-REACTION'

In 1914 Walter B. Cannon first coined the phrase "fight or flight" to describe the body's appropriate response to a stressful stimuli. When an individual is exposed to real or perceived danger, a series of complex, interactive neurophysiological reactions occur in the brain, the autonomic nervous system, the hypothalamic-pituitary adrenocortical (HPA) axis and the immune system. These responses evolved to provide the critical total body mobilization required for the individual to survive a life-threatening danger.

In the initial phases, first labeled 'the alarm reaction' and the 'stage of resistance' by Hans Selye in 1936, portions of the brain involved in arousal, attention and concentration functions become activated resulting in hypervigilance to the threat and a decrease in attention to less pressing environmental stimuli -- a soldier in the midst of a fire fight, for example, may not know he has been wounded until the end of the fight. If an affective state is experienced during the alarm reaction (again, the hypervigilance may be so intense during the acute phase of a traumatic event that the individual does not attend to his or her own internal state), it is anxiety. The degree of anxiety varies with the degree of threat, ranging from 'jitters' to outright panic and terror. In addition to changes in brain functioning, other organ systems are involved in the alarm reaction. The sympathetic division of the autonomic nervous system (SNS), which originates in the brain and distributes throughout the rest of the body, plays a major role in effecting and orchestrating the brain's mobilization of the rest of the body. The activation of the SNS increases blood pressure and pulse, dilates the pupils, increases respiratory rate and increases the blood supply to the muscles. The HPA axis is activated releasing a variety of stress related hormones including ACTH and beta-endorphin (which decreases pain perception). Neural and hormonal signals (e.g., ACTH) activate the adrenal glands, which release important stress related hormones including epinephrine (or adrenaline) and cortisol. These hormones enter the bloodstream rapidly, acting in all organ systems to prepare the body to 'fight' or 'flee'.

These neurophysiological activation responses are rapid and reversible. The cost of this adaptive hyper-arousal mechanism is great; the alarm reaction consumes energy and depletes stores of available neurotransmitter and hormone. With sufficient time between threatening events, however, the body can return to a previous homeostasis or equilibrium by replenishing the stores of neurotransmitter, hormone, glucose and other important chemicals. When the stressful event is of a sufficient duration, intensity, or frequency, however, the body does not have the capability to sustain this high state of arousal -- the stress-responding apparatus becomes fatigued.

THE FATIGUED STRESS-RESPONSE AND PTSD

When the state of hyper-arousal and neurophysiological activation associated with a traumatic event persists, the brain changes (Perry 1988, Perry 1991). In much the same way that repeated exposure to a cognitive stimulus results in a cognitive memory, repeated or continuous exposure to this state of arousal results in a 'state memory'. The system has been in the aroused state so much that the brain, likely using the same molecular mechanisms underlying learning/memory (Kandel 1989), has readjusted to these new environmental demands. The arousal is no longer reversible; there is a new homeostatic set point for neurotransmitter systems (e.g., norepinephrine, epinephrine) in the brain which regulate arousal, attention, affect and sympathetic nervous system functioning (Perry 1991). These 'state memories' are the basis for the characteristic symptoms in PTSD. The hypervigilance, increased startle, affective lability, anxiety, dysphoria, and the increased SNS activity and reactivity can all be related to the altered functioning key neurotransmitter systems in the brain (see Krystal et al., 1989; Perry et al., 1990; Perry 1991).

A number of factors determine whether or not an individual will develop PTSD following a traumatic event. Clearly, the nature of a stressor plays a major role in the development of a 'state memories' and the associated psychophysiology. While this remains a poorly characterized area, it is clear that the more unexpected, violent and persisting the trauma, the more likely the adverse psychophysiological effect (see Wolf and Mosnaim 1990). The degree of control an individual has in a traumatic event is important as well. In retrospective clinical interviews and in research settings, less control of a situation is associated with increased PTSD-like symptoms (Breier et al., 1987).

Even if the nature of the stressor is similar, not all individual will develop PTSD. Some individuals are vulnerable and some resilient. This is likely related to individual differences in the preexisting homeostatic equilibrium or 'set point' of those systems involved in mediating the stress response, i.e., certain brain neurotransmitter systems, the sympathetic nervous system, the HPA axis. An individual with a baseline which is characterized by moderate anxiety and affective lability, for example, may not have the neurophysiological 'reserve' to sustain a moderately long alarm reaction, resulting in 'fatigue' before an individual with more 'reserve' (see Perry 1991). It seems likely that given a traumatic event of sufficient duration and quality, however, any individual would develop PTSD-like symptoms.

In addition to individual differences it is clear that the same traumatic event will have different long-term effects when experienced at different phases of development -- a three year old will experience a severe burn in a different fashion than a thirty year old. Breier and co-workers (1988) studied the effect of parental loss during childhood on the development of psychopathology in adulthood. They found that the subjects with psychopathology had significant biological and immunological changes related to early parental loss. The authors concluded that early parental loss (a traumatic event) accompanied by the lack of a supportive relationship subsequent to the loss (an external stress reducing factor) is related to the development of adult psychopathology.

It is likely that there are developmental phases during which an individual is most vulnerable to traumatic stressors. It has been hypothesized that this most vulnerable period occurs during the development of the complex stress-mediating organ systems. Indeed it is likely that the set point and 'reserve' capabilities of the brain systems mediating stress in the adult are determined by the nature of the 'stress' experiences during these critical developmental periods (Perry, 1988, 1991). Individuals exposed to predictable, controllable and mild stressors during the first three years of life are likely to be have a well-integrated, efficient stress response apparatus with more 'reserve' than individuals exposed to unpredictable, severe stressors. As the functioning of these important neurophysiological systems mediating stress appears critical in determining future health, research on the effects of trauma and stress during the first years of life has important implications for understanding the etiology, course and interventions for many psychiatric disorders.

CLINICAL IMPLICATIONS

Among the important clinical implications arise from these recent studies of the neurophysiology of trauma are 1) the critical need for identifying individuals at risk for developing PTSD to facilitate early intervention and 2) likelihood that pharmacological interventions may improve symptoms and minimize some of the neurophysiological adaptations which, over time, become maladaptations. In this regard we have used clonidine, a well known antihypertensive medication, to significantly decrease the symptoms of PTSD in abused children (Perry 1991). Other pharmacological interventions have been successful in treating the physiological hyperarousal seen in combat veterans with PTSD (see Wolf and Mosnaim 1990).

FUTURE DIRECTIONS

Many questions remain regarding the neurophysiology of the stress response and the relationship between 'stress' and psychopathology. What is a stress ? How can stress be quantified ? Why is one event stressful to one individual but not another ? Can the critical developmental periods for determining the 'set point' for these systems be identified ? Can early life interventions provide resilience ? What role does genetics play ? Can therapeutic interventions be developed to shift the 'set point' back to baseline following a traumatic event and the development of PTSD ? Do all individuals with a neurophysiological state memory of a traumatic event develop PTSD ? What role do these neurophysiological mechanisms play in other psychiatric disorders -- in health ? Do these neurophysiological state memories play a role in medical conditions such as essential hypertension and sudden cardiac death ? How is the immune system linked into this complex neurophysiology?

Clearly, further research is needed. With the high incidence of sexual abuse, physical abuse and violence in our society, the need to understand these complex issues is great.

REFERENCES

Breier, A., Albus, M., Pickar, D., Zahn, T. P., Wolkowitz, O.M., Paul, S. M. (1987). Controllable and uncontrollable stress in humans: alterations in mood and neuroendocrine and psychophysiological function. Am. J. Psychiatry, 144:11, 1419-1425.

Breier, A. B., Kelsoe, J. R., Kirwin, P. D., Beller, S., Wolkowitz, O. M., Pickar, D. (1988). Early parental loss and development of adult psychopathology. Arch. Gen. Psychiatry, 45: 987-993.

Cannon, W. B. (1914). The emergency function of the adrenal medulla in pain and the major emotions. Am. J. Physiol. 33: 356-372.

Kandel ER (1989) Genes, nerve cells, and remembrance of things past. J. Neuropsychiatry Clin. Neurosci.1: 103-125.

Krystal, J.H., Kosten, T., Perry, B.D., Mason, J., Southwick, S. and Giller, E.L. (1989) Neurobiological aspects of post-traumatic stress disorder: review of clinical and preclinical studies. Behavior Therapy 20: 177-198.

Perry, B.D. (1988) Placental and blood element neurotransmitter receptor regulation in humans: potential models for studying neurochemical mechanisms underlying behavioral teratology. Prog Brain Res 73: 189-206.

Perry, B.D. (199) Neurobiological sequelae of childhood trauma: Post traumatic stress disorders in children. In (M. Murberg, Ed.) Catecholamines in Post traumatic Stress Disorder: Emerging Concepts. American Psychiatric Press, Inc., Washington, DC pp 100-128.

Perry, B. D., Southwick, S. M., Giller, E. J. (1990). Adrenergic receptors in posttraumatic stress disorder. In: (E. L. Giller, Ed.) Biological Assessment and Treatment of Posttraumatic Stress Disorder. American Psychiatric Press, Inc., Washington, DC pp 89-114

Selye, H. (1936). A syndrome produced by diverse nocuous agents. Nature, 138:32.

Wolf, W.E., Mosnaim A.D. (Eds) Post traumatic Stress Disorder : Biological Mechanisms and Clinical Aspects. American Psychiatric Press, Inc, Washington, DC, 1990.

POINTS TO REMEMBER

1. The "fight or flight" response is a normal reaction to real or perceived stress. It produces a state of hyper-arousal mediated through complex interactions of the brain, the autonomic nervous system, the HPA axis and the immune system.

2. Severe or persisting stress can fatigue the normal stress response. When this happens, the neurophysiological systems involved in the stress response 'adapt' by establishing a new, homeostatic set point. The result is a 'state memory'.

3. Numerous factors, including the nature of the traumatic event and the baseline neurophysiological 'set point' of an individual, are associated with vulnerability to traumatic events.

4. In many cases, the altered neurophysiological functioning following traumatic events results in the development of Post-traumatic Stress Disorder (PTSD).

5. Identification of risk factors, biological markers, and "protective" factors are crucial to our understanding of the cause of PTSD as well as prevention and treatment.

6. This is an important area for research due to the significant morbidity of PTSD and the high incidence of physical abuse, sexual abuse and violence in our society.

QUESTIONS

1. The "fight or flight" response:

a) Is an abnormal reaction a trauma.

b) Causes post-traumatic stress disorder.

c) Is a normal response producing a state of "hyper-arousal".

d) Slows the heart and respiratory rate producing a state of relaxation.

e) All of the above

2. The following systems are involved in the body's response to stress:

a) The autonomic nervous system

b) Immune system

c) Hypothalamic-pituitary adrenocortical axis

d) Sympathetic nervous system

e) All of the above

3. Post-Traumatic Stress Disorder:

a) Has been described in victims of sexual abuse, natural disasters and combat veterans.

b) Always occurs in response to extreme trauma

c) Is characterized by reexperience of traumatic events, hyperarousal and persistent avoidance of trauma-associated stimuli.

d) Is a DSM-III R diagnostic category.

e) All of the above

4. Which of the following is true?

a) Hans Selye described the "fight-or-flight" response.

b) During exposure to stress, the heart rate increases, blood pressure increases, and skeletal muscle has increased blood supply.

c) The syndrome now called PTSD was first described 10 years ago.

d) Children rarely develop PTSD in comparison to adults.

e) None of the above