Neurobiological Mechanisms of PTSD
Running head: NEUROBIOLOGICAL MECHANISMS OF PTSD
Neurobiological Mechanisms of
Posttraumatic Stress Disorder
Ontario Institute for Studies in Education
University of Toronto
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Neurobiological Mechanisms of PTSD
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Introduction.
In their survey exploring the lifetime prevalence of exposure to trauma in Canadians,
Stein, Walker, Hazden & Ford (1997) found that 74% of women and 81% of men interviewed
had experienced some type of trauma (e.g., rape, sexual molestation or physical attack, combat,
witnessing a severe injury or death, being threatened with a weapon, serious motor vehicle
accident, fire or natural disaster (Stein, Walker, Hazden & Ford, 1997). Psychological disorders
such as Posttraumatic Stress Disorder (PTSD) which is characterized by flashbacks, nightmares,
anxiety, avoidance, sleep disturbance and depression (American Psychiatric Association, 2000),
frequently develop after exposure to traumatic events. This paper will discuss the development of
PTSD by exploring the various neurobiological mechanisms which are known and hypothesized
to be involved in the development of disabling traumatic stress symptomatology.
Research suggests that there is a period of neuroplasticity which is believed to occur
directly following the experience of a traumatic event (Shalev 2000). This paper will explore that
plasticity and its interaction with the various processes which may be activated in the brain and
body during and following a traumatic experience. This interaction is proposed as the basis of the
disabling symptomatology which characterizes PTSD. This paper presents a model that
endeavours to explain the implications of trauma-related plasticity for personality development,
followed by a discussion of implications for treatment.
Neurobiological mechanisms and trauma.
A traumatic event, as defined within the Diagnostic and Statistical Manual of Mental
Disorders – Fourth Edition (DSM-IV), is an experience which involves witnessing or hearing
about the actual or threatened death, serious injury or otherwise endangerment of the physical
Neurobiological Mechanisms of PTSD
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integrity of oneself or another person to which one responds with feelings of “intense fear,
helplessness, or horror" (American Psychiatric Association, 2000, p. 463). A variety of
neurobiological systems are activated during and directly following a traumatic event, often
persisting in their activation long after the traumatic event has ended, the threat removed, and
safety re-established.
As with any stimulus in an individual’s environment, the sensory systems, namely the
sensory cortex and the subcortical limbic areas which include the brain stem, hypothalamus,
thalamus and striatum, are the first to be activated during a traumatic event and are thus the first
to identify the stimulus or stimuli as threatening (Devinsky & D’Esposito, 2004). This initial,
basic perception of threat and other emotionally significant sensory information are then
processed by the amygdala, which attaches emotional and motivational significance to the data
(Devinsky & D’Esposito, 2004). The amygdala then communicates this information back to
subcortical areas and upwards to cortical areas, like the orbitofrontal cortex, dorsomedial and
lateral prefrontal cortex, which further influence the perception of danger (Lewis, 2007). This is
often followed by the experience of fear and the execution of self-protective action (Devinsky &
D’Esposito, 2004). Typically described as the fight or flight response, this response is
orchestrated by the activation of autonomic, arousal, endocrine and skeletomotor responses
through the hypothalamus and brain stem (Devinsky & D’Esposito, 2004). Lewis and Todd
(2007) describe reciprocal functioning between the subcortical-cortical network and limbic
systems. The brain stem sends messages back to the hypothalamus activating the release of
neuromodulators to further facilitate the fight or flight response (Lewis & Todd, 2007).
Influenced by the amygdala, the anterior cingulate cortex is involved in the selection of strategies
Neurobiological Mechanisms of PTSD
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or the making of choices, directing attention and self-monitoring towards the goal of ensuring
one’s self protection or escape from harm (Lewis & Todd, 2007).
As part of the neurocircuitry of fear, the central nucleus of the amygdala continues to be
activated, as well as the locus coeruleus within the brainstem, both of which influence the release
of catecholamines (adrenalin and noradrenalin) which fuel the fight or flight response (Goddard
& Charney, 1997). Those same catecholamines also result in the manifestation of reactions and
symptoms typically seen during or following traumatic events, including hyperventilation,
trembling, sweating and rapid heart rate (Vaiva, Decroc, Jezequel, Averland, Lestavel, Brunet &
Marmar, 2003). Understanding the various neurobiological mechanisms which are activated
during and after a traumatic event provides a background from which to better understand the
development of traumatic stress symptomatology.
Neural plasticity.
While the amygdala interfaces with the subcortical-cortical network and limbic system to
facilitate the immediate safety of the individual, it simultaneously initiates a protective
mechanism which is crucial to the individual’s future survival: the mechanism of memory
consolidation. Following its initial assignment of emotional valence to sensory stimuli, the
amygdala sends projections about the stimuli to the hippocampus, which then imprints the
information in the neocortex (Devinsky & D’Esposito, 2004). This process is described as
amygdala-mediated associative learning (Lewis & Todd, 2007) and may be best explained in
terms of neural plasticity. The term neural plasticity is used to describe the brain’s
reorganizational capabilities and the processes the brain undergoes throughout development
which serve to improve its functioning. These processes include: synaptic elaboration
Neurobiological Mechanisms of PTSD
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(proliferation and strengthening) and the paring down or streamlining of synapses (Lewis, 2005),
as well as the incorporation of new information via learning and memory (Johnson, 2000;
Kempermann, Kuhn & Gage, 1998; LeDoux, 1996; Nelson, 2000). The limbic structures of the
brain are highly plastic, thus the hippocampus and the amygdala both acquire synapses that
mediate memory (Lewis & Todd, 2007). The hippocampus acquires synapses which contribute
to the development of semantic memories (e.g., meanings, understanding and concepts) and
episodic memories (e.g., events, times, places and other experience related information) of the
traumatic event. The amygdala acquires synapses which facilitate the development of associative
memories about the traumatic event (e.g., patterns or mappings of specific input representations)
(Kohonen, 1984; Lewis & Todd, 2007). In other words, experience-dependent shaping of
synaptic networks takes place and associations about experiences and related stimuli are laid
down which will affect the individual’s reactions, appraisals and behaviours for the rest of their
lives (Greenough & Black, 1992; LeDoux, 1995; Nelson, 2000).
Throughout the reciprocal processes described above, the amygdala continues to
contribute to the development of trauma-related memories through its influence on emotional
and physiological arousal (Pitman & Delahanty, 2005). It has been well documented that humans
maintain better retention of emotionally arousing stimuli than they do neutral stimuli, and
evidence is accumulating which suggests that the degree of emotional arousal is the underlying
effect which contributes to that retention (McLeery & Harvey, 2004). Research suggests that the
amygdala and the central noradrenergic mechanisms, key components facilitating emotional
arousal, are therefore essential to memory enhancement in human beings (McLeery & Harvey,
2004). The neurohormones like the catecholamines: adrenalin and noradrenaline, whose release
are directly influenced by the amygdala, have been shown to facilitate the consolidation of
Neurobiological Mechanisms of PTSD
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memories and the development of acquired conditioned emotional responses (Pitman &
Delahanty, 2005).
Fear conditioning, an adaptive self-protective mechanism wherein organisms learn to
fear and thus avoid dangerous stimuli, appears to be influenced by this process. Conditioned fear,
develops following the association of a specific cue (e.g., a large dog) with an aversive stimulus
(e.g., a painful bite). Often, the conditioned fear extends to the context within which the cue and
aversive stimulus were encountered, called context conditioning (e.g., the dog park where the
trauma occured). It has been found that when exogenously administered after a learning task,
adrenalin serves to strengthen the consolidation of memories and fear conditioning (Hatfield &
McGaugh 1999; Introini-Collison et al., 1992; Pitman, Sanders, Zusman, Healy, Cheema, Lasko,
Cahill & Orr, 2002; Sullivan, McGaugh & Leon, 1991). Essentially, physiological and emotional
arousal, namely adrenergic activation, serve to highlight the traumatic experience as a significant
one and therefore function to ensure the individual’s remembrance of it (Pitman et al, 2002).
Functional aspects of a posttraumatic neural plasticity mechanism.
By exploring these processes from an evolutionary perspective, such mechanisms can be
viewed as highly adaptive. As McGaugh (1990) wrote, “significance facilitates remembrance.”
Hence, the evolution of a posttraumatic neural plasticity mechanism which ensures that the
details of threatening events are remembered serves to protect an individual from approaching
the potentially dangerous in future, therefore averting injury or death. Details can include
individuals, locations, context, objects and animals. Conditioned fear is learned quickly, is likely
to take place after only a single aversive experience or encounter with a stimulus, and is long
lasting (LeDoux, 1995). After all, in the wild, the survival of an individual hinges on whether it
Neurobiological Mechanisms of PTSD
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remembers and later is able to recognize dangerous or potentially dangerous stimuli based on
past experience. It is only when these processes become overactive that this otherwise adaptive
neural mechanism becomes problematic or even pathological as in the case of traumatic stressrelated disorders like Posttraumatic Stress Disorder (PTSD).
The pathogenesis of PTSD.
It has been widely hypothesized that a period of increased neural plasticity occurs within
the brain directly following an individual’s experience of extreme traumatic events (Pitman &
Delahanty, 2005; Shalev 2000; Viav et al, 2003). Researchers postulate that during this critical
period, long lasting neuronal changes take place which result in the development of traumatic
stress disorders (Shalev 2000; Pitman & Delahanty, 2005). This can be explained in terms of fear
conditioning, the process detailed earlier, where the amygdala and hippocampus acquire
synapses and essentially hard-wire memories and information about a dangerous stimulus into
the brain. In the case of PTSD, it is believed that an exceptionally potent unconditioned stimulus,
the extreme trauma, activates the fear conditioning mechanisms within the amygdala to a
particularly powerful degree, which then leads to powerfully potentiated synaptic links being
made within the brain, rendering the situation, sights, sounds, objects, individuals and other
trauma-related sensory information as conditioned stimuli (LeDoux, 1995). When the individual
comes in contact with these conditioned stimuli or related stimuli, these highly potentiated
circuits elicit extreme fear responses. LeDoux (1995) suggested that because the subcortical
pathways are not able to effectively distinguish between stimuli, generalization readily occurs,
meaning that the individual will experience a similar fear response to specific trauma-related
stimuli like a gun shot, as they would to a slamming door which is banal but sounds similar.
Neurobiological Mechanisms of PTSD
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Generalization, in which more and more stimuli begin to trigger the fear response, is likely a
self-perpetuating process in that through long term potentiation, which includes frequency of use,
these pathways to the amygdala become permanently streamlined to ensure efficiency of future
synaptic transmissions (Lewis, 2005). Over time, “exposure to stimuli that even remotely
resemble those occurring during the trauma would then pass, like greased lightening, over the
potentiated pathways to the amygdala, unleashing the fear reaction” (LeDoux, 1995, p. 258).
Pitman and Delahanty (2005) proposed that PTSD results from a normal acute stress
reaction, which fails to resolve itself. The DSM-IV notes the presence of intense fear, rather than
just fear, as a precondition for a PTSD diagnosis (American Psychiatric Association, 2000). It is
the experience of intense fear or terror and its connection to the amygdala and noradrenergic
activation, which researchers have specifically implicated in the development of traumatic stress
symptomatology. For over 25 years, the neurobiological literature on memory and PTSD has
suggested that the extreme emotional response or arousal that is evoked during the experience of
threatening events may lead to the over-consolidation of memories of the traumatic event which
are then difficult to abrogate (Pitman, 1989). The intense emotional response elicited by extreme
trauma results in prolonged adrenergic activation, in turn resulting in greater exposure to
corticotropins leading to overly strong emotional memory consolidation (McLeery & Harvey,
2004; Orr et al, 2005). These over-consolidated trauma memories become problematic as they
are intensely more vivid than average memories and evoke a dramatic emotional and
physiological response when recalled (McLeery & Harvey, 2004). Pitman (1989) theorized that
trauma-related over-consolidated emotional memories and fear conditioning are subsequently
manifested in the intrusive thoughts or recollections and re-experiencing symptomatology that
are characteristic of PTSD.
Neurobiological Mechanisms of PTSD
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PTSD symptomatology itself may serve to further influence memory consolidation as a
self-perpetuating system. For example, re-experiencing symptoms provoke sympathetic arousal,
thus resulting in the release of catecholamines which may then facilitate further consolidation of
the trauma-related memories (Pitman & Delahanty, 2005). It is likely that this represents a
vicious cycle wherein the repeated reactivation of memories and fear responses by PTSD
symptoms further consolidate the memories and fear conditioning and therefore perpetuate the
persistence of the symptoms (Charney, 2004; Pitman, 1989).
Posttraumatic neural plasticity and personality development.
Thus far, trauma and traumatic stress disorders have been discussed in terms of the
neurobiological mechanisms which influence and are influenced by them. Exploring these
mechanisms in terms of stimuli experienced and the brain/body’s response has touched upon the
cognitive and emotional components of that process, but will herein examine these in greater
detail. Lewis (2005a), argued that “all brain processes have cognitive appraisal aspects (i.e.,
interpretation of the world) and emotional response aspects (i.e., an urge to act in keeping with
that interpretation)”(p.3). LeDoux (1995) proposed that in persons with PTSD, trauma may have
served to bias the brain such that “the thalamic pathways to the amygdala predominate over the
cortical ones, allowing these low-level networks to take the lead in the learning and storage of
information” (p. 257). This serves as an interesting, although brief, explanation of the
neurobiological mechanisms which may underpin cognitive biases. Cognitive biases, act much
like a lens through which one views the world. They are particular patterns of judgment or
appraisal which influence an individual’s perception or understanding of experiences (Beck,
1995). As discussed above, the synaptogenesis and synaptic streamlining which take place
Neurobiological Mechanisms of PTSD 10
through experience-dependent learning, shape the brain and likely therefore shape the
individual’s perceptions of future experiences. Cognitive biases, appraisal orientations and
underlying beliefs may develop out of, and be continually fuelled by, those neurobiological
mechanisms. The amygdala, through pathways to the hippocampus and cortical structures,
highlights particular interpretations and influences appraisals, which, like memories, become
consolidated over time (Pare, Collins, & Pelletier, 2002). These meanings, built up within one’s
limbic networks, help one to make sense of the world and one’s own experience of it (Lewis,
2005a). They influence how we think and behave which are the fundamental components of
what constitutes personality.
In normal development, personality develops over time and is based on the culmination
of one’s life experiences (Schore, 2003). Devinsky & D’Esposito (2004) describe personality as
“the perceptual, cognitive and behavioural response characteristics that make individuals unique”
(p. 331). When an individual experiences a severe trauma which results in the development of
traumatic stress symptomatology, it may be argued that the same principles through which their
pre-trauma personality has been built, may serve to undermine or alter that personality in the
extreme.
The traumatic events and individual experiences provide them with unique information
and learning which shapes them as an individual. Part of that shaping is a literal, physical
shaping of their neural networks. Trauma-related cognitive biases are laid down over time
through the repeated activation of the corticolimbic structures which were potentiated during the
trauma and its immediate aftermath. The amydala-influenced appraisals of danger and threat and
the consolidation of memory and meaning lead to the development of biased appraisal
orientations. As a result, an individual’s perception of the world and appraisals of situations and
Neurobiological Mechanisms of PTSD 11
stimuli become increasing more phobic. Their biased beliefs become generalized and therefore
shift from being trauma-specific (e.g., large men are dangerous) to progressively more general
(e.g., all men are dangerous, all people are dangerous). An individual’s fundamental beliefs
about the world, themselves and others may shift dramatically, sometimes over a very short
period of time and sometimes immediately (Foa, 1998). They may begin to appraise many
innocuous situations as potentially threatening, capricious or inequitable, and additionally may
perceive themselves as vulnerable, weak, unlucky or inadequate (Brewin, 2001). They become
individuals for whom the world may appear to be an intrinsically unsafe place, where their belief
in their own ability to effectively deal with adversity or stress is diminished. In other words, their
personalities may be observed to have shifted from reasonably confident, competent and
generally highly-functioning, to fearful, inhibited, distressed and in many ways disabled.
In addition to contributing to the development of cognitive biases and appraisal
orientations, repetitive activation of the mechanisms described in the sections above, memory
and emotional/physiological arousal are believed to sensitize or kindle trauma survivors to
stressful experiences (Harkness & Tucker, 2000). Individuals with PTSD not only experience
increased physiological reactivity at exposure to trauma-related cues, but often become easily
aroused when faced with stressors of any kind. Much in the same way that, through
generalization, fear responses begin to become elicited easily by stimuli which are only slightly
or vaguely related to the trauma, so too may individuals begin to respond with fear to situations
representing any adversity or stress as though they were dangerous. This low stress-tolerance
threshold is likely related to diminished arousal control ability which again may be attributed to a
vulnerability in limbic areas (Harkness & Tucker, 2000), namely the same potentiated or
hypersensitive neural pathways between the amygdala and cortical structures involved in over-
Neurobiological Mechanisms of PTSD 12
appraisal of danger and threat, structures which unduly influence the sympathetic arousal system.
Further learning takes place with each new experience of low stress-tolerance which contributes
to new fear-based memories which are then consolidated within the brain.
The newly established post-trauma characteristics of threat or vulnerability based
appraisal orientations, stress-sensitivity or hyperarousal, displayed by persons with PTSD are
similar to the traits of anxiety-based appraisal orientations and hyper-reactivity or over-arousal
which are considered to be characteristic of an anxiety-based personality structure (American
Psychiatric Association, 2000; Shore, 2003). Anxiety-based personalities, like other personality
types, are theorized to be experience-dependent, being influenced by early attachment
experiences with caregivers and other social interactions throughout childhood and adolescence
(Shore, 2003). In keeping with notions of the brain as a self-organizing system whose
development occurs in the context of interactions with other individuals (Eisenberg, 1995;
Schore, 2003), early insecure attachment and other negative experiences are hardwired within the
brain by the mechanisms of neural plasticity and are believed to hinder self-regulation of
emotional and physiological arousal which then influences the establishment of anxiety-based or
negatively-biased appraisal systems (Schore, 2003). The increasingly sensitive or streamlined
neural networks shape an individual’s nonconcious processes, appraisals, behaviour and response
style which consolidates over time to establish an anxiety-based personality. The notion that a
similar, if only significantly expedited, process of personality development, or shift, may be
occurring following trauma, highlights the importance of developing effective, early
interventions. It is interesting to note that despite the relative consistency of personality after
adolescence, experiences like trauma may have such a dramatic and lasting impact on an
individual.
Neurobiological Mechanisms of PTSD 13
Summary and Discussion of Implications for Treatment.
This paper explored the development of PTSD by detailing and discussing the various
neurobiological mechanisms both known and hypothesized to be involved in the development of
disabling traumatic stress symptomatology. Neural plasticity is theorized to occur during and
directly following the experience of an extremely traumatic event (Shalev, 2000). Posttraumatic
neural plasticity may lead to fundamental changes in an individual’s biological, cognitive and
emotional functioning, which may then manifest as debilitating symptomatology and altered
personality. If the neurobiological mechanisms work as proposed, treatments that focus on
interrupting reinforcing cycles will be most effective for working with trauma survivors. For
example, drug treatments which reduce or inhibit the production of catecholamines can be
administered directly post-trauma in an effort to attenuate traumatic memory consolidation
(Grillon, Cordova, Morgan, Charney & Davis, 2004; Orr, Milad, Metzger, Lasko, Gilbertson &
Pitman, 2006). Other approaches could involve combining adrenergic arousal inhibiting
interventions with psychotherapy. For example, when combined with narrative therapy,
traumatic memories and events could then be reprocessed without the fear response. Cognitive
and behavioural interventions which use graded exposure to systematically desensitize clients to
fear response-inducing stimuli, might be made more effective and efficient through the use of
adrenergic activation blocking agents. More research into the impact of trauma on personality is
needed and would serve to further elucidate the lasting impact of PTSD on individuals and
subsequently serve to inform treatment.
Neurobiological Mechanisms of PTSD 14
Comments
I think you really took off in this paper. The intriguing nature of personality development,
which you obviously resonate to in a general way, has led you to a fascination with these
particular junctures between trauma and the resetting of appraisal, through which, as you
say, personality development is rapidly overwritten. Indeed, in the case of trauma, all of the
features of an anxious disposition are acquired quickly and usually irreversibly, thus
cutting through the usual developmental requirements of time and upbringing to bring
about a robust change in interpretation, reaction, and disposition. The paper got off to a
somewhat weak start because a fair bit of the neuroanatomy was vague or simply wrong.
But you seemed to develop more of a voice, with increasing precision and accurate detail,
as you went along. Not only did your discussion of brain processes become technically
confident, but the way you used them, to weave a distinct claim about personality change,
was powerful and compelling. It’s gratifying to see that you got that momentum out of the
course. Even though you’re maybe not the “science type,” what you got out of the science
provided a more robust platform for discussing the humanistic issues that interest you
most.
Paper grade: A
Neurobiological Mechanisms of PTSD 15
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