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This page contains information and summaries of
published research that are intended for people with professional training in
mental health. We urge caution since
it may be difficult to know how to interpret the information without advanced
training in psychology or psychiatry.
We recommend that readers interested in information intended for
the general public check other areas of this web site (such as Info
for Adults or Info
for Children). They contain similar information, but in a more readable
form. Also, elsewhere we have provided links
to other websites that we feel may be helpful.
BIOLOGICAL
FINDINGS & THEORY
HPA
Axis Dysregulaton and Decreased Basal Cortisol Levels:
Based
on neurobiological evidence that uncontrolled life-threatening trauma affects
the opiate and neuropeptidergic systems, HPA axis, and autonomic nervous system
 | “Rather
than the classic profile of increased adrenocortical activity and resultant
dysregulation of this system described in studies of stress and other
psychiatric disorders, trauma survivors with PTSD show evidence of a highly
sensitized HPA axis characterized by decreased basal cortisol levels
and increased negative feedback regulation” (Yehuda, 1997)
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During
stress, neuropeptides in the brain cause the release of corticotropin
releasing factor (CRF) from the hypothalamus, which initiates the release
of adrenocorticotropic hormone (ACTH) from the pituitary and cortisol from
the adrenals.
Cortisol
is supposed to stop neural defensive reactions that have been activated by
stress
Cortisol
is usually markedly elevated in most types of stress as well as in
depression. However, basal
cortisol levels are low with PTSD
| “Higher
CSF CRF concentrations in patients with PTSD
may reflect alterations in stress-related neurotransmitter systems. The
higher CSF CRF concentrations may
play a role in disturbances of arousal in patients with PTSD”
(Bremner
et al., 1997).
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Glucocorticoid Receptor Upregulation:
| Lymphocyte
glucocorticoid
receptor densities are higher (upregulated) in PTSD; chronic increases in
hypothalamic CRF leads to decreased responsivity of the pituitary to CRF
(again, the opposite of Major Depression and consistent with negative
feedback sensitivity in the HPA axis) (Yehuda
et al., 1991).
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Other Findings on
Cortisol:
Yehuda et al. (2000) note that not only direct
exposure to traumatic stressors, but also parental
PTSD can affect cortisol levels of
their offspring through nongenomic transmission:
·
“[I]t appears that
parental PTSD is an even more important correlate of cortisol levels
in the offspring than whether or not the offspring developed his or
her own PTSD
after exposure to a traumatic event, as there was a significant
correlation between cortisol level and parental PTSD
even after controlling for the lifetime PTSD status of
the offspring. . . This pattern of associations does not imply that the
offspring’s own PTSD
was unrelated to cortisol level. Offspring
with both parental PTSD and lifetime PTSD
had significantly lower cortisol levels than either offspring without
lifetime PTSD or comparison subjects.”
·
“Nongenomic
transmission of stress response characteristics has been
demonstrated in rats, and this process includes both a behavioral and
neuroendocrine response bias. Moreover, this effect of maternal
behavior has recently been shown
to persist across multiple generations and to be associated with increased
hippocampal glucocorticoid receptor expression. Thus, putative animal
models exist that provide a template for generating hypotheses
concerning the intergenerational transmission of stress
vulnerability.” (see Liu et al.,
1997; Caldji et al., 1998; and Francis et al., 1999 for more info)
Noradrenergic
Findings:
| In
addition to changes in cortisol and CRF concentrations, recent studies have
noted the presence of greater
CNS noradrenergic activity under baseline conditions in
patients with chronic PTSD,
even three decades following the traumatic incident (this was a Vet study) (Geracioti
et al., 2001).
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| The
severity of PTSD Sx correlated directly with noradrenergic activity.
Notably despite elevated CNS noradrenergic activity there were no
elevations in peripheral activity.
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| Noradrenergic
effects on the amygdala may enhance encoding of emotional memories,
sensitization, and fear conditioning. Notably, the medial
prefrontal cortex, which normally inhibits the amygdala, may show deficits
in people with PTSD (Elzinga & Bremner, 2002)
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Benzodiazepine
Receptors:
People with PTSD also appear
to have fewer benzodiazepine receptors
and/or reduced affinity of receptor binding in the medial prefrontal
cortex:
| “PTSD patients had 41%
lower distribution volumes (the measure of benzodiazepine receptor
binding) in the prefrontal cortex. The
prefrontal cortex mediates several cognitive and behavioral processes
that are potentially relevant to PTSD.
The medial prefrontal
cortex has been implicated in the inhibition of cognition (which
may relate to intrusive memories in PTSD) and emotional and social behavior” (Bremner
et al., 2000).
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Reduced
Hippocampal Volume:
Animal
studies have found that stress can damage the hippocampus, and there is some
evidence that people with PTSD, overall, tend to have reduced right
hippocampal volume, which may result in functional deficits in verbal memory
(Pitman, 1997; Bremner et al., 1995). Several
different explanations have been posited for this finding:
| Repeated
exposure to high levels of cortisol that happen as a response to exposure to
stressors damages the hippocampus
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| It
appears that people with PTSD do not have reduced hippocampal volume before
the trauma, and that reduced
hippocampal volume does not occur within the first six months of the
disorder (Bonne
et al., 2001). Although alcohol
abuse is common with PTSD and alcohol may preferentially damage the
hippocampus, so far evidence does not support alcohol abuse as being the
cause of reduced hippocampal volume in PTSD (Agartz et al.,
1999; Vellarreal et al, 2002).
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| Bonne
et al. (2001) offer a possible explanation for the fact that no reductions
in hippocampal size were found 6 months post trauma: “Subcortical gray
matter and limbic structures (septal area, hippocampus, and
amygdala) show an increase in volume until the third decade of
life. In two of the four previous MRI studies the subjects were
traumatized as children. The two others concerned
Vietnam
veterans, most of whom would have
served in
Vietnam
between the ages of 18 and 21.
All four studies, therefore, examined adults whose traumatic
events occurred during a period of normal development of
subcortical structures.”
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| The
hippocampus is involved in
declarative memory, and damage to it may be implicated in deficits in
declarative memory found in some studies of people with PTSD (Elzinga
& Bremner, 2002)
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Localized
functional changes that have been
extensively replicated include increased
activation of the amygdala and reduced activation of the Broca’s speech area
following symptom provocation (
Hull
, 2002; Pitman et al, 2001).
These changes suggest the importance of emotional memory coupled with a
difficulty in labeling experiences.
Regional
Cerebral Blood Flow:
| During
recall of traumatic events, regional cerebral blood flow (rCBF) increases
in anterior paralimbic regions, the orbitofrontal cortex, and anterior
temporal pole in people with PTSD, compared to people without PTSD who
had relatively greater increases in rCBF to the anterior cingulate gyrus (Shin
et al., 1999).
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Physiological
Reactivity (McDonagh-Coyle et al, 2001):
| PTSD
symptoms severity correlates positively with psychophysiological changes (frontalis
EMG and heart rate) and negative emotions during exposure to traumatic
imagery under controlled conditions.
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| During a mental arithmetic task, however, physiological reactivity
was lower in people with PTSD vs.
people without PTSD. There was
also little reactivity to neutral, pleasant, or sexual imagery tasks.
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However, before relying too much on physiological assessment for
PTSD, note that there is about a 33% false negative (Type II error)
rate for this approach. Standardized
interviews combined with psychometrics are recommended as the most
important elements in diagnosis
Self-reported numbing did not correlate with physiological changes
during the trauma imagery task, but did correlate negatively with
physiological arousal during mental arithmetic
Kindling/Sensitization:
| repeated
presentation of a sub threshold stimulus can “kindle” limbic circuits,
producing a lower threshold of firing. Sensitization
is the similar concept that brief exposure to a single or repeated stimulus
may sensitize animals to stressors of lower intensity (Foa & Rothbaum, 1998; Post, 1985)
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Inescapable
Shock:
| accompanied by initial mobilization of
catecholamines (norepinephrine and dopamine) followed by their depletion (Foa
& Rothbaum, 1998)
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Suggests
that intrusive and avoidant symptoms correspond to hypersensitivity to
catecholamines
Drugs
that stimulate or down regulate the locus coeruleus (noradrenergically
rich “alarm center”) provoke or inhibit PTSD Sx in combat vets with
PTSD
Findings
regarding inescapable shock and opioids: “First, inescapable shock leads
to a more durable analgesia than does escapable shock.
Second, the analgesia produced by extensive inescapable shock is mediated by
opioids to a greater extent than analgesia produced by escapable shock.
Third, inescapable shock leads
to a sensitization of the opioid system, so that it facilitates the
production of future opioid-mediated analgesia” (Foa et al., 1992).
Behaviorally,
also recall Seligman’s experiments with inescapable shock resulting in
“learned helplessness” and
deficits in learning active escape behaviors and enhancements in passive
avoidance
Conditioned
avoidance:
| may be mediated serotonergically
by pathways arising in the dorsal raphe and projecting to the amygdala (Foa
& Rothbaum, 1998)
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