` Posttraumatic Stress Disorder in Children and Adolescents:

Neuroendocrine Perspectives
Panagiota Pervanidou and George P. Chrousos (9 October 2012)
Science Signaling 5 (245), pt6. [DOI: 10.1126/scisignal.2003327]

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A Presentation from the European

Society for Paediatric Endocrinology
(ESPE) New Inroads to Child Health
(NICHe) Conference on Stress Response and Child Health in Heraklion,
Crete, Greece, 18 to 20 May 2012.

ENDOCRINOLOGY

Posttraumatic Stress Disorder

in Children and Adolescents:
Neuroendocrine Perspectives
Panagiota Pervanidou* and George P. Chrousos

Presentation Notes
Slide 1: Science Signaling logo
The slideshow and notes for this presentation are provided by Science Signaling
(http://www.sciencesignaling.org).
Slide 2: Posttraumatic stress disorder in
children and adolescents: Neuroendocrine
perspectives
In this talk, I will discuss neuroendocrine
findings in the prediction, development, and
maintenance of posttraumatic stress disorder (PTSD) in children and adolescents, as
well as potential mechanisms linking pediatric to adult findings.
Slide 3: Posttraumatic stress disorder
(PTSD)
PTSD is a syndrome of distress that develops after exposure to events or circumstances that involved death, injury, or a threat to
the physical integrity of the individual or
others, and evoked intense feelings of fear,
helplessness, or horror. PTSD includes the
Unit of Developmental and Behavioral Pediatrics, First Department of Pediatrics, University
of Athens Medical School, Aghia Sophia Childrens Hospital, 115 27 Athens, Greece.
*Presenter and corresponding author. E-mail:
ppervanid@med.uoa.gr

following clustering of symptoms: reexperience of the initial trauma, avoidance of

stimuli associated with the traumatic event,
and symptoms of excessive arousal (1).
PTSD is classified as an anxiety disorder
in the Diagnostic and Statistical Manual
of Mental DisordersIV (DSM-IV), but it
is also a syndrome of chronic stress with
potential metabolic and cardiovascular consequences (2). In children, PTSD can be
considered as an externally induced developmental disorder.
Slide 4: Symptoms in children after
surviving or witnessing trauma
Symptoms in children and adolescents
with PTSD after surviving or witnessing
trauma include symptoms of reexperience,
including intrusive memories, flashbacks
or dreams about the event, feeling as if the
trauma were continuing to occur, and intense distress upon exposure to cues that
recall the event. Other symptoms in children include symptoms of avoidance such
as avoiding reminders of trauma, emotional
numbness or reduction in overall emotional
responsiveness, and diminished interest
in everyday activities. These children also
exhibit symptoms of excessive arousal: insomnia, angry outbursts, hypervigilance,

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Posttraumatic stress disorder (PTSD) is a syndrome of distress that develops

after exposure to traumatic life experiences. Dysregulation of both the hypothalamic-pituitary-adrenal (HPA) axis and the locus caeruleus/norepinephrinesympathetic nervous system (LC/NE-SNS) is associated with the pathophysiology
of the disorder. Studies have demonstrated a neuroendocrine profile unique to
adults with PTSD, with centrally elevated corticotropin-releasing hormone (CRH),
low cortisol in the periphery, and elevated catecholamines. Traumatic stress experiences in early life are strong predisposing factors for later PTSD development. In addition, early life stress programs the developing brain to overreact
to future stressors. In children and adolescents involved in motor vehicle accidents, we found that high evening salivary cortisol and morning serum interleukin 6 concentrations were predictive of PTSD development 6 months later. We
demonstrated a progressive divergence of the HPA and LC/NE-SNS axes of the
stress system, which may be part of the pathophysiologic mechanism responsible for PTSD maintenance. An initial elevation of cortisol in the aftermath of the
trauma, followed by a gradual normalization and finally low cortisol secretion,
together with a gradual elevation of catecholamines over time, may represent the
natural history of neuroendocrine changes in pediatric PTSD. Thus, the low cortisol concentrations found in adults with PTSD may reflect prior trauma and might
represent a biologic vulnerability factor for later PTSD development.

exaggerated startle response, and difficulty

concentrating. Additional symptoms in
children include behavioral reenactment
(repetitive play), somatic symptoms (stomach aches or headaches), and regression to
earlier developmental stages (14).
Slide 5: PTSDA disorder of the stress
system
The stress system, including the hypothalamic-pituitary-adrenal (HPA) axis and
the locus caeruleus/norepinephrinesympathetic nervous system (LC/NE-SNS), is
critical in the physiologic response of the
individual to stressors. Normally, activation
of the stress system leads to adaptive behavioral and physical changes that improve
an individuals ability to survive (5, 6), but
chronic or abnormal activation of the stress
system can have deleterious physiological
consequences. The majority of neuroendocrine studies of adults with PTSD have
demonstrated the following abnormalities
in the HPA axis: Basal concentrations of
corticotropin-releasing hormone (CRH) in
cerebrospinal fluid (CSF) are elevated (7,
8), and urinary cortisol concentration is low.
However, some studies have shown variable
results, such as no differences in plasma
or urinary cortisol concentrations or, more
rarely, increased urinary cortisol excretion
relative to healthy individuals (911). Regarding the SNS, the most consistent finding in patients with PTSD is increased noradrenergic activity, both centrally (12) and
peripherally (13, 14).
Slide 6: Biological findings in sexually
maltreated girls
PTSD is the most common trauma-related disorder, and it occurs in 40 to 90% of
children subjected to sexual abuse and in
11 to 50% of physically abused children.
However, the first neuroendocrine studies
in maltreated children have not examined
PTSD per se, but children with a history
of maltreatment exhibiting various relevant stress-related symptoms or disorders,
such as anxiety or depression (1519).
One of the first neuroendocrine studies of
maltreated children, in 1994, showed that
sexually abused girls with histories of depression and suicidal behavior exhibited
significantly higher 24-hour urinary con-

indicator of the SNS, and cortisol reactivity

to a social stressor. Control (non-maltreated)
youth showed a significant relation between
the sAA and cortisol responses to the social stress test, whereas maltreated youth
had no significant associations between the
responses in these two biomarkers. The researchers concluded that maltreatment status
altered the relation between sAA and cortisol
responses (18). Normally, the HPA axis and
the SNS are connected at multiple neuroendocrine levels so that activity in these two
systems shows some degree of symmetry;
thus, the extent of the stress response in the
SNS covaries with the extent of response in
the HPA axis. In contrast, among maltreated
youth, responses across the two systems are
not associated, suggesting asymmetry (18).
A second study in girls with a history of
maltreatment showed that in response to the
Trier social stress test (TSST), the maltreated group exhibited an attenuated cortisol
response, whereas the control group showed
a typical increase in cortisol concentrations
and gradual flattening over time (19). A
more recent longitudinal study in girls after familial maltreatment, with assessments
of the subjects at several time points, demonstrated that the linear trend for abused
females was significantly less steep when
cortisol was examined across development
from age 6 to age 30, providing support for
the attenuation hypothesis (cortisol hyposecretion subsequent to a period of heightened
secretion) in victims of abuse (20). However, children in the above-mentioned studies
were not assessed for the PTSD diagnosis.
Slide 10: Early life stress and PTSD
Early life stress and trauma are risk factors
for both adult traumatization and PTSD, and
neuroendocrine changes in response to early
adversity are correlated with neuroendocrine
findings in adults with PTSD. Thus, the low
cortisol concentrations found in most studies
of adult PTSD may reflect the continuation
of a response to an earlier exposure to adversity (21, 22). Indeed, several longitudinal
data sets have demonstrated that low cortisol
in the aftermath of trauma is predictive of
future PTSD development (2325). These
findings may lead to the consideration of hypocortisolism as a risk factor related to prior
traumatization and a predisposing factor for
further traumatization and PTSD development rather than a consequence of PTSD.
Slide 11: Potential mechanisms of low
cortisol in PTSD
Although stress is traditionally associated
with increased HPA axis activity, there is ev-

idence showing low cortisol concentrations

or a hypoactive HPA axis in several stressrelated disorders, such as PTSD, chronic fatigue syndrome, burnout, and fibromyalgia
(6). Several pathophysiological mechanisms
have been proposed to explain the biologic
findings of PTSD. The unique neuroendocrine profile in PTSD (high CRH centrally
and low or normal cortisol and high catecholamines in the periphery) suggests an
increased cortisol signaling capacity, so that
lower cortisol concentrations may suppress
more efficiently the HPA axis, thus exerting
increased negative feedback. This may lead
to decreased exposure of the LC/NE system
to the negative actions of cortisol, contributing to increased sympathetic activation
(26). Childhood trauma is associated with
dysregulation of the HPA axis, consisting of
hyporesponsiveness of the pituitary to CRH
and normal overall cortisol secretion in response to a CRH challenge. Mechanisms of
down-regulation of pituitary CRH receptors
secondary to elevated CRH and enhanced
negative feedback inhibition of the pituitary
to cortisol may also lead to lower peripheral
cortisol concentrations in adults (27).
Slide 12: Why is stress more damaging
during childhood?
There is evidence that chronic traumatic
stress during childhood and adolescence
has substantial and permanent effects on
brain development, relative to the effects
of stress on mature brain structures during
adulthood. Studies in animals have shown
that chronically elevated concentrations of
glucocorticoids and catecholamines may
lead to alterations in brain development
through mechanisms of accelerated loss of
neurons (28), delays in myelination (29), or
abnormalities in developmentally appropriate neural synaptic pruning (30). Elevated
concentrations of glucocorticoids resulting
from chronic stress may also result in frontal
lobe deficiencies, amygdala hyperfunctioning, hippocampal damage, and consequent
learning and concentration difficulties (31).
Slide 13: Brain structures vulnerable to
stress
Certain brain regions are particularly vulnerable to the effects of traumatic stress
during development. The hippocampus,
which has a high density of glucocorticoid receptors, is important for learning,
memory, and control of the stress system.
In the amygdala, which regulates fear,
anger, and emotional memory, stress attenuates the development of the -aminobutyric
acid (GABA) receptor complex, reducing the

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centrations of catecholamines and their metabolites relative to matched controls (15).

The same group of abused girls exhibited
reduced evening basal and ovine CRH-stimulated plasma adrenocorticotropic hormone
(ACTH) concentrations relative to matched
non-abused girls. Plasma cortisol responses
to CRH injection did not differ between the
two groups (16).
Slide 7: Biological findings in maltreated and neglected children
Another study, in 2001, investigated cortisol secretion in children with a history of
maltreatment in the context of a day camp
program (17). Significant variation in average morning or average afternoon cortisol
concentrations were found that were based
on the subtypes of maltreatment that the
children had experienced. Children who had
both been physically and sexually abused as
well as neglected or emotionally abused,
or both, exhibited substantial elevations in
morning salivary cortisol concentrations.
In contrast to the multiple abuse group, the
group of children who had experienced only
physical abuse showed a trend toward lower
morning cortisol relative to non-maltreated
children, and a smaller decrease in cortisol abundance from morning to afternoon.
Normally, plasma cortisol concentrations
undergo circadian fluctuations and are high
in the morning and low in the evening. In
this same cohort, maltreated children who
exhibited internalizing problems, such as
anxiety or depression, demonstrated higher
morning, afternoon, and average daily cortisol, whereas non-maltreated boys with
externalizing problems, such as oppositional-defiant or conduct problems, were more
likely to show the expected diurnal decrease
in cortisol. This study was one of the first to
clarify the diversity of neuroendocrine patterns and to demonstrate that these patterns
depend on the type of maltreatment and the
resulting childhood psychopathology.
Slide 8: Stress biology in children
The neuroendocrine profile of children after
traumatic life experiences is variable and may
depend on age, sex, personality characteristics before the trauma, developmental stage
of the individual, nature of the event, time
elapsed since the trauma, chronicity (duration), and type of past and current symptoms.
Slide 9: More recent studies in maltreated children
More recent studies have also examined neuroendocrine markers in maltreated youth and
found an asymmetry between concentrations
of secreted salivary alpha amylase (sAA), an

relation to PTSD development in children.

In a study of young survivors of motor vehicle accidents, cortisol and adrenaline in
urine over a 24-hour period were associated
with increased risk for PTSD development,
especially in young males (39). Other studies showed increased heart rate immediately
after admission at the hospital for an injury
to predict PTSD, whereas a more recent
study showed that the combination of a
standardized child trauma screening questionnaire together with heart rate predicted
PTSD symptoms (4041).
Slide 18: PTSD after motor vehicle accidents (MVAs)Study design I
Our study, which is presented in the next
few slides, was conducted over a 2.5-year
period from May 2002 to December 2004.
The subjects were 60 children and adolescents aged 7 to 18 years who had experienced a motor vehicle accident (MVA) and
were hospitalized for at least 1 day following the MV. The subjects were evaluated
three times: immediately after the accident,
1 month later, and 6 months later. A control group of 40 healthy participants who
had not experienced an MVA was also included. The portion of the study participants
showing PTSD symptoms at months 1 and
6 following the accident are shown on the
slide (42). Criteria for determining PTSD
were based on DSM-IV (slides 3 and 4). At
the end of 1 month, 23 of 56 participants
exhibited PTSD and four participants had
dropped out of the study. After 6 months,
nine of the participants dropped out of the
study. Of the participants who did not show
PTSD 1 month after the MVA, only one developed (late-onset) PTSD after 6 months.
Of the 23 participants showing PTSD after
1 month, only eight continued to exhibit
PTSD after 6 months.
Slide 19: PTSD after motor vehicle
accidents (MVAs)Study design II
At months 1 and 6 following the accident,
the children were interviewed using the
PTSD-specific module of the Kiddie Schedule for Affective Disorders and SchizophreniaLifetime version (K-SADS-L). Additional self-reported questionnaires were
completed by children and parents: the
Youth Self Report (YSR), the Childrens
Behavior Checklist (CBCL), the Childrens Posttraumatic Stress Reaction Index
(CPTS-RI), and the adult version for parents,
and the Symptom Checklist-90Revised
(SCL-90-R) for parents. During the first day
of hospitalization, salivary samples for the
determination of cortisol were collected at

8 hours, 12 hours, 15 hours, 18 hours, and

21 hours, and morning serum samples were
collected for the determination of catecholamines, cortisol, and interleukin-6 (IL-6).
IL-6 is a proinflammatory cytokine indicative of the inflammatory response to physical
and emotional stress. This cytokine interacts
with the HPA axis at the hypothalamic, pituitary, and adrenal levels, and its concentrations represent a biomarker of distress.
Cortisol was measured by electrochemiluminescence, the catecholamines by highperformance liquid chromatography with
electrochemical detection, and IL-6 by enzyme-linked immunosorbent assay (ELISA)
(42). Clinical evaluations, diagnostic interviews, and blood and salivary sampling were
performed also at months 1 and 6.
Slide 20: Prediction of PTSD development (time 0)
In the following slides, we present predictive factors in the aftermath of the trauma
for later PTSD development in children and
adolescents. The findings have been published in the articles referenced in the slides.
Slide 21: Circadian cortisol profiles
immediately after the accident and PTSD
development at month 1
This plot shows the circadian cortisol profiles immediately after the accident for children who developed (red) or did not develop
(green) PTSD at month 1 and the control
group of children who had not experienced
a motor vehicle accident (white). Relative
to the non-PTSD and control groups, the
children who developed PTSD 1 month later had higher cortisol concentrations at 12
hours, 18 hours, and 21 hours during the first
day of hospitalization after the accident (43).
Slide 22: Circadian cortisol profiles
immediately after the accident and PTSD
development at month 6
This plot shows the circadian cortisol profiles immediately after the accident for children who developed (red) or did not develop
(green) PTSD at month 6 and the control
group (white). Relative to the non-PTSD
and control groups, the children who developed PTSD 6 months later had an irregular
cortisol rhythm and higher cortisol concentrations at 12 hours, 15 hours, 18 hours, and
21 hours on the first day of hospitalization
following the accident (43).
Slide 23: Interleukin-6 immediately
after the accident and PTSD development
at months 1 and 6
Morning serum IL-6 immediately after the
accident was not significantly higher in children who developed PTSD 1 month later

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density of GABA receptors. This may result

from reduced composition or altered function of GABA receptors in individuals under
chronic stress. Fluctuations of stress mediators, such as cortisol and CRH, during periods of high brain plasticity may permanently
program the brain to overreact to stress (32).
Slide 14: PTSD after chronic versus
acute stressors
Chronic stressors, such as child abuse, should
be differentiated from acute stressors. Physical or sexual abuse and neglect represent
chronic complex stressors, because in most
cases they coexist with other psychosocial
risk factors, such as dysfunction within the
family, disturbed child-parent interactions,
low socioeconomic status, unemployment,
parental psychopathology, drug or alcohol
abuse, anxiety, and depression. Single acute
stressors (such as automobile accidents,
natural catastrophies, attacks) affect children
from across the general population without
regard to specific risk factors for psychopathology or familial dysfunction.
Slide 15: Factors influencing neuroendocrine endophenotypes in PTSD
Diverse patterns of aberrant cortisol secretion, as a peripheral biomarker of HPA axis
function, have been reported in individuals
with PTSD, whereas markers of SNS activity are more consistent between patients,
showing high plasma or urine catecholamine
concentrations. Several parameters affect the
direction in which the HPA axis is affected
(increased or decreased cortisol production) in PTSD: (i) biological vulnerability,
as expressed by genetic polymorphisms and
epigenetic changes; (ii) early experiences of
the individuals, including previous trauma as
well as environmental influences in the management of early stress; (iii) the nature of the
trauma, whether it was chronic or acute; (iv)
the developmental stage, age at the time of
trauma, and gender; (v) the time since the
trauma occurred; and (vi) comorbidities such
as anxiety or depression (33, 34).
Slide 16: PTSD biology in adults after
motor vehicle accidents
Several studies have examined PTSD development after the impact of single acute
stressors in adults. Low serum or urine
cortisol concentrations, high noradrenaline
concentrations in urine, and increased heart
rate are predictive of PTSD development in
such studies (3538).
Slide 17: PTSD biology in children after
motor vehicle accidents
Fewer studies have examined biologic factors in the aftermath of an acute stressor in

These results indicated an abnormal hormonal load in children with PTSD with potential deleterious consequences in the long
term. The term allostasis or cacostasis describes the status of maintaining homeostasis through a change, where the chronically
abnormal concentrations of stress hormones
have damaging effects on the body. We reported the natural history of neuroendocrine
changes of PTSD development and maintenance in two publications (42, 46).
Slide 29: Months 1 and 6, crosssectionally
In examining the groups cross-sectionally
at months 1 and 6 (independent analysis of
children with or without PTSD for months
1 and 6, comparing individuals between
the groups), morning plasma noradrenaline
concentrations were significantly higher
in the PTSD group than in the other two
groups at both month 1 and month 6 (42).
Slide 30: Month 1, cross-sectionally
At month 1, salivary cortisol concentrations were higher at 18 hours and 21 hours
in the PTSD group than in the other two
groups (42).
Slide 31: The natural history of PTSD
Longitudinal plasma noradrenaline
In the longitudinal analysis, we examined
the group that developed PTSD at month
1 and maintained the diagnosis at month
6 (PTSD 1&6) and the group that did not
show symptoms of PTSD at neither month
1 nor month 6 (non-PTSD 1&6). Children
with PTSD at month 1 who lost the diagnosis at month 6, and one child with late-onset
PTSD (only at month 6) were excluded from
the analysis. The longitudinal PTSD group
consists of 8 children with a continuous diagnosis, as opposed to the cross-sectional
PTSD groups for month 1 (23 children) and
month 6 (9 children). A significantly greater
gradual elevation of morning plasma noradrenaline was noted in the PTSD group
than in the non-PTSD and control groups
(42). The semitransparent bar represents the
normal range of values.
Slide 32: The natural history of PTSD
Longitudinal plasma adrenaline
A similar pattern was also noted for adrenaline; however, this was not statistically
significant.
Slide 33: The natural history of PTSD
Salivary cortisol at time 0
Circadian cortisol profiles (at 8 hours, 12
hours, 15 hours, 18 hours, and 21 hours)
during the first day of hospitalization after
the accident for children who developed
PTSD at month 1 and maintained it at month

6 (red) or did not show symptoms of PTSD

at month 1 or at month 6 (green), along with
the control group (white), are presented in
the figure. Relative to the non-PTSD and
control groups, the children in the longitudinal PTSD group had an irregular cortisol
rhythm and higher cortisol concentrations at
8 and 21 hours in the first day of hospitalization after the accident (42).
Slide 34: The natural history of PTSD
Salivary cortisol at month 1
Cortisol rhythm and salivary cortisol values
gradually normalized at month 1 in the longitudinal PTSD group (42).
Slide 35: The natural history of PTSD
Salivary cortisol at month 6
Cortisol rhythm and salivary cortisol values were comparable in the three groups at
month 6 (42).
Slide 36: The natural history of PTSD
Progressive divergence of cortisol and
noradrenaline
A progressive divergence of evening salivary
cortisol and morning plasma noradrenaline
from time 0, after the accident, to month 6
was noted in the longitudinal PTSD group;
we hypothesized that this progressive divergence might be an indicator of the underlying
pathophysiologic mechanisms responsible
for PTSD development and maintenance
over time. Posttraumatic symptoms may
thus be attributed to cortisol dysregulation
that fails to shut down the catecholaminergic
response in limbic structures, such as locus
caeruleus and the amygdala.
Slide 37: Proposed longitudinal
divergence of cortisol and noradrenaline
responsible for PTSD maintenance
This figure shows the longitudinal neuroendocrine changes in pediatric PTSD. Early
stress, in the absence of previous trauma,
results in immediate elevation of circulating
cortisol and catecholamines. In individuals
with PTSD, elevated evening cortisol concentrations progressively decrease, whereas
noradrenaline increases over time. Low cortisol accompanied by high noradrenaline is
a common finding in adult PTSD and may
represent the end stage in the natural history of the disorder, as well as a biological
vulnerability factor for PTSD development
in adulthood (46).
Slide 38: A simplified representation of
stress responses in children versus adults
with PTSD versus normal stress responses
This figure depicts stress responses in individuals under normal circumstances, pediatric patients with PTSD, and adult patients
with PTSD. Normally, the acute stress reac-

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than in children who did not develop it and

the control group. However, the difference
in morning IL-6 concentrations after the accident between the three groups was significant at month 6 (43).
Slide 24: Hierarchical regression analysis
for the prediction of PTSD at months 1 and 6
A hierarchical regression analysis was performed to examine the ability of the several
parameters to predict PTSD development
at month 6. These parameters included a
measure of the trauma on the injury severity
scale (ISS), gender, age, body mass index
(BMI), morning serum cortisol, evening
salivary cortisol at 21 hours, and morning serum IL-6 after the accident and were
examined as independent variables, with
PTSD diagnosis at 6 months being the dependent variable. Morning serum IL-6 and
evening salivary cortisol were highly interrelated, so we performed two regression
analyses that were identical except that one
included IL-6 and the other evening cortisol
in the independent variables. Both increased
evening salivary cortisol and morning serum IL-6 concentrations predicted PTSD
development at month 6 (43).
Slide 25: Multiple logistic regression
analysis for the prediction of PTSD at
months 1 and 6
Another analysis of the data, including information on parental psychopathology,
revealed that only current maternal PTSD
symptomatology predicted child PTSD at
month 1, and only salivary cortisol at 21
hours predicted child PTSD at month 6 (44).
Slide 26: Physical versus emotional
stressSerum cortisol and IL-6
We also examined the effects of stressassociated physical injury (PI) group versus
emotional-only stress (ES) on circulating
cortisol, catecholamine, IL-6, leptin, and
adiponectin concentrations longitudinally,
at three time points. Within 24 hours after
the accident, serum cortisol concentration
was greater than the controls in the PI group
but not the ES group, whereas serum IL-6
concentrations were greater in both trauma
groups than in the controls, showing that
circulating IL-6 concentrations were influenced equally by the physical and emotional
stress of the trauma (45).
Slide 27: The longitudinal IL-6 group
In the longitudinal analysis, serum IL-6
concentrations gradually normalized at
months 1 and 6 in all three groups (45).
Slide 28: PTSD and allostatic load
The natural history of neuroendocrine
changes

Editors Note: This contribution is not intended to be equivalent to an original research paper. Note, in particular, that the
text and associated slides have not been
peer-reviewed.
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tion includes a brief elevation of CRH and

cortisol (A). In children with PTSD, elevated CRH and cortisol are often reported.
Cortisol inhibits the release of CRH from
the hypothalamus and ACTH from the pituitary (B). In adults with PTSD, the majority of studies report high CSF CRH and
low circulating cortisol (C). An enhanced
negative feedback inhibition of the HPA
axis was suggested as the pathophysiologic
mechanism of the hypocortisolism of these
individuals (4).
Slide 39: Conclusions
In children and adolescents exposed to an
acute, single stressor such as a motor vehicle accident, increased evening salivary
cortisol and morning serum IL-6 concentrations immediately after the event were
predictive markers of PTSD development
6 months later. The group that developed
PTSD at month 1 and maintained the diagnosis at month 6 gradually normalized
cortisol concentrations and rhythmicity and
showed increased plasma concentrations of
noradrenaline. Progressive divergence of
these two main axes of the stress system
may be the underlying pathophysiologic
mechanism that maintains PTSD diagnosis
over time.
Slide 40: Consequences of chronic stress
The chronic dysregulation of the stress system in individuals with PTSD may lead to
various physical and mental health problems and disorders. In chronically stressed
individuals, both behavioral and neuroendocrine mechanisms promote obesity and metabolic abnormalities. Unhealthy behaviors
(for example, sedentary lifestyle, smoking,
low adherence to self-care activities, lack
of sleep) in conjunction with dysregulation
of stress hormones and cytokines may lead
to the development of central obesity, insulin resistance, and metabolic syndrome
conditions that constitute major risk factors
for cardiovascular disease and acute clinical
events in later life (47).

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10.1126/scisignal.2003327

Citation: P. Pervanidou, G. P. Chrousos, Posttraumatic stress disorder in children and adolescents:

Neuroendocrine perspectives. Sci. Signal. 5, pt6
(2012).

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