Download Name of Disorder: Posttraumatic stress disorder Essay Title: The

Name of Disorder: Posttraumatic stress disorder
Essay Title: The neuroendocrine aspects of posttraumatic stress disorder
Author: Dr Nickolas Lavidis, PhD.
Institution: The University of Queensland
Date: 24/06/2014
Content:
Posttraumatic stress disorder (PTSD) is a psychological and physiological
manifestation resulting from exposure to a significantly traumatic event and is the
single anxiety disorder most experienced by Australians, affecting up to 6.4% of
people aged 16-85 years of age [1]. Psychological symptoms of PTSD include
recurring nightmares and distress following either reminder or memory of the
traumatic event, all of which reconsolidate the feelings of fear and helplessness
involved in development of the disorder [2]. Persistent PTSD also has a high rate of
comorbidity with other stress-related conditions including aggression, anxiety, and
depression [3]. However, unlike most other stress-related conditions, PTSD patients
often present with abnormally low concentrations of the stress hormone, cortisol,
while sympathetic catecholamine concentrations, responsible for the fight or flight
response, are relatively high. This, coupled with the observation of elevated
corticotrophin-releasing hormone (CRH) from the hypothalamus, indicate that the
hypothalamic-pituitary-adrenal (HPA) axis is dysregulated in PTSD [4].
Three discrete axes mediate the response to an acute stressful situation. The
sympatho-adrenal-medullary (SAM) axis via the locus coeruleus centrally, and the
adrenal medulla peripherally, uses catecholaminergic signalling to enable rapid
energy expenditure in order to avoid the stressor. Part of this response involves the
priming the hypothalamic secretory neurons of the HPA axis. A second
hypothalamic-spinal-adrenal (HSA) axis is recruited concurrently with the SAM axis
and uses a direct connection between the hypothalamus and the adrenal gland to
prime the adrenal cortex for secretion of stress hormones. Finally, the HPA axis
releases the short-range neurotransmitter and hormone, CRH, through specialised
blood vessels to the pituitary gland, resulting in the release of adrenocorticotropic
hormone (ACTH) into the general circulation where it acts directly on the adrenal
gland to release cortisol. These systems are subject to negative feedback at multiple
levels in order to rapidly reinstate homeostasis in the absence of stressful stimuli.
Evidence of this feedback system can be observed with the administration of the
synthetic glucocorticoid, dexamethasone, to measure the functionality of the pituitary
and adrenal glands.
Patients suffering PTSD display a hypersensitivity to glucocorticoid negative
feedback, with dexamethasone significantly decreasing both ACTH and cortisol. The
sensitisation of glucocorticoid receptors at least at the level of the pituitary gland is
thought to be the most likely cause of this irregularity [4]. Consequently, the pituitary
output of ACTH, and subsequently adrenal cortisol, is diminished, while the
hypothalamus endeavours to rectify this by increasing the output of CRH. As CRH
also acts as a neurotransmitter, this affects other neural regions, most notably the
locus coeruleus, which in turn maintains the SAM axis activity to increase
catecholamines. Clinically, this can be observed in PTSD by monitoring the urinary
output of catecholamines of which both adrenaline and noradrenaline are
significantly elevated in PTSD patients. This, in combination with the
characteristically low urinary output of cortisol, can be used as a reasonably specific
ratio (catecholamine/cortisol) to distinguish PTSD from other neurological conditions
including major depressive disorder, bipolar, and schizophrenia [5, 6].
The activity of the HPA axis normally exhibits a prominent 24-hour circadian rhythm
with the circadian peak and trough occurring in the morning (waking) and evening
respectively. This biological rhythm has many important functions in the timing and
distribution of energy reserves in addition to regulating the availability of other
hormones important for growth and reproduction. Patients suffering PTSD display a
‘flattened’ circadian secretion of cortisol, with low waking and elevated evening
concentrations which overall results in a decreased cortisol output [7]. One major
symptom resulting from this loss of endocrine rhythmicity is the disruption of the
sleep-wake cycle, subsequently leading to insomnia, and increased incidence of
emotional disturbance.
There is a higher incidence of PTSD among females, with 8.3% of Australian anxiety
disorders being attributed to females aged 16-85 years old compared to the 4.6%
attributed to males [1]. Although psychological reasons such as differing coping
strategies are still widely debated, physiologically, females exhibit substantially
higher basal and stress-responsive cortisol concentrations. This is the result of the
higher HPA axis output due to the stimulatory effects of oestrogen. Increased
reactivity and prolonged duration of HPA axis activity may be one explanation for the
higher susceptibility of female PTSD incidence during a significant traumatic event.
However, due to the large variability in the initial causative trauma, in addition to
differing psychological profiles preceding trauma exposure, the development and
progression of PTSD and the direct mechanisms underlying this disorder remain
debateable from a neuroendocrine perspective.
References:
[1] ABS National Survey of Mental Health and Wellbeing 2007, Summary of Results.
[2] Creamer, M.; Burgess, P.; McFarlane, A. C. Post-traumatic stress disorder:
findings from the Australian National Survey of Mental Health and Well-being.
Psychol Med 31:1237-1247; 2001.
[3] Forbes, D.; Creamer, M.; Phelps, A.; Bryant, R.; McFarlane, A.; Devilly, G. J.;
Matthews, L.; Raphael, B.; Doran, C.; Merlin, T.; Newton, S. Australian
guidelines for the treatment of adults with acute stress disorder and posttraumatic stress disorder. Aust N Z J Psychiatry 41:637-648; 2007.
[4] Yehuda, R.; Golier, J. A.; Halligan, S. L.; Meaney, M.; Bierer, L. M. The ACTH
response to dexamethasone in PTSD. Am J Psychiatry 161:1397-1403; 2004.
[5] Mason, J. W.; Giller, E. L.; Kosten, T. R.; Harkness, L. Elevation of urinary
norepinephrine/cortisol ratio in posttraumatic stress disorder. J Nerv Ment Dis
176:498-502; 1988.
[6] Kosten, T. R.; Mason, J. W.; Giller, E. L.; Ostroff, R. B.; Harkness, L. Sustained
urinary norepinephrine and epinephrine elevation in post-traumatic stress
disorder. Psychoneuroendocrinology 12:13-20; 1987.
[7] Aardal-Eriksson, E.; Eriksson, T. E.; Thorell, L. H. Salivary cortisol, posttraumatic
stress symptoms, and general health in the acute phase and during 9-month
follow-up. Biol Psychiatry 50:986-993; 2001.