NO ABSTRACT: This is 750 word encyclopedia entr

Bracha, Dr. H. Stefan

Lenze, Stacy M.

Macy, Caitlin

Shelton, Jessica M.

Tsang-Mui-Chung, Michelle

English

CogPrints Cognitive Sciences Eprint Archive

The Locus Ceruleus in PTSD

Cognitive Sciences ePrint Archive

Robinson ’ s  Gilead, Khaled Hosseini ’ s  The Kite 
Runner and  A Thousand Splendid Sons, Cormac 
McCarthy ’ s  All the Pretty Horses and  The 
Road, Richard Powers ’ s  The Echo Maker, Kate 
Grenville ’ s  The Secret River, and Azar Nafi si ’ s 
Reading Lolita in Tehran. 
 Extensive commentaries and new writings 
on topics related to psychological trauma are 
available contemporaneously in texts such 
as Tal (1995), the Air Force Academy ’ s lit-
erary journal  War, Literature, and Art, and 
periodic special articles and issues of jour-
nals in the traumatic stress fi eld such as the 
 Journal of Trauma and Dissociation (e.g., 
Gold, 2004; Goldsmith  & Satterlee, 2004), 
 Journal of Psychological Trauma, Trauma, 
Violence and Abuse, and  Journal of Aggression, 
Maltreatment, and Trauma. 
 REFERENCES 
 Birmes, P., Hatton, L., Brunet, A.,  & Schmitt, L. (2003). 
Early historical literature for post - traumatic symp-
tomatology.  Stress and Health, 19, 17 – 26. 
 Gold, S. (2004). Fight club: A depiction of contempo-
rary society as dissociogenic.  Journal of Trauma 
and Dissociation, 5 (2), 13 – 34. 
 Goldsmith, R.,  & Satterlee, M. (2004). Representations 
of trauma in clinical psychology and fi ction. 
 Journal of Trauma and Dissociation, 5 (2), 35 – 59. 
 Shay, J. (1994).  Achilles in Vietnam: Combat trauma 
and the undoing of character. New York: Atheneum. 
 Shay, J. (2002).  Odysseus in America: Combat trauma 
and the trials of homecoming. New York: Scribner. 
 Tal, K. (1995).  Worlds of hurt: Reading the literature of 
trauma. Cambridge: Cambridge University Press. 
 JULIAN D. FORD 
 University of Connecticut School of Medicine 
 See also: Movie Depictions of Psychological Trauma 
 LOCUS CERULEUS 
 The locus ceruleus (LC) is a small (needle -
 sized) bluish nucleus of 25,000 neurons on 
each side of the dorsorostral pons, an area 
within the brainstem. These 50,000 neurons 
are highly elaborated ( “ arborized ” ) and  provide 
70% to 90% of the nervous system ’ s norepine-
phrine (NE). The LC is the noradrenergic 
 component of the fear - response circuitry, and 
plays a central role, especially in acute and 
posttraumatic stress. Psychotropic medica-
tions that are specifi cally useful for the treat-
ment and secondary prevention of acute PTSD 
symptoms, act by blocking activation of neu-
rons in the LC postsynaptically. For example, 
propranolol, a postsynaptic NE beta receptor 
antagonist (Beta blocker), administered in the 
immediate aftermath of motor vehicle acci-
dents has been found to be effi cacious for the 
secondary prevention of PTSD (Pitman et al., 
2002; Vaiva et al., 2003). 
 The LC is the primary location of the neu-
rotransmitter norepinephrine in the brain. 
The LC transmits neural signals throughout 
the brain:  “ this small nucleus innervates a 
greater variety of brain areas than does any 
other single nucleus yet described ” (Aston -
 Jones, Valentino, Van Bockstaele,  & Meyerson, 
1994). The neural pathways from the LC to 
other brain areas ( Ascending efferents ) can 
be conceptualized as the main  ‘ alarm siren ’ of 
the brain. The most extreme activation of LC 
efferents occurs during (and in the immedi-
ate aftermath of) acute traumatic events in 
which there is an actual threat to personal 
survival or to physical integrity. In military 
veterans with PTSD, LC activity also abruptly 
increases during the startle response (such as 
in response to sudden noise and abrupt awak-
ening). Sudden decrease in LC activity has 
been implicated in the pathophysiology of psy-
chogenic fainting and in a range of other con-
version and dissociative symptoms including 
 La Belle Indifference. However, LC plays only 
a minimal role in mood disorders and is unaf-
fected in psychotic disorders. 
 The LC also is linked to the rest of the body 
via  “ descending efferents, ” which activate the 
sympathetic arm of the autonomic nervous 
system (ANS) via projections to pregangli-
onic sympathetic neurons in the spinal cord. 
Furthermore, the LC simultaneously inhibits 
the parasympathetic arm of the ANS via pro-
jections to the vagus nerve (via the nucleus 
ambiguus). The resulting abrupt change in 
396 LOCUS CERULEUS
c12.indd   396 9/23/08   10:07:25 AM
 sympatho - vagal ratio results in physical symp-
toms of fear:  palpitations, sweaty palms, cold 
sweat, hyperventilation, dilated pupils, upper 
abdominal discomfort (gastric vasoconstriction), 
dry mouth, jaw clenching, decreased vocali-
zation, muscle tensing, tonic immobility, and 
increased pain threshold. 
 Neural projections into the LC ( afferents ) 
emanate primarily from other parts of the 
brain ’ s fear circuits, and provide highly proc-
essed information concerning external sur-
vival - relevant stimuli.  Inhibitory afferents from 
the anterior cingulate cortex and GABA - ergic 
afferents from the rostral medulla inhibit LC 
activity. The LC receives extensive serotoniner-
gic projections from the Raphe nuclei. The ther-
apeutic effects of the antidepressant selective 
serotonin reuptake inhibitors (SSRIs) in PTSD 
are due partly to this seratoninergic pathway. 
 Excitatory afferents into the LC originate in 
the amygdala and a midbrain area involved in 
pain and defensive behaviors (the periaquaduc-
tal gray). Excitatory (and possibly excitotoxic —
 causing damage to brain cells) non - NMDA 
glutamatergic activation of the LC (originating 
in the ventrolateral - rostral medulla) occurs dur-
ing extreme stress (Aston - Jones et al., 1994). 
During more chronic stress, NE synthesis in the 
LC is increased by corticotropin releasing hor-
mone (CRH). 
 The LC is the only brain nucleus in which 
neuron loss has been observed in PTSD. In a 
postmortem study of the right hemisphere ’ s LC, 
three WWII veterans with war - related PTSD 
were found to have about 30% fewer neurons in 
comparison to four healthy veterans (Bracha, 
Garcia - Rill, Mrak,  & Skinner, 2005). Most of 
the psychophysiological research in PTSD is 
consistent with a hyperresponsiveness of the 
LC target neurons to NE, possibly a compen-
satory upregulation of LC postsynaptic recep-
tors after trauma - induced loss of LC neurons. 
This pathophysiological mechanism may be 
clinically conceptualized as  “ burning out ” or 
 “ overuse injury ” to the LC in PTSD — similar to 
the nonpsychiatric example of cartilage loss in 
the knees of aging professional athletes. Acute 
and/or subacute tachycardia in an otherwise 
healthy young individual is a useful clinical 
marker of LC overactivity. Drugs of abuse that 
increase the activity (fi ring) of the LC neurons 
(e.g., Yohimbe and Cocaine) aggravate PTSD 
symptoms. 
 REFERENCES 
 Aston - Jones, G., Valentino, R. J., Van Bockstaele, 
E. J.,  & Meyerson, A. T. (1994). Locus coeruleus, 
stress, and PTSD: Neurobiological and clinical 
parallels. In M. M. Murburg (Ed.),  Catecholamine 
function in posttraumatic stress disorder (pp. 
17 – 62). Washington, DC: American Psychiatric 
Press. 
 Bracha, H. S., Garcia - Rill, E., Mrak, R. E.,  & 
Skinner, R. (2005). Postmortem locus coeruleus 
neuron count in three American veterans with 
probable or possible war - related PTSD.  Journal 
of Neuropsychiatry and Clinical Neurosciences, 
17, 503 – 509. 
 Pitman, R. K., Sanders, K. M., Zusman, R. M., Healy, 
A. R., Cheema, F., Lasko, N. B., et al. (2002). 
Pilot study of secondary prevention of posttrau-
matic stress disorder with propranolol.  Biological 
Psychiatry, 51, 189 – 192. 
 Vaiva, G., Ducrocq, F., Jezequel, K., Averland, B., 
Lestavel, P., Brunet, A., et al. (2003). Immediate 
treatment with propranolol decreases posttrau-
matic stress disorder two months after trauma. 
 Biological Psychiatry, 54, 947 – 949. 
 H. STEFAN BRACHA 
 National Center for Posttraumatic Stress Disorder 
 CAITLIN E. MACY 
 Hawai ’ i Pacifi c University 
 STACY M. LENZE 
 Hawai ’ i Pacifi c University 
 JESSICA M. SHELTON 
 University of Hawai ’ i 
 MICHELLE TSANG MUI CHUNG 
 University of Hawai ’ i 
 See also: Biology, Brain Structure, and Function, Adult; 
Biology, Brain Structure, and Function, Child; Biology, 
Neurochemistry; Conditioned Fear 
 LONGITUDINAL STUDIES 
 See: Research Methodology 
 LONGITUDINAL STUDIES 397
c12.indd   397 9/23/08   10:07:26 AM


Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma.

Locus coeruleus, stress, and PTSD: Neurobiological and clinical parallels.

Pilot study of secondary prevention of posttraumatic stress disorder with propranolol.

Postmortem locus coeruleus neuron count in three American veterans with probable or possible war - related PTSD.

The Locus Ceruleus in PTSD

Abstract

Similar works

Full text

Available Versions

CogPrints Cognitive Sciences Eprint Archive

Cognitive Sciences ePrint Archive