Expert Review of Neurotherapeutics

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Neurobiology of suicidal behavior in post-

traumatic stress disorder

Leo Sher

To cite this article: Leo Sher (2010) Neurobiology of suicidal behavior in post-traumatic stress
disorder, Expert Review of Neurotherapeutics, 10:8, 1233-1235, DOI: 10.1586/ern.10.114

To link to this article: https://doi.org/10.1586/ern.10.114

Published online: 09 Jan 2014.

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 Editorial
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Neurobiology of suicidal behavior in

post-traumatic stress disorder
Expert Rev. Neurother. 10(8), 1233–1235 (2010)

Leo Sher
“It is likely that certain biological changes, including
hypothalamic–pituitary–adrenal axis, serotonergic and
Department of Psychiatry,
Columbia University, noradrenergic abnormalities, underlie both post-traumatic stress
1051 Riverside Drive, Unit 42, disorder with or without comorbid disorders and
New York, NY 10032, USA
Tel.: +1 212 543 6240
suicidal behavior.”
Fax: +1 212 543 6017
drleosher@gmail.com

Post-traumatic stress disorder (PTSD) is
a frequent and severe disorder that can
develop after exposure to a traumatic
event [1,2] . People with PTSD suffer from
a range of symptoms that interfere with
their capacities to enjoy normal life.
The characteristic symptoms resulting
from the exposure to a traumatic event
include persistent re-experiencing of the
traumatic event, persistent avoidance of
stimuli associated with the trauma and
numbing of general responsiveness and
persistent symptoms of increased arousal.
Re-experiencing symptoms consist of
intrusions of the traumatic memory in
the form of distressing images, night-
mares or dissociative experiences, such as
flashbacks. Avoidance symptoms include
actively avoiding reminders of the trau-
matic event, including persons, places
or things associated with the trauma,
and more passive behaviors ref lecting
emotional numbing and constriction.
Hyperarousal symptoms include insom-
nia, irritability, impaired concentration,
hypervigilance and increased startle
responses. In the USA, the lifetime prev-
alence of PTSD is 7.8%, with women
(10.4%) twice as likely as men (5%) to
have PTSD at some point in their lives [3] .
Post-traumatic stress disorder is fre-
quently comorbid with other psychiatric
disorders [3,4] . According to the National
Comorbidity Survey in the USA, 88%
of men and 79% of women with life-
time PTSD have at least one comorbid
psychiatric disorder [3] . Major depres-
sive disorder is present in 48% of men
and in 49% of women with PTSD [3] . It
is believed that depression amplifies the
effects of traumatic events, and PTSD
increases vulnerability to depression [4] .
Among individuals who meet criteria for
lifetime PTSD, 51.9% of men and 27.9%
of women also have lifetime alcohol abuse
or dependence [3] .
Multiple lines of evidence suggest an
important relationship between PTSD
and suicidal behavior [5–8] . The associa-
tion between PTSD and suicidal behavior
has been observed both in clinical and in
general population samples, and is irre-
spective of the type of trauma that led
to PTSD. High rates of suicidal behavior
have been found among PTSD patients
exposed to combat trauma, physical or
sexual abuse, intimate partner violence and
natural disasters. In a nationally represen-
tative, cross-sectional study conducted in
the USA, PTSD was associated with sui-
cidal ideation and suicide attempts, with
odds ratios of 2.8 (95% CI: 2.0–3.8) and
2.7 (95% CI: 1.8–3.9), respectively [9] . A
recent study in Denmark has shown that
a registry-based diagnosis of PTSD is a
risk factor for completed suicide [10] . The
odds ratio associating PTSD with suicide
was 9.8 (95% CI: 6.7–15). The association

Keywords : hypothalamic–pituitary–adrenal axis • pathophysiology • post-traumatic stress disorder

• serotonin • suicide

www.expert-reviews.com 10.1586/ERN.10.114 © 2010 Expert Reviews Ltd ISSN 1473-7175 1233

 Editorial Sher
between PTSD and completed suicide remained after controlling
for psychiatric and demographic confounders (odds ratio: 5.3;
95% CI: 3.4–8.1).
“Some studies suggest that the presence of
comorbid depression increases the effect of
post-traumatic stress disorder on suicidality.”
Lieutenant James F Devine (Retired), former director of the New
York Police Department Counseling Services, said: “PTSD is a
greater cop killer than all the guns ever fired at police officers” [101] .
Indeed, at least 300 police officers kill themselves every year in the
USA, more than are murdered by felons. Many of these suicides are
committed by officers suffering from symptoms of PTSD.
Depression, alcohol abuse, personality and other psychiatric
disorders in association with PTSD lead to more suicidal thoughts
and behaviors compared with PTSD alone [6] . Depression is asso-
ciated with suicidal behavior: approximately 60% of individuals
who commit suicide suffer from depression [11] . Some studies
suggest that the presence of comorbid depression increases the
effect of PTSD on suicidality [4] . At least one study has shown
that depression is a mediating factor in the relationships between
PTSD and suicidal behavior [4] . Another study has demonstrated
that persons with PTSD and depression had a greater rate of
completed suicide than expected based on their independent
effects  [10] . In Vietnam war veterans, PTSD comorbid with
depression is associated with increased suicidality [12] , and the
risk for completed suicide is nearly double among veterans with
PTSD and comorbid psychiatric disorders relative to those with
PTSD only [13] .
Considerable evidence suggests that alcohol-use disorders are
associated with nonfatal and fatal suicide attempts [14] . It has
been observed that in individuals with substance-use disorders,
comorbid PTSD increases the risk for suicidal behavior [4] .
In summary, available clinical and epidemiological data suggest
that suicidal behavior in individuals with PTSD may be related to:
• The diagnosis of PTSD
• Comorbid depression, alcohol use disorders and/or other
psychiatric disorders.
• A combination of PTSD and comorbid psychiatric disorders
Therefore, suicidal behavior in persons with PTSD may be
related to:
• Neurobiological alterations associated with PTSD
• Neurobiological abnormalities associated with comorbid
depression, alcohol use disorders and/or other psychiatric
disorders
• Neurobiological changes associated with a combination of
PTSD and comorbid psychiatric disorders
Neurobiological changes observed in PTSD include alterations
in the hypothalamic–pituitary–adrenal (HPA) axis, increased
noradrenergic activity, and changes in the serotonergic and other
1234
neurotransmitter systems [15–17] . Pathophysiological changes in
patients with PTSD also include reduced volume of the hippo-
campus, exaggerated amygdala responsiveness and abnormali-
ties in prefrontal cortex function. Neurobiological abnormalities
observed in depressed patients and individuals with alcohol-
use disorders also include HPA axis dysregulation, serotonergic
alterations and changes in the prefrontal cortex, amygdala and
the hippocampus [17,18] . Pathophysiological changes observed in
PTSD, depression and alcoholism are different. For example,
changes in the HPA axis function observed in PTSD include
low basal cortisol secretion, enhanced negative feedback control
of the HPA axis and increased brain corticotrophin-releasing
hormone activity, while depression is associated with increased
cortisol levels, reduced cortisol suppression to dexamethasone
and reduced glucocorticoid receptor responsiveness [17,19] . There
is evidence that the activity of three neurobiological systems
has a role in the pathophysiology of suicidal behavior [20] . This
includes both hyper- and hypo-activity of the HPA axis, dys-
function of the serotonergic system and excessive activity of the
noradrenergic system  [20–22] . It is likely that certain biological
changes, including HPA axis, serotonergic and noradrenergic
abnormalities, underlie both PTSD with or without comorbid
disorders and suicidal behavior.
“It is interesting to hypothesize that the same
neurobiological factors that predispose some
individuals to develop post-traumatic stress
disorder may also increase vulnerability to
suicidal behavior.”
Many people are exposed to traumatic events. However, only
a minority of them fail to recover from initial reactions. Certain
pretraumatic genetic, epigenetic and possibly other environmen-
tal influences increase the probability of developing PTSD fol-
lowing trauma exposure, and modulate biological alterations
associated with its pathophysiology [17] . For example, a study
of combat veterans showed that the risk for developing PTSD
after trauma exposure was significantly higher for monozygotic
than for dizygotic noncombat exposed cotwins of PTSD-affected
individuals  [23] . Also, maternal PTSD has been identified as a
risk factor for PTSD in second-generation offspring and altera-
tions reflecting enhanced glucocorticoid receptor responsiveness
have been demonstrated in second-generation offspring with
maternal PTSD  [17,24] . It is interesting to hypothesize that the
same neurobiological factors that predispose some individuals to
develop PTSD may also increase vulnerability to suicidal behav-
ior. In other words, individuals with PTSD phenotype may have
a predisposition to suicidal behavior.
Another interesting aspect is a potential role of the endo­
cannabinoid system in the neurobiology of suicidal behavior in
PTSD. The endocannabinoid system is formed by the cannabi-
noid receptors and endogenous ligands [25,26] . The cannabinoid
receptors type 1 play a role in the extinction of aversive memo-
ries, reducing fear and anxiety. The endocannabinoid system is
also involved in the mechanisms of sleep regulation [25–27] . For
Expert Rev. Neurother. 10(8), (2010)
 Neurobiology of suicidal behavior in post-traumatic stress disorder Editorial

example, it has been reported that the endocannabinoid anan-
damide increased adenosine in the basal forebrain and increased
sleep [27] . Sleep abnormalities and other symptoms of PTSD
may contribute to increased suicidality in PTSD patients [28] .
Therefore, further studies of the role of the endocannabinoid
system in the pathophysiology of PTSD may help to develop
new modalities to treat PTSD and suicidal behavior in persons
with PTSD.
Millions of people around the world suffer from PTSD with
or without comorbid psychiatric, neurological or medical con-
ditions. Suicidal behavior in PTSD is a critical issue. Studies
of the pathophysiology of suicidal behavior in PTSD may help
identify targets for therapeutic drugs to treat suicidal behavior
in PTSD.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial conflict with
the subject matter or materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or options, expert
testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.

11 Nakao M, Takeuchi T. The suicide 22 Westrin A, Frii K, Träskman-Bendz L.

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