Вы находитесь на странице: 1из 10


Sleep-Disordered Breathing in Patients with Post-traumatic

Stress Disorder
Philippe Jaoude1,2, Leah N. Vermont1, Jahan Porhomayon1, and Ali A. El-Solh1,2,3
The Veterans Affairs Western New York Healthcare System, Buffalo, New York; 2Division of Pulmonary, Critical Care, and Sleep
Medicine, Department of Medicine, and 3Department of Social and Preventive Medicine, State University of New York at Buffalo School
of Medicine and Biomedical Sciences and School of Public Health and Health Professions, Buffalo, New York

Abstract the methods used to diagnose the coexisting disorders. Similar

therapeutic challenges face patients and providers when treating
Post-traumatic stress disorder (PTSD) and sleep-disordered concomitant PTSD and SDB. Although continuous positive airway
breathing (SDB) are shared by many patients. They both affect sleep pressure therapy imparts a mitigating effect on PTSD symptomatology,
and the quality of life of affected subjects. A critical review of the lack of both acceptance and adherence are common. Future research
literature supports an association between the two disorders in should focus on ways to improve adherence to continuous positive airway
both combat-related and noncombat-related PTSD. The exact pressure therapy and on the use of alternative therapeutic methods for
mechanism linking PTSD and SDB is not fully understood. A treating SDB in patients with PTSD.
complex interplay between sleep fragmentation and neuroendocrine
pathways is suggested. The overlap of symptoms between PTSD and Keywords: sleep-disordered breathing; obstructive sleep apnea;
SDB raises diagnostic challenges that may require a novel approach in post-traumatic stress disorder; treatment

(Received in original form July 5, 2014; accepted in final form December 15, 2014 )
Supported by Merit Review Grant CX000478 from the Department of Veterans Affairs (A.A.E.-S.).
The views expressed in this review do not communicate an official position of the Department of Veterans Affairs.
Author Contributions: P.J. and A.A.E.-S. determined the scope and structure of the review. L.N.V. and J.P. conducted the majority of the literature review. P.J.
and A.A.E.-S. drafted and made critical revisions to the manuscript. All authors have given final approval of the manuscript.
Correspondence and requests for reprints should be addressed to Ali A. El-Solh, M.D., M.P.H., Medical Research, Building 20 (151) VISN02, VA Western New
York Healthcare System, 3495 Bailey Avenue, Buffalo, NY 14215-1199. E-mail: solh@buffalo.edu
Ann Am Thorac Soc Vol 12, No 2, pp 259268, Feb 2015
Copyright 2015 by the American Thoracic Society
DOI: 10.1513/AnnalsATS.201407-299FR
Internet address: www.atsjournals.org

Based on the Diagnostic and Statistical The earliest historical reference to time during the Vietnam War after its
Manual of Mental Disorders, fth edition a post-traumatic condition was deciphered description by Friedman in 1980 as the
(DSM-V), post-traumatic stress disorder from a cuneiform tablet detailing the death Post-Vietnam Syndrome (8). It is estimated
(PTSD) is characterized by the development of King Ur-Namma on the battleeld that the lifetime prevalence of the disease
of a specic cluster of symptoms after against the Gutians (6). The inscription varies from 15 to 30% in Vietnam combat
exposure to a traumatic event that elicits described signicant sleep problems in the veterans (9) and 11 to 17% of those
a response of fear, helplessness, or horror. survivors. Ancient Greek and Roman returning from Iraq and Afghanistan (10)
A constellation of indicators from four accounts of war included similar references compared with 7.8 to 12.3% in the general
symptom clusters, including intrusion, to sleep ailments in soldiers returning from adult population of the United States
avoidance, negative alterations in cognitions battles. American writers have referred to (3, 11).
and mood, and alterations in arousal and this condition as Soldiers heart during Sleep disturbances remain a common
reactivity, is required (1) (Table 1). Typical the U.S. Civil War (a reference to the complaint of those aficted with the
examples of traumatic experiences that autonomic hyperarousal), shell shock condition and may even be a predictor of
may predispose to PTSD include sexual during World War I (a description of the PTSD progression. Despite the intensied
assault, military combat, mass conict numbing and dissociation), and combat campaign in highlighting the sequelae of
and displacement, and life-threatening neurosis during World War II (7). The PTSD on the quality of life of these patients,
physical illness (25). term PTSD was introduced for the rst the literature has been scarce on providing

Focused Reviews 259


Table 1. Classication of mental and behavioral disorders for post-traumatic were fewer objective snoring and more
stress disorder upper airway resistance syndrome ndings
on PSG (24). The sleep prole was
A. The patient must have been exposed to a stressful event or situation (either short or long dominated with frequent insomnia,
lasting) of exceptionally threatening or catastrophic nature, which would be likely to cognitive-affective symptoms, and higher
cause pervasive distress in almost anyone. psychotropic medication use compared
B. There must be persistent remembering of reliving of the stressor in intrusive with patients without PTSD (24).
ashbacks, vivid memories or recurring dreams, or in experiencing distress when
exposed to circumstances resembling or associated with the stressor. Accordingly, it has been suggested that
C. The patient must exhibit an actual or preferred avoidance of circumstances resembling or underlying SDB should be ruled out when
associated with the stressor which was not present before exposure to the stressor. response to PTSD treatment is lacking.
D. Either of the following must be present: The small sample size of these studies
(1) inability to recall, either partially or completely, some important aspects of the period of raised doubts about the relationship
exposure to the stressor;
(2) persistent symptoms of increased psychological sensitivity and arousal (not present between SBD and PTSD. However, in one
before exposure to the stressor), shown by any two of the following: of the largest studies conducted by the
(a) difculty in falling or staying asleep Veterans Health Administration, whereby
(b) irritability or outbursts of anger the medical records of 4 million Veterans
(c) difculty in concentrating
(d) hypervigilance were examined for the association between
(e) exaggerated startle response. psychiatric disorders and sleep apnea (19),
E. Criteria B, C, and D must all be met within 6 months of the stressful event or of the end of PTSD was present in 11.85% of the apneic
a period of stress. (For some purposes, onset delayed more than 6 months may be group compared with 4.74% of the
included, but this should be clearly specied). nonapneic group (odds ratio, 2.7 [95%
Adapted from Reference 68. condence interval, 2.652.74]). Later,
many authors reported similar association
between PTSD and SDB. Some used
questionnaires to assess the presence of
effective management of sleep-related with PTSD, no studies addressing the SDB, such as the Cleveland Sleep Habits
complaints. Although nightmares and association between PTSD and central sleep Questionnaire or the Pittsburgh Sleep
insomnia are common features of PTSD- apnea have been identied. Quality Index (20, 29). The use of these
related sleep disturbances, there is growing questionnaires was deemed problematic
evidence that an increased prevalence of because it addressed variables that might be
sleep-disordered breathing (SDB) is also Association between SDB shared by PTSD and SDB, such as sleep-
present in patients suffering from PTSD. In and PTSD related issues, chronic fatigue, and daytime
addition, PTSD-related sleep disturbances sleepiness. Others, however, conrmed
can persist long after the original trauma has Many studies have claimed a link between SDB with objective sleep testing (21, 22).
subsided. SDB and PTSD (13, 1727) (Table 2). Another confounding element that
In the last decade, several studies have Youakim and coworkers (28) were the rst undermined the association between
documented a broad array of comorbid to report on the association between OSA PTSD and SDB came from the fact that
sleep disorders in subjects with PTSD, and PTSD in a Vietnam veteran. The case many patients with PTSD are overweight
including insomnia, nightmares, SDB, and described a man with PTSD and OSA or obese (21, 22). In these cases, the
sleep arousal and dream enactment behavior whose PTSD symptoms abated after potential for SDB was strongly correlated
(12, 13). Sleep impairment accounts for treatment with continuous positive airway with body mass index (BMI), increase
a signicant portion of the variance in pressure (CPAP). A subsequent report from in arousal symptoms, and greater PTSD
physical health complaints even after women with PTSD who experienced sexual severity. However, the reports of obesity in
controlling for other PTSD symptoms trauma identied SDB in 52% of the sample patients with SDB were not universal, and
and depression (14). It follows that the (13). Although the diagnosis of SDB was PTSD spanned across the entire BMI
signicant and chronic sleep loss based on self-report, a follow-up study spectrum.
commonly endorsed in individuals with using polysomnography (PSG) conrmed In addition to combat-related PTSD,
PTSD contributes to additional worsening that 90% of the participants had clinically SDB has been found to be frequent in
of health-related quality of life. signicant levels of SDB (23). The patients with PTSD related to other types
Although different aspects of PTSD association between the two disorders was of trauma. One cohort reported 90%
sleep disturbances have been reviewed further highlighted by the fact that trauma prevalence of SDB in crime victims (23).
recently (15, 16), the purpose of this article survivors with SDB exhibited worse Similarly, 95% of re evacuees with PTSD
is to present a critical review of the evidence symptoms of PTSD compared with trauma had SDB on portable sleep testing (25),
and the research on SDB in patients with survivors without SDB (24). Women with although a selection bias and diagnostic
PTSD, the interrelation between the two both sexual traumarelated PTSD and SDB inaccuracies may have been responsible
disorders, existing treatment options, and had worse nightmares, major depression, for this excessively high prevalence. More
future research. Although obstructive sleep and impaired quality of life (24). recently, a study of 501 Israeli subjects
apnea (OSA) and respiratory effortrelated Interestingly, those with PTSD had atypical living along the Gaza strip established
arousals are frequently reported in patients phenotypic expression of their SDB; there presence of PTSD in 5.5% of this highly

260 AnnalsATS Volume 12 Number 2 | February 2015


Potential Mechanisms
upper airway
collapsibility PTSD and SDB share disturbed sleep as
a common feature. It is hypothesized that
the two disorders act as a catalyst for one
Arousals/Sleep OSA another. SDB may exacerbate, accentuate,
fragmentation or perpetuate preexisting PTSD, and vice
versa. Sleep fragmentation represents the
common thread in this relationship (Figure 1).

OSA Effects on PTSD

Knowing that adequate sleep is important
Insomnia PTSD
fragmentation for synaptic plasticity and memory
formation, interruption of the sleep
continuity by obstructive airway events
HPA Axis followed by short arousal compromises
dysfunction the benecial process of fear extinction.
Hippocampus The latter is a process of forgetting the
Dysfunction association between a certain neutral trigger
interruption and an aversive stimulus. Longitudinal
studies have reported an association
GH between sleep disturbances in the early
aftermath of trauma and the development
of PTSD (34, 35). Additionally, studies
Memory have found that sleep disturbances before
consolidation/ Fear
extinction traumatic events predict PTSD (36, 37).
Although results of EEG ndings during
Figure 1. Proposed interactions between post-traumatic stress disorder (PTSD) and sleep-
sleep in patients with PTSD have been
disordered breathing. GH = growth hormone; HPA = hypothalamic-pituitary-adrenal; OSA = inconsistent, a metaanalysis concluded that
obstructive sleep apnea. individuals with PTSD had more stage 1
sleep, greater REM density, and decreased
slow wave sleep than individuals without
exposed cohort and depression in an a difference in the prevalence of SDB PTSD (38). More recently, van Liempt
additional 3.8%. Clinical sleep disturbance, between patients with and without PTSD and colleagues (39) showed an increase
assessed using the 18-item Pittsburgh Sleep despite the increased rate of SDB (76.8%) in in awakenings in veterans with PTSD
Quality Index, was present in 37.4% of active duty military personnel (32). These compared with control patients who had
the cohort but reached 82% among those conicting conclusions emanate from the experienced trauma and to healthy control
identied with PTSD and 79% among those heterogeneity in the study populations that patients. The increased frequency of
who were depressed (29). Not surprisingly, differ from each other in terms of stress awakenings was documented during REM
epidemiologic investigations documented severity and intensity of exposure. sleep (40). Given that REM sleep enhances
increased prevalence of SDB in patients In addition, there were signicant the process of fear extinction (41), several
with World Trade Centerrelated PTSD methodological differences in the authors have concluded that interruption
(26) and in postGulf War Iraqi preexistent research addressing the of memory consolidation contributes to
immigrants (27). In one of these studies, relation between PTSD and SDB. The the resurgence of maladaptive fear and
researchers linked particulate matter diagnosis of sleep apnea was based on anxiety in patients with PTSD. This process
inhalation to a surge in inammatory myriad of diagnostic tools, including is accentuated in SDB, where sleep
response resulting in upper airway nonstandardized sleep questionnaires, fragmentation, commonly more severe
obstruction and OSA. portable monitoring devices, and in-lab during REM sleep, may worsen the severity
Despite the multiple reports linking the polysomnography (Table 3). Even with of preexisting PTSD.
two disorders, the association between the latter technique, usage of both a nasal Other potential mechanisms for the
PTSD and SDB has not been consistent pressure transducer and a nasal-oral link between SDB and PTSD have been
(3033) (Table 3). In one small study of thermistor to monitor respiration could postulated, including a derangement within
14 injured victims from trafc-related not be ascertained across these studies. the neuroendocrine and neuroanatomical
accidents, no difference between patients Inconsistency in scoring rules and pathways expressed by a dysfunctional
with and without PTSD were noted on any variability in the night-to-night degree of hypothalamic-pituitary-adrenal (HPA)
of the PSG measures (30). The two groups SDB, particularly in this population with axis and by anatomical alterations in
did not differ from each other with respect high comorbid conditions, may have the hippocampus (42). Changes in the
to awakening thresholds during REM accounted also for these opposite functioning of the HPA axis have
sleep. Other authors could not also elicit ndings. repeatedly been associated with PTSD

Focused Reviews 261

Table 2. Studies supporting an association between sleep-disordered breathing and post-traumatic stress disorder

Study Reference Study Design PTSD/Total No. Objective/PTSD Exposure Methods to Diagnose OSA Findings/Comments
of Participants

Lavie et al. (17) Observational 12/24 Compare sleep between subjects In-lab PSG done on 4 Patients with PTSD had more
cross-sectional with and without PTSD/combat nonconsecutive nights. consistent SDB ndings on
Prevalence of SDB was not repeated PSGs (using AHI . 10).
a primary objective. Air ow
measured by nasal thermistor.
Engdahl Observational 30/59 Comparing subjects with and In-lab PSG done on 3 consecutive Despite excluding suspected SDB
et al. (18) cross-sectional without PTSD in elderly war nights. Subjects suspected to from study, 4 out of 30 patients
veterans/combat have SDB on screening were with PTSD had SDB diagnosed
excluded. on PSG.
Sharafkhaneh Retrospective 14,054/118,105 Study association between OSA Database review of all VHA Large cohort. Of 118,105 patients
et al. (19) cross-sectional and comorbid psychiatric outpatient clinic le or patient with diagnosis of SDB, 11.9%
disorders/veterans (combat) treatment le records between had PTSD, compared with 4.74%
years1998 and 2001, using ICD- of the group without apnea. OR,
9-CM codes. 2.7 (95% CI, 2.652.74)
Ocasio-Tascon Observational 24/245 Study sleep disorders and related Used the CSHQ to assess probability Probability of OSA assessed by
et al. (20) cross-sectional conditions in veterans/combat for OSA. Mainly Hispanic male questionnaire (CSHQ) without
veterans conrmatory PSG. There was
higher number of patients with
high pretest probability for OSA
in subjects with PTSD
Yesavage Observational 105/105 Study prevalence of SDB in Vietnam Unattended overnight PSG. Airow 69% of the subjects had an
et al. (21) cross-sectional veterans/combat determined by nasal and oral AHI > 10
Williams Retrospective 130/130 Study sleep disorders in active Review of records of 130 OSA was present in 67.3% of
et al. (22) duty soldiers with PTSD/combat consecutive soldiers with PTSD subjects in cohort (80% had
diagnosis. OSA diagnosed based PSG). No control group. Possible
on AHI > 5 selection bias
Krakow Observational 148/156 Study sleep disorders in subjects Used an algorithm (including EDS, SDB assessment was based on
et al. (13) cross-sectional with sexual assaultrelated PTSD snoring, witnessed apnea) to questionnaire (not PSG).
determine the need to refer for Potential SDB reported in 52% of
PSG, indicating a potential SDB subjects and was strongly
correlated with BMI, an increase
in arousal symptoms, and greater
PTSD severity
Krakow Observational 44/39 Study sleep disorders in crime victims Participants underwent in-lab PSG SDB diagnosis based on RDI . 15.
et al. (23) cross-sectional (nasal pressure transducer to 90% of the participants had
measure airow) and home clinically signicant SDB. No
monitoring test age-matched control group.
Many patients were diagnosed
with UARS. RERAs were more
frequent than apnea and
(Continued )

AnnalsATS Volume 12 Number 2 | February 2015

Table 2. (Continued )
Study Reference Study Design PTSD/Total No. Objective/PTSD Exposure Methods to Diagnose OSA Findings/Comments
of Participants

Krakow Observational 187/187 Study SDB, distress, and related Different sleep testing methods: (1) 168 with suspected SDB (21 with
et al. (24) conditions in sexual assault PSG with nasal pressure conrmed SDB). Women with

Focused Reviews
survivors with post-traumatic transducer, (2) PSG with thermal diagnosed or suspected SDB
stress symptoms sensor, (3) Autoset portable reported worse nightmares,
monitoring device with built-in sleep quality, anxiety,
nasal pressure transducer depression, post-traumatic stress,
and impaired quality of life
Krakow Observational 46/78 Assess and treat re evacuees with Subjects with potential SDB Out of a cohort of 78 subjects with

et al. (25) post-traumatic sleep disturbances/ diagnosis underwent sleep post-traumatic sleep
natural disaster testing with Autoset portable disturbances, 50% underwent
monitoring device with built-in portable sleep testing; 95% of
nasal pressure transducer them screened positive for SDB
Webber Observational cohort 998/11,701 Study the relationship between The risk for SDB was assessed Patients with PTSD had a 1.96
et al. (26) WTC-related conditions and using the FDNY sleep apnea adjusted OR for being at high risk
being at high risk for SDB questionnaire for OSA (95% CI, 1.652.34).
SDB risk was based on
questionnaires without
conrmatory PSG
Arnetz Observational 27/350 Study prevalence of SDB in Iraqi Used survey questionnaires. SDB There was a signicant association
et al. (27) immigrants from pre-GW era diagnosis based on preexisting between PTSD and the presence
compared with post-GW era/war physician diagnosis or current of SDB diagnosis. No PSG data
use of CPAP therapy conrming SDB diagnosis

Definition of abbreviations: AHI = apnea-hypopnea index; BMI = body mass index; CI = confidence interval; CSHQ = Cleveland Sleep Habits Questionnaire; CPAP = continuous positive airway
pressure; EDS = excessive daytime sleepiness; FDNY = Fire Department of the City of New York; GW = Gulf War; ICD-9-CM = International Classification of Disease, 9th revision, Clinical
Modification; OR = odds ratio; OSA = obstructive sleep apnea; PSG = polysomnography; PTSD = post-traumatic stress disorder; RDI = Respiratory Distress Index; RERA = respiratory effort
related arousal; SDB = sleep-disordered breathing; UARS = upper airway resistance syndrome; VHA = Veterans Health Administration; WTC = World Trade Center.
to adrenocorticotropic hormone

on a memory task after a night of

(54). Although these ndings were

remains unknown. Future research

resonance imaging study in healthy

the HPA axis in patients with SDB.

receptor-mediated synaptic currents

N-methyl-D-aspartate receptor loss is

patients exhibit higher corticotropin-

activation and impaired performance

absence of GH, N-methyl-D-aspartate

(53). In one of the rst neuroimaging

replicated subsequently in adults with

in magnetic resonance imagingbased
investigating stress and post-traumatic

changes are accompanied by structural

decrease in hippocampal neurons (50).
glucocorticoid receptor sensitivity (46).
expression in lymphocytes, and greater

Yet, most studies report low to normal

In parallel, growth hormone (GH)

(44, 45), higher glucocorticoid receptor

(51). Using delayed recall as dependent

secretion were signicant predictors for

of awakenings, the response of adrenals

symptoms should focus on the dynamic

transformations in hippocampal volume

GH injections were administered during
accentuated, as is a decline in long-term
SDB mitigates the HPA axis dysfunction

of coexisting SDB. Taken together, SDB-

in patients with combat-related PTSD in
releasing factor in the cerebrospinal uid

with awakenings during the night. In the

related sleep fragmentation may augment

peripheral cortisol values in patients with

This reduction in GH secretion correlates

stimulation may be attenuated in patients

sleep deprivation (50). Interestingly, these

of these studies entertained the possibility

comparison with matched control subjects
and up-regulation of receptors involved in

chronic longstanding PTSD (55, 56), none

potentiation. A recent functional magnetic
characteristics of the HPA axis, sensitivity,

levels are decreased in patients with PTSD

volunteers showed decreased hippocampus

(42, 43). Noticeably, increased responsivity

variable, both sleep fragmentation and GH

studies of PTSD, there was an 8% decrease

experimentally induced sleep fragmentation

measurement of right hippocampal volume

task (52). These processes normalized when
hormone is positively related to the number
PTSD (47, 48). Because adrenocorticotropic

compared with healthy control subjects (49).

with PTSD and SDB. Whether treatment of
to dexamethasone has been described. Such

memory retention of a declarative memory


the structural and functional impairment of

between subjects with and without

between groups with and without

Using an AHI cutoff of 10 events/h,

PTSD. No association between

and OSA were associated with
the hippocampus in patients with PTSD.

PTSD. Only 12 of the patients

(AHI . 5). Comorbid insomnia

those with (78.6%) or without

62.7% of participants had OSA

with PTSD had current PTSD
No signicant difference noted

Rates of OSA were high in the

signicantly different among

whole sample but were not
The resulting drop in GH secretion

no difference was present

compromises fear extinction, synaptic
plasticity, and recovery, hence perpetuating

PTSD and OSA only.

(59 had past PTSD)
PTSD symptomatology.

PTSD (75.0%).
PTSD Effects on OSA
Although inconclusive, the background of
hyperarousability in patients with PTSD

may contribute to the development of

Definition of abbreviations: AHI = apnea-hypopnea index; OSA = obstructive sleep apnea; PSG = polysomnography; PTSD = post-traumatic stress disorder.
obstructive and hypopneic events. Series
and colleagues (57) demonstrated

sensors and pressure transducer)

3 nights PSG 1 year after accident

In-lab PSG done on 2 consecutive

previously that SDB abnormalities were

In-lab PSG; airow determined by

determined using thermocouple
Reviewed charts of patients who

oronasal-thermal sensors and

frequent after sleep fragmentation. In
nights. Airow determined by

nasal pressure transducers

these patients, the critical pressure was
nasal and oral thermistor

signicantly lower after sleep fragmentation

had in-lab PSG (airow

than after sleep deprivation corresponding


to increased airway collapsibility. The

Table 3. Studies lacking association between sleep-disordered breathing and post-traumatic stress disorder

difference in critical pressure between each

condition was independent of age or BMI.
In cases of PTSD, concomitant insomnia
appears to reinforce that concept. Although
some studies have shown increased arousal
and sleep fragmentation in patients with
PTSD, these ndings have not been
Study sleep disturbances in trafc

consistent. Sleep fragmentation is, however,

duty military coming back from

Study sleep disorders in military

a common feature of insomnia (40). It is

Study sleep disorders in active

Iraq and Afghanistan/combat

personnel referred for sleep

Study sleep in lifetime PTSD/

possible that patients with PTSD who suffer


from insomnia have a particularly increased

accidentrelated PTSD


sleep fragmentation that may predispose


subjects to develop OSA. Progressive

traumatic event

development of OSA may reect

a particular phenotype of patients
with PTSD.

Confounding Factors
Although a genuine association between
SDB and PTSD can be explained by
PTSD/Total No.
of Participants

the described mechanisms, numerous

uncertainties are raised by the overlap of


symptoms between the two conditions,

which may lead to a nonfactual association
between the two disorders. Sleep
disturbances are a hallmark of PTSD
symptoms but are also tightly related to

Study Design

SDB. Patients with SDB may present with

chart review




frequent awakenings and disturbed sleep

architecture. Negative dream emotions and
increased number of violent and highly
anxious dreams have been described in
patients with untreated sleep apnea (58).
Mysliwiec et al. (33)
Study Reference

In addition, SDB can be associated with

Capaldi et al. (32)
Breslau et al. (31)

abnormal motor activity during sleep (59).

Klein et al. (30)

Some of these symptoms are shared by

PTSD and are part of the diagnostic criteria
for the disorder (1), such as alterations
in arousal and reactivity, depression-like
symptoms, and concentration difculties.

264 AnnalsATS Volume 12 Number 2 | February 2015


Conceivably, SDB-related nocturnal and reported from a retrospective review of would need conrmation in future
diurnal symptoms may be erroneously 15 patients with PTSD and SDB (62). In prospective trials.
attributed to a post-traumatic experience. that study, nine had 75% improvement in In view of the poor adherence, it is
For instance, a clear distinction between their PTSD symptoms after CPAP therapy, important to consider alternative methods
nightmares and SDB-related violent dreams whereas four of the six who refused or for conditioning patients with PTSD to
ought to be made so as not to overestimate did not tolerate positive airway pressure CPAP. Cognitive behavioral therapy has
PTSD in this population. Hence, specic had worsening symptoms (62). The been promising in improving CPAP
diagnostic criteria need to be established improvement of both sleep-related and adherence (66), although its efcacy has yet
to avoid the pitfall of inaccurate diagnosis PTSD symptoms with CPAP treatment to be demonstrated in subjects with PTSD.
of PTSD. suggests that a potential complex interplay For those intolerant to CPAP, alternative
Diagnostic challenges may also may exist between the two disorders. measures (i.e., oral appliances, nasal
be encountered when interpreting Although these studies are promising, there expiratory positive airway pressure) may be
polysomnography in patients with PTSD. are number of methodological problems considered. A randomized trial comparing
Because increased arousals and awakenings including, but not limited to, small sample the efcacy of CPAP to oral appliance in
are seen in those patients, a strict adherence size, selection bias, retrospective design, and PTSD with SDB is underway (NCT01569022).
to the American Academy of Sleep Medicine lack of comparative intervention. Future Other trials involving alternative or
criteria for scoring of respiratory events longitudinal studies are needed to elucidate combination therapy should be the subject of
should be ascertained. Even then, it may the strength and direction of these future research to conrm their effectiveness in
be particularly challenging to differentiate associations. the coexisting PTSD and SDB population.
spontaneous arousals (which may be related A major determinant of the
to PTSD) from respiratory eventsrelated effectiveness of CPAP therapy is patient
arousals during REM sleep, where compliance. Despite the overall Future Directions
signicant irregularities in breathing improvement in PTSD symptomatology
pattern and air ow are often observed. with CPAP therapy (63), adherence to The growing population of combat veterans
In the absence of due diligence, it is treatment is far worse in these patients returning from recent wars will be facing
conceivable that respiratory eventsrelated compared with the general population with signicant clinical challenges in managing
arousals are overscored, leading to an OSA (64, 65). Although not statistically their concomitant disorders. Although
overestimation of the apneahypopnea signicant, insomnia tended to be more studies to date have demonstrated sleep
index. common in the PTSD group. Whether disturbances as a fundamental issue in
insomnia alone can account for the trauma-exposed populations, the current
difference in CPAP compliance is open to research into PTSD and sleep disorders is
Treatment of OSA in Patients debate. However, the retrospective nature limited by the fact that: (1) the vast majority
with PTSD of these studies did not allow an assessment of the work to date has been retrospective
of the severity of insomnia and its relation or cross-sectional in design, with the
Managing patients with PTSD and SDB with CPAP compliance in this PTSD exception of a few small prospective studies
is challenging. Although it is suggested population. in trauma-exposed study groups and
that treatment of SDB may lead to an Mask discomfort, claustrophobia, and treatment studies. A minority of the latter
improvement in PTSD symptoms, PTSD air hunger were among the reported reasons have included objective clinical assessments
itself seems to hinder OSA therapy. for CPAP nonadherence in the PTSD group of PTSD that may provide insights into
CPAP remains the mainstay of therapy (64). It is somewhat intuitive to consider the physiological or neural underpinnings
for OSA. CPAP therapy exerts its benecial that having a mask on the face with positive of the relationships of sleep to PTSD
effects by acting as a pneumatic splint to pressure may awake dormant memories or symptoms; (2) the effect of comorbid
prevent the upper airway soft tissue from experiences in patients with combat-related psychiatric disorders that are associated
collapsing. Other effects include a change in PTSD. Interestingly, nightmares were more with sleep disturbances in PTSD has
the upper airway muscle tone and increasing frequently reported in those who were not been explored; (3) despite effective
functional residual capacity (60). CPAP nonadherent to CPAP, which suggest treatment of OSA with CPAP, adherence
therapy has been demonstrated to resolve that nightmares may be one of the to therapy is poor and no alternative
SDB events and improve many aspects of factors infringing on CPAP compliance treatment has been studied; (4) no long-
OSA syndrome. To that effect, adequate in patients with PTSD. It may also term prospective studies have evaluated
treatment of SDB has been shown to indicate a bidirectional relationship, with the impact of sleep disturbances on
improve anxiety, depression, and other nightmare-related anxiety leading to cardiovascular and behavioral outcomes;
cognitive symptoms (61). In a case report reduced CPAP use or, alternatively, CPAP- (5) and the longitudinal implications of
by Youakim and colleagues (28), CPAP related increases in nightmare propensity non-SDB (i.e., insomnia) in PTSD with
therapy resulted in dramatic improvement worsening adherence to treatment. The OSA across the lifespan have not been
in sleep quality and daytime sleepiness of latest evidence seems to favor the former investigated.
a Vietnam veteran with PTSD. There was hypothesis. A recent retrospective study Two general areas of research are
a reduction in nightmare frequency and suggests that CPAP therapy is associated needed to advance understanding of why
severity as well as an improvement in with decrease in frequency of PTSD-related traumatic events increase the likelihood
daytime ashbacks. Similar results were nightmares (63). However, these results of developing sleep problems. First, it is

Focused Reviews 265


important to consider the characteristics of alternative treatments for CPAP. Would mutually affect and perpetuate each other,
the traumatic event exposure. The time mandibular advancement devices, although creating a vicious cycle of symptoms. With
since the traumatic event, type of traumatic less effective, prove to be more successful the increasing rate of PTSD among veterans
event exposure, and number of traumatic in reducing PTSD symptomatology by the returning from the Iraq and Afghanistan
event exposures may differentially affect mere fact of being better tolerated than wars, there is a growing urgency to
sleep. Direct prospective tests of the relation CPAP? Would combination of cognitive identify gaps in the quality of care
between specic traumatic event types and behavioral therapy with CPAP improve provided to these patients. Among these
the development of sleep problems are adherence? Finally, as pharmacological unmet needs is the approach to the
needed. Second, future investigations interventions focused on PTSD symptom management of SDB in veterans with
using full PSG are integral to our reduction alone (e.g., monoamine PTSD. Both diagnostic and therapeutic
understanding how changes in REM sleep oxidase inhibitors, benzodiazepines, challenges are faced by clinicians caring
(or more generally, sleep physiology and tricyclic antidepressants) have for patients who may be suffering
neurobiology) contribute to increased risk been shown to increase sleep from both disorders. A thorough sleep
of poor psychiatric outcomes in patients problems (67), the exploration of assessment should be done when
with PTSD and SDB. To the best of our psychopharmacologic interventions that evaluating patients for PTSD, and extreme
knowledge, no study has directly tested target neuroanatomical structures care should be taken to avoid inaccurate
the role of undiagnosed SDB problems implicated in both PTSD and sleep diagnosis of PTSD based on SDB-related
prospectively on subsequent traumatic event problems are sorely needed. symptoms. A screening protocol for
exposure. Analog designs that aim to OSA ought to be implemented for all
experimentally test the effects of OSA- patients with PTSD exhibiting symptoms
related sleep fragmentation on reactivity Summary of excessive daytime sleepiness and for
to traumatic event cues could shed light those who fail to respond to standard
on how sleep problems may maintain PTSD and SDB share common features: PTSD treatment. Disturbed sleep is
traumatic eventrelated affective reactivity. they have common symptoms that overlap, a modiable risk factor, and sleep
Research in this domain is necessary to and they both affect quality of sleep and restoration through effective targeted
better conceptualize the interplay between quality of life. Although not consistent, there sleep treatments may accelerate recovery
sleep problems and traumatic event is mounting evidence that an association from trauma exposure and PTSD. n
exposure. between PTSD and OSA exists and can be
In terms of treatment, randomized explained by more than one mechanistic Author disclosures are available with the text
clinical trials are paramount in determining theory. In addition, both disorders seem to of this article at www.atsjournals.org.

References 11 Edmondson D, Richardson S, Falzon L, Davidson KW, Mills MA, Neria

Y. Posttraumatic stress disorder prevalence and risk of recurrence in
1 American Psychiatric Association. Diagnostic and statistical manual acute coronary syndrome patients: a meta-analytic review. PLoS
of mental disorders. Washington, DC: American Psychiatric ONE 2012;7:e38915.
Association; 2013. 12 Krakow B, Hollield M, Johnston L, Koss M, Schrader R, Warner TD,
2 Chivers-Wilson KA. Sexual assault and posttraumatic stress disorder: Tandberg D, Lauriello J, McBride L, Cutchen L, et al. Imagery
a review of the biological, psychological and sociological factors and rehearsal therapy for chronic nightmares in sexual assault survivors
treatments. Mcgill J Med 2006;9:111118. with posttraumatic stress disorder: a randomized controlled trial.
3 Resnick HS, Kilpatrick DG, Dansky BS, Saunders BE, Best CL. Prevalence JAMA 2001;286:537545.
of civilian trauma and posttraumatic stress disorder in a representative 13 Krakow B, Germain A, Tandberg D, Koss M, Schrader R, Hollield M,
national sample of women. J Consult Clin Psychol 1993;61:984991. Cheng D, Edmond T. Sleep breathing and sleep movement disorders
4 Grieger TA, Cozza SJ, Ursano RJ, Hoge C, Martinez PE, Engel CC, masquerading as insomnia in sexual-assault survivors. Compr
Wain HJ. Posttraumatic stress disorder and depression in battle- Psychiatry 2000;41:4956.
injured soldiers. Am J Psychiatry 2006;163:17771783; quiz 1860. 14 Clum GA, Nishith P, Resick PA. Trauma-related sleep disturbance and
5 Steel Z, Chey T, Silove D, Marnane C, Bryant RA, van Ommeren M. self-reported physical health symptoms in treatment-seeking female
Association of torture and other potentially traumatic events with rape victims. J Nerv Ment Dis 2001;189:618622.
mental health outcomes among populations exposed to mass 15 Spoormaker VI, Montgomery P. Disturbed sleep in post-traumatic
conict and displacement: a systematic review and meta-analysis. stress disorder: secondary symptom or core feature? Sleep Med Rev
JAMA 2009;302:537549. 2008;12:169184.
6 Ezra MB. Earliest evidence of post-traumatic stress? Br J Psychiatry
16 Germain A. Sleep disturbances as the hallmark of PTSD: where are we
now? Am J Psychiatry 2013;170:372382.
7 Crocq MA, Crocq L. From shell shock and war neurosis to
posttraumatic stress disorder: a history of psychotraumatology. 17 Lavie P, Katz N, Pillar G, Zinger Y. Elevated awaking thresholds during
Dialogues Clin Neurosci 2000;2:4755. sleep: characteristics of chronic war-related posttraumatic stress
8 Friedman MJ. Post-Vietnam syndrome: recognition and management. disorder patients. Biol Psychiatry 1998;44:10601065.
Psychosomatics 1981;22:931943. 18 Engdahl BE, Eberly RE, Hurwitz TD, Mahowald MW, Blake J. Sleep
9 Jordan BK, Marmar CR, Fairbank JA, Schlenger WE, Kulka RA, Hough in a community sample of elderly war veterans with and without
RL, Weiss DS. Problems in families of male Vietnam veterans with posttraumatic stress disorder. Biol Psychiatry 2000;47:520525.
posttraumatic stress disorder. J Consult Clin Psychol 1992;60: 19 Sharafkhaneh A, Giray N, Richardson P, Young T, Hirshkowitz M.
916926. Association of psychiatric disorders and sleep apnea in a large
10 Hoge CW, Castro CA, Messer SC, McGurk D, Cotting DI, Koffman RL. cohort. Sleep 2005;28:14051411.
Combat duty in Iraq and Afghanistan, mental health problems, and 20 Ocasio-Tasc on ME, Alicea-Col on E, Torres-Palacios A,
barriers to care. N Engl J Med 2004;351:1322. Rodr guez-Cintr on W. The veteran population: one at

266 AnnalsATS Volume 12 Number 2 | February 2015


high risk for sleep-disordered breathing. Sleep Breath of rapid eye movement sleep deprivation on fear extinction recall and
2006;10:7075. prediction error signaling. Hum Brain Mapp 2012;33:23622376.
21 Yesavage JA, Kinoshita LM, Kimball T, Zeitzer J, Friedman L, Noda A, 42 de Kloet CS, Vermetten E, Geuze E, Kavelaars A, Heijnen CJ,
David R, Hernandez B, Lee T, Cheng J, OHara R. Sleep-disordered Westenberg HG. Assessment of HPA-axis function in posttraumatic
breathing in Vietnam veterans with posttraumatic stress disorder. stress disorder: pharmacological and non-pharmacological
Am J Geriatr Psychiatry 2012;20:199204. challenge tests, a review. J Psychiatr Res 2006;40:550567.
22 Williams SG, Collen J, Orr N, Holley AB, Lettieri CJ. Sleep disorders in 43 Golier JA, Caramanica K, Makotkine I, Sher L, Yehuda R. Cortisol
combat-related PTSD. Sleep Breath (In press) response to cosyntropin administration in military veterans with or
23 Krakow B, Melendrez D, Pedersen B, Johnston L, Hollield M, Germain without posttraumatic stress disorder. Psychoneuroendocrinology
A, Koss M, Warner TD, Schrader R. Complex insomnia: insomnia and 2014;40:151158.
sleep-disordered breathing in a consecutive series of crime victims 44 Baker DG, West SA, Nicholson WE, Ekhator NN, Kasckow JW, Hill KK,
with nightmares and PTSD. Biol Psychiatry 2001;49:948953. Bruce AB, Orth DN, Geracioti TD Jr. Serial CSF corticotropin-releasing
24 Krakow B, Melendrez D, Johnston L, Warner TD, Clark JO, Pacheco M, hormone levels and adrenocortical activity in combat veterans with
Pedersen B, Koss M, Hollield M, Schrader R. Sleep-disordered posttraumatic stress disorder. Am J Psychiatry 1999;156:585588.
breathing, psychiatric distress, and quality of life impairment in 45 Bremner JD, Licinio J, Darnell A, Krystal JH, Owens MJ, Southwick SM,
sexual assault survivors. J Nerv Ment Dis 2002;190:442452. Nemeroff CB, Charney DS. Elevated CSF corticotropin-releasing
25 Krakow B, Haynes PL, Warner TD, Santana E, Melendrez D, Johnston L, factor concentrations in posttraumatic stress disorder. Am
Hollield M, Sisley BN, Koss M, Shafer L. Nightmares, insomnia, and J Psychiatry 1997;154:624629.
sleep-disordered breathing in re evacuees seeking treatment for 46 de Kloet CS, Vermetten E, Geuze E, Lentjes EG, Heijnen CJ, Stalla GK,
posttraumatic sleep disturbance. J Trauma Stress 2004;17:257268. Westenberg HG. Elevated plasma corticotrophin-releasing hormone
26 Webber MP, Lee R, Soo J, Gustave J, Hall CB, Kelly K, Prezant D. levels in veterans with posttraumatic stress disorder. Prog Brain Res
Prevalence and incidence of high risk for obstructive sleep apnea in 2008;167:287291.
World Trade Center-exposed rescue/recovery workers. Sleep Breath 47 Klaassens ER, Giltay EJ, Cuijpers P, van Veen T, Zitman FG. Adulthood
2011;15:283294. trauma and HPA-axis functioning in healthy subjects and PTSD patients:
27 Arnetz BB, Templin T, Saudi W, Jamil H. Obstructive sleep apnea, a meta-analysis. Psychoneuroendocrinology 2012;37:317331.
posttraumatic stress disorder, and health in immigrants. Psychosom 48 Meewisse ML, Reitsma JB, de Vries GJ, Gersons BP, Olff M. Cortisol
Med 2012;74:824831. and post-traumatic stress disorder in adults: systematic review and
28 Youakim JM, Doghramji K, Schutte SL. Posttraumatic stress disorder meta-analysis. Br J Psychiatry 2007;191:387392.
and obstructive sleep apnea syndrome. Psychosomatics 1998;39: 49 Abedelmalek S, Souissi N, Chtourou H, Denguezli M, Aouichaoui C,
168171. Ajina M, Aloui A, Dogui M, Haddouk S, Tabka Z. Effects of partial
29 Johnson K. Sleep Problems, PTSD, Obesity Related, but to What sleep deprivation on proinammatory cytokines, growth hormone,
Degree? Clinical Psychiatry News 2014;38:46. and steroid hormone concentrations during repeated brief sprint
30 Klein E, Koren D, Arnon I, Lavie P. No evidence of sleep disturbance in interval exercise. Chronobiol Int 2013;30:502509.
post-traumatic stress disorder: a polysomnographic study in injured 50 Kim E, Grover LM, Bertolotti D, Green TL. Growth hormone rescues
victims of trafc accidents. Isr J Psychiatry Relat Sci 2002;39:310. hippocampal synaptic function after sleep deprivation. Am J Physiol
31 Breslau N, Roth T, Burduvali E, Kapke A, Schultz L, Roehrs T. Sleep Regul Integr Comp Physiol 2010;298:R1588R1596.
in lifetime posttraumatic stress disorder: a community-based 51 van Zuiden M, Geuze E, Willemen HL, Vermetten E, Maas M, Heijnen
polysomnographic study. Arch Gen Psychiatry 2004;61:508516. CJ, Kavelaars A. Pre-existing high glucocorticoid receptor number
32 Capaldi VF II, Guerrero ML, Killgore WD. Sleep disruptions among predicting development of posttraumatic stress symptoms after
returning combat veterans from Iraq and Afghanistan. Mil Med 2011; military deployment. Am J Psychiatry 2011;168:8996.
176:879888. 52 van Liempt S. Sleep disturbances and PTSD: a perpetual circle?
33 Mysliwiec V, Gill J, Lee H, Baxter T, Pierce R, Barr TL, Krakow B, Roth Eur J Psychotraumatol 2012;3.
BJ. Sleep disorders in US military personnel: a high rate of comorbid 53 Bremner JD. Stress and brain atrophy. CNS Neurol Disord Drug Targets
insomnia and obstructive sleep apnea. Chest 2013;144:549557. 2006;5:503512.
34 Kobayashi I, Sledjeski EM, Spoonster E, Fallon WF Jr, Delahanty DL. 54 Bremner JD, Randall P, Scott TM, Bronen RA, Seibyl JP, Southwick
Effects of early nightmares on the development of sleep SM, Delaney RC, McCarthy G, Charney DS, Innis RB. MRI-based
disturbances in motor vehicle accident victims. J Trauma Stress measurement of hippocampal volume in patients with combat-
2008;21:548555. related posttraumatic stress disorder. Am J Psychiatry 1995;152:
35 Koren D, Arnon I, Lavie P, Klein E. Sleep complaints as early 973981.
predictors of posttraumatic stress disorder: a 1-year prospective study 55 Stein MB, Koverola C, Hanna C, Torchia MG, McClarty B. Hippocampal
of injured survivors of motor vehicle accidents. Am J Psychiatry 2002;159: volume in women victimized by childhood sexual abuse. Psychol
855857. Med 1997;27:951959.
36 Bryant RA, Creamer M, ODonnell M, Silove D, McFarlane AC. Sleep 56 Schuff N, Neylan TC, Lenoci MA, Du AT, Weiss DS, Marmar CR, Weiner
disturbance immediately prior to trauma predicts subsequent MW. Decreased hippocampal N-acetylaspartate in the absence of
psychiatric disorder. Sleep 2010;33:6974. atrophy in posttraumatic stress disorder. Biol Psychiatry 2001;50:
37 Mellman TA, Bustamante V, Fins AI, Pigeon WR, Nolan B. REM sleep 952959.
and the early development of posttraumatic stress disorder. Am 57 Series F, Roy N, Marc I. Effects of sleep deprivation and sleep
J Psychiatry 2002;159:16961701. fragmentation on upper airway collapsibility in normal subjects.
38 Kobayashi I, Boarts JM, Delahanty DL. Polysomnographically Am J Respir Crit Care Med 1994;150:481485.
measured sleep abnormalities in PTSD: a meta-analytic review. 58 Carrasco E, Santamaria J, Iranzo A, Pintor L, De Pablo J, Solanas A,
Psychophysiology 2007;44:660669. Kumru H, Martnez-Rodrguez JE, Boget T. Changes in dreaming
39 van Liempt S, Arends J, Cluitmans PJ, Westenberg HG, Kahn RS, induced by CPAP in severe obstructive sleep apnea syndrome
Vermetten E. Sympathetic activity and hypothalamo-pituitary- patients. J Sleep Res 2006;15:430436.
adrenal axis activity during sleep in post-traumatic stress disorder: 59 Guilleminault C. Obstructive sleep apnea syndrome. A review. Psychiatr
a study assessing polysomnography with simultaneous blood Clin North Am 1987;10:607621.
sampling. Psychoneuroendocrinology 2013;38:155165. 60 Rapoport DM, Garay SM, Goldring RM. Nasal CPAP in obstructive
40 Mellman TA, Kulick-Bell R, Ashlock LE, Nolan B. Sleep events among sleep apnea: mechanisms of action. Bull Eur Physiopathol Respir
veterans with combat-related posttraumatic stress disorder. Am 1983;19:616620.
J Psychiatry 1995;152:110115. 61 McMahon JP, Foresman BH, Chisholm RC. The inuence of CPAP on
41 Spoormaker VI, Schroter MS, Andrade KC, Dresler M, Kiem SA, Goya- the neurobehavioral performance of patients with obstructive sleep
Maldonado R, Wetter TC, Holsboer F, Samann PG, Czisch M. Effects apnea hypopnea syndrome: a systematic review. WMJ 2003;102:3643.

Focused Reviews 267


62 Krakow B, Lowry C, Germain A, Gaddy L, Hollield M, Koss M, 65 Collen JF, Lettieri CJ, Hoffman M. The impact of posttraumatic stress
Tandberg D, Johnston L, Melendrez D. A retrospective study on disorder on CPAP adherence in patients with obstructive sleep
improvements in nightmares and post-traumatic stress disorder apnea. J Clin Sleep Med 2012;8:667672.
following treatment for co-morbid sleep-disordered breathing. 66 Richards D, Bartlett DJ, Wong K, Malouff J, Grunstein RR. Increased
J Psychosom Res 2000;49:291298. adherence to CPAP with a group cognitive behavioral treatment
63 Tamanna S, Parker JD, Lyons J, Ullah MI. The effect of continuous intervention: a randomized trial. Sleep 2007;30:635640.
positive air pressure (CPAP) on nightmares in patients with 67 Maher MJ, Rego SA, Asnis GM. Sleep disturbances in patients with
posttraumatic stress disorder (PTSD) and obstructive sleep apnea post-traumatic stress disorder: epidemiology, impact and
(OSA). J Clin Sleep Med 2014;10:631636. approaches to management. CNS Drugs 2006;20:567590.
64 El-Solh AA, Ayyar L, Akinnusi M, Relia S, Akinnusi O. Positive airway 68 World Health Organization. Pocket guide to the ICD-10
pressure adherence in veterans with posttraumatic stress disorder. classication of mental and behavioral disorders. Washington,
Sleep 2010;33:14951500. DC: American Psychiatric Press; 1994. pp.168169.

268 AnnalsATS Volume 12 Number 2 | February 2015