REM SLEEP AND THE DURATION OF PTSD IN A YOUNG ADULT POPULATION http://dx.doi.org/10.5665/sleep.3922
A Relationship between REM Sleep Measures and the Duration of Posttraumatic Stress Disorder in a Young Adult Urban Minority Population Thomas A. Mellman, MD; Ihori Kobayashi, PhD; Joseph Lavela, BS; Bryonna Wilson, BS; Tyish S. Hall Brown, PhD Howard University College of Medicine Department of Psychiatry and Behavioral Sciences, Howard University, Washington, DC
Study Objective: To determine relationships of polysomnographic (PSG) measures with posttraumatic stress disorder (PTSD) in a young adult, urban African American population. Design: Cross-sectional, clinical and laboratory evaluation. Setting: Community recruitment, evaluation in the clinical research unit of an urban University hospital. Participants: Participants (n = 145) were Black, 59.3% female, with a mean age of 23.1 y (SD = 4.8). One hundred twenty-one participants (83.4%) met criteria for trauma exposure, the most common being nonsexual violence. Thirty-nine participants (26.9%) met full (n = 19) or subthreshold criteria (n = 20) for current PTSD, 41 (28.3%) had met lifetime PTSD criteria and were recovered, and 65 (45%) were negative for PTSD. Measurements and Results: Evaluations included the Clinician Administered PTSD Scale (CAPS) and 2 consecutive nights of overnight PSG. Analysis of variance did not reveal differences in measures of sleep duration and maintenance, percentage of sleep stages, and the latency to and duration of uninterrupted segments of rapid eye movement (REM) sleep by study group. There were significant relationships between the duration of PTSD and REM sleep percentage (r = 0.53, P = 0.001), REM segment length (r = 0.43, P = 0.006), and REM sleep latency (r = -0.34, P < 0.03) among those with current PTSD that persisted when removing cases with, or controlling for, depression. Conclusions: The findings are consistent with observations in the literature of fragmented and reduced REM sleep with posttraumatic stress disorder (PTSD) relatively proximate to trauma exposure and nondisrupted or increased REM sleep with chronic PTSD. Keywords: minority, polysomnography, posttraumatic stress disorder, sleep Citation: Mellman TA, Kobayashi I, Lavela J, Wilson B, Hall Brown TS. A relationship between REM sleep measures and the duration of posttraumatic stress disorder in a young adult urban minority population. SLEEP 2014;37(8):1321-1326.
INTRODUCTION Sleep disturbances, which are denoted by diagnostic criteria of trauma-related nightmares and difficulty initiating and maintaining sleep, are highly prevalent features of posttraumatic stress disorder (PTSD)1,2 and have been linked to the development of the disorder.3–5 It is therefore important to understand the nature of sleep disturbances in PTSD beyond the level of reported symptoms. Polysomnography (PSG) provides assessment of the timing, duration, and continuity of sleep states and their associated neurophysiologic activity. There has been substantial PTSD research using PSG that has lent some clarity as well as continuing controversy regarding the nature of sleep disturbances in the disorder. Overall, this body of research has provided evidence for and against objective impairment of sleep initiation, maintenance, and depth, and abnormalities related to rapid eye movement (REM) sleep. In a meta-analysis of 20 PTSD PSG studies done before 2007, there were no significant effects of PTSD for sleep latency and efficiency, and wake after sleep onset (WASO); however, participants with PTSD exhibited lighter sleep (more stage 1, less stage 3) compared with controls.6 Generalizability of the meta-analysis is limited by the preponderance of the
A commentary on this article appears in this issue on page 1281. Submitted for publication November, 2013 Submitted in final revised form January, 2014 Accepted for publication January, 2014 Address correspondence to: Thomas A. Mellman, Howard University College of Medicine, 520 W. St, NW, Washington DC 20059; Tel: 202-8067818; E-mail: [email protected].
studies (14 of 20) having featured male veteran combat populations, mostly with PTSD durations exceeding a decade. In fact, two more recent studies that featured predominantly female samples with non-military trauma did find objective differences in sleep initiation and/or maintenance; however, variance with the prior studies also may have been related to recordings done in home environments.7,8 Interest in possible abnormalities related to REM sleep in PTSD has been inspired by the occurrence of nightmares that are distinct from normal dreams in terms of their recurring nature and, to varying degrees, replicating past (traumatic) experiences.9 Dreams most commonly arise from REM sleep10 and do not normally represent unaltered memories of specific events.11 In addition, the REM sleep state provides conditions that are conducive to modification of memory networks, including their decoupling from affective arousal (which is postulated to aid emotional adaptation),12 and this process appears to be impaired in PTSD. A final rationale for examining REM sleep with PTSD is to determine the overlap or contrast with REM sleep abnormalities that have been documented for depression,13 a condition that has both common clinical features and frequent comorbidity with PTSD.14 Studies, including the aforementioned meta-analysis, have not found consistent reductions in the latency to REM sleep or increased percentages of REM sleep that characterize major depression. Kobayashi et al.6 did report increased REM density (frequency of eye movements within REM periods) with PTSD. Increased REM density has also been associated with depression,14 but also with the intensive dreaming15 and learning periods.16 In a study that uniquely obtained PSG data within 1 mo of trauma exposure, REM density was increased with trauma exposure but not with developing PTSD.17 Thus,
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REM Sleep and PTSD Duration—Mellman et al.
the pathophysiological significance of REM density in PTSD remains unclear. Most nightmares and other symptomatic awakenings in PTSD have been found to arise from, and thereby disrupt, REM sleep.18,19 In the study from the early aftermath of trauma, the lengths of uninterrupted segments of REM sleep (REM segment length) were shorter among the injured patients developing PTSD.17 An earlier, more anecdotal report observed “severe deficiency in REM sleep” in association with acute combat fatigue.20 Findings from some21–23 but not all23–25 of the studies of established PTSD that have examined relevant indices are consistent with fragmentation or reduction of REM sleep. That such patterns have been observed in acute posttraumatic states,17,20 and in patients recruited from acute treatment episodes with a mean 15 mo duration of PTSD,21 and 2–2.5 y of combat neurosis,”22 whereas no REM sleep disruption25 and increased REM sleep percentage26 have been observed with combat-related PTSD of approximately 20 y, suggests that the duration of PTSD may influence patterns of REM sleep. Considerations of sex effects on relationships between REM sleep and PTSD were raised in a recent study of Richards et al.,27 where an increase in REM sleep percentage with PTSD was seen in females but not in males. Studies that increase the diversity of populations represented in the sleep PTSD literature and allow for examination of possible effects of PTSD duration and sex are indicated. The current study reports data from a nonclinical urban minority population with high rates of trauma exposure. With the exception of the study of Breslau et al., in which 59 of the 71 cases of PTSD had remitted,23 such groups are not represented in the sleep PTSD literature. The purpose of this report is to provide evaluation of relationships of PSG measures and PTSD that include examination of the duration of the disorder and participant sex, in a young adult urban African American population. METHODS Participants The study advertised to recruit young adult (age 18–35 y) African Americans for a study that examined associations between trauma, PTSD, sleep, and nocturnal blood pressure. The participants were recruited from the Washington, DC metropolitan area through study fliers posted in strategic community settings and through referrals from previous participants. During the initial screening, potential participants were excluded if they were found to have a body mass index ≥ 40, chronic medical conditions or psychotic disorders, bipolar disorder, severe recurrent depression, daily use of any medication, excessive use of caffeine (more than five cups of coffee per day or its equivalent), heavy smoking (more than 20 cigarettes per day) and drinking (more than 14 drinks/w in men, more than seven drinks/w in women), and regular night shift work or unusual sleep-wake schedules. Additional exclusion criteria were sleep, breathing, and movement disorders (screened through the first night PSG), current alcohol or drug abuse or dependence (screened through a structured clinical interview), and positive urine toxicology for illicit drugs. The study was approved by the
Howard University Institutional Review Board and all participants signed approved consent forms after they were given time to review and ask questions. Measures Self-Report
The Life Event Checklist (LEC) was administered during the initial meeting to obtain preliminary information regarding participants’ trauma exposure. The LEC includes a list of 16 types of potentially traumatic experiences (e.g., transportation accident, assault with a weapon, sexual assault). Participants were asked to indicate whether they had experienced or witnessed any of these events as an adult or a child and which of those experiences distressed them the most.28 The Patient Health Questionnaire (PHQ-9) was administered to obtain a continuous measure of depression severity.29 The nine question-items are based directly on the diagnostic criteria for major depressive disorder in the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) with response options ranging from “0” (not at all) to “3” (nearly every day). Interview
The Clinician Administered PTSD Scale (CAPS),30 a structured clinical interview, was used to determine lifetime and current PTSD diagnostic status and symptom severity according to the diagnostic criteria of the DSM-IV. After the most distressing potentially traumatic event (the index event) initially screened by the LEC was confirmed, the event was further assessed at the beginning of the interview to determine whether it met the diagnostic criteria for a traumatic event (Criterion A). If criteria were met, the frequency and intensity of each of 17 PTSD symptoms were rated on five-point scales ranging from 0 (Never [frequency], Not at all [intensity]) to 4 (Daily or almost daily, Extremely) for both the current period (past month) and the most symptomatic period of the participant’s life. To determine diagnostic status, a symptom was considered present when the participant reported at least the frequency rating of 1 and the intensity rating of 2 for the symptom. When a participant met criteria for two of the three DSM-IV symptom diagnostic clusters, he or she was considered to have a subthreshold PTSD diagnosis. For participants who had met full disorder criteria in the past but no longer met full or subthreshold diagnostic criteria, the time frame for when the PTSD remitted was carefully assessed. PTSD duration was determined as the number of months from the onset of PTSD symptoms (during or just following trauma exposure in all but one case where PTSD related to childhood sexual abuse was precipitated by early adult experiences) to the time of remission or the time of the assessment for those who continued to meet full or subthreshold criteria for PTSD. Current and lifetime diagnoses of mood disorders, psychotic disorders, anxiety disorders other than PTSD, substance abuse and dependence, and eating disorders were assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID).31 All CAPS and SCID interviews were conducted by trained staff members (psychology graduate students and clinical
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psychology postdoctoral fellows), and a licensed psychiatrist (TAM) reviewed all cases. Practice interviews were completed prior to data collection until the trainee and the trainer reached the 90% agreement rate on practice cases. For all of the included participants meeting criteria for current major depression, the episode was determined to be secondary in temporal onset and in severity to PTSD. Polysomnography Participants underwent two consecutive overnight PSG recordings in the Howard University Clinical Research Unit. None were shift workers or had regular nocturnal activity, and recordings were scheduled to approximate their natural bedtimes. Recordings were conducted using an Embla (Denver, Co) titanium portable unit. PSG collection included a standard electroencephalogram montage with bilateral frontal, central, and occipital leads, two electrooculograms (EOG), and chin electromyogram (EMG) with limb EMGs and respiratory monitors on the first night only. Scorers were trained by a registered PSG technician. Rules for the onset and termination of REM sleep and other American Academy of Sleep Medicine (AASM) criteria32 were emphasized during the training. Records of novice scorers were also independently scored by experienced scorers, and any discrepancies were addressed. Independent scoring required 90% concordance of epoch scoring for at least three records. Scorers were blinded to participants’ PTSD status and visually scored sleep records on a computer monitor and designated the sleep stage of each 30-sec epoch. After recording time in bed, the REM logic scoring system (Embla) calculated standard measures including sleep onset latency, total sleep time, WASO, sleep efficiency, the latency to REM sleep, and the percentages of total sleep composed of N1, N2, N3 (slow wave sleep), and REM sleep. Calculation of REM segment length used our previous criteria17 of at least two epochs of consecutive REM sleep with no more than one, 30-sec epoch of non-REM sleep interruption. Eye movements during REM sleep were also scored based on previously used criteria of EOG lead excursions of at least 25 µV within 500 milliseconds.17 REM density was calculated by dividing the number of eye movements (EMs) by minutes of REM sleep. Data Analysis Demographic data and clinical and sleep measures were compared between participants based on PTSD status by one-way analysis of variance (ANOVA) and possible differences between the study groups with current full PTSD, current subthreshold PTSD, lifetime PTSD, and PTSD negative with trauma exposure and PTSD negative without trauma exposure were explored by independent t-tests. We then examined Pearson correlations between PTSD severity and duration and the sleep measures. The square root transformation of PTSD duration was used to correct for the skewed distribution of the variable. To exclude potentially confounding roles of remission and depression on relationships between the sleep measures of interest, we also conducted analyses of just those with current (full and subthreshold) PTSD with and without those with concurrent criteria for major depression, as well as regression analyses that included depression severity as measured by the Patient Health Questionnaire (PHQ-9) as a covariate.
Screened/self-report n = 543
Invited for interview/lab n = 177
Excluded: • Tox screen + (n = 15) • Apnea (n = 6) • Other protocol violations or technical problems (n = 11)
Final sample n = 145 Figure 1—Study enrollment.
RESULTS Participants Of the 177 participants invited to the laboratory phase of the study, 15 were excluded for positive urine screenings for illicit drugs. An additional six participants (one with current PTSD, five negative for PTSD) were found to have apnea/hypopnea indices exceeding 10 events/h on the first night PSG. An additional 11 were not included because of loss to follow-up or poor quality recordings (Figure 1). The demographic, clinical and sleep measures for the remaining 145 participants are presented in Table 1. All of the final sample participants were Black with 123 self-identifying as African American, 11 African, 11 Caribbean, and 86 (59.3%) were female. Their mean age was 23.1 (standard deviation [SD] = 4.8). There were 121 participants (83.4%) who were determined by the CAPS to have experienced a criterion A trauma. The most common categories of index traumas were physical abuse and assault for 23.1% of the total participants and sexual trauma for 18.8% (27.8% of the females). Other categories for index traumas included witnessing community violence (13.4%), sudden unexpected deaths (12.2%), transportation accidents (7.3%), disasters (6.9%), and other (1.7%). Nineteen participants met full current criteria for PTSD, 20 met current subthreshold criteria (10 of whom met full PTSD criteria in the past), totaling 39 participants or 26.9% of the group with current PTSD. Forty-one participants (28.3%) had met lifetime criteria and were recovered and 65 (44.8%), including 24 who were not trauma exposed, had never met criteria for PTSD (PTSD negative). There were no significant differences in age between these major groupings. There was a trend toward different sex distributions, with 64% of those in the current PTSD group, 71% of those from the lifetime (recovered) group, and 49% of the PTSD negative group being female (chi square = 5.3, df = 2, P < 0.07). As expected, CAPS scores were highest for those with current PTSD (41.9, SD = 17.7) followed by the lifetime recovered group (12.9, SD = 8.6) and the PTSD negative group (6.6, SD = 7.5) [F(2,118) = 97.3, 118; P < 0.001]. For the current PTSD and lifetime recovered groups, the mean duration of PTSD was 35.6 mo (SD = 51.3) and for the current PTSD group alone, 64.1 mo (SD = 62.9)
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REM Sleep and PTSD Duration—Mellman et al.
Table 1—Sleep measures by groups defined by posttraumatic stress disorder and trauma
Female, n (%) Age CAPS score (n = 120) Duration (mo) PTSD (n = 80)1 Total sleep (min) Latency (min) WASO (min) Sleep efficiency (% TIB spent asleep) N1 (% TST) N2 (% TST) N3 (% TST) REM sleep (% TST) REM latency (min) REM segment length (min) REM density (mean eye movements/ min REM sleep)
Total (n = 145) 86 (59.3%) 23.1 (4.8) 20.1(19.4) 35.6 (51.3) 385.3 (73.4) 34.1 (44.3) 26.3 (25.4) 86.5 (10.2) 2.5 (1.7) 51.9 (7.7) 24.6 (9.2) 21.1 (6.0) 79.1(34.9) 15.5 (5.9) 2.4 (2.3)
Current (subthreshold) PTSD (n = 20) 11 (55%) 21.7 (3.8) 29.3 (7.3) 47.2 (47.9) 377.5 (60.4) 42.9 (52.0) 25.4 (15.3) 85.5 (10.8) 2.4 (1.0) 51.8 (8.2) 26.2 (9.0) 19.8 (6.2) 84.1 (34.0) 16.1 (5.9) 2.3 (1.5)
Current (full) PTSD (n = 19) 14 (64.1%) 22.4 (4.7) 41.9 (17.7) 75.4 (72.6) 385.2 (73.4) 23.4 (32.5) 36.2 (37.7) 87.5 (10.2) 2.2 (1.2) 51.3 (9.4) 25.3 (10.9) 21.1 (6.0) 89.2 (48.6) 16.1 (6.1) 1.7 (1.3)
Lifetime (recovered) PTSD (n = 41) 29 (70.7%) 24.3 (5.1) 12.9 (8.6) 11.0 (13.9) 388.1 (70.5) 34.6 (41.3) 20.5 (13.9) 86.5 (11.6) 2.3 (1.8) 53.0 (6.0) 24.0 (7.7) 20.9 (6.2) 80.3 (30.4) 14.5 (5.6) 2.3 (2.0)
Trauma No PTSD (n = 41) 21 (49.2%) 22.9 (4.6) 6.6 (7.5) NA 368.4 (77.5) a 35.5 (54.3) 26.8 (31.9) 86.3 (11.1) 2.5 (2.0) 49.9 (7.9) a 25.0 (10.0) 22.6 (5.6) 74.6 (35.8) 16.9 (6.3) 2.9 (2.8)
Trauma Negative (n = 24) 11 (45.8%) 23.7 (5.8) NA NA 416.3 (76.1) a 31.9 (31.1) 28.2 (22.0) 87.0 (8.4) 2.4 (2.0) 54.3 (7.7) a 23.1(9.4) 20.0 (5.8) 73.1 (28.1) 14.1 (5.4) 2.4 (2.7)
P < 0.05 by exploratory t-tests. Values reported are mean (standard deviation) unless indicated otherwise. CAPS, Clinician Administered PTSD Scale; PTSD, posttraumatic stress disorder; REM, rapid eye movement; WASO, wake after sleep onset.
a
(see Table 1 for subgroup means). Durations were significantly greater for those with current full [t(58) = 3.84; P = 0.001] and subthreshold PTSD [t (59) = 3.24, P = 0.004] compared with those in the lifetime recovered group. Sleep Measures by Groups There was no effect of combining individuals with full versus subthreshold current PTSD in the current PTSD group or trauma exposed versus unexposed in the PTSD negative group and on the findings of no significant differences between groups by one-way ANOVA. The t-tests exploring possible differences between the subgroups were significant without correction for multiple comparisons only for trauma exposed versus trauma unexposed PTSD negatives for total sleep time [368.4 ± 77.5 versus 416.3 ± 76.1; t(63) = 2.42, P = 0.02] and percentage of N2 sleep [49.9 ± 7.9 versus 54.3 ± 7.7; t (63) = 2.15, P = 0.04] (see Table 1). REM density was the only sleep measure that differed between males and females [2.9 EMs per min of REM sleep for females, SD = 2.59 versus 1.8 for males, SD = 1.47; t(143) = 2.95; P < 0.004]. Sleep Measures and PTSD Severity and Duration Pearson correlations were significant for the (square root transformed) duration of PTSD and WASO (r = 0.32, P = 0.004) as well as the percentage (r = 0.25, P = 0.03) and segment length (r = 0.30, P = 0.007) of REM sleep in the combined current PTSD and lifetime groups (n = 80). Relationships with REM percentage (r = 0.53, P = 0.001), and REM segment length (r = 0.43, P = 0.006) but not WASO remained significant and also included a negative association of PTSD duration and REM sleep latency (r = -0.34, P = 0.03) within the current PTSD group (n = 39). The strength and significance of the associations with REM latency and REM percentage
but not REM segment length remained when the eight participants with current major depression were excluded from the analysis (see Table 2). In regression analyses, however, REM segment length (beta = 0.30, t = 2.61, P < 0.01) (as well as WASO) were significantly associated with PTSD duration with depression severity measured by the PHQ-9 included in the model (see Table 3). Inverse correlations of REM latency with PTSD severity (measured by the CAPS) in the current PTSD group were close to meeting the threshold for statistical significance (r = 0.31, P = 0.06 with major depressive episode, MDE included; r = 0.33, P = 0.07 with MDE excluded) (see Table 2). DISCUSSION The current study contributes new findings from a no-clinical population with limited representation in the sleep/PTSD literature, specifically, a minority group with high rates of exposure to traumas that most commonly relate to urban violence. Our study population is among the largest for the sleep PTSD literature and features comparable numbers of male and female participants with varying and well-characterized degrees and duration of PTSD. Other than a possible reduction in sleep time associated with trauma exposure, analyses did not detect group differences based on PTSD or trauma exposure status. None of the PSG findings reported in the sleep PTSD literature including reduced slow wave sleep,6,27 impaired sleep maintenance,7,8,18 elevated REM density,6 and patterns of fragmented REM sleep17,21–23 have been consistently found across all studies. The absence of differences by PTSD categories here could be related to the relatively low PTSD severity in our nontreatmentseeking study group, as well as the degree to which sleep was compromised in the overall study population of young adult minorities living in stressful urban environments (e.g. mean
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REM Sleep and PTSD Duration—Mellman et al.
Table 2—Relationships of wake after sleep onset and rapid eye movement measures to posttraumatic stress disorder severity and duration (Pearson correlations). All trauma exposed participants (n = 121) CAPS 0.10 0.16 -0.05 0.01
WASO REM latency REM percentage Ave. REM segment length
Current PTSD (n = 39)
PTSD Duration a (n = 80 b) 0.32 d -0.17 0.25 c 0.30 d
CAPS 0.18 0.31 0.03 0.08
Current PTSD no MDE (n = 31)
PTSD Duration 0.25 -0.34 c 0.53 d 0.43 d
CAPS 0.27 0.33 -0.16 -0.05
PTSD Duration 0.04 -0.45 c 0.48 d 0.29
Square root transformed. b 80 participants with current full or subthreshold PTSD or lifetime recovered PTSD. c P < 0.05. d P < 0.01. CAPS, Clinician Administered PTSD Scale; PTSD, posttraumatic stress disorder; REM, rapid eye movement; WASO, wake after sleep onset.
a
Table 3—Regressions – posttraumatic stress disorder duration and depression severity (Patient Health Questionnaire) on wake after sleep onset and rapid eye movement sleep measures WASO PTSD duration a PHQ-9 a
Beta 0.24 0.14
t 2.35 1.19
REM latency Sig. 0.04 0.24
Beta -0.15 0.05
t -1.19 0.41
REM percentage Sig. 0.24 0.68
Beta 0.19 0.17
t 1.56 1.42
Sig. 0.12 0.16
REM segment Beta 0.30 0.21
t 2.61 1.89
Sig. 0.01 0.06
Square root transformed. PHQ-9, Patient Health Questionnaire; PTSD, posttraumatic stress disorder; REM, rapid eye movement; WASO, wake after sleep onset.
6.4 h of total sleep, mean of 26 min of wake after falling asleep prior to the terminal awakening). As reviewed in the Introduction, the prior studies that have varied with regard to the amount and continuity of REM sleep feature a wide range of PTSD durations. Our analyses revealed significant positive relationships of REM sleep segment length and the percentage of REM sleep with the number of months participants had or continued to have PTSD symptoms. These correlations were strengthened and included a negative association with REM sleep latency, when only those with current PTSD were analyzed. The correlations between REM sleep percentage and REM sleep latency with PTSD duration remained significant after removing participants with major depression, and for REM segment length, when controlling for depression severity. Thus, our findings are consistent with prior literature where reduction or fragmentation of REM sleep has been observed in the acute aftermath of trauma exposure,17,20 and in acutely symptomatic populations within several years of the onset of PTSD,21,22 and the observations of undisrupted or increased REM sleep made in veterans approximately 20 y after combat exposure.25,26 Our new findings and those from the literature are consistent with processes where reactions to trauma among those in whom PTSD develops are suppressive or disruptive to REM sleep, whereas secondary processes over time promote REM sleep. Acute suppressive and disruptive effects of trauma exposure on REM sleep are consistent with a model of fear conditioning in stress sensitive rodents.33 That REM sleep would recover over time is consistent with observations of “rebound” that occurs following experimental REM sleep deprivation or withdrawal of REM suppressive pharmacological agents or substances.34 Adaptations of brainstem adrenergic receptors to overstimulation could be a mechanism that underlies recovery of REM
sleep over the course of PTSD. Models of sleep state regulation posit that noradrenergic (NA) deactivation is permissive to REM sleep onset, and NA stimulation is critical to terminating the REM state.35 Increased NA activity and/or sensitivity has been implicated in the general pathophysiology of PTSD36 and in hyperarousal during sleep.37,38 Theories that REM sleep can serve an adaptive role in processing trauma memories12,17 would posit that increases in REM sleep duration and consolidation over time could aid PTSD recovery. Conversely, given high rates of comorbid depression with chronic PTSD14 and the association of depression with indices of increased pressure for REM sleep,13 increasing REM sleep activity could be indicative of biological processes common to the progression of PTSD and major depression. Our observations were not accounted for by co-occurring major depression, however, and were from a population that was largely functioning despite their PTSD symptoms. Other findings of note include an exploratory observation of a possible effect of trauma on sleep duration, and between the duration of PTSD and sleep disruption as indicated by WASO. There are bidirectional possibilities for explaining the latter relationship, where impaired sleep maintenance could impede PTSD recovery and/or persisting PTSD could promote disrupted sleep. It is of note that the significant correlative relationships were with PTSD duration and with the exception of a relationship between REM sleep latency that was close to significance (P < 0.06), not with PTSD severity. It is possible that a study population with more severe PTSD represented would have exhibited such relationships. Possible inaccuracies of reporting times of PTSD onset and remission are also limitations of our study. Prospective longitudinal data under naturalistic and/or treatment conditions would more definitively elucidate the nature and significance of
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relationships between REM sleep measures and the course of PTSD. In addition to being cross-sectional, other limitations of our study include the use of participants with full and subthreshold diagnoses and reliance on a single night recording (obtained after an adaptation night) from the setting of a clinical research unit. The findings do suggest that there are time-dependent relationships of PTSD and sleep, particularly REM sleep, which likely have implications for the persistence or recovery of the disorder. We hope future investigations will examine these relationships prospectively while probing their underlying mechanisms and effect on outcomes. ACKNOWLEDGMENTS The authors acknowledge the contributions of Duaa Altee and Latesha McLaughlin for recruiting and evaluating participants and managing data, and Enkutash Alemeyhu, Edward Huntley, and Nancy Cowdin for scoring PSG records, all of whom were compensated. DISCLOSURE STATEMENT This was not an industry supported study. This research was supported by a National Heart, Lung, and Blood Institute grant R01HL087995 to Dr Mellman and a National Center for Advancing Translational Sciences grant UL1RR031975 for the Georgetown-Howard Universities Center for Clinical and Translational Science. The study was conducted at the Howard University Clinical Research Unit. The authors have indicated no financial conflicts of interest. REFERENCES
1. Green BL. Disasters and posttraumatic stress disorder. In: Davidson JRT, Foa EB, eds. Posttraumatic stress disorder DSM-IV and beyond. Washington, DC: American Psychiatric Press, 1993:75–97. 2. Neylan T, Marmar C, Metzler T, et al. Sleep disturbances in the Vietnam generation: findings from a nationally representative sample of male Vietnam veterans. Am J Psychiatry 1998;155:929–33. 3. Bryant RA, Creamer M, O’Donnell M, Silove D, McFarlane AC. Sleep disturbance immediately prior to trauma predicts subsequent psychiatric disorder. Sleep 2010;33:69–74. 4. Mellman T, David D, Kulick-Bell R, Hebding J, Nolan B. Sleep disturbance and its relationship to psychiatric morbidity following Hurricane Andrew. Am J Psychiatry 1995;152:1659–63. 5. Koren D, Arnon I, Lavie P, Klein E. Sleep complaints as early predictors of posttraumatic stress disorder: a 1-year prospective study of injured survivors of motor vehicle accidents. Am J Psychiatry 2002;159:855–7. 6. Kobayashi I, Boarts J, Delahanty D. Polysomnographically measured sleep abnormalities in PTSD: A meta-analytic review. Psychophysiology 2007;44:660–9. 7. Germain A, Hall M, Shear KM, Nofzinger E, Buysse D. Ecological study of sleep disruption in PTSD: a pilot study. Ann N Y Acad Sci 2006;1071:438–41. 8. Calhoun P, Wiley M, Dennis M, Means M, Edinger J, Beckham J. Objective evidence of sleep disturbance in women with posttraumatic stress disorder. J Traumatic Stress 2007;20: 1009–18. 9. Ross RJ, Ball WA, Sullivan KA, et al. Sleep disturbance as the hallmark of posttraumatic stress disorder. Am J Psychiatry 1989;146:697–707. 10. Foulkes WD. Dream reports from different stages of sleep. J Abnorm Soc Psychol 1969;65:14–25. 11. Fosse MJ, Fosse R, Hobson JA, Stickgold RJ. Dreaming and episodic memory: A functional dissociation? J Cogn Neurosci 2003;15:1–9. 12. Walker MP, van der Helm E. Overnight therapy? The role of sleep in emotional brain processing. Psychol Bull 2009;135:731–48. 13. Benca RM, Okawa M, Uchiyama M, et al. Sleep and mood disorders. Sleep Med Rev 1997;1:45–56.
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14. Kessler R, Sonnega A, Bromet E, Hughes M, Nelson C. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1995;52:48–60. 15. Rechtschaffen A. The psychophysiology of mental activity during sleep. In: McGuigan FJ, Shoonover RA, eds. The psychophysiology of thinking. New York: Academic Press, 1973:153–205. 16. Smith CT. Nixon MR. Nader RS. Posttraining increases in REM sleep intensity implicate REM sleep in memory processing and provide a biological marker of learning potential. Learn Mem 2004;11:714–9. 17. Mellman TA, Bustamante V, Fins AI, Pigeon WR, Nolan B. REM sleep and the early development of posttraumatic stress disorder. Am J Psychiatry 2002;159:1696–701. 18. Mellman T, Kulick-Bell R, Ashlock L, Nolan B. Sleep events among veterans with combat-related posttraumatic stress disorder. Am J Psychiatry 1995;152:110–5. 19. Woodward SH, Arsenault NJ, Michel GE, Santerre CS, Groves WK, Stewart WK: Polysomnographic characteristics of trauma-related nightmares. Sleep 2000;23(Abstract Suppl):A356–57. 20. Schlosberg A, Benjamin M. Sleep patterns in three acute combat fatigue cases. J Clin Psychiatry 1978;39:546–9. 21. Habukawa M, Uchimura N, Maeda M, Kotorii N, Maeda H. Sleep findings in young adult patients with posttraumatic stress disorder. Biol Psychiatry 2007;62:1179–82. 22. Lavie P. Hefez A. Halperin G. Enoch D. Long-term effects of traumatic war-related events on sleep. Am J Psychiatry 1979;136:175–8. 23. Breslau N, Roth T, Burduvali E, Kapke A, Schults L, Roehrs T. Sleep in lifetime posttraumatic stress disorder a community-based polysomnographic study. Arch Gen Psychiatry 2004;61:508–16. 24. Ulmer CS, Sutherland M, Edinger JD, et al. REM sleep bout duration and frequency in PTSD. Journal of Aggression, Maltreatment & Trauma. 2012; 21:67–76. 25. Hurwitz TD, Mahowald MW, Kuskowski M, Engdahl BE. Polysomnographic sleep is not clinically impaired in Vietnam combat veterans with chronic posttraumatic stress disorder. Biol Psychiatry 1998;44:1066–73. 26. Ross RJ, Ball WA, Dinges DF, et al. Rapid eye movement sleep disturbance in posttraumatic stress disorder. Biol Psychiatry 1994;35:195–202. 27. Richards A, Metzler TJ, Ruoff LM, et al. Sex differences in objective measures of sleep in post-traumatic stress disorder and healthy control subjects. J Sleep Res 2013;22:679–87. 28. Gray MJ, Litz BT, Hsu JL, Lombardo TW. Psychometric properties of the life events checklist. Assessment 2004;11:330–41. 29. Spitzer R, Kroenke K, Williams J. Validation and utility of a self-report version of PRIME-MD: the PHQ primary care study. Primary Ccare evaluation of mental disorders. Patient Health Questionnaire. JAMA 1999;282:1737–44. 30. Weathers FW, Keane TM, Davidson JRT. Clinician-administered PTSD scale: a review of the first ten years of research. Depress Anxiety 2001;13:132. 31. First M, Spitzer R, Miriam G, Williams J. Structured clinical interview for DSM-IV Axis I disorders. Washington, DC: American Psychiatric Press, Inc., 1996. 32. Iber C, Ancoli-Israel S, Chesson A, Quan S. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications. Westchester, IL: American Academy of Sleep Medicine, 2007. 33. DaSilva JK, Lei Y, Madan V, et al. Fear conditioning fragments REM sleep in stress-sensitive Wistar-Kyoto, but not Wistar, rats. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:67–73. 34. Vogel GW. A review of REM sleep deprivation. Arch Gen Psychiatry 1975;32:749. 35. Luppi P, Fort P. Neurochemistry of sleep: an overview of animal experimental work. In: Montagna P, Chokroverty S, eds. Handbook of clinical neurology. Amsterdam, Netherlands, Elsevier, 2011:173–90. 36. Southwick SM, Bremner JD, Rasmusson A, Morgan CA 3rd, Arnsten A, Charney DS. Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder. Biol Psychiatry 1999;46:1192–204. 37. Mellman T, Kumar A, Kulick-Bell R, Kumar M, Nolan B. Nocturnal/ daytime urine noradrenergic measures and sleep in combat-related PTSD. Biol Psychiatry 1995;38:174–9. 38. Raskind MA, Peterson KW, Hoff T, et al. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am J Psychiatry 2013;170:1003–10.
REM Sleep and PTSD Duration—Mellman et al.
A Relationship between REM Sleep Measures and the Duration of Posttraumatic Stress Disorder in a Young Adult Urban Minority Population Thomas A. Mellman, MD; Ihori Kobayashi, PhD; Joseph Lavela, BS; Bryonna Wilson, BS; Tyish S. Hall Brown, PhD Howard University College of Medicine Department of Psychiatry and Behavioral Sciences, Howard University, Washington, DC
Study Objective: To determine relationships of polysomnographic (PSG) measures with posttraumatic stress disorder (PTSD) in a young adult, urban African American population. Design: Cross-sectional, clinical and laboratory evaluation. Setting: Community recruitment, evaluation in the clinical research unit of an urban University hospital. Participants: Participants (n = 145) were Black, 59.3% female, with a mean age of 23.1 y (SD = 4.8). One hundred twenty-one participants (83.4%) met criteria for trauma exposure, the most common being nonsexual violence. Thirty-nine participants (26.9%) met full (n = 19) or subthreshold criteria (n = 20) for current PTSD, 41 (28.3%) had met lifetime PTSD criteria and were recovered, and 65 (45%) were negative for PTSD. Measurements and Results: Evaluations included the Clinician Administered PTSD Scale (CAPS) and 2 consecutive nights of overnight PSG. Analysis of variance did not reveal differences in measures of sleep duration and maintenance, percentage of sleep stages, and the latency to and duration of uninterrupted segments of rapid eye movement (REM) sleep by study group. There were significant relationships between the duration of PTSD and REM sleep percentage (r = 0.53, P = 0.001), REM segment length (r = 0.43, P = 0.006), and REM sleep latency (r = -0.34, P < 0.03) among those with current PTSD that persisted when removing cases with, or controlling for, depression. Conclusions: The findings are consistent with observations in the literature of fragmented and reduced REM sleep with posttraumatic stress disorder (PTSD) relatively proximate to trauma exposure and nondisrupted or increased REM sleep with chronic PTSD. Keywords: minority, polysomnography, posttraumatic stress disorder, sleep Citation: Mellman TA, Kobayashi I, Lavela J, Wilson B, Hall Brown TS. A relationship between REM sleep measures and the duration of posttraumatic stress disorder in a young adult urban minority population. SLEEP 2014;37(8):1321-1326.
INTRODUCTION Sleep disturbances, which are denoted by diagnostic criteria of trauma-related nightmares and difficulty initiating and maintaining sleep, are highly prevalent features of posttraumatic stress disorder (PTSD)1,2 and have been linked to the development of the disorder.3–5 It is therefore important to understand the nature of sleep disturbances in PTSD beyond the level of reported symptoms. Polysomnography (PSG) provides assessment of the timing, duration, and continuity of sleep states and their associated neurophysiologic activity. There has been substantial PTSD research using PSG that has lent some clarity as well as continuing controversy regarding the nature of sleep disturbances in the disorder. Overall, this body of research has provided evidence for and against objective impairment of sleep initiation, maintenance, and depth, and abnormalities related to rapid eye movement (REM) sleep. In a meta-analysis of 20 PTSD PSG studies done before 2007, there were no significant effects of PTSD for sleep latency and efficiency, and wake after sleep onset (WASO); however, participants with PTSD exhibited lighter sleep (more stage 1, less stage 3) compared with controls.6 Generalizability of the meta-analysis is limited by the preponderance of the
A commentary on this article appears in this issue on page 1281. Submitted for publication November, 2013 Submitted in final revised form January, 2014 Accepted for publication January, 2014 Address correspondence to: Thomas A. Mellman, Howard University College of Medicine, 520 W. St, NW, Washington DC 20059; Tel: 202-8067818; E-mail: [email protected].
studies (14 of 20) having featured male veteran combat populations, mostly with PTSD durations exceeding a decade. In fact, two more recent studies that featured predominantly female samples with non-military trauma did find objective differences in sleep initiation and/or maintenance; however, variance with the prior studies also may have been related to recordings done in home environments.7,8 Interest in possible abnormalities related to REM sleep in PTSD has been inspired by the occurrence of nightmares that are distinct from normal dreams in terms of their recurring nature and, to varying degrees, replicating past (traumatic) experiences.9 Dreams most commonly arise from REM sleep10 and do not normally represent unaltered memories of specific events.11 In addition, the REM sleep state provides conditions that are conducive to modification of memory networks, including their decoupling from affective arousal (which is postulated to aid emotional adaptation),12 and this process appears to be impaired in PTSD. A final rationale for examining REM sleep with PTSD is to determine the overlap or contrast with REM sleep abnormalities that have been documented for depression,13 a condition that has both common clinical features and frequent comorbidity with PTSD.14 Studies, including the aforementioned meta-analysis, have not found consistent reductions in the latency to REM sleep or increased percentages of REM sleep that characterize major depression. Kobayashi et al.6 did report increased REM density (frequency of eye movements within REM periods) with PTSD. Increased REM density has also been associated with depression,14 but also with the intensive dreaming15 and learning periods.16 In a study that uniquely obtained PSG data within 1 mo of trauma exposure, REM density was increased with trauma exposure but not with developing PTSD.17 Thus,
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the pathophysiological significance of REM density in PTSD remains unclear. Most nightmares and other symptomatic awakenings in PTSD have been found to arise from, and thereby disrupt, REM sleep.18,19 In the study from the early aftermath of trauma, the lengths of uninterrupted segments of REM sleep (REM segment length) were shorter among the injured patients developing PTSD.17 An earlier, more anecdotal report observed “severe deficiency in REM sleep” in association with acute combat fatigue.20 Findings from some21–23 but not all23–25 of the studies of established PTSD that have examined relevant indices are consistent with fragmentation or reduction of REM sleep. That such patterns have been observed in acute posttraumatic states,17,20 and in patients recruited from acute treatment episodes with a mean 15 mo duration of PTSD,21 and 2–2.5 y of combat neurosis,”22 whereas no REM sleep disruption25 and increased REM sleep percentage26 have been observed with combat-related PTSD of approximately 20 y, suggests that the duration of PTSD may influence patterns of REM sleep. Considerations of sex effects on relationships between REM sleep and PTSD were raised in a recent study of Richards et al.,27 where an increase in REM sleep percentage with PTSD was seen in females but not in males. Studies that increase the diversity of populations represented in the sleep PTSD literature and allow for examination of possible effects of PTSD duration and sex are indicated. The current study reports data from a nonclinical urban minority population with high rates of trauma exposure. With the exception of the study of Breslau et al., in which 59 of the 71 cases of PTSD had remitted,23 such groups are not represented in the sleep PTSD literature. The purpose of this report is to provide evaluation of relationships of PSG measures and PTSD that include examination of the duration of the disorder and participant sex, in a young adult urban African American population. METHODS Participants The study advertised to recruit young adult (age 18–35 y) African Americans for a study that examined associations between trauma, PTSD, sleep, and nocturnal blood pressure. The participants were recruited from the Washington, DC metropolitan area through study fliers posted in strategic community settings and through referrals from previous participants. During the initial screening, potential participants were excluded if they were found to have a body mass index ≥ 40, chronic medical conditions or psychotic disorders, bipolar disorder, severe recurrent depression, daily use of any medication, excessive use of caffeine (more than five cups of coffee per day or its equivalent), heavy smoking (more than 20 cigarettes per day) and drinking (more than 14 drinks/w in men, more than seven drinks/w in women), and regular night shift work or unusual sleep-wake schedules. Additional exclusion criteria were sleep, breathing, and movement disorders (screened through the first night PSG), current alcohol or drug abuse or dependence (screened through a structured clinical interview), and positive urine toxicology for illicit drugs. The study was approved by the
Howard University Institutional Review Board and all participants signed approved consent forms after they were given time to review and ask questions. Measures Self-Report
The Life Event Checklist (LEC) was administered during the initial meeting to obtain preliminary information regarding participants’ trauma exposure. The LEC includes a list of 16 types of potentially traumatic experiences (e.g., transportation accident, assault with a weapon, sexual assault). Participants were asked to indicate whether they had experienced or witnessed any of these events as an adult or a child and which of those experiences distressed them the most.28 The Patient Health Questionnaire (PHQ-9) was administered to obtain a continuous measure of depression severity.29 The nine question-items are based directly on the diagnostic criteria for major depressive disorder in the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition (DSM-IV) with response options ranging from “0” (not at all) to “3” (nearly every day). Interview
The Clinician Administered PTSD Scale (CAPS),30 a structured clinical interview, was used to determine lifetime and current PTSD diagnostic status and symptom severity according to the diagnostic criteria of the DSM-IV. After the most distressing potentially traumatic event (the index event) initially screened by the LEC was confirmed, the event was further assessed at the beginning of the interview to determine whether it met the diagnostic criteria for a traumatic event (Criterion A). If criteria were met, the frequency and intensity of each of 17 PTSD symptoms were rated on five-point scales ranging from 0 (Never [frequency], Not at all [intensity]) to 4 (Daily or almost daily, Extremely) for both the current period (past month) and the most symptomatic period of the participant’s life. To determine diagnostic status, a symptom was considered present when the participant reported at least the frequency rating of 1 and the intensity rating of 2 for the symptom. When a participant met criteria for two of the three DSM-IV symptom diagnostic clusters, he or she was considered to have a subthreshold PTSD diagnosis. For participants who had met full disorder criteria in the past but no longer met full or subthreshold diagnostic criteria, the time frame for when the PTSD remitted was carefully assessed. PTSD duration was determined as the number of months from the onset of PTSD symptoms (during or just following trauma exposure in all but one case where PTSD related to childhood sexual abuse was precipitated by early adult experiences) to the time of remission or the time of the assessment for those who continued to meet full or subthreshold criteria for PTSD. Current and lifetime diagnoses of mood disorders, psychotic disorders, anxiety disorders other than PTSD, substance abuse and dependence, and eating disorders were assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID).31 All CAPS and SCID interviews were conducted by trained staff members (psychology graduate students and clinical
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psychology postdoctoral fellows), and a licensed psychiatrist (TAM) reviewed all cases. Practice interviews were completed prior to data collection until the trainee and the trainer reached the 90% agreement rate on practice cases. For all of the included participants meeting criteria for current major depression, the episode was determined to be secondary in temporal onset and in severity to PTSD. Polysomnography Participants underwent two consecutive overnight PSG recordings in the Howard University Clinical Research Unit. None were shift workers or had regular nocturnal activity, and recordings were scheduled to approximate their natural bedtimes. Recordings were conducted using an Embla (Denver, Co) titanium portable unit. PSG collection included a standard electroencephalogram montage with bilateral frontal, central, and occipital leads, two electrooculograms (EOG), and chin electromyogram (EMG) with limb EMGs and respiratory monitors on the first night only. Scorers were trained by a registered PSG technician. Rules for the onset and termination of REM sleep and other American Academy of Sleep Medicine (AASM) criteria32 were emphasized during the training. Records of novice scorers were also independently scored by experienced scorers, and any discrepancies were addressed. Independent scoring required 90% concordance of epoch scoring for at least three records. Scorers were blinded to participants’ PTSD status and visually scored sleep records on a computer monitor and designated the sleep stage of each 30-sec epoch. After recording time in bed, the REM logic scoring system (Embla) calculated standard measures including sleep onset latency, total sleep time, WASO, sleep efficiency, the latency to REM sleep, and the percentages of total sleep composed of N1, N2, N3 (slow wave sleep), and REM sleep. Calculation of REM segment length used our previous criteria17 of at least two epochs of consecutive REM sleep with no more than one, 30-sec epoch of non-REM sleep interruption. Eye movements during REM sleep were also scored based on previously used criteria of EOG lead excursions of at least 25 µV within 500 milliseconds.17 REM density was calculated by dividing the number of eye movements (EMs) by minutes of REM sleep. Data Analysis Demographic data and clinical and sleep measures were compared between participants based on PTSD status by one-way analysis of variance (ANOVA) and possible differences between the study groups with current full PTSD, current subthreshold PTSD, lifetime PTSD, and PTSD negative with trauma exposure and PTSD negative without trauma exposure were explored by independent t-tests. We then examined Pearson correlations between PTSD severity and duration and the sleep measures. The square root transformation of PTSD duration was used to correct for the skewed distribution of the variable. To exclude potentially confounding roles of remission and depression on relationships between the sleep measures of interest, we also conducted analyses of just those with current (full and subthreshold) PTSD with and without those with concurrent criteria for major depression, as well as regression analyses that included depression severity as measured by the Patient Health Questionnaire (PHQ-9) as a covariate.
Screened/self-report n = 543
Invited for interview/lab n = 177
Excluded: • Tox screen + (n = 15) • Apnea (n = 6) • Other protocol violations or technical problems (n = 11)
Final sample n = 145 Figure 1—Study enrollment.
RESULTS Participants Of the 177 participants invited to the laboratory phase of the study, 15 were excluded for positive urine screenings for illicit drugs. An additional six participants (one with current PTSD, five negative for PTSD) were found to have apnea/hypopnea indices exceeding 10 events/h on the first night PSG. An additional 11 were not included because of loss to follow-up or poor quality recordings (Figure 1). The demographic, clinical and sleep measures for the remaining 145 participants are presented in Table 1. All of the final sample participants were Black with 123 self-identifying as African American, 11 African, 11 Caribbean, and 86 (59.3%) were female. Their mean age was 23.1 (standard deviation [SD] = 4.8). There were 121 participants (83.4%) who were determined by the CAPS to have experienced a criterion A trauma. The most common categories of index traumas were physical abuse and assault for 23.1% of the total participants and sexual trauma for 18.8% (27.8% of the females). Other categories for index traumas included witnessing community violence (13.4%), sudden unexpected deaths (12.2%), transportation accidents (7.3%), disasters (6.9%), and other (1.7%). Nineteen participants met full current criteria for PTSD, 20 met current subthreshold criteria (10 of whom met full PTSD criteria in the past), totaling 39 participants or 26.9% of the group with current PTSD. Forty-one participants (28.3%) had met lifetime criteria and were recovered and 65 (44.8%), including 24 who were not trauma exposed, had never met criteria for PTSD (PTSD negative). There were no significant differences in age between these major groupings. There was a trend toward different sex distributions, with 64% of those in the current PTSD group, 71% of those from the lifetime (recovered) group, and 49% of the PTSD negative group being female (chi square = 5.3, df = 2, P < 0.07). As expected, CAPS scores were highest for those with current PTSD (41.9, SD = 17.7) followed by the lifetime recovered group (12.9, SD = 8.6) and the PTSD negative group (6.6, SD = 7.5) [F(2,118) = 97.3, 118; P < 0.001]. For the current PTSD and lifetime recovered groups, the mean duration of PTSD was 35.6 mo (SD = 51.3) and for the current PTSD group alone, 64.1 mo (SD = 62.9)
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Table 1—Sleep measures by groups defined by posttraumatic stress disorder and trauma
Female, n (%) Age CAPS score (n = 120) Duration (mo) PTSD (n = 80)1 Total sleep (min) Latency (min) WASO (min) Sleep efficiency (% TIB spent asleep) N1 (% TST) N2 (% TST) N3 (% TST) REM sleep (% TST) REM latency (min) REM segment length (min) REM density (mean eye movements/ min REM sleep)
Total (n = 145) 86 (59.3%) 23.1 (4.8) 20.1(19.4) 35.6 (51.3) 385.3 (73.4) 34.1 (44.3) 26.3 (25.4) 86.5 (10.2) 2.5 (1.7) 51.9 (7.7) 24.6 (9.2) 21.1 (6.0) 79.1(34.9) 15.5 (5.9) 2.4 (2.3)
Current (subthreshold) PTSD (n = 20) 11 (55%) 21.7 (3.8) 29.3 (7.3) 47.2 (47.9) 377.5 (60.4) 42.9 (52.0) 25.4 (15.3) 85.5 (10.8) 2.4 (1.0) 51.8 (8.2) 26.2 (9.0) 19.8 (6.2) 84.1 (34.0) 16.1 (5.9) 2.3 (1.5)
Current (full) PTSD (n = 19) 14 (64.1%) 22.4 (4.7) 41.9 (17.7) 75.4 (72.6) 385.2 (73.4) 23.4 (32.5) 36.2 (37.7) 87.5 (10.2) 2.2 (1.2) 51.3 (9.4) 25.3 (10.9) 21.1 (6.0) 89.2 (48.6) 16.1 (6.1) 1.7 (1.3)
Lifetime (recovered) PTSD (n = 41) 29 (70.7%) 24.3 (5.1) 12.9 (8.6) 11.0 (13.9) 388.1 (70.5) 34.6 (41.3) 20.5 (13.9) 86.5 (11.6) 2.3 (1.8) 53.0 (6.0) 24.0 (7.7) 20.9 (6.2) 80.3 (30.4) 14.5 (5.6) 2.3 (2.0)
Trauma No PTSD (n = 41) 21 (49.2%) 22.9 (4.6) 6.6 (7.5) NA 368.4 (77.5) a 35.5 (54.3) 26.8 (31.9) 86.3 (11.1) 2.5 (2.0) 49.9 (7.9) a 25.0 (10.0) 22.6 (5.6) 74.6 (35.8) 16.9 (6.3) 2.9 (2.8)
Trauma Negative (n = 24) 11 (45.8%) 23.7 (5.8) NA NA 416.3 (76.1) a 31.9 (31.1) 28.2 (22.0) 87.0 (8.4) 2.4 (2.0) 54.3 (7.7) a 23.1(9.4) 20.0 (5.8) 73.1 (28.1) 14.1 (5.4) 2.4 (2.7)
P < 0.05 by exploratory t-tests. Values reported are mean (standard deviation) unless indicated otherwise. CAPS, Clinician Administered PTSD Scale; PTSD, posttraumatic stress disorder; REM, rapid eye movement; WASO, wake after sleep onset.
a
(see Table 1 for subgroup means). Durations were significantly greater for those with current full [t(58) = 3.84; P = 0.001] and subthreshold PTSD [t (59) = 3.24, P = 0.004] compared with those in the lifetime recovered group. Sleep Measures by Groups There was no effect of combining individuals with full versus subthreshold current PTSD in the current PTSD group or trauma exposed versus unexposed in the PTSD negative group and on the findings of no significant differences between groups by one-way ANOVA. The t-tests exploring possible differences between the subgroups were significant without correction for multiple comparisons only for trauma exposed versus trauma unexposed PTSD negatives for total sleep time [368.4 ± 77.5 versus 416.3 ± 76.1; t(63) = 2.42, P = 0.02] and percentage of N2 sleep [49.9 ± 7.9 versus 54.3 ± 7.7; t (63) = 2.15, P = 0.04] (see Table 1). REM density was the only sleep measure that differed between males and females [2.9 EMs per min of REM sleep for females, SD = 2.59 versus 1.8 for males, SD = 1.47; t(143) = 2.95; P < 0.004]. Sleep Measures and PTSD Severity and Duration Pearson correlations were significant for the (square root transformed) duration of PTSD and WASO (r = 0.32, P = 0.004) as well as the percentage (r = 0.25, P = 0.03) and segment length (r = 0.30, P = 0.007) of REM sleep in the combined current PTSD and lifetime groups (n = 80). Relationships with REM percentage (r = 0.53, P = 0.001), and REM segment length (r = 0.43, P = 0.006) but not WASO remained significant and also included a negative association of PTSD duration and REM sleep latency (r = -0.34, P = 0.03) within the current PTSD group (n = 39). The strength and significance of the associations with REM latency and REM percentage
but not REM segment length remained when the eight participants with current major depression were excluded from the analysis (see Table 2). In regression analyses, however, REM segment length (beta = 0.30, t = 2.61, P < 0.01) (as well as WASO) were significantly associated with PTSD duration with depression severity measured by the PHQ-9 included in the model (see Table 3). Inverse correlations of REM latency with PTSD severity (measured by the CAPS) in the current PTSD group were close to meeting the threshold for statistical significance (r = 0.31, P = 0.06 with major depressive episode, MDE included; r = 0.33, P = 0.07 with MDE excluded) (see Table 2). DISCUSSION The current study contributes new findings from a no-clinical population with limited representation in the sleep/PTSD literature, specifically, a minority group with high rates of exposure to traumas that most commonly relate to urban violence. Our study population is among the largest for the sleep PTSD literature and features comparable numbers of male and female participants with varying and well-characterized degrees and duration of PTSD. Other than a possible reduction in sleep time associated with trauma exposure, analyses did not detect group differences based on PTSD or trauma exposure status. None of the PSG findings reported in the sleep PTSD literature including reduced slow wave sleep,6,27 impaired sleep maintenance,7,8,18 elevated REM density,6 and patterns of fragmented REM sleep17,21–23 have been consistently found across all studies. The absence of differences by PTSD categories here could be related to the relatively low PTSD severity in our nontreatmentseeking study group, as well as the degree to which sleep was compromised in the overall study population of young adult minorities living in stressful urban environments (e.g. mean
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Table 2—Relationships of wake after sleep onset and rapid eye movement measures to posttraumatic stress disorder severity and duration (Pearson correlations). All trauma exposed participants (n = 121) CAPS 0.10 0.16 -0.05 0.01
WASO REM latency REM percentage Ave. REM segment length
Current PTSD (n = 39)
PTSD Duration a (n = 80 b) 0.32 d -0.17 0.25 c 0.30 d
CAPS 0.18 0.31 0.03 0.08
Current PTSD no MDE (n = 31)
PTSD Duration 0.25 -0.34 c 0.53 d 0.43 d
CAPS 0.27 0.33 -0.16 -0.05
PTSD Duration 0.04 -0.45 c 0.48 d 0.29
Square root transformed. b 80 participants with current full or subthreshold PTSD or lifetime recovered PTSD. c P < 0.05. d P < 0.01. CAPS, Clinician Administered PTSD Scale; PTSD, posttraumatic stress disorder; REM, rapid eye movement; WASO, wake after sleep onset.
a
Table 3—Regressions – posttraumatic stress disorder duration and depression severity (Patient Health Questionnaire) on wake after sleep onset and rapid eye movement sleep measures WASO PTSD duration a PHQ-9 a
Beta 0.24 0.14
t 2.35 1.19
REM latency Sig. 0.04 0.24
Beta -0.15 0.05
t -1.19 0.41
REM percentage Sig. 0.24 0.68
Beta 0.19 0.17
t 1.56 1.42
Sig. 0.12 0.16
REM segment Beta 0.30 0.21
t 2.61 1.89
Sig. 0.01 0.06
Square root transformed. PHQ-9, Patient Health Questionnaire; PTSD, posttraumatic stress disorder; REM, rapid eye movement; WASO, wake after sleep onset.
6.4 h of total sleep, mean of 26 min of wake after falling asleep prior to the terminal awakening). As reviewed in the Introduction, the prior studies that have varied with regard to the amount and continuity of REM sleep feature a wide range of PTSD durations. Our analyses revealed significant positive relationships of REM sleep segment length and the percentage of REM sleep with the number of months participants had or continued to have PTSD symptoms. These correlations were strengthened and included a negative association with REM sleep latency, when only those with current PTSD were analyzed. The correlations between REM sleep percentage and REM sleep latency with PTSD duration remained significant after removing participants with major depression, and for REM segment length, when controlling for depression severity. Thus, our findings are consistent with prior literature where reduction or fragmentation of REM sleep has been observed in the acute aftermath of trauma exposure,17,20 and in acutely symptomatic populations within several years of the onset of PTSD,21,22 and the observations of undisrupted or increased REM sleep made in veterans approximately 20 y after combat exposure.25,26 Our new findings and those from the literature are consistent with processes where reactions to trauma among those in whom PTSD develops are suppressive or disruptive to REM sleep, whereas secondary processes over time promote REM sleep. Acute suppressive and disruptive effects of trauma exposure on REM sleep are consistent with a model of fear conditioning in stress sensitive rodents.33 That REM sleep would recover over time is consistent with observations of “rebound” that occurs following experimental REM sleep deprivation or withdrawal of REM suppressive pharmacological agents or substances.34 Adaptations of brainstem adrenergic receptors to overstimulation could be a mechanism that underlies recovery of REM
sleep over the course of PTSD. Models of sleep state regulation posit that noradrenergic (NA) deactivation is permissive to REM sleep onset, and NA stimulation is critical to terminating the REM state.35 Increased NA activity and/or sensitivity has been implicated in the general pathophysiology of PTSD36 and in hyperarousal during sleep.37,38 Theories that REM sleep can serve an adaptive role in processing trauma memories12,17 would posit that increases in REM sleep duration and consolidation over time could aid PTSD recovery. Conversely, given high rates of comorbid depression with chronic PTSD14 and the association of depression with indices of increased pressure for REM sleep,13 increasing REM sleep activity could be indicative of biological processes common to the progression of PTSD and major depression. Our observations were not accounted for by co-occurring major depression, however, and were from a population that was largely functioning despite their PTSD symptoms. Other findings of note include an exploratory observation of a possible effect of trauma on sleep duration, and between the duration of PTSD and sleep disruption as indicated by WASO. There are bidirectional possibilities for explaining the latter relationship, where impaired sleep maintenance could impede PTSD recovery and/or persisting PTSD could promote disrupted sleep. It is of note that the significant correlative relationships were with PTSD duration and with the exception of a relationship between REM sleep latency that was close to significance (P < 0.06), not with PTSD severity. It is possible that a study population with more severe PTSD represented would have exhibited such relationships. Possible inaccuracies of reporting times of PTSD onset and remission are also limitations of our study. Prospective longitudinal data under naturalistic and/or treatment conditions would more definitively elucidate the nature and significance of
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REM Sleep and PTSD Duration—Mellman et al.
relationships between REM sleep measures and the course of PTSD. In addition to being cross-sectional, other limitations of our study include the use of participants with full and subthreshold diagnoses and reliance on a single night recording (obtained after an adaptation night) from the setting of a clinical research unit. The findings do suggest that there are time-dependent relationships of PTSD and sleep, particularly REM sleep, which likely have implications for the persistence or recovery of the disorder. We hope future investigations will examine these relationships prospectively while probing their underlying mechanisms and effect on outcomes. ACKNOWLEDGMENTS The authors acknowledge the contributions of Duaa Altee and Latesha McLaughlin for recruiting and evaluating participants and managing data, and Enkutash Alemeyhu, Edward Huntley, and Nancy Cowdin for scoring PSG records, all of whom were compensated. DISCLOSURE STATEMENT This was not an industry supported study. This research was supported by a National Heart, Lung, and Blood Institute grant R01HL087995 to Dr Mellman and a National Center for Advancing Translational Sciences grant UL1RR031975 for the Georgetown-Howard Universities Center for Clinical and Translational Science. The study was conducted at the Howard University Clinical Research Unit. The authors have indicated no financial conflicts of interest. REFERENCES
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