REM Sleep and the Early Development of Posttraumatic Stress Disorder

Patients were recruited from the level I trauma center that serves Miami-Dade County, Fla., except for the final four injured subjects, who were recruited from the level I trauma service affiliated with Dartmouth Medical School in New Hampshire after relocation of the principal investigator. A total of 104 patients who were admitted for traumatic injuries and met initial screening criteria signed consent forms for participation in the general study after receiving a full explanation of the purpose and methods of its components. The initial inclusion criteria included having memory of the traumatic incident; having reacted to the experience with fear, helplessness, or horror; and having been conscious and alert on arrival to the trauma center. Additional initial criteria were unimpaired orientation and recall, absence of postconcussive symptoms, no clinical or laboratory evidence for intoxication, absence of radiological signs of CNS injury, and not meeting criteria for a psychiatric disorder in the 6 months preceding admission to the trauma center.

Patients were recruited for polysomnographic evaluation within a month of injury, if by that time they had discontinued narcotic analgesic medication and endorsed that their pain was not significantly interfering with sleep. These subjects also had no histories or signs suggesting primary sleep pathology (e.g., hypersomnolence, obesity, loud snoring). Continuing use of oral narcotics and difficulty returning to the hospital setting (for those not eligible before discharge) were the most common reasons for not administering polysomnographic recordings to the patients who met the initial screening criteria. The final group of 21 injured, trauma-exposed subjects who underwent polysomnographic recordings had a mean age of 35.4 years (SD=9.5); the group included five women (24%), 11 Hispanics (52%), seven non-Hispanic whites (33%), and three non-Hispanic blacks (14%). Thirteen (62%) had been in motor vehicle accidents, two (10%) had been in industrial accidents, and six (29%) had gunshot wounds from assaults of an impersonal nature (e.g., robbery). Principal injuries were internal abdominal in 13 of the patients (62%) and thoracic in three (14%); three others (14%) had bone fractures, and two patients (10%) had partial limb amputations.

In order to evaluate the effects of trauma and injury on sleep in addition to associations of sleep measures with the development of PTSD, 10 healthy noninjured comparison subjects were also recruited for polysomnographic recording (three women; three Hispanics, six whites, one black; mean age=35.4 years, SD=12.0). These subjects were screened to not have significant medical problems, more than infrequent use of alcohol, more than moderate consumption of caffeine, active medication use, and a history of psychiatric episodes in the previous 12 months.

Assessments were conducted in Spanish if that was the subject’s preferred language. Initial criteria for being alert and responsive were determined by reviewing Glasgow Coma Scale (23) scores. Orientation and recall were evaluated with the Galveston Orientation and Amnesia Test (24). Psychiatric exclusion and trauma-incident psychiatric disorder criteria were determined by use of the Structured Clinical Interview for DSM-IV (SCID) (25). PTSD symptoms were rated by the Clinician-Administered PTSD Scale (26). A Spanish translation of the Clinician-Administered PTSD Scale was developed and validated by the study team. Diagnostic criteria were assigned on the basis of the presence of a symptom of at least moderate severity at the second evaluation; severity ratings were anchored to the week of the assessment (26). These interviews were all conducted by clinicians (M.D., Ph.D., or Psy.D.), with independent assessment occurring after 100% agreement at the level of diagnosis had been achieved on five consecutive evaluations. Assessments were initiated during inpatient stays as soon as patients were medically and surgically stable. The initial Clinician-Administered PTSD Scale was repeated if polysomnographic recording was delayed so that all of the initial Clinician-Administered PTSD Scale scores reported here rated symptoms for the week that led up to and included the day of the polysomnographic recording. A follow-up Clinician-Administered PTSD Scale and SCID were conducted by the same interviewer 6 weeks after the initial assessment (approximately 2 months after the trauma), at which time all patients had been discharged from the hospital.

Polysomnographic recordings were obtained on average 17.1 days (SD=8.2) after the traumatic incidents (range=3–30). Recordings were not performed until patients had discontinued narcotic analgesics and other medications affecting CNS function for at least five half-lives of the medication. The determination of pain not significantly interfering with sleep was based on a rating of less than 25 mm on a 100-mm visual-analogue scale indicating pain interfering on a continuum between “not at all” and “extremely.” When eligibility preceded discharge, recordings were conducted from patients’ hospital beds (N=10) by using a portable polysomnographic recording unit. The remaining 11 patients returned to the hospital setting and were recorded from a sleep laboratory bed within 2 to 14 days of discharge. The mean number of days from the traumatic incidents to the polysomnographic recording were similar for the groups recorded during their admissions (mean=16.3, SD=10.1) or after discharge (mean=18.2, SD=7.6). While the goal was to obtain two consecutive recordings, timing of narcotic discontinuation and discharge and injury-related constraints on transportation limited this to accomplishment with only nine of the injured subjects. In order to maintain consistency between groups, primary analyses were conducted on first-night recordings. In the subgroup of injured patients with two nights recorded, mean values for sleep latency similar to those from the first night (mean=12.9 minutes, SD=16.1) and the second night (mean=12.1 minutes, SD=15.6) and sleep duration (total sleep time) (night 1 mean=297.9 minutes, SD=82.7; night 2 mean=306.5 minutes, SD=78.4) suggested stable habituation to the sleep environment. In an attempt to create somewhat homologous conditions, most of the noninjured comparison subjects (eight of 10) had unrecorded overnight habituation to the sleep environment before polysomnographic recordings. Recordings for all subjects used two standard central and reference EEG leads, bilateral horizontal electro-oculograms, submental electromyogram, an ECG lead, finger oximetry, and respiratory strain gauge monitors.

Each 30-second epoch of the sleep recording was visually scored from a computer screen by using standard criteria (27). The four technicians who scored patients for the study had all been trained and achieved the threshold of 90% concordance for epoch staging with a criterion record. Epoch stages were entered into a computer program that calculated standard measures of sleep initiation, maintenance, and architecture. Sleep latency was defined as the time from “lights out” to the first epoch of at least 10 minutes of uninterrupted sleep. The amount of wake activity after sleep onset before the final awakening (wake during sleep) was used for the index of sleep maintenance. REMs occurring during REM sleep were identified by a previously used criterion of excursions of at least 25 μV occurring within 200 msec (28). All scorers for the study achieved correlations of r>0.90, with a criterion tabulation of the number of REMs. REM density was calculated by dividing the number of REMs by minutes of REM sleep. This calculation was made for the entire night as well as for the first period of REM sleep lasting at least 3 minutes, as both initial REM density and total REM density have been considered indices of REM “pressure” (29). REM sleep periods were determined by calculating the time from the beginning of at least two consecutive epochs of REM sleep to the last epoch of any subsequent REM sleep not separated by more than 20 minutes of non-REM sleep. Since a conventionally defined REM period can include substantial amounts of non-REM sleep, we additionally determined the duration of continuous REM sleep by calculating the time from the onset of at least 1 minute of REM sleep to the occurrence of at least two consecutive epochs (1 minute) of non-REM sleep or wake time.

Exploratory analyses were conducted to determine if there were relationships between sleep measures and location of the polysomnographic recording (inpatient bed or sleep laboratory) (grouped t tests) or time from the traumatic incident (Pearson’s product-moment correlations). Sleep measures, including the average duration of continuous REM sleep for subjects, were then compared among the injured patients who were positive and negative for PTSD symptoms at follow-up and the noninjured healthy comparison subjects by analysis of variance with post hoc testing with least-square difference set at p<0.05. Relationships of initial (concurrent) and follow-up PTSD severity and sleep measures in the combined group of injured patients were evaluated by calculation of Pearson’s correlations.

At the time of the follow-up evaluation, six of the 21 injured subjects met full criteria for PTSD. An additional four subjects met criteria for two of the three DSM-IV diagnostic clusters (all were one or two symptoms shy of the cluster C numbing and avoidance criteria) and were experiencing distress from their psychiatric symptoms. These 10 patients were grouped as positive for PTSD symptoms. This grouping provided a more balanced statistical comparison but also appears to be more effective than including only patients with full criteria for delineating subjects with and without significant trauma-related psychiatric morbidity. In an epidemiological sample, “partial” PTSD was found to be associated with levels of impairment in home and social functioning and in rates for seeking help similar to those with full PTSD (30). The mean 17-item Clinician-Administered PTSD Scale score at follow-up for our group with PTSD was 49.6 (SD=14.7), and the mean score for the injured group without significant PTSD symptoms was 13.2 (SD=9.9) (t=6.3, df=19, p<0.001). Two of the 10 patients with PTSD met criteria for major depressive disorder that had developed between the time of their polysomnographic recording and the follow-up assessment and was determined to be secondary in onset and severity to PTSD.

None of the subjects’ polysomnographic recording findings indicated the presence of a sleep-related breathing disorder.

Comparisons of sleep measures among the injured patients with and without PTSD subjects and the noninjured comparison subjects are shown in Table 1. Analyses reveal a significant difference for wake during sleep, with post hoc testing indicating more wake during sleep in the group without PTSD than in the comparison subjects. There was a main effect for initial REM density, with significantly greater activity in the group without PTSD than in the noninjured comparison subjects by post hoc testing. Significant main effects were found for the number of REM periods and the average duration of continuous REM sleep. The group members with PTSD exhibited a greater number of REM sleep periods than the group without PTSD; they also had a shorter average duration of continuous REM sleep than the group without PTSD and the noninjured comparison subjects. Mean sleep measures were similar for injured subjects recorded in the sleep laboratory versus in their hospital beds; none of the comparisons achieved significance. None of the correlations between sleep measures and time from the traumatic incident to the polysomnographic recording achieved significance except for the average duration of continuous REM sleep (r=–0.50, p<0.04). The difference for this measure between patients with and without PTSD remained significant when time from the incident was incorporated into an analysis of covariance (F=7.71, df=1, 19, p<0.01).

Correlations between PTSD severity and sleep measures for the combined injured patients with and without PTSD are listed in Table 2 and demonstrate similar relationships. The correlations between PTSD severity and the indices of sleep maintenance, architecture, and REM density were weak and not significant. Follow-up PTSD severity was significantly positively correlated with the number of REM sleep periods and negatively correlated with the average duration of continuous REM sleep. Relationships were similar but not as consistent for these sleep measures and initial (concurrent) PTSD severity.