Imaging studies of 12 veterans showed that posttraumatic stress disorder was associated with hyperactivation of the brain’s fear/arousal system that persisted from wakefulness to deep sleep.
MINNEAPOLIS—Patients with posttraumatic stress disorder (PTSD) may experience nightmares partly because of hyperactivation of the brain’s fear/arousal system during REM sleep, according to research presented at the 25th Anniversary Meeting of the Associated Professional Sleep Societies.
The arousal system is hyperactivated in patients with PTSD during wakefulness, noted Anne Germain, PhD, Associate Professor of Psychiatry at the University of Pittsburgh School of Medicine. “Now the question is, ‘Do we see the same kind of pattern in REM sleep, when nightmares are more prominent?’” she said. “The answer is ‘yes.’” She emphasized, however, that her group’s findings are very preliminary and are undergoing peer review.
Looking for Hyperactivation
PTSD is “an abnormal and persistent activity of the brain’s threat response system after exposure to a traumatic event,” Dr. Germain explained. “From a brain perspective, that means a hyperactivation of the amygdala—the fear detection center—or hypoactive or altered functioning of brain regions that are supposed to suppress the amygdala, including the prefrontal cortex or the hippocampus.”
To look for similar activation problems in patients with PTSD during REM sleep, the researchers studied 12 combat veterans—six with and six without PTSD—of Operation Enduring Freedom or Operation Iraqi Freedom. The investigators performed in-laboratory polysomnography and fluorodeoxyglucose (FDG) PET studies on these participants during wakefulness and REM sleep. For the sleep studies, the participants were injected with FDG after entering REM sleep, awakened after a 20-minute uptake period, and given PET scans. For the waking studies, they were injected with FDG while awake and asked to lie in bed during the 20-minute uptake period before the PET scans. Statistical parametric mapping was used to compare the groups’ relative regional cerebral metabolic rate of glucose (rCMRGlc) across wakefulness and REM sleep.
A Ceiling Effect
The veterans were ages 18 to 50, with a mean age of 29. An extensive intake evaluation ensured that none of them had any psychiatric comorbidities or was using any drugs. Although all participants with PTSD had nightmares and insomnia associated with PTSD, no participants had any other sleep disorder. Participants with PTSD, as well as those without the disorder, remained in the intended states—either REM sleep or wakefulness—for at least 90% of their FDG uptake periods. REM density and percentage of REM sleep were slightly higher in participants with PTSD than in those without the disorder.
The PET scans indicated that “there’s hypermetabolism in wakefulness in limbic and paralimbic regions in veterans with PTSD compared with those who do not have PTSD, and this activation actually persists during REM sleep,” Dr. Germain said. Participants with PTSD had significantly greater relative rCMRGlc than those without the disorder in large clusters of the brain—including the amygdala, orbitofrontal cortex, occipitotemporal and parahippocampal gyri, cerebellum, brainstem, precuneus, thalamus, and dorsal striatum, as well as the posterior, dorsal, anterior, and subgenual cingulate cortices—during wakefulness and REM sleep. They also had greater relative rCMRGlc in some brain regions that are more associated with reward processing than with arousal, such as the caudate, the putamen, and the medial prefrontal cortex.
A more unexpected finding was that rCMRGIc in the amygdala did not increase more from wakefulness to REM sleep in participants with PTSD than it did in participants without the disorder. According to Dr. Germain, rCMRGIc declined more from wakefulness to REM sleep in the amygdala, the posterior cingulate, the hippocampal gyrus, the hippocampus, the uncus, the thalamus, the brainstem, and the precentral gyrus among patients with PTSD than among those without the disorder.
These findings suggest “a ceiling effect, where there’s so much activity in these regions during wakefulness that there’s really no room for further increase in REM sleep among patients with PTSD,” said Dr. Germain. “There was a greater decrease in activity levels in frontal cortical regions, but that just means that they were so high from the beginning in these participants that they had more room to go down.”
Unanswered Questions
The study findings may indicate that PTSD causes changes in the waking brain that persist into REM sleep, Dr. Germain suggested, but another possibility is that the disorder causes changes in the sleeping brain that persist into wakefulness. “The directionality of these observations is not clear, and we can’t test it with this kind of design,” she said. “There’s really no evidence to discard either possibility or the possibility that both states are independently affected after trauma exposure.”
Further studies of PTSD and sleep are under way, Dr. Germain added. She said that they have larger cohorts than the current study, which will help to determine whether brain activity patterns during REM sleep correlate with PTSD severity or nightmares and whether they can be used to determine the presence of PTSD.