Abstract
Sleep abnormalities, such as insomnia, nightmares, hyper-arousal, and difficulty initiating or maintaining sleep, are diagnostic criteria of posttraumatic stress disorder (PTSD). The vivid dream state, rapid eye movement (REM) sleep, has been implicated in processing emotional memories. We have hypothesized that REM sleep is maladaptive in those suffering from PTSD. However, the precise neurobiological mechanisms regulating sleep disturbances following trauma exposure are poorly understood. Using single prolonged stress (SPS), a well-validated rodent model of PTSD, we measured sleep alterations in response to stressor exposure and over a subsequent 7-day isolation period during which the PTSD-like phenotype develops. SPS resulted in acute increases in REM sleep and transition to REM sleep, and decreased waking in addition to alterations in sleep architecture. The severity of the PTSD-like phenotype was later assessed by measuring freezing levels on a fear-associated memory test. Interestingly, the change in REM sleep following SPS was significantly correlated with freezing behavior during extinction recall assessed more than a week later. Reductions in theta (4–10 Hz) and sigma (10–15 Hz) band power during transition to REM sleep also correlated with impaired fear-associated memory processing. These data reveal that changes in REM sleep, transition to REM sleep, waking, and theta and sigma power may serve as sleep biomarkers to identify individuals with increased susceptibility to PTSD following trauma exposure.
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Abbreviations
- SPS:
-
Single prolonged stress
- REM sleep:
-
Rapid eye movement sleep
- NREM sleep:
-
Non-rapid eye movement sleep
- PTSD:
-
Posttraumatic stress disorder
- EEG:
-
Electroencephalographic
- EMG:
-
Electromyographic
References
American Psychiatric Association (2013) Trauma- and stressor-related disorders. In: Diagnostic and statistical manual of mental disorders, 5th edn. doi:10.1176/appi.books.9780890425596.dsm07
Brewin CR, Andrews B, Valentine JD (2000) Meta-analysis of risk factors for posttraumatic stress disorder in trauma-exposed adults. J Consult Clin Psychol 68:748–766
Brown TH, Mellman TA, Alfano CA, Weems CF (2011) Sleep fears, sleep disturbance, and PTSD symptoms in minority youth exposed to Hurricane Katrina. J Trauma Stress 24:575–580. doi:10.1002/jts.20680
Charney DS (2004) Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress. Am J Psychiatry 161:195–216
Cohen S, Kozlovsky N, Matar MA, Kaplan Z, Zohar J, Cohen H (2012) Post-exposure sleep deprivation facilitates correctly timed interactions between glucocorticoid and adrenergic systems, which attenuate traumatic stress responses. Neuropsychopharmacology 37:2388–2404. doi:10.1038/npp.2012.94
Cowdin N, Kobayashi I, Mellman TA (2014) Theta frequency activity during rapid eye movement (REM) sleep is greater in people with resilience versus PTSD. Exp Brain Res. doi:10.1007/s00221-014-3857-5
Fogel SM, Smith CT (2011) The function of the sleep spindle: a physiological index of intelligence and a mechanism for sleep-dependent memory consolidation. Neurosci Biobehav Rev 35:1154–1165. doi:10.1016/j.neubiorev.2010.12.003
Fogel SM, Nader R, Cote KA, Smith CT (2007) Sleep spindles and learning potential. Behav Neurosci 121:1–10
Germain A (2013) Sleep disturbances as the hallmark of PTSD: where are we now? Am J Psychiatry 170:372–382. doi:10.1176/appi.ajp.2012.12040432
Greenwood BN, Thompson RS, Opp MR, Fleshner M (2014) Repeated exposure to conditioned fear stress increases anxiety and delays sleep recovery following exposure to an acute traumatic stressor. Front Psychiatry 5:146. doi:10.3389/fpsyt.2014.00146
Gross BA, Walsh CM, Turakhia AA, Booth V, Mashour GA, Poe GR (2009) Open-source logic-based automated sleep scoring software using electrophysiological recordings in rats. J Neurosci Methods 184:10–18. doi:10.1016/j.jneumeth.2009.07.009
Knox D, George SA, Fitzpatrick CJ, Rabinak CA, Maren S, Liberzon I (2012) Single prolonged stress disrupts retention of extinguished fear in rats. Learn Mem 19:43–49. doi:10.1101/lm.024356.111
Koenen KC, Amstadter AB, Nugent NR (2009) Gene–environment interaction in posttraumatic stress disorder: an update. J Trauma Stress 22:416–426. doi:10.1002/jts.20435
Levin R, Nielsen TA (2007) Disturbed dreaming, posttraumatic stress disorder, and affect distress: a review and neurocognitive model. Psychol Bull 133:482–528. doi:10.1037/0033-2909.133.3.482
Liberzon I, Krstov M, Young EA (1997) Stress–restress: effects on ACTH and fast feedback. Psychoneuroendocrinology 22:443–453
Liberzon I, Lopez JF, Flagel SB, Vazquez DM, Young EA (1999) Differential regulation of hippocampal glucocorticoid receptors mRNA and fast feedback: relevance to post-traumatic stress disorder. J Neuroendocrinol 11:11–17
Mellman TA, David D, Kulick-Bell R, Hebding J, Nolan B (1995) Sleep disturbance and its relationship to psychiatric morbidity after Hurricane Andrew. Am J Psychiatry 152:1659–1663
Mellman TA, Bustamante V, Fins AI, Pigeon WR, Nolan B (2002) REM sleep and the early development of posttraumatic stress disorder. Am J Psychiatry 159:1696–1701
Merica H, Blois R (1997) Relationship between the time courses of power in the frequency bands of human sleep EEG. Neurophysiol Clin 27:116–128. doi:10.1016/S0987-7053(97)85664-X
Milad MR, Pitman RK, Ellis CB et al (2009) Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biol Psychiatry 66:1075–1082. doi:10.1016/j.biopsych.2009.06.026
Mitchell DJ, McNaughton N, Flanagan D, Kirk IJ (2008) Frontal-midline theta from the perspective of hippocampal “theta”. Prog Neurobiol 86:156–185. doi:10.1016/j.pneurobio.2008.09.005
Pitman RK, Rasmusson AM, Koenen KC et al (2012) Biological studies of post-traumatic stress disorder. Nat Rev Neurosci 13:769–787. doi:10.1038/nrn3339
Poe GR, Walsh CM, Bjorness TE (2010) Both duration and timing of sleep are important to memory consolidation. Sleep 33:1277–1278
Ross RJ (2014) The changing REM sleep signature of posttraumatic stress disorder. Sleep 37:1281–1282. doi:10.5665/sleep.3912
Ross RJ, Ball WA, Sullivan KA, Caroff SN (1989) Sleep disturbance as the hallmark of posttraumatic stress disorder. Am J Psychiatry 146:697–707
Tamminen J, Payne JD, Stickgold R, Wamsley EJ, Gaskell MG (2010) Sleep spindle activity is associated with the integration of new memories and existing knowledge. J Neurosci 30:14356–14360. doi:10.1523/JNEUROSCI.3028-10.2010
van der Helm E, Yao J, Dutt S, Rao V, Saletin JM, Walker MP (2011) REM sleep depotentiates amygdala activity to previous emotional experiences. Curr Biol 21:2029–2032. doi:10.1016/j.cub.2011.10.052
van Liempt S (2012) PhD summary: sleep disturbances and PTSD: a perpetual circle?
van Liempt S, van Zuiden M, Westenberg H, Super A, Vermetten E (2013) Impact of impaired sleep on the development of PTSD symptoms in combat veterans: a prospective longitudinal cohort study. Depress Anxiety. doi:10.1002/da.22054
Vanderheyden WM, Poe GR, Liberzon I (2014) Trauma exposure and sleep: using a rodent model to understand sleep function in PTSD. Exp Brain Res. doi:10.1007/s00221-014-3890-4
Vanderwolf CH, Stewart DJ (1986) Joint cholinergic–serotonergic control of neocortical and hippocampal electrical activity in relation to behavior: effects of scopolamine, ditran, trifluoperazine and amphetamine. Physiol Behav 38:57–65
Walker MP (2009) The role of sleep in cognition and emotion. Ann N Y Acad Sci 1156:168–197. doi:10.1111/j.1749-6632.2009.04416.x
Walker MP (2010) Sleep, memory and emotion. Prog Brain Res 185:49–68. doi:10.1016/B978-0-444-53702-7.00004-X
Walker MP, van der Helm E (2009) Overnight therapy? The role of sleep in emotional brain processing. Psychol Bull 135:731–748. doi:10.1037/a0016570
Watts A, Gritton HJ, Sweigart J, Poe GR (2012) Antidepressant suppression of non-REM sleep spindles and REM sleep impairs hippocampus-dependent learning while augmenting striatum-dependent learning. J Neurosci 32:13411–13420. doi:10.1523/Jneurosci.0170-12.2012
Wellman LL, Yang L, Ambrozewicz MA, Machida M, Sanford LD (2013) Basolateral amygdala and the regulation of fear-conditioned changes in sleep: role of corticotropin-releasing factor. Sleep 36:471–480. doi:10.5665/sleep.2526
Yamamoto S, Morinobu S, Takei S, Fuchikami M, Matsuki A, Yamawaki S, Liberzon I (2009) Single prolonged stress: toward an animal model of posttraumatic stress disorder. Depress Anxiety 26:1110–1117. doi:10.1002/da.20629
Acknowledgments
This work was funded by NIHRO1-MH60670 (G.P.), T32HL110952-01A1 (W.V.), and the Department of Anesthesiology at the University of Michigan.
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Vanderheyden, W.M., George, S.A., Urpa, L. et al. Sleep alterations following exposure to stress predict fear-associated memory impairments in a rodent model of PTSD. Exp Brain Res 233, 2335–2346 (2015). https://doi.org/10.1007/s00221-015-4302-0
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DOI: https://doi.org/10.1007/s00221-015-4302-0