The DOI matches its Crossref record; 224 of the 230 references it cites were found in a registry or an index.
REM sleep dysregulation in depression: State of the art
Abstract
Disturbances of sleep are typical for most depressed patients and belong to the core symptoms of the disorder. Since the 1960s polysomnographic sleep research has demonstrated that besides disturbances of sleep continuity, depression is associated with altered sleep architecture, i.e., a decrease in slow wave sleep (SWS) production and disturbed rapid eye movement (REM) sleep regulation. Shortened REM latency (i.e., the interval between sleep onset and the occurrence of the first REM period), increased REM sleep duration and increased REM density (i.e., the frequency of rapid eye movements per REM period) have been considered as biological markers of depression which might predict relapse and recurrence. High risk studies including healthy relatives of patients with depression demonstrate that REM sleep alterations may precede the clinical expression of depression and may thus be useful in identifying subjects at high risk for the illness. Several models have been developed to explain REM sleep abnormalities in depression, like the cholinergic-aminergic imbalance model or chronobiologically inspired theories, which are reviewed in this overview. Moreover, REM sleep alterations have been recently considered not only as biological "scars" but as true endophenotypes of depression. This review discusses the genetic, neurochemical and neurobiological factors that have been implicated to play a role in the complex relationships between REM sleep and depression. We hypothesize on the one hand that REM sleep dysregulation in depression may be linked to a genetic predisposition/vulnerability to develop the illness; on the other hand it is conceivable that REM sleep disinhibition in itself is a part of a maladaptive stress reaction with increased allostatic load. We also discuss whether the REM sleep changes in depression may contribute themselves to the development of central symptoms of depression such as cognitive distortions including negative self-esteem and the overnight consolidation of negatively toned emotional memories.
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“Actually, the role of REM sleep in the mood regulation is somehow controversial since several studies found that this stage has a depressant effect (Palagini et al., 2013).”
From The Functional Role of Dreaming in Emotional Processes (2019) · cites this paper as Palagini et al., 2013
In the citing paper
“Depressed subjects also show reductions in slow wave (stage 3/4) sleep, increases in rapid eye movement (REM) sleep, including a shorter latency to REM initiation, a protraction of the REM sleep period, and increases in REM density (Palagini et al., 2013; Riemann et al., 2001; Tsuno et al., 2005).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Palagini et al., 2013
In the citing paper
“Depressed subjects also show reductions in slow wave (stage 3/4) sleep, increases in rapid eye movement (REM) sleep, including a shorter latency to REM initiation, a protraction of the REM sleep period, and increases in REM density (Palagini et al., 2013; Riemann et al., 2001; Tsuno et al., 2005).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Palagini et al., 2013
In the citing paper
“Depressed subjects also show reductions in slow wave (stage 3/4) sleep, increases in rapid eye movement (REM) sleep, including a shorter latency to REM initiation, a protraction of the REM sleep period, and increases in REM density (Palagini et al., 2013; Riemann et al., 2001; Tsuno et al., 2005).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Palagini et al., 2013
In the citing paper
“Depressed subjects also show reductions in slow wave (stage 3/4) sleep, increases in rapid eye movement (REM) sleep, including a shorter latency to REM initiation, a protraction of the REM sleep period, and increases in REM density (Palagini et al., 2013; Riemann et al., 2001; Tsuno et al., 2005).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Palagini et al., 2013
In the citing paper
“Depressed subjects also show reductions in slow wave (stage 3/4) sleep, increases in rapid eye movement (REM) sleep, including a shorter latency to REM initiation, a protraction of the REM sleep period, and increases in REM density (Palagini et al., 2013; Riemann et al., 2001; Tsuno et al., 2005).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Palagini et al., 2013
In the citing paper
“However, exogenously-induced inflammation using both endotoxin and IFN-α also led to a suppression of REM sleep (Mullington et al., 2000; Raison et al., 2010), which is the opposite of changes observed in depressed patients (Palagini et al., 2013; Riemann et al., 2001; Tsuno et al., 2005).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Palagini et al., 2013
In the citing paper
“and remediate one of the sleep problems influenced by inflammation (Palagini et al., 2013; Riemann et al., 2001)”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Palagini et al., 2013
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“Polysomnography (PSG) has consistently shown sleep-architecture abnormalities in depression such as shortened REM latency and increased REM density (Leitner et al. 2025) and, in meta-analysis, reduced slow-wave sleep (SWS) relative to controls (Palagini et al. 2013; Wichniak et al. 2017).”
The Sentinel Sleep Theory: Unweaving the biological function of REM sleep
Spinassi, R. (2026) · Sleep Medicine X · doi:10.1016/j.sleepx.2026.100186
Hervalpredictoren na elektroconvulsietherapie: een update
Bastijns, H., den Eynde, L. V., & Sienaert, P. A. (2026) · Tijdschrift voor Geneeskunde · doi:10.47671/tvg.82.25.087
Drugli, E. H., Lehmann, O. E., Pallesen, S., Saxvig, I. W., Waage, S., & Bjorvatn, B. (2026) · Frontiers in Sleep · doi:10.3389/frsle.2026.1806980
“Given that depression is known to alter REM sleep architecture (Cri¸san et al., 2024; Palagini et al., 2013), this may offer a plausible explanation for its association with REM-related parasomnias, though the underlying mechanisms warrant further investigation.”
Nishwa, D. E., Abbas, Z., & Lee, S. W. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1727014
“Sleep disturbances, particularly insuf fi cient sleep or insomnia, are consistently linked with elevated symptoms of anxiety (13, 14).”
Furukawa, S., Horigome, T., Shiga, K., Fujioka, M., Kobayashi, N., Uchida, H., & Kishimoto, T. (2026) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2026.152719
Peltz, J. S., Rogge, R. D., & Zeitzer, J. M. (2026) · Journal of Sleep Research · doi:10.1111/jsr.70373
Yang, X., Gao, T. Y., Wang, S. Y., Hu, L., Huang, F., Cui, W., & Zhang, L. (2026) · Journal of Clinical Anesthesia · doi:10.1016/j.jclinane.2026.112246
Shaw, V., Ngo, Q. C., Pah, N. D., Khandoker, A. H., Mahapatra, P. K., Pankaj, D., & Kumar, D. K. (2026) · Sleep Science and Practice · doi:10.1186/s41606-026-00179-6
“OSA disrupts Deep-Sleep through frequent arousals and oxygen desaturation (Ratnavadivel et al. 2009), whereas MDD has been linked to shortened REM latency and reduced slow-wave activity (Palagini et al. 2013; Ma et al. 2023).”
Gauthier, N., Butt, L., Kennedy, S. H., Bhat, V., Tonon, A. C., & Dunlop, K. (2026) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2026.152728
Jiang, D., Chen, W., Qin, N., Li, L., Wang, S. W., Zhang, N., Huang, J., He, J., & Wang, C. (2026) · Frontiers in Psychology · doi:10.3389/fpsyg.2026.1833260
“However, depression is also a highly heterogeneous condition, with substantial variation in emotional symptoms, sleep disturbance, physiological dysregulation, and cognitive-behavioral performance (Palagini et al., 2013; Kreppke et al., 2026).”
Generalized Camera-Based Contactless Seq2Seq Sleep Staging
Xia, M., Wang, Q., Huang, D., Cheng, H., Peifen, C., Zi, M., & Wang, W. (2026) · IEEE Internet of Things Journal · doi:10.1109/jiot.2026.3706945
“For example, deep sleep declines markedly with age [19], females enjoy longer deep sleep than males [18], and certain neurological conditions can also disturb the REM regulation [41].”
Rao, J. K., Emani, L. S., Padhi, S., Sharafkhaneh, A., Nami, M., & Rao, K. S. J. (2026) · Progress in brain research · doi:10.1016/bs.pbr.2026.07.002
Lee, H., Jang, M., Jung, T., Byeon, J., Yoon, S., & Lee, H. (2026) · Journal of Affective Disorders · doi:10.1016/j.jad.2026.122270
Che, X., Chai, S., Zhao, D., Wang, W., & Zhou, C. (2026) · Psychological Medicine · doi:10.1017/s0033291726105182
“Moreover, sleep alterations have been recently conceptualized as biological ‘ scars ’ of depression (Palagini et al., 2013).”
Sanan, M., Yao, S., Wareesawetsuwan, N., Zhang, P., & Song, X. (2026) · World Journal of Psychiatry · doi:10.5498/wjp.v16.i8.118042
Lai, N., Wang, J., Lou, J., Miao, L., Zhou, R., Fan, X., Wang, Y., & Zhang, X. (2026) · Neuropharmacology · doi:10.1016/j.neuropharm.2026.111127
Wang, Q., Deng, M., Wang, Y., Gu, D., Zhu, W., Chen, L., Wang, J., & Luan, P. (2026) · BMC Psychiatry · doi:10.1186/s12888-026-08470-7
“REM sleep abnormalities are considered among the reproducible polysomno-graphic features of depression, and previous studies have linked REM dysregulation to altered neuroimmune and stress-response pathways [48].”
Huang, C., Tan, G., Li, J., Xu, H., & Liu, L. (2026) · Epilepsia · doi:10.1002/epi.70413
Yang, L., Wang, Y., Zhang, R., Jia, S., Wu, X., Su, Y., & Li, J. (2026) · Brain and Behavior · doi:10.1002/brb3.71693
“The significantly lower N3% observed in the SI group aligns with research linking impaired slow-wave sleep to emotion dysregulation (Palagini et al. 2013 ), poor stress recovery (Radwan et al. 2021 ), and increased vulnerability to suicidal thoughts (Goetz et al. 2001 ).”
Mirtazapine and Slow-Wave Sleep: A Focused Narrative Review of Human Polysomnographic Evidence
MS, B. P. D. M. (2026) · Cureus · doi:10.7759/cureus.114784
“…effects of mirtazapine on sleep physiology, whereas studies in depressive populations offer greater clinical relevance but require cautious interpretation, as observed changes may reflect both medication effects and possible improvement in depression-associated sleep abnormalities [21].”
Nagpal, A., Patterson, A., Ross, A., Knol, L., Shukla, S., Miller, A. B., Baker, F. C., Schmalenberger, K. M., & Eisenlohr-Moul, T. A. (2026) · SLEEP · doi:10.1093/sleep/zsag220
KADOTANI, H., 角幸頼, 乳原, 彩., Nishikawa, K., 松田, 有., OZEKI, Y., Omichi, C., Sumi, Y., Ubara, A., & Matsuda, A. (n.d.) · Institutional Repositories DataBase (IRDB)
Caiazza, C., Palagini, L., Toni, C., Maffucci, A., Sampogna, G., Riemann, D. W., & Fiorillo, A. (2026) · Sleep Medicine · doi:10.1016/j.sleep.2026.109249
Self-citationChen, L., Wang, B., Kuang, D., & Chen, L. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1926299
“…features were additionally quantified, comprising rapid-eye-movement density (the number of discrete ocular movements per minute of REM sleep) and the non-REM alpha intrusion index (the percentage of non-REM epochs containing alpha-frequency intrusion) (Palagini et al., 2013; Riemann et al., 2020).”
Zhou, W., Zhu, Z., Hong, T., Zhu, Y., Zhuang, K., Wang, D., Chen, Y., Zhang, H., Wang, Y., Li, Z., et al. (2026) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2026.08.023
Dziki, K., Kucab, E., Kula, I. K., Kołodziej, A., Kołodziej, R., Klecha, J., Lulek, S., Półchłopek, S., Szpanelewski, K., Adamiec, W., et al. (2026) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.3(51).2026.5753
Metadata
- Authors
- Palagini, L., Baglioni, C., Ciapparelli, A., Gemignani, A., & Riemann, D.
- Affiliations
- University of Pisa (IT)
- University of Freiburg (DE)
- Corresponding author
- Palagini, Laura
- Venue
- Sleep Medicine Reviews
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 17
- Issue
- 5
- Pages
- 377-390
- ISSN
- 1087-0792 (ISSN-L)
- OpenAlex
- W2022024201
- Cited by
- 513
- References
- 230
- Citations by year
- 2026: 53 · 2025: 59 · 2024: 42 · 2023: 61 · 2022: 35 · 2021: 45 · 2020: 31 · 2019: 38 · 2018: 35 · 2017: 24 · 2016: 31 · 2015: 30 · 2014: 18 · 2013: 10
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Sleep Medicine Reviews (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- REM sleep, depression, REM latency, REM density, REM sleep duration, sleep architecture, slow-wave sleep, depression biomarkers, endophenotypes, chronobiology, genetic susceptibility, allostatic load, maladaptive stress response, emotional memory consolidation, cognitive distortions, recurrence prediction
- MeSH terms
- Antidepressive Agents, Brain, Depression, Humans, Sleep Deprivation, Sleep Wake Disorders, Sleep, REM, Stress, Psychological
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