Russian MedicineRussian MedicineРоссийский медицинский журнал0869-21062412-9100Eco-Vector63714110.17816/medjrf637141RLSTIFReviewsНаучные обзорыResearch ArticleSleep disturbances: from insomnia to depression. From animals to humansНарушение сна. От бессонницы к депрессии. От животных к человекуhttps://orcid.org/0009-0002-3337-90481883-6337YankovskyVladislav S.ЯнковскийВладислав Сергеевич
Russian Federation
vld.s.yan567@gmail.comhttps://orcid.org/0000-0002-6797-97227351-6661BorozdenkoDenis A.БорозденкоДенис Андреевич
Russian Federation

MD

borozdenko@phystech.eduhttps://orcid.org/0000-0001-6852-89423658-3258NegrebetskyVadim V.НегребецкийВадим Витальевич
Russian Federation

Dr. Sci. (Chemistry)

д-р хим. наук

nmr_rsmu@yahoo.comThe Russian National Research Medical University named after N.I. PirogovРоссийский национальный исследовательский медицинский университет имени Н.И. Пирогова13062025110620253132632701610202415042025Copyright ©; 2025, Eco-VectorCopyright ©; 2025, Эко-Вектор2025Eco-VectorЭко-Векторhttps://creativecommons.org/licenses/by-nc-nd/4.0/https://medjrf.com/0869-2106/article/view/637141

This review presents data on the physiology of sleep, the pathophysiological basis of sleep disturbances, and the epidemiology of these disorders. Major hypotheses concerning the development of depressive disorders are discussed, including the monoamine, inflammatory, and neuroendocrine models. Current findings from clinical studies and meta-analyses are summarized, highlighting key factors by which sleep deprivation affects human somatic and mental functions. Sleep monitoring using electroencephalography has demonstrated a common pathophysiological link between rapid eye movement sleep behavior disorder in patients with depressive disorders and sleep deprivation. The role of sleep deprivation as an experimental and controversial method for treating depressive disorders is discussed.

The main preclinical models of disease in laboratory animals—total and paradoxical sleep deprivation—are presented and classified. Behavioral patterns observed in various paradigms, such as the Morris water maze and Y-maze tests, are analyzed. Changes in gene expression during disease modeling and alterations in neurometabolites following different sleep deprivation techniques are presented. The review outlines future directions in preclinical sleep disorder research, emphasizing unexplored areas, particularly the therapeutic potential of sleep deprivation in various depression models.

В обзоре представлены данные о физиологии сна, патофизиологических основах его нарушений и об эпидемиологии данного заболевания. Рассмотрены основные гипотезы формирования депрессивных расстройств: моноаминовая, воспалительная, нейроэндокринная. Приведены актуальные данные клинических исследований и результаты метаанализов, установлены ключевые факторы влияния депривации сна на соматические и психические функции человека. По данным мониторинга сна с использованием электроэнцефалографии показана общая патофизиологическая связь нарушения быстрой фазы сна у пациентов с депрессивными расстройствами и нарушениями сна. Обсуждается роль депривации сна как одного из экспериментальных и неоднозначных методов терапии депрессивных расстройств.

Представлены и классифицированы основные доклинические модели патологии на лабораторных животных: тотальной и парадоксальной депривации сна. Проанализированы примеры поведенческих паттернов животных в различных поведенческих установках (водный лабиринт Морриса, Y-образный лабиринт). Показаны изменения экспрессии генов на фоне моделирования заболевания и изменения нейрометаболитов после использования различных методик депривации сна. Обсуждены перспективы дальнейших доклинических исследований в области патологии сна, выявлены ещё не изученные области (в частности, терапевтическое влияние депривации сна на различные модели депрессии).

sleep deprivationdepressionmodelingneuroinflammationbehavioral responsesдепривация снадепрессиямоделированиенейровоспалениеповеденческие реакцииMinistry of Health of the Russian FederationМинистерство здравоохранения Российской Федерации121051700257-3Patel AK, Reddy V, Shumway KR, Araujo JF. Physiology, sleep stages. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526132/Payne JD, Schacter DL, Propper RE, et al. The role of sleep in false memory formation. Neurobiol Learn Mem. 2009;92(3):327–334. doi: 10.1016/j.nlm.2009.03.007Rosenwasser AM, Turek FW. Neurobiology of circadian rhythm regulation. Sleep Med Clin. 2015;10(4):403–412. doi: 10.1016/j.jsmc.2015.08.003Kerkhof GA. Epidemiology of sleep and sleep disorders in The Netherlands. Sleep Med. 2017;30:229–239. doi: 10.1016/j.sleep.2016.09.015Brunner DP, Dijk DJ, Borbély AA. Repeated partial sleep deprivation progressively changes in EEG during sleep and wakefulness. Sleep. 1993;16(2):100–113. doi: 10.1093/sleep/16.2.100Perotta B, Arantes-Costa FM, Enns SC, et al. Sleepiness, sleep deprivation, quality of life, mental symptoms and perception of academic environment in medical students. BMC Med Educ. 2021;21(1):111. doi: 10.1186/s12909-021-02544-8 EDN: MZPZXOSeoane HA, Moschetto L, Orliacq F, et al. Sleep disruption in medicine students and its relationship with impaired academic performance: A systematic review and meta-analysis. Sleep Med Rev. 2020;53:101333. doi: 10.1016/j.smrv.2020.101333 EDN: GIHDJXTomaso CC, Johnson AB, Nelson TD. The effect of sleep deprivation and restriction on mood, emotion, and emotion regulation: three meta-analyses in one. Sleep. 2021;44(6):zsaa289. doi: 10.1093/sleep/zsaa289 EDN: IHZIGDKöhler CA, Freitas TH, Maes M, et al. Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand. 2017;135(5):373–387. doi: 10.1111/acps.12698Kim YK, Won E. The influence of stress on neuroinflammation and alterations in brain structure and function in major depressive disorder. Behav Brain Res. 2017;329:6–11. doi: 10.1016/j.bbr.2017.04.020Mulinari S. Monoamine theories of depression: historical impact on biomedical research. J Hist Neurosci. 2012;21(4):366–392. doi: 10.1080/0964704X.2011.623917Spencer RL, Deak T. A users guide to HPA axis research. Physiol Behav. 2017;178:43–65. doi: 10.1016/j.physbeh.2016.11.014Zajkowska Z, Gullett N, Walsh A, et al. Cortisol and development of depression in adolescence and young adulthood — a systematic review and meta-analysis. Psychoneuroendocrinology. 2022;136:105625. doi: 10.1016/j.psyneuen.2021.105625 EDN: NRVQQVLi X, Wu T, Yu Z, et al. Apocynum venetum leaf extract reverses depressive-like behaviors in chronically stressed rats by inhibiting oxidative stress and apoptosis. Biomed Pharmacother. 2018;100:394–406. doi: 10.1016/j.biopha.2018.01.137Kv A, Madhana RM, Js IC, et al. Antidepressant activity of vorinostat is associated with amelioration of oxidative stress and inflammation in a corticosterone-induced chronic stress model in mice. Behav Brain Res. 2018;344:73–84. doi: 10.1016/j.bbr.2018.02.009Roberts RE, Duong HT. The prospective association between sleep deprivation and depression among adolescents. Sleep. 2014;37(2):239–244. doi: 10.5665/sleep.3388Dong L, Xie Y, Zou X. Association between sleep duration and depression in US adults: A cross-sectional study. J Affect Disord. 2022;296:183–188. doi: 10.1016/j.jad.2021.09.075 EDN: GKCGSZCrișan CA, Milhem Z, Stretea R, et al. A narrative review on REM sleep deprivation: a promising non-pharmaceutical alternative for treating endogenous depression. J Pers Med. 2023;13(2):306. doi: 10.3390/jpm13020306 EDN: PZUDFJLandsness EC, Goldstein MR, Peterson MJ, et al. Antidepressant effects of selective slow wave sleep deprivation in major depression: a high-density EEG investigation. J Psychiatr Res. 2011;45(8):1019–1026. doi: 10.1016/j.jpsychires.2011.02.003Hu B, Liu C, Mou T, et al. Meta-analysis of sleep deprivation effects on patients with depression. Front Psychiatry. 2021;12:783091. doi: 10.3389/fpsyt.2021.783091 EDN: KYWCNTChai Y, Gehrman P, Yu M, et al. Enhanced amygdala-cingulate connectivity associates with better mood in both healthy and depressive individuals after sleep deprivation. Proc Natl Acad Sci U S A. 2023;120(26):e2214505120. doi: 10.1073/pnas.2214505120Goldschmied JR, Boland E, Palermo E, et al. Antidepressant effects of acute sleep deprivation are reduced in highly controlled environments. J Affect Disord. 2023;340:412–419. doi: 10.1016/j.jad.2023.07.116 EDN: ZOYSPVBerro LF, Santos R, Hollais AW, et al. Acute total sleep deprivation potentiates cocaine-induced hyperlocomotion in mice. Neurosci Lett. 2014;579:130–133. doi: 10.1016/j.neulet.2014.07.028Fenzl T, Romanowski CP, Flachskamm C, et al. Fully automated sleep deprivation in mice as a tool in sleep research. J Neurosci Methods. 2007;166(2):229–235. Erratum in: J Neurosci Methods. 2008;170(1):179. doi: 10.1016/j.jneumeth.2007.07.007Lopez-Rodriguez F, Kim J, Poland RE. Total sleep deprivation decreases immobility in the forced-swim test. Neuropsychopharmacology. 2004;29(6):1105–1111. doi: 10.1038/sj.npp.1300406Lemons A, Saré RM, Beebe Smith C. Chronic sleep deprivation in mouse pups by means of gentle handling. J Vis Exp. 2018;(140):58150. doi: 10.3791/58150Youngblood BD, Zhou J, Smagin GN, et al. Sleep deprivation by the «flower pot» technique and spatial reference memory. Physiol Behav. 1997;61(2):249–256. doi: 10.1016/s0031-9384(96)00363-0Han C, Li F, Ma J, et al. Distinct behavioral and brain changes after different durations of the modified multiple platform method on rats: An animal model of central fatigue. PLoS One. 2017;12(5):e0176850. doi: 10.1371/journal.pone.0176850Chanana P, Kumar A. GABA-BZD receptor modulating mechanism of panax quinquefolius against 72-h sleep deprivation induced anxiety like behavior: possible roles of oxidative stress, mitochondrial dysfunction and neuroinflammation. Front Neurosci. 2016;10:84. doi: 10.3389/fnins.2016.00084Kumar A, Singh A. Possible involvement of GABAergic mechanism in protective effect of melatonin against sleep deprivation-induced behaviour modification and oxidative damage in mice. Fundam Clin Pharmacol. 2009;23(4):439–448. doi: 10.1111/j.1472-8206.2009.00737.xChen D, Zhang Y, Wang C, et al. Modulation of hippocampal dopamine and synapse-related proteins by electroacupuncture improves memory deficit caused by sleep deprivation. Acupunct Med. 2020;38(5):343–351. doi: 10.1177/0964528420902147 EDN: KOSRRWda Silva Rocha-Lopes J, Machado RB, Suchecki D. Chronic REM sleep restriction in juvenile male rats induces anxiety-like behavior and alters monoamine systems in the amygdala and hippocampus. Mol Neurobiol. 2018;55(4):2884–2896. doi: 10.1007/s12035-017-0541-3 EDN: YEIASDJansen PR, Watanabe K, Stringer S, et al. Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways. Nat Genet. 2019;51(3):394–403. doi: 10.1038/s41588-018-0333-3 EDN: KRPIJMWang Z, Chen L, Zhang L, Wang X. Paradoxical sleep deprivation modulates depressive-like behaviors by regulating the MAOA levels in the amygdala and hippocampus. Brain Res. 2017;1664:17–24. doi: 10.1016/j.brainres.2017.03.022Rico-Rosillo MG, Vega-Robledo GB. Sleep and immune system. Rev Alerg Mex. 2018;65(2):160–170. doi: 10.29262/ram.v65i2.359Gonzalez-Castañeda RE, Galvez-Contreras AY, Martínez-Quezada CJ, et al. Sex-related effects of sleep deprivation on depressive- and anxiety-like behaviors in mice. Exp Anim. 2016;65(1):97–107. doi: 10.1538/expanim.15-0054 EDN: WUEMCT