Are you feeling anxious? Did you sleep poorly last night? Sleep disruption is a recognized feature of all anxiety disorders. Here, we investigate the basic brain mechanisms underlying the anxiogenic impact of sleep loss. Additionally, we explore whether subtle, societally common reductions in sleep trigger elevated next-day anxiety. Finally, we examine what it is about sleep, physiologically, that provides such an overnight anxiety-reduction benefit. We demonstrate that the anxiogenic impact of sleep loss is linked to impaired medial prefrontal cortex activity and associated connectivity with extended limbic regions. In contrast, non-rapid eye movement (NREM) slow-wave oscillations offer an ameliorating, anxiolytic benefit on these brain networks following sleep. Of societal relevance, we establish that even modest night-to-night reductions in sleep across the population predict consequential day-to-day increases in anxiety. These findings help contribute to an emerging framework explaining the intimate link between sleep and anxiety and further highlight the prospect of non-rapid eye movement sleep as a therapeutic target for meaningfully reducing anxiety.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Infraslow closed-loop brain training for anxiety and depression (ISAD): a protocol for a randomized, double-blind, sham-controlled pilot trial in adult females with internalizing disorders
Trials Open Access 17 November 2022
Scientific Reports Open Access 26 April 2021
Scientific Reports Open Access 14 October 2020
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
The data that support the findings of this study are available from the corresponding authors upon request.
Babson, K. A., Trainor, C. D., Feldner, M. T. & Blumenthal, H. A test of the effects of acute sleep deprivation on general and specific self-reported anxiety and depressive symptoms: an experimental extension. J. Behav. Ther. Exp. Psychiatry 41, 297–303 (2010).
Pires, G. N., Bezerra, A. G., Tufik, S. & Andersen, M. L. Effects of acute sleep deprivation on state anxiety levels: a systematic review and meta-analysis. Sleep. Med. 24, 109–118 (2016).
Papadimitriou, G. N. & Linkowski, P. Sleep disturbance in anxiety disorders. Int. Rev. Psychiatry 17, 229–236 (2005).
Breslau, N., Roth, T., Rosenthal, L. & Andreski, P. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol. Psychiatry 39, 411–418 (1996).
Neckelmann, D., Mykletun, A. & Dahl, A. A. Chronic insomnia as a risk factor for developing anxiety and depression. Sleep 30, 873–880 (2007).
Kessler, R. C. et al. The global burden of mental disorders: an update from the WHO World Mental Health (WMH) surveys. Epidemiol. Psychiatr. Sci. 18, 23–33 (2009).
Mellman, T. A. Sleep and anxiety disorders. Sleep. Med. Clin. 3, 261–268 (2008).
Stein, M. B., Simmons, A. N., Feinstein, J. S. & Paulus, M. P. Increased amygdala and insula activation during emotion processing in anxiety-prone subjects. Am. J. Psychiatry 164, 318–327 (2007).
Simmons, A. N. et al. Anxiety positive subjects show altered processing in the anterior insula during anticipation of negative stimuli. Hum. Brain Mapp. 32, 1836–1846 (2011).
Etkin, A. & Wager, T. D. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am. J. Psychiatry 164, 1476–1488 (2007).
Simmons, A. et al. Anxiety vulnerability is associated with altered anterior cingulate response to an affective appraisal task. Neuroreport 19, 1033–1037 (2008).
Straube, T., Schmidt, S., Weiss, T., Mentzel, H.-J. & Miltner, W. H. Dynamic activation of the anterior cingulate cortex during anticipatory anxiety. Neuroimage 44, 975–981 (2009).
Carlson, J. M., Greenberg, T., Rubin, D. & Mujica-Parodi, L. R. Feeling anxious: anticipatory amygdalo-insular response predicts the feeling of anxious anticipation. Soc. Cogn. Affect. Neurosci. 6, 74–81 (2010).
Ewbank, M. P. et al. Anxiety predicts a differential neural response to attended and unattended facial signals of anger and fear. Neuroimage 44, 1144–1151 (2009).
Xu, P. et al. Neural basis of emotional decision making in trait anxiety. J. Neurosci. 33, 18641–18653 (2013).
Simmons, A., Strigo, I., Matthews, S. C., Paulus, M. P. & Stein, M. B. Anticipation of aversive visual stimuli is associated with increased insula activation in anxiety-prone subjects. Biol. Psychiatry 60, 402–409 (2006).
Bishop, S., Duncan, J., Brett, M. & Lawrence, A. D. Prefrontal cortical function and anxiety: controlling attention to threat-related stimuli. Nat. Neurosci. 7, 184 (2004).
Kim, M. J., Gee, D. G., Loucks, R. A., Davis, F. C. & Whalen, P. J. Anxiety dissociates dorsal and ventral medial prefrontal cortex functional connectivity with the amygdala at rest. Cereb. Cortex 21, 1667–1673 (2010).
Prater, K. E., Hosanagar, A., Klumpp, H., Angstadt, M. & Luan Phan, K. Aberrant amygdala–frontal cortex connectivity during perception of fearful faces and at rest in generalized social anxiety disorder. Depress. Anxiety 30, 234–241 (2013).
Campbell-Sills, L. et al. Functioning of neural systems supporting emotion regulation in anxiety-prone individuals. Neuroimage 54, 689–696 (2011).
Pezawas, L. et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat. Neurosci. 8, 828 (2005).
Forbes, E. E. et al. Objective sleep in pediatric anxiety disorders and major depressive disorder. J. Am. Acad. Child Adolesc. Psychiatry 47, 148–155 (2008).
Fuller, K. H., Waters, W. F., Binks, P. G. & Anderson, T. Generalized anxiety and sleep architecture: a polysomnographic investigation. Sleep 20, 370–376 (1997).
Arriaga, F. & Paiva, T. Clinical and EEG sleep changes in primary dysthymia and generalized anxiety: a comparison with normal controls. Neuropsychobiology 24, 109–114 (1990).
Stein, M. B., Enns, M. W. & Kryger, M. H. Sleep in nondepressed patients with panic disorder: II. Polysomnographic assessment of sleep architecture and sleep continuity. J. Affect. Disord. 28, 1–6 (1993).
Yetkin, S., Aydin, H. & Özgen, F. Polysomnography in patients with post‐traumatic stress disorder. Psychiatry Clin. Neurosci. 64, 309–317 (2010).
Horváth, A. et al. Effects of state and trait anxiety on sleep structure: a polysomnographic study in 1083 subjects. Psychiatry Res. 244, 279–283 (2016).
Sysoeva, Y. Y. & Verbitsky, E. Influence of the level of trait anxiety on sleep EEG of men and women. Hum. Physiol. 39, 655–662 (2013).
Woodward, S. H., Murburg, M. M. & Bliwise, D. L. PTSD-related hyperarousal assessed during sleep. Physiol. Behav. 70, 197–203 (2000).
Norbury, R. & Evans, S. Time to think: subjective sleep quality, trait anxiety and university start time. Psychiatry Res. 271, 214–219 (2018).
Gross, J. J. & Levenson, R. W. Emotion elicitation using films. Cogn. Emot. 9, 87–108 (1995).
Knight, R. G., Waal‐Manning, H. J. & Spears, G. F. Some norms and reliability data for the State‐Trait Anxiety Inventory and the Zung Self‐Rating Depression scale. Br. J. Clin. Psychol. 22, 245–249 (1983).
Etkin, A., Egner, T. & Kalisch, R. Emotional processing in anterior cingulate and medial prefrontal cortex. Trends Cogn. Sci. 15, 85–93 (2011).
Phillips, M. L., Drevets, W. C., Rauch, S. L. & Lane, R. Neurobiology of emotion perception I: the neural basis of normal emotion perception. Biol. Psychiatry 54, 504–514 (2003).
Hahn, A. et al. Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder. Neuroimage 56, 881–889 (2011).
Goldin, P. R., Manber, T., Hakimi, S., Canli, T. & Gross, J. J. Neural bases of social anxiety disorder: emotional reactivity and cognitive regulation during social and physical threat. Arch. Gen. Psychiatry 66, 170–180 (2009).
Etkin, A., Prater, K. E., Hoeft, F., Menon, V. & Schatzberg, A. F. Failure of anterior cingulate activation and connectivity with the amygdala during implicit regulation of emotional processing in generalized anxiety disorder. Am. J. Psychiatry 167, 545–554 (2010).
Bishop, S. J. Neurocognitive mechanisms of anxiety: an integrative account. Trends Cogn. Sci. 11, 307–316 (2007).
Åkerstedt, T., Kecklund, G. & Axelsson, J. Impaired sleep after bedtime stress and worries. Biol. Psychol. 76, 170–173 (2007).
Cropley, M., Dijk, D.-J. & Stanley, N. Job strain, work rumination, and sleep in school teachers. Eur. J. Work Organ. Psychol. 15, 181–196 (2006).
Hirschfeld, R. M. The comorbidity of major depression and anxiety disorders: recognition and management in primary care. Prim. Care Companion J. Clin. Psychiatry 3, 244 (2001).
Goldstein, A. N. & Walker, M. P. The role of sleep in emotional brain function. Annu. Rev. Clin. Psychol. 10, 679–708 (2014).
Krause, A. J. et al. The sleep-deprived human brain. Nat. Rev. Neurosci. 18, 404 (2017).
Beck, A. T., Epstein, N., Brown, G. & Steer, R. A. An inventory for measuring clinical anxiety: psychometric properties. J. Consult. Clin. Psychol. 56, 893 (1988).
Creamer, M., Foran, J. & Bell, R. The Beck Anxiety Inventory in a non-clinical sample. Behav. Res. Ther. 33, 477–485 (1995).
Motomura, Y. et al. Sleep debt elicits negative emotional reaction through diminished amygdala-anterior cingulate functional connectivity. PLoS One 8, e56578 (2013).
Minkel, J. D. et al. Sleep deprivation and stressors: evidence for elevated negative affect in response to mild stressors when sleep deprived. Emotion 12, 1015–1020 (2012).
Wu, H. et al. Effects of sleep restriction periods on serum cortisol levels in healthy men. Brain Res. Bull. 77, 241–245 (2008).
Walker, M. P. & van Der Helm, E. Overnight therapy? The role of sleep in emotional brain processing. Psychol. Bull. 135, 731 (2009).
Uhde, T. W., Cortese, B. M. & Vedeniapin, A. Anxiety and sleep problems: emerging concepts and theoretical treatment implications. Curr. Psychiatry Rep. 11, 269–276 (2009).
Shin, L. M. et al. A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder. Arch. Gen. Psychiatry 62, 273–281 (2005).
Blair, K. et al. Response to emotional expressions in generalized social phobia and generalized anxiety disorder: evidence for separate disorders. Am. J. Psychiatry 165, 1193–1202 (2008).
Lane, R. D., Reiman, E., Ahern, G. L. & Thayer, J. 21. Activity in medial prefrontal cortex correlates with vagal component of heart rate variability during emotion. Brain Cogn. 47, 97–100 (2001).
Yoo, S.-S., Gujar, N., Hu, P., Jolesz, F. A. & Walker, M. P. The human emotional brain without sleep—a prefrontal amygdala disconnect. Curr. Biol. 17, R877–R878 (2007).
Simon, E. B. et al. Losing neutrality: the neural basis of impaired emotional control without sleep. J. Neurosci. 35, 13194–13205 (2015).
Diekelmann, S. & Born, J. The memory function of sleep. Nat. Rev. Neurosci. 11, 114 (2010).
Ekman, P. E. & Davidson, R. J. The Nature of Emotion: Fundamental Questions (Oxford Univ. Press, 1994).
Kecklund, G. & Åkerstedt, T. Apprehension of the subsequent working day is associated with a low amount of slow wave sleep. Biol. Psychol. 66, 169–176 (2004).
Krystal, A. D., Edinger, J. D., Wohlgemuth, W. K. & Marsh, G. R. NREM sleep EEG frequency spectral correlates of sleep complaints in primary insomnia subtypes. Sleep 25, 626–636 (2002).
Hall, M. et al. Psychological stress is associated with heightened physiological arousal during NREM sleep in primary insomnia. Behav. Sleep Med. 5, 178–193 (2007).
Dijk, D.-J. Slow-wave sleep, diabetes, and the sympathetic nervous system. Proc. Natl Acad. Sci. USA 105, 1107–1108 (2008).
Beissner, F., Meissner, K., Bär, K.-J. & Napadow, V. The autonomic brain: an activation likelihood estimation meta-analysis for central processing of autonomic function. J. Neurosci. 33, 10503–10511 (2013).
Fan, J. et al. Spontaneous brain activity relates to autonomic arousal. J. Neurosci. 32, 11176–11186 (2012).
Chouchou, F. & Desseilles, M. Heart rate variability: a tool to explore the sleeping brain? Front. Neurosci. 8, https://doi.org/10.3389/fnins.2014.00402 (2014).
Hall, M. et al. Acute stress affects heart rate variability during sleep. Psychosom. Med. 66, 56–62 (2004).
Bierwolf, C., Struve, K., Marshall, L., Born, J. & Fehm, H. L. Slow wave sleep drives inhibition of pituitary‐adrenal secretion in humans. J. Neuroendocrinol. 9, 479–484 (1997).
Buckley, T. M. & Schatzberg, A. F. On the interactions of the hypothalamic-pituitary-adrenal (HPA) axis and sleep: normal HPA axis activity and circadian rhythm, exemplary sleep disorders. J. Clin. Endocrinol. Metab. 90, 3106–3114 (2005).
Lang, P. J. & McTeague, L. M. The anxiety disorder spectrum: fear imagery, physiological reactivity, and differential diagnosis. Anxiety Stress Coping 22, 5–25 (2009).
Craske, M. et al. Anxiety disorders. Nat. Rev. Dis. Prim. 3, 17024 (2017).
Simon, E. B. & Walker, M. P. Sleep loss causes social withdrawal and loneliness. Nat. Commun. 9, 3146 (2018).
Spielberger, C. D. Manual for the State–Trait Anxiety Inventory STAI (Form Y) (“Self-evaluation Questionnaire”) (Consulting Psychologists Press, 1983).
Hutcherson, C. et al. Attention and emotion: does rating emotion alter neural responses to amusing and sad films? Neuroimage 27, 656–668 (2005).
Kragel, P. A., Reddan, M. C., LaBar, K. S. & Wager, T. D. Emotion schemas are embedded in the human visual system. Sci. Adv. 5, eaaw4358 (2019).
Marteau, T. M. & Bekker, H. The development of a six-item short-form of the state scale of the Spielberger State–Trait Anxiety Inventory (STAI). Br. J. Clin. Psychol. 31, 301–306 (1992).
Ohayon, M. M., Carskadon, M. A., Guilleminault, C. & Vitiello, M. V. Meta-analysis of quantitative sleep parameters from childhood to old age in healthy individuals: developing normative sleep values across the human lifespan. Sleep 27, 1255–1273 (2004).
Lehnkering, H. & Siegmund, R. Influence of chronotype, season, and sex of subject on sleep behavior of young adults. Chronobiol. Int. 24, 875–888 (2007).
Åkerstedt, T. et al. Sleep duration and mortality – does weekend sleep matter? J. Sleep. Res. 28, e12712 (2019).
Watson, D., Clark, L. A. & Tellegen, A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J. Personal. Soc. Psychol. 54, 1063 (1988).
Thompson, E. R. Development and validation of an internationally reliable short-form of the positive and negative affect schedule (PANAS). J. Cross Cult Psychol. 38, 227–242 (2007).
Goldstein, A. N. et al. Tired and apprehensive: anxiety amplifies the impact of sleep loss on aversive brain anticipation. J. Neurosci. 33, 10607–10615 (2013).
Poldrack, R. A. & Mumford, J. A. Independence in ROI analysis: where is the voodoo? Soc. Cogn. Affect. Neurosci. 4, 208–213 (2009).
Rouder, J. N., Speckman, P. L., Sun, D., Morey, R. D. & Iverson, G. Bayesian t tests for accepting and rejecting the null hypothesis. Psychon. Bull. Rev. 16, 225–237 (2009).
Berset, M., Elfering, A., Lüthy, S., Lüthi, S. & Semmer, N. K. Work stressors and impaired sleep: rumination as a mediator. Stress Health 27, e71–e82 (2011).
Xu, R. Measuring explained variation in linear mixed effects models. Stat. Med. 22, 3527–3541 (2003).
Peugh, J. L. A practical guide to multilevel modeling. J. Sch. Psychol. 48, 85–112 (2010).
Mazaika, P. K., Hoeft, F., Glover, G. H. & Reiss, A. L. Methods and software for fMRI analysis of clinical subjects. Neuroimage 47, S58 (2009).
Behzadi, Y., Restom, K., Liau, J. & Liu, T. T. A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. Neuroimage 37, 90–101 (2007).
Friston, K. J. et al. Statistical parametric maps in functional imaging: a general linear approach. Hum. Brain Mapp. 2, 189–210 (1994).
Patel, R., Spreng, R. N., Shin, L. M. & Girard, T. A. Neurocircuitry models of posttraumatic stress disorder and beyond: a meta-analysis of functional neuroimaging studies. Neurosci. Biobehav. Rev. 36, 2130–2142 (2012).
Cha, J. et al. Hyper-reactive human ventral tegmental area and aberrant mesocorticolimbic connectivity in overgeneralization of fear in generalized anxiety disorder. J. Neurosci. 34, 5855–5860 (2014).
Blair, K. S. et al. Atypical modulation of medial prefrontal cortex to self-referential comments in generalized social phobia. Psychiatry Res. Neuroimaging 193, 38–45 (2011).
Burklund, L. J., Torre, J. B., Lieberman, M. D., Taylor, S. E. & Craske, M. G. Neural responses to social threat and predictors of cognitive behavioral therapy and acceptance and commitment therapy in social anxiety disorder. Psychiatry Res. Neuroimaging 261, 52–64 (2017).
Friston, K. et al. Psychophysiological and modulatory interactions in neuroimaging. Neuroimage 6, 218–229 (1997).
Rechtschaffen, A. & Kales, A. A Manual of Standardized Terminology, Techniques, and Scoring Systems for Sleep Stages of Human Subjects (Public Health Service, US Government Printing Office, 1968).
The authors thank R. Mak-McCully for valuable assistance with data analysis, and the ISEF foundation for their continuous support. This work was supported by NIH (nos. R01AG031164, R01AG054019, RF1AG054019 and R01MH093537 to M.P.W). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
The authors declare no competing interests.
Peer review information Primary handling editor: Mary Elizabeth Sutherland.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Extended Data Fig. 1 Sleep rested physiology in relation to next-day anxiety (PSG replication study).
(a), Anxiety association in relation to REM and non-REM sleep stages (left panel). Time spent in deep NREM sleep (NREM3) was associated with a significant reduction in next-day anxiety (right scatter plot). (b), Power in the Delta band (SWA, 0.8-4.6 Hz) during NREM sleep (left panel) was associated with lower morning anxiety (right scatter plot), most pronounced for posterior derivations (circled by a dashed line). Dashed grey lines denote zero crossing.
Item values for in-lab STAI-state questionnaire (mean ± SD, higher values indicate greater anxiety).
Item values for the online short STAI-state questionnaire (day 1; mean ± SD, higher values indicate greater anxiety).
Item values for Beck Anxiety Inventory (day1; mean ± SD, higher values indicate greater anxiety).
Polysomnography sleep characteristics for the sleep-rested night (Mean ± SD). WASO, wake after sleep onset; NREM, non rapid-eye-movement sleep; SWS, slow-wave sleep (SWS, NREM stages 3 and 4); REM, rapid-eye-movement sleep.
About this article
Cite this article
Ben Simon, E., Rossi, A., Harvey, A.G. et al. Overanxious and underslept. Nat Hum Behav 4, 100–110 (2020). https://doi.org/10.1038/s41562-019-0754-8
This article is cited by
Journal of Child & Adolescent Trauma (2023)
Infraslow closed-loop brain training for anxiety and depression (ISAD): a protocol for a randomized, double-blind, sham-controlled pilot trial in adult females with internalizing disorders
Affective Science (2022)
Scientific Reports (2021)
Intermittent Hypoxia Activates N-Methyl-D-Aspartate Receptors to Induce Anxiety Behaviors in a Mouse Model of Sleep-Associated Apnea
Molecular Neurobiology (2021)