Exercise as part of anxiety coping management in the Covid-19 pandemic era


Denny Agustiningsih(1*), Rakhmat Ari Wibowo(2)

(1) Department of Physiology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta
(2) Department of Physiology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta
(*) Corresponding Author


Containment effort in the COVID-19 pandemic could disrupt circadian rhythms
which play an essential role in the development of mood and anxiety disorders.
Exercise is one of several recommendations for anxiety coping during the
COVID-19 pandemic. However, not every person has a similar response to an
exercise stimulus and gets the same optimal benefits. For the best exercise
results, we must consider individual needs and capacities, including circadian
rhythm, in determining the exercise dose. This review briefly summarizes the
exercise’ mechanism as an anxiolytic through skeletal muscle-brain crosstalk
and designing exercise program with the individual optimal dose as part of
anxiety coping management in the COVID-19 pandemic situation, considering
exercise as good stress and circadian rhythm.


anxiety; pandemic COVID-19; circadian rhythm; skeletal muscle-brain crosstalk; exercise

Full Text:



1.World Health Organization (WHO). Director-General’s opening remarks at the media briefing on COVID-19 - Mar 11, 2020. WHO Director General’s speeches. (2020). 4. https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020
2.Brooks SK, Webster RK, Smith LE, Woodland L, Wessely S, Greenberg N, et al. The psychological impact of quarantine and how to reduce it: a rapid review of the evidence. Lancet 2020; 395(10227):912-20.
3.Walker WH, Walton JC, DeVries AC, Nelson RJ. Circadian rhythm disruption and mental health. Transl Psychiatry 2020; 10(1):28.
4.Stonerock GL, Hoffman BM, Smith PJ, Blumenthal JA. Exercise as treatment for anxiety: systematic review and analysis. Ann Behav Med 2015; 49(4):542-56.
5.World Health Organization (WHO). Coping with stress during the 2019-nCoV outbreak. World Health Organization. 2019; 2019. https://www.who.int/docs/default-source/coronaviruse/coping-with-stress.pdf?sfvrsn=9845bc3a_2
6.National Center for Immunization and Respiratory Diseases (NCIRD) Division of Viral Diseases. Stress and Coping. 2020 Apr 16;1. https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/managing-stress-anxiety.html
7.Anderson E, Shivakumar G. Effects of exercise and physical activity on anxiety. Front Psychiatry 2013; 4:27.
8.Filiou MD, Sandi C. Anxiety and brain mitochondria: a bidirectional crosstalk. Trends Neurosci 2019; 42(9):573-88.
9.Steiner JL, Murphy EA, Mcclellan JL, Carmichael MD, Davis JM. Exercise training increases mitochondrial biogenesis in the brain. J Appl Physiol 2011; 111(4):1066-71.
10.de Oliveira Bristot VJ, de Bem Alves AC, Cardoso RL, da Luz Scheffer D, Aguair SA. The Role of PGC-1α/UCP2 signaling in the beneficial effects of physical exercise on the brain. Front Neurosci 2019; 13:292.
11.Szuhany KL, Smiths JAJ, Asmundson GJG, Otto MW. Exercise for mood and anxiety disorders: a review of efficacy, mechanisms, and barriers. In: Oxford Handbooks Online 2014.1-19.
12.Pedersen BK. Physical activity andmuscle-brain crosstalk. Nat Rev Endocrinol 2019; 15(7):383-92.
13.Schott EFP, Amole MC, Aue T, Balconi M, Bylsma LM, Critchley H, et al. Physiological feelings. Neurosci Biobehav Rev 2019; 103:267-304.
14.Helgadóttir B, Forsell Y, Ekblom Ö. Physical activity patterns of people affected by depressive and anxiety disorders as measured by accelerometers: a cross-sectional study. PloS One 2015; 10(1):e0115894.
15.Jazaieri H, Lee IA, Goldin PR, Gross JJ. Pre-treatment social anxiety severity moderates the impact of mindfulness-based stress reduction and aerobic exercise. Psychol Psychother 2016; 89(2):229-34.
16.Herring MP, Jacob ML, Suveg C, Dishman RK, O'Connor PJ. Feasibility of exercise training for the short-term treatment of generalized anxiety disorder: a randomized controlled trial. Psychother Psychosom 2012; 81(1):21-8.
https://doi.org/ 10.1159/000327898
17.Seo JH. Treadmill exercise alleviates stress-induced anxiety-like behaviors in rats. J Exerc Rehabil 2018; 14(5):724-30.
18.Wegner M, Helmich I, Machado S, Nardi AE, Arias-Carrion O, Budde H. Effects of exercise on anxiety and depression disorders: review of meta-analyses and neurobiological mechanisms. CNS Neurol Disord Drug Targets 2014; 13(6):1002-14.
19.Anacker C, Luna VM, Stevens GS. Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus. Nature 2018; 559(7712):98-102.
20.Revest JM, Dupret D, Koehel M, Reiter CF, Grosjean N, Piazza PV, et al. Adult hippocampal neurogenesis is involved in anxiety-related behaviors. Mol Psychiatry. 2009; 14(10):959-67.
21.Puig LS, Albeni MV, Canto C, Pillon NJ. Circadian rhythms and mitochondria: Connecting the dots. Front Genet 2018; 9:452.
22.Allen J, Tallon RR, Brymer KJ, Caruncho HJ, Kalynchuk LE. Mitochondria and mood : mitochondrial dysfunction as a key player in the manifestation of depression. Front Neurosci 2018; 12:386.
23.Smith SM, Vale WW. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin Neurosci 2006; 8(4):383-95..
24.Cocks G, Carta MG, Carrión OA, Nardi AE. Neural plasticity and neurogenesis in mental disorders. Neural Plast 2016; 2016:3738015.
25.Evans DL, Foa EB, Gur RE, Hendin H, O'Brien CP, Seligman MEP, Walsh T. (Eds.). Treating and preventing adolescent mental health disorders: What we know and what we don't know: A research agenda for improving the mental health of our youth. Oxford University Press. 2005.
26.Almokhtar AA, Jbireal JM, Azab AE. Anxiety: insights into signs, symptoms, etiology, pathophysiology, and treatment. East African Scholars J Med Sci 2019; 2(10):580-91.
27.Lapmanee S, Charoenphandhu J, Teerapornpuntakit J, Krishnamra N, Charoenphandhu N. Agomelatine, venlafaxine, and running exercise effectively prevent anxiety- and depression-like behaviors and memory impairment in restraint stressed rats. PLoS ONE 2017; 12(11):e0187671.
28.Otsuka T, Nishii A, Amemiya S, Kubota N, Nishijima T, Kita I. Effects of acute treadmill running at different intensities on activities of serotonin and corticotropin-releasing factor neurons, and anxiety-and depressive-like behaviors in rats. Behav Brain Res 2016; 298(Pt B):44-51.
29.Herring MP, Lindheimer JB, O’Connor PJ. The effect of exercise training on anxiety symptoms among patients: a systematic review. Arch Intern Med 2010; 170(4):321-31.
30.Rebar AL, Stanton R, Geard D, Short C, Duncan MJ, Vandelanotte C. A meta-meta-analysis of the effect of physical activity on depression and anxiety in non-clinical adult populations. Health Psychol Rev 2015; 9(3):366-78.
31.McDowell CP, Dishman RK, Gordon BR, Herring MP. Physical activity and anxiety: a systematic review and meta-analysis of prospective cohort studies. Am J Prev Med 2019; 57(4):545-56.
32.Chen HM, Tsai CM, Wu YC, Lin KC, Lin CC. Randomised controlled trial on the effectiveness of home-based walking exercise on anxiety, depression, and cancer-related symptoms in patients with lung cancer. Br J Cancer 2015; 112(3):438-45.
33.Aidar FJ, de Oliveira RJ, de Matos DG, Chilibeck PD, de Souza RF, Carneiro AL, et al. A randomized trial of the effects of an aquatic exercise program on depression, anxiety levels, and functional capacity of people who suffered an ischemic stroke. J Sports Med Phys Fitness 2018; 58(7-8):1171-7.
34.Dziubek W, Kowalska J, Kusztal M, Rogowski Ł, Gołębiowski T, Nikifur M, et al. The level of anxiety and depression in dialysis patients undertaking regular physical exercise training - a preliminary study. Kidney Blood Press Res 2016; 41(1):86-98.
35.Tang M, Huang H, Li S, Zhou M, Liu Z, Huang R, et al. Hippocampal proteomic changes of susceptibility and resilience to depression or anxiety in a rat model of chronic mild stress. Transl Psychiatry 2019; 9(1):260.
36.Petrik D, Lagace DC, Eisch AJ. The neurogenesis hypothesis of affective and anxiety disorders: are we mistaking the scaffolding for the building? Neuropharmacology 2012; 62(1):21-34.
37.Levone BR, Cryan JF, O'Leary OF. Role of adult hippocampal neurogenesis in stress resilience. Neurobiol Stress 2014; 1:147-55.
38.Picard M, McEwen BS. Psychological stress and mitochondria: a systematic review. Psychosom Med 2018; 80(2):141-153.
39.Hill AS, Sahay A, Hen R. Increasing adult hippocampal neurogenesis is sufficient to reduce anxiety and depression-like behaviors. Neuropsychopharmacology 2015; 40(10):2368-78.
40.Delezie J, Handschin C. Endocrine crosstalk between skeletal muscle and the brain. Front Neurol 2018; 9:698.
41.Markham A, Bains R, Franklin P, Spedding M. Changes in mitochondrial function are pivotal in neurodegenerative and psychiatric disorders: how important is BDNF? Br J Pharmacol 2014; 171(8):2206-29.
42.Broman-Fulks JJ, Abraham CM, Thomas K, Canu WH, Nieman DC. Anxiety sensitivity mediates the relationship between exercise frequency and anxiety and depression symptomology. Stress Health 2018; 34(4):500-8.
43.Agudelo LZ, Femenía T, Orhan F, Porsmyr-Palmertz M, Goiny M, Martinez-Redondo V, et al. Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. Cell 2014; 159(1):33-45.
44.Pekkala S, Wiklund PK, Hulmi JJ, Ahtiainen JP, Horttanainen M, Pöllänen E, et al. Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health? J Physiol 2013; 591(21):5393-400.
45.Martin KS, Azzolini M, Ruas JL. The kynurenine connection: how exercise shifts muscle tryptophan metabolism and affects energy homeostasis, the immune system, and the brain. Am J Physiol Cell Physiol 2020; 318(5):C818-30.
46.Raichlen DA, Foster AD, Seillier A, Giuffrida A, Gerdeman GL. Exercise-induced endocannabinoid signaling is modulated by intensity. Eur J App Physiol 2013; 113(4):869-75.
47.Rajala E. Endocannabinoids and exercise. Finland; 2015. http://urn.fi/urn:nbn:fi:uef-20150844
48.Brandt N, Dethlefsen MM, Bangsbo J, Pilegaard H. PGC-1α and exercise intensity dependent adaptations in mouse skeletal muscle. PLoS One 2017; 12(10):e0185993.
49.Silvennoinen M, Ahtiainen JP, Hulmi JJ, Pekkala S, Taipale RS, Nindl BC, et al. PGC-1 isoforms and their target genes are expressed differently in human skeletal muscle following resistance and endurance exercise. Physiol Rep 2015; 3(10):e12563.
50.Schwarz NA, McKinley-Barnard SK, Spillane MB, Andre TL, Gann JJ, Willoughby DS. Effect of resistance exercise intensity on the expression of PGC-1α isoforms and the anabolic and catabolic signaling mediators, IGF-1 and myostatin, in human skeletal muscle. Appl Physiol Nutr Metab 2016; 41(8):856-63.
51.Ruas JL, White JP, Rao RR, Kleiner S, Brannan KT, Harrison BC, et al. A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy. Cell 2012; 151(6):1319-31.
52.Aleixo IM, Alves ES, Balça MM, Rizo-Roca D, Moreira PI, Oliveira PJ, et al. Physical exercise improves brain cortex and cerebellum mitochondrial bioenergetics and alters apoptotic, dynamic and auto(mito)phagy markers. Neuroscience 2015; 301:480-95.
53.Eaton M, Granata C, Barry J, Safdar A, Bishop D, Little JP. Impact of a single bout of high-intensity interval exercise and short-term interval training on interleukin-6, FNDC5, and METRNL mRNA expression in human skeletal muscle. J Sport Health Sci 2018; 7(2):191-6.
54.Zsuga J, More CE, Erdei T, Papp C, Harsanyi S, Gesztelyi R. Blind spot for sedentarism: redefining the diseasome of physical inactivity in view of circadian system and the Irisin/BDNF axis. Front Neurol 2018; 9:818.
55.Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, et al. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab 2013; 18(5):649-59.
56.Erden Y, Tekin S, Sandal S, Onalan EE, Tektemur A, Kirbag S. Effects of central irisin administration on the uncoupling proteins in rat brain. Neurosci Lett 2016; 618:6-13.
57.Kim YK, Jeon SW. Neuroinflammation and the Immune-kynurenine pathway in anxiety disorders. Curr Neuropharmacol 2018; 16(5):574-82.
58.Rauf S, Soesatyo MH, Agustiningsih D, Partadiredja G. Moderate intensity intermittent exercise upregulates neurotrophic and neuroprotective genes expression and inhibits Purkinje cell loss in the cerebellum of ovariectomized rats. Behav Brain Res 2020; 382:112481.
59.Markham A, Cameron I, Franklin P, Spedding M. BDNF increases rat brain mitochondrial respiratory coupling at complex I, but not complex II. Eur J Neurosci 2004; 20(5):1189-96.
60.Scarante FF, Vila-Verde C, Detoni VL, Ferreira-Junior NC, Guimarães FS, Campos AC. Cannabinoid modulation of the stressed hippocampus. Front Mol Neurosci 2017; 10:411.
61.Mochcovitch MD, Deslandes AC, Freire RC, Garcia RF, Nardi AE. The effects of regular physical activity on anxiety symptoms in healthy older adults: a systematic review. Braz J Psychiatry 2016; 38(3):255-61.
62.Haj-Dahmane S, Shen RY. Modulation of the serotonin system by endocannabinoid signaling. Neuropharmacology 2011; 61(3):414-20.
63.Di Marzo V. New approaches and challenges to targeting the endocannabinoid system. Nat Rev Drug Discov2018; 17(9):623-39
64.Williams SE, Carroll D, Veldhuijzen van Zanten JJ, Ginty AT. Anxiety symptom interpretation: A potential mechanism explaining the cardiorespiratory fitness-anxiety relationship. J Affect Disord 2016; 193:151-6.
65.Riebe D, Ehrman JK, Liguori G, Magal M. ACSM’s Guidelines for exercise testing and prescription. 10th ed. Philadelphia: Wolters Kluwer; 2018. 143.
66.Gądek-Michalska A, Tadeusz J, Rachwalska P, Bugajski J. Cytokines, prostaglandins and nitric oxide in the regulation of stress-response systems. Pharmacol Rep 2013; 65(6):1655-62.
67.Leasure JL, Jones M. Forced and voluntary exercise differentially affect brain and behavior. Neuroscience 2008; 156(3):456-65.
68.Mayo Clinic. Mindfulness exercises. Healthy Lifestyle. 2018 Aug 18;1.
https://www.mayoclinic.org/healthy-lifestyle/consumer-health/in-depth/mindfulness-exercises/art-20046356#:~:text=Mindfulness is a type ofmind and help reduce stress.
69.Strickland JC, Smith MA. The anxiolytic effects of resistance exercise. Front Psychol 2014; 5:753.
70.Wolff CA, Esser KA. Exercise timing and circadian rhythms. Curr Opin Physiol 2019; 10:64-9.
71.Tahara Y, Aoyama S, Shibata S. The mammalian circadian clock and its entrainment by stress and exercise. J Physiol Sci 2017; 67(1):1-10.
72.Louchart AM, Staels B, Duez H. Skeletal muscle functions around the clock. Diabetes Obes Metab 2015; 17 Suppl 1:39-46.
73.van Moorsel D, Hansen J, Havekes B, Scheer FAJL, Jörgensen JA, Hoeks J, et al. Demonstration of a day-night rhythm in human skeletal muscle oxidative capacity. Mol Met 2016; 5(8):635-45.
74.Youngstedt SD, Elliott JA, Kripke DF. Human circadian phase-response curves for exercise. J Physiol 2019; 597(8):2253-68.
75.Kim SY, Jeon SW, Lee MY, Shin DW, Lim WJ, Shin YC, et al. The Association between physical activity and anxiety symptoms for general adult populations: an analysis of the dose-response relationship. Psychiatry Investig. 2020; 17(1):29-36.
76.Wipfli BM, Rethorst CD, Landers DM. The anxiolytic effects of exercise: a meta-analysis of randomized trials and dose-response analysis. J Sport Exerc Psychol 2008; 30(4):392-410.
77.Stubbs B, Vancampfort D, Rosenbaum S, Firth J, Cosco T, Veronese N, et al. An examination of the anxiolytic effects of exercise for people with anxiety and stress-related disorders: A meta-analysis. Psychiatry Res 2017; 249:102-108.
78.Garber CE, Blissmer B, Deschenes MR, Franklin BA, Lamonte MJ, Lee IM, et al. American College of Sports Medicine. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc 2011; 43(7):1334-59.
79.Herring MP, O'Connor PJ, Dishman RK. The effect of exercise training on anxiety symptoms among patients: a systematic review. Arch Intern Med 2010; 170(4):321-31.
80.Aylett E, Small N, Bower P. Exercise in the treatment of clinical anxiety in general practice - a systematic review and meta-analysis. BMC Health Serv Res 2018; 18(1):559.
81.Kandola A, Vancampfort D, Herring M, Rebar A, Hallgren M, Firth J, et al. Moving to beat anxiety: epidemiology and therapeutic issues with physical activity for anxiety. Curr Psychiatry Rep 2018; 20(8):63.
82.Saeed SA, Antonacci DJ, Bloch RM. Exercise, yoga, and meditation for depressive and anxiety disorders. Am Fam Physician 2010; 81(8):981-6.
83.Sharma M, Haider T. Tai chi as an alternative and complimentary therapy for anxiety: a systematic review. J Evid Based Complementary Altern Med 2015; 20(2):143-53.
84.Field T. Yoga research review. Complement Ther Clin Pract 2016; 24:145-61.

DOI: https://doi.org/10.19106/JMedSci005303202109

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