职业倦怠潜在生物标志物的研究进展

摘要/Abstract

摘要：

职业倦怠是影响人们工作状态及导致生活疲惫不堪的一种状态，探寻其发病机制有助于对职业倦怠进行评估、诊断及治疗，而职业倦怠的生物标志物指标对进一步阐明职业倦怠的发病机制有重要的指导意义。本文将神经内分泌指标、代谢指标、氧化及抗氧化、炎症及免疫系统在职业倦怠患者中的研究进展进行综述。现有研究已证实部分标志物可能对于职业倦怠存在预测能力，但由于研究人群及方法的不同，研究间存在一定的异质性。未来还需要针对不同压力阶段和不同人群展开大样本前瞻性研究，明确倦怠发生机制以提高倦怠症状的预防、诊断和治疗水平。

关键词: 职业倦怠, 生物标志物, 研究进展, 综述, 神经内分泌, 代谢, 氧化, 免疫指标

Abstract:

Burnout is a state that affects people's work status and leads to life exhaustion，and exploring its pathogenesis can help us assess，diagnose and treat burnout，while biomarker indicators of burnout are of great significance for further elucidating the pathogenesis of burnout. This article reviews the research progress of neuroendocrine indexes，metabolic indexes，oxidative and antioxidant，inflammation and immune system in patients with burnout. It has been demonstrated in existing studies that some of the markers may have predictive ability for burnout，but there is some heterogeneity among studies due to differences in study populations and methods. In the future，large-sample prospective studies are needed for different stress stages and different populations to clarify the mechanisms of burnout to improve the prevention，diagnosis and treatment of burnout symptoms.

Key words: Burnout, Biomarkers, Research progress, Review, Neuroendocrine, Metabolism, Oxidation, Immune indicators

中图分类号:

R181.3+1

崔雅宁, 朱帆, 韦晓潞, 王轩, 苏茜. 职业倦怠潜在生物标志物的研究进展. [J]职业与健康, 2026, 42(16): 2284-2289.

CUI Yaning, ZHU Fan, WEI Xiaolu, WANG Xuan, SU Qian. Research progress on potential biomarkers of burnout. [J]OCCUPATION AND HEALTH, 2026, 42(16): 2284-2289.

参考文献 73

[1]	MASLACH C, LEITER M P J P R J. The truth about burnout:How organizations cause personal stress and what to do about it[M]. San Francisco: Jossey-Bass,1997:1.
[2]	MASLACH C. Job burnout:New directions in research and intervention[J]. Curr Dir Psychol SCI, 2003, 12(5):189-192. DOI URL
[3]	LIU S, DUAN X, HAN P, et al. Occupational benefit perception of acute and critical care nurses:A qualitative meta-synthesis[J]. Front Public Health, 2022, 10:976146. DOI URL
[4]	WEISS E M, CANAZEI M, PERCHTOLD-STEFAN C M, et al. Different facets of creativity in employees covering Non-Clinical to clinical manifestations of burnout[J]. J Intell, 2022, 10(4):105. DOI URL
[5]	马志楠, 张雪竹. 血管性轻度认知障碍的潜在生物标志物研究进展[J]. 吉林大学学报(医学版), 2023, 49(4):1083-1091.
[6]	LUO Y, LI J, ZHANG Y, et al. The scalp prefrontal-limbic functional connectivity moderates stress-related rumination effects on stress recovery[J]. Psychophysiology, 2024, 61(3):e14462. DOI URL
[7]	MITHEN L M, WEAVER N, WALKER F R, et al. Feasibility of biomarkers to measure stress,burnout and fatigue in emergency nurses:a cross-sectional study[J]. BMJ Open, 2023, 13(8):e072668. DOI URL
[8]	ZUCCARELLA-HACKL C, PRINCIP M, HOLZGANG S A, et al. Cortisol reactivity to acute psychosocial stress in physician burnout[J]. Biomedicines, 2024, 12(2):335. DOI URL
[9]	YAMAGUCHI S, FUJITA T, KATO S, et al. Utility of salivary cortisol profile as a predictive biomarker in nurses' turnover risk:A preliminary study[J]. J Physiol Anthropol, 2024, 43(1):1. DOI
[10]	FERNANDEZ-SANCHEZ J C, PEREZ-MARMOL J M, BLASQUEZ A, et al. Association between burnout and cortisol secretion,perceived stress,and psychopathology in palliative care unit health professionals[J]. Palltat Support Care, 2018, 16(3):286-297.
[11]	OLIVÉ V, NAVINÉS R, MACíAS L, et al. Psychosocial and biological predictors of resident physician burnout[J]. Gen Hosp Psychiatry, 2022, 78:68-71. DOI URL
[12]	DENEVA T, IANAKIEV Y, KESKINOVA D. Burnout syndrome in physicians-psychological assessment and biomarker research[J]. Medicina-Lithuania, 2019, 55(5):209.
[13]	EISENACH J H, SPRUNG J, CLARK M M, et al. The psychological and physiological effects of acute occupational stress in new anesthesiology residents:A pilot trial[J]. Anesthesiology, 2014, 121(4):878-893. DOI URL
[14]	LI Z, KONG W, PARK H Y, et al. Association of hair cortisol concentration with brain-derived neurotrophic factor gene methylation:The role of sex as a moderator[J]. Stress Health, 2024, 40(4):e3401. DOI URL
[15]	MAIMON L, MILO T, MOYAL R S, et al. Timescales of human hair cortisol dynamics[J]. Iscience, 2020, 23(9):101501. DOI URL
[16]	MALKIEWICZ M A, GRZYWINSKA M, MALINOWSKI K S, et al. Effect of series of periodic limb movements in sleep on blood pressure,heart rate and high frequency heart rate variability[J]. Neurol Neurochir Pol, 2024, 58(2):167-175. DOI URL
[17]	WEKENBORG M K, HILL L K, THAYER J F, et al. The longitudinal association of reduced vagal tone with burnout[J]. Psychosom Med, 2019, 81(9):791-798. DOI PMID
[18]	PAZZAGLIA C, CUCCAGNA C, GATTO D M, et al. Modification of heart rate variability induced by focal muscle vibration in patients with severe acquired brain injury[J]. Brain Inj, 2024, 38(6):436-442. DOI PMID
[19]	TRAUNMULLER C, STEFITZ R, GAISBACHGRABNER K, et al. Psychophysiological concomitants of burnout:Evidence for different subtypes[J]. J Psychosom Res, 2019, 118:41-48. DOI URL
[20]	SHI Y, JIANG R, ZHU C, et al. High job burnout predicts low heart rate variability in the working population after a first eEpisode of acute coronary syndrome[J]. Int J Environ Res Public Health, 2021, 18(7):3431. DOI URL
[21]	LO E V, WEI Y H, HWANG B F. Association between occupational burnout and heart rate variability:A pilot study in a high-tech company in Taiwan[J]. Medicine, 2020, 99(2):e18630. DOI URL
[22]	KANTHAK M K, STALDER T, HILL L K, et al. Autonomic dysregulation in burnout and depression:evidence for the central role of exhaustion[J]. Scand J Work Environ Health, 2017, 43(5):475-484. DOI URL
[23]	CHEN T Y, KAO C W, CHENG S M, et al. Mediating effect of heart rate variability on the relationship between anxiety symptoms and blood pressure in patients with primary hypertension[J]. Appl Psychophysiol Biofeedback, 2024, 49(3):473-482. DOI
[24]	AFULANI P A, ONGERI L, KINYUA J, et al. Psychological and physiological stress and burnout among maternity providers in a rural county in Kenya:individual and situational predictors[J]. BMC Public Health, 2021, 21(1):453. DOI
[25]	ERIKSSON P S, WALLIN L. Functional consequences of stress-related suppression of adult hippocampal neurogenesis-a novel hypothesis on the neurobiology of burnout[J]. Acta NeurolScand, 2004, 110(5):275-280.
[26]	LV D, XIAO B, LIU H, et al. Enhanced NMDA receptor pathway and glutamate transmission in the hippocampal dentate gyrus mediate the spatial learning and memory impairment of obese rats[J]. Pflug Arch Eur J Phy, 2024, 476(5):821-831. DOI
[27]	SERTOZ O O, BINBAY I T, KOYLU E, et al. The role of BDNF and HPA axis in the neurobiology of burnout syndrome[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2008, 32(6):1459-1465. DOI URL
[28]	HE S C, ZHANG Y Y, ZHAN J Y, et al. Burnout and cognitive impairment:Associated with serum BDNF in a Chinese Han population[J]. Psychoneuroendocrinology, 2017, 77:236-243. DOI URL
[29]	SJÖRS DAHLMAN A, BLENNOW K, ZETTERBERG H, et al. Growth factors and neurotrophins in patients with stress-related exhaustion disorder[J]. Psychoneuroendocrinology, 2019, 109:104415. DOI URL
[30]	FERRER A, LABAD J, SALVAT-PUJOL N, et al. BDNF genetic variants and methylation:effects on cognition in major depressive disorder[J]. Transl Psychiatry, 2019, 9(1):265. DOI
[31]	MALHEIROS R T, DELGADO H O, FELBER D T, et al. Mood disorders are associated with the reduction of brain derived neurotrophic factor in the hypocampus in rats submitted to the hipercaloric diet[J]. Metab Brain Dis, 2021, 36(1):145-151. DOI PMID
[32]	BAKUSIC J, GHOSH M, POLLI A, et al. Epigenetic perspective on the role of brain-derived neurotrophic factor in burnout[J]. Transl Psychiatry, 2020, 10(1):354. DOI
[33]	GABRYELSKA A, TURKIEWICZ S, DITMER M, et al. BDNF and proBDNF serum protein levels in obstructive sleep apnea patients and their involvement in Insomnia and Depression symptoms[J]. J Clin Med, 2022, 11(23):7135. DOI URL
[34]	HE S-C, WU S, WANG C, et al. Interaction between job stress,serum BDNF level and the BDNF rs2049046 polymorphism in job burnout[J]. J Affect Disord, 2020, 266:671-677. DOI URL
[35]	LI Y, XUE T, JIN J, et al. Interaction between the BDNF gene rs16917237 polymorphism and job stress on job burnout of Chinese university teachers[J]. J Affect Dis, 2022, 309:282-288. DOI URL
[36]	JIA H, HE M, ZHANG X, et al. The relationship between job stress and job burnout moderated by BDNF rs6265 polymorphism[J]. Psychopharmacology, 2021, 238(10):2963-2971. DOI PMID
[37]	DAWE K, MONTGOMERY A, MCGEE H, et al. The effects of perceived stress on biological parameters in healthcare professionals:A systematic review[J]. J Health Psychol, 2016, 21(5):607-618. DOI URL
[38]	TSAI H J, TSOU M T. Age,Sex,and Profession difference among health care workers with burnout and metabolic syndrome in Taiwan Tertiary Hospital-A cross-section study[J]. Front Med, 2022, 9:854403. DOI URL
[39]	CHICO-BARBA G, JIMÉNEZ-LIMAS K, SÁNCHEZ-JIMÉNEZ B, et al. Burnout and Metabolic syndrome in female nurses:An observational study[J]. Int J Environ Res Public Health, 2019, 16(11):1993. DOI URL
[40]	JOHN A, BOUILLON-MINOIS J B, BAGHERI R, et al. The influence of burnout on cardiovascular disease:A systematic review and meta-analysis[J]. Front Psychiatry, 2024, 15:1326745. DOI URL
[41]	DAS MERCES M C, COSTA SANTANA A I, LUA I, et al. Metabolic syndrome among primary health care nursing professionals:A cross-sectional population-based study[J]. Int J Environ Res Public Health, 2019, 16(15):2686. DOI URL
[42]	MIAO L, NIU X, HUANG M, et al. Association between body mass index and burnout among nurses in China:a cross-sectional study[J]. BMJ Open, 2024, 14(3):e081203. DOI URL
[43]	DING L, ZHANG H, DAI C, et al. The prognostic value of the stress hyperglycemia ratio for all-cause and cardiovascular mortality in patients with diabetes or prediabetes:insights from NHANES 2005-2018[J]. Cardiovasc Diabetol, 2024, 23(1):84. DOI
[44]	ROBERTS G W, QUINN S J, VALENTINE N, et al. Relative hyperglycemia,a Marker of critical illness:Introducing the stress hyperglycemia ratio[J]. J Clin Endocrinol Metab, 2015, 100(12):4490-4497. DOI URL
[45]	DENEVA T I, IANAKIEV Y P. Evaluation of anxiety,depression,and biological markers in health professionals?with burnout[J]. Folia Med, 2021, 63(1):122-128.
[46]	TSOU M T, PAI T P, CHIANG T M, et al. Burnout and metabolic syndrome among different departments of medical center nurses in Taiwan-Cross-sectional study and biomarker research[J]. J Occup Health, 2021, 63(1):e12188. DOI URL
[47]	KANG H G, LEE S, JEONG P S, et al. Lycopene improves in vitro development of porcine embryos by reducing oxidative stress and apoptosis[J]. Antioxidants(Basel), 2021, 10(2):230.
[48]	SANDER W J, FOURIE C, SABIU S, et al. Rev Med Virol[J]. Rev Med Virol, 2022, 32(1):e2240. DOI URL
[49]	CAROCCI A, BARBAROSSA A, LEUCI R, et al. Novel Phenothiazine/Donepezil-like H、hybrids endowed with antioxidant activity for a multi-target approach to the therapy of alzheimer's disease[J]. Antioxidants(Basel), 2022, 11(9):1631.
[50]	IACOPETTA D, CATALANO A, CERAMELLA J, et al. Synthesis,anticancer and antioxidant properties of new indole and pyranoindole derivatives[J]. Bioorg Chem, 2020, 105:104440. DOI URL
[51]	CAROCCI A, ROSELLI M, BUDRIESI R, et al. Synthesis and evaluation of voltage-gated sodium channel blocking pyrroline derivatives endowed with both antiarrhythmic and antioxidant activities[J]. Chem Med Chem 2021, 16(3):578-588.
[52]	DE BELLIS M, SANARICA F, CAROCCI A, et al. Dual action of mexiletine and its pyrroline derivatives as skeletal muscle sodium channel blockers and anti-oxidant compounds:Toward novel therapeutic potential[J]. Front Pharmacol, 2018, 8:907. DOI URL
[53]	BIGANEH J, ABOLGHASEMI J, ALIMOHAMMADI I, et al. Influences of occupational burnout and personality on lipid peroxidation among nurses in Shahroud city,Iran[J]. J UOEH, 2021, 43(4):397-408. DOI URL
[54]	BAGHERI HOSSEINABADI M, KHANJANI N, EBRAHIMI M H, et al. Investigating the effects of exposure to extremely low frequency electromagnetic fields on job burnout syndrome and the severity of depression; the role of oxidative stress[J]. J Occup Health, 2020, 62(1):e12136. DOI URL
[55]	WANG Y, BRANICKY R, NOЁ A, et al. Superoxide dismutases:Dual roles in controlling ROS damage and regulating ROS signaling[J]. J Cell Biol, 2018, 217(6):1915-1928. DOI URL
[56]	LALSANGPUII F, ROKHUM S L, NGHAKLIANA F, et al. Mikania micrantha silver nanoparticles exhibit anticancer activities against human lung adenocarcinoma via caspase-mediated apoptotic cell death[J]. Artif Cell Nanomed B, 2024, 52(1):186-200.
[57]	PANAHI D, PIRPOSHTEH E A, MORADI B, et al. Effectiveness of educational intervention on reducing oxidative stress caused by occupational stress in nurses:A health promotion approach[J]. J Educ Health Promot, 2022, 11:273.
[58]	MORAGóN A C, DE LUCAS GARCÍA N, ENCARNACIóN LóPEZ FERNÁNDEZ M, et al. Antioxidant enzymes,occupational stress and burnout in workers of a prehospitalary emergency service[J]. Eur J Emerg Med, 2005, 12(3):111-115. DOI URL
[59]	CALIRI A W, TOMMASI S, BESARATINIA A. Relationships among smoking,oxidative stress,inflammation,macromolecular damage,and cancer[J]. Mutat Res Rev Mutat Res, 2021, 787:108365. DOI URL
[60]	MAHMOOD N A, SALAH F S, ABDULGHANY Z S. Evaluation of antioxidants enzymes and autophagy genes in the blood of Iraqi smoker volunteers[J]. Wiad Lek, 2023, 76(3):500-507. DOI PMID
[61]	CASADO Á, CASTELLANOS A, LóPEZ-FERNÁNDEZ M E, et al. Determination of oxidative and occupational stress in palliative care workers[J]. Clin Chem Lab Med, 2011, 49(3):471-477. DOI PMID
[62]	VIANA SILVA M, VALENTE R S, ANNES K, et al. Effect of IL-10 and TNF-α on the competence and cryosurvival of in vitro produced Bos indicus embryos[J]. Theriogenology, 2024, 215:170-176. DOI PMID
[63]	LUNDIN J I, PETERS U, HU Y, et al. Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations[J]. Epigenetics, 2024, 19(1):2333668. DOI URL
[64]	NAGAR S D, CONLEY A B, SHARMA S, et al. Comparing genetic and socioenvironmental contributions to ethnic differences in C-Reactive protein[J]. Front Genet, 2021, 12:738485. DOI URL
[65]	KALTENEGGER H C, MARQUES M D, BECKER L, et al. Prospective associations of technostress at work,burnout symptoms,hair cortisol,and chronic low-grade inflammation[J]. Brain Behav Immun, 2024, 117:320-329. DOI URL
[66]	KASEMY Z A, ABD-ELLATIF E E, ABDEL LATIF A A, et al. Prevalence of workaholism among Egyptian healthcare workers with assessment of its relation to quality of life,mental health and burnout[J]. Front Public Health, 2020, 8:581373. DOI URL
[67]	VON KANEL R, BELLINGRATH S, KUDIELKA B M. Association between burnout and circulating levels of pro-and anti-inflammatory cytokines in schoolteachers[J]. J Psychosom Res, 2008, 65(1):51-59. DOI URL
[68]	GAJEWSKI P D, BODEN S, FREUDE G, et al. Executive control,ERP and pro-inflammatory activity in emotionally exhausted middle-aged employees.Comparison between subclinical burnout and mild to moderate depression[J]. Psychoneuroendocrinology, 2017, 86:176-186. DOI URL
[69]	REIS E S, MASTELLOS D C, HAJISHENGALLIS G, et al. New insights into the immune functions of complement[J]. Nat Rev Immunol, 2019, 19(8):503-516. DOI PMID
[70]	MOMMERSTEEG P M, HEIJNEN C J, KAVELAARS A, et al. Immune and endocrine function in burnout syndrome[J]. Psychosom Med, 2006, 68(6):879-886. PMID
[71]	CUI J, REN Y H, ZHAO F J, et al. Cross-sectional study of the effects of job burnout on immune function in 105 female oncology nurses at a tertiary oncology hospital[J]. Med Sci Monit, 2021, 27:e929711.
[72]	邓长飞, 蒲杰, 熊萍, 等. 四川省托育从业人员职业倦怠状况及其影响因素研究[J]. 现代预防医学, 2024, 51(19):3507-3512.
[73]	高丽佳, 汪晖. 护士共情能力及心理资本与职业倦怠的关系[J]. 护理学杂志, 2024, 39(16):56-59,72.