Psychological stress and wound healing in humans: a systematic review and meta-analysis.

OBJECTIVE The current review aims to synthesize existing knowledge about the relationship between psychological stress and wound healing. METHODS A systematic search strategy was conducted using electronic databases to search for published articles up to the end of October 2007. The reference lists of retrieved articles were inspected for further studies and citation searches were conducted. In addition, a meta-analysis of a subset of studies was conducted to provide a quantitative estimation of the influence of stress on wound healing. RESULTS Twenty-two papers met the inclusion criteria of the systematic review and a subsample of 11 was included in a meta-analysis. The studies assessed the impact of stress on the healing of a variety of wound types in different contexts, including acute and chronic clinical wounds, experimentally created punch biopsy and blister wounds, and minor damage to the skin caused by tape stripping. Seventeen studies in the systematic review reported that stress was associated with impaired healing or dysregulation of a biomarker related to wound healing. The relationship between stress and wound healing estimated by the meta-analysis was r=-0.42 (95% CI=-0.51 to -0.32) (P<.01). CONCLUSION Attention now needs to be directed towards investigating potential moderators of the relationship, mediating mechanisms underpinning the association, as well as the demonstration of a causal link by the development of experimental interventions in healthy populations.

[1]  M. Denda,et al.  Immobilization‐induced and crowded environment‐induced stress delay barrier recovery in murine skin , 1998, The British journal of dermatology.

[2]  P. Mecray,et al.  Nutrition and wound healing. , 1955, The American journal of clinical nutrition.

[3]  J. Bouwstra,et al.  Structural investigations of human stratum corneum by small-angle X-ray scattering. , 1991, The Journal of investigative dermatology.

[4]  M. Biondi,et al.  Human psychoneuroimmunology today , 1990, Journal of clinical laboratory analysis.

[5]  T. Kamarck,et al.  A global measure of perceived stress. , 1983, Journal of health and social behavior.

[6]  J. Cacioppo,et al.  Depressive Symptoms Predict Mucosal Wound Healing , 2007, Psychosomatic medicine.

[7]  J. Fox,et al.  The measurement of stress-related immune dysfunction in psychoneuroimmunology , 1999, Neuroscience & Biobehavioral Reviews.

[8]  J. Kiecolt-Glaser,et al.  Mucosal Wound Healing Is Impaired by Examination Stress , 1998, Psychosomatic medicine.

[9]  W. Hiatt,et al.  Wound healing and functional outcomes after infrainguinal bypass with reversed saphenous vein for critical limb ischemia. , 2006, Journal of vascular surgery.

[10]  R. Poland,et al.  Urinary cortisol and catecholamines in mothers of child cancer survivors with and without PTSD , 2002, Psychoneuroendocrinology.

[11]  • Epidermis,et al.  WOUND healing. , 1959, The Medical journal of Australia.

[12]  W. G. Cochran The combination of estimates from different experiments. , 1954 .

[13]  Robert C. Lee,et al.  STANDARD QUALITY ASSESSMENT CRITERIA FOR EVALUATING PRIMARY RESEARCH PAPERS FROM A VARIETY OF FIELDS , 2004 .

[14]  Jacob Cohen,et al.  A power primer. , 1992, Psychological bulletin.

[15]  Michael W. Bridges,et al.  Optimism and rehospitalization after coronary artery bypass graft surgery. , 1999, Archives of internal medicine.

[16]  Stephanie L. Dickinson,et al.  Hostile marital interactions, proinflammatory cytokine production, and wound healing. , 2005, Archives of general psychiatry.

[17]  Jacob Cohen A Coefficient of Agreement for Nominal Scales , 1960 .

[18]  Karina W Davidson,et al.  The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology. , 2005, Journal of the American College of Cardiology.

[19]  J. R. Landis,et al.  The measurement of observer agreement for categorical data. , 1977, Biometrics.

[20]  S. Cohen,et al.  Psychological interventions and the immune system: a meta-analytic review and critique. , 2001, Health psychology : official journal of the Division of Health Psychology, American Psychological Association.

[21]  J. Aker,et al.  Can Medical Hypnosis Accelerate Post-Surgical Wound Healing? Results of a Clinical Trial , 2003, The American journal of clinical hypnosis.

[22]  P. Elias Stratum corneum defensive functions: an integrated view. , 2005, The Journal of investigative dermatology.

[23]  S. French,et al.  The effects of stress on wound healing in male tree lizards (Urosaurus ornatus). , 2006, General and comparative endocrinology.

[24]  H. Flor,et al.  Altered cortisol awakening response in posttraumatic stress disorder , 2006, Psychoneuroendocrinology.

[25]  L. Chow,et al.  Pro-inflammatory cytokine, matrix metalloproteinases and TIMP-1 are involved in wound healing after mastectomy in invasive breast cancer patients. , 2007, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[26]  H. Mathews,et al.  Issues in the Design and Implementation of Psychoneuroimmunology Research , 2002, Biological research for nursing.

[27]  Jennifer E. Graham,et al.  Stress and Wound Healing , 2007, Neuroimmunomodulation.

[28]  Jay Brand,et al.  File Drawer Problem , 2022, The SAGE Encyclopedia of Research Design.

[29]  K. Vedhara,et al.  The assessment of the emotional and immunological consequences of examination stress , 1996, Journal of Behavioral Medicine.

[30]  R. MacCallum,et al.  Stress-related changes in proinflammatory cytokine production in wounds. , 1999, Archives of general psychiatry.

[31]  T. Kao,et al.  Comparison of elastic versus nonelastic compression in bilateral venous ulcers: a randomized trial. , 2005, Journal of vascular surgery.

[32]  M. Dyson,et al.  Enhanced wound healing after emotional disclosure intervention. , 2008, British journal of health psychology.

[33]  R. Rosenthal The file drawer problem and tolerance for null results , 1979 .

[34]  I. Olkin,et al.  Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement , 1999, The Lancet.

[35]  F. Gottrup,et al.  A new concept of a multidisciplinary wound healing center and a national expert function of wound healing. , 2001, Archives of surgery.

[36]  N. Quan,et al.  Impaired wound contraction and delayed myofibroblast differentiation in restraint-stressed mice , 2005, Brain, Behavior, and Immunity.

[37]  F. Dhabhar,et al.  Immune Function in PTSD , 2006, Annals of the New York Academy of Sciences.

[38]  S. Maier,et al.  Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. , 1998, Psychological review.

[39]  A. Stalder,et al.  Barrier disruption increases gene expression of cytokines and the 55 kD TNF receptor in murine skin , 1997, Experimental dermatology.

[40]  A. Field,et al.  The Problems in Using Fixed-Effects Models of Meta-Analysis on Real-World Data , 2003 .

[41]  B. Jobe,et al.  Clinical review: Healing in gastrointestinal anastomoses, Part II , 2006, Microsurgery.

[42]  S. Segerstrom,et al.  Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. , 2004, Psychological bulletin.

[43]  J. Cacioppo,et al.  Mucosal wound healing: the roles of age and sex. , 2006, Archives of surgery.

[44]  N. Tarrier,et al.  The influence of pre-existing psychiatric illness on recovery in burn injury patients: the impact of psychosis and depression. , 2005, Burns : journal of the International Society for Burn Injuries.

[45]  L. Kamolz,et al.  Treatment of patients with severe burn injuries: the impact of schizophrenia. , 2003, Burns : journal of the International Society for Burn Injuries.

[46]  K. Harding,et al.  Psychological Factors and Delayed Healing in Chronic Wounds , 2001, Psychosomatic medicine.

[47]  J. Kiecolt-Glaser,et al.  Stress-induced immune dysfunction: implications for health , 2005, Nature Reviews Immunology.

[48]  M. Chren,et al.  Psychological stress perturbs epidermal permeability barrier homeostasis: implications for the pathogenesis of stress-associated skin disorders. , 2001, Archives of dermatology.

[49]  C. Holden-Lund,et al.  Effects of relaxation with guided imagery on surgical stress and wound healing. , 1988, Research in nursing & health.

[50]  W. Wood,et al.  Oxford textbook of surgery , 2000 .

[51]  Sandy L. Jones,et al.  Human Anatomy and Physiology. 6th ed , 1970 .

[52]  F. Dhabhar,et al.  Stress-induced changes in skin barrier function in healthy women. , 2001, The Journal of investigative dermatology.

[53]  S. Levenstein The Very Model of a Modern Etiology: A Biopsychosocial View of Peptic Ulcer , 2000, Psychosomatic medicine.

[54]  D. S. Scott,et al.  The effects of psychological factors and physical trauma on recovery from oral surgery , 1980, Journal of Behavioral Medicine.

[55]  Stephanie L. Dickinson,et al.  Pain and wound healing in surgical patients , 2006, Annals of behavioral medicine : a publication of the Society of Behavioral Medicine.

[56]  Comparison of elastic versus nonelastic compression in bilateral venous ulcers: a randomized trial , 2006 .

[57]  A. Field Meta-analysis of correlation coefficients: a Monte Carlo comparison of fixed- and random-effects methods. , 2001, Psychological methods.

[58]  W. Lindblad,et al.  Considerations for selecting the correct animal model for dermal wound-healing studies , 2008, Journal of biomaterials science. Polymer edition.

[59]  T. Robles Stress, Social Support, and Delayed Skin Barrier Recovery , 2007, Psychosomatic medicine.

[60]  J. Wardle,et al.  Do stress-related psychosocial factors contribute to cancer incidence and survival? , 2008, Nature Clinical Practice Oncology.

[61]  R. Marks The stratum corneum barrier: the final frontier. , 2004, The Journal of nutrition.

[62]  K. Soon,et al.  Pain-induced stress: a barrier to wound healing , 2006 .

[63]  J. Sheridan,et al.  Restraint Stress Slows Cutaneous Wound Healing in Mice , 1998, Brain, Behavior, and Immunity.

[64]  N. Muizzuddin,et al.  Impact of stress of marital dissolution on skin barrier recovery: tape stripping and measurement of trans‐epidermal water loss (TEWL) , 2003, Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging.

[65]  P. Elias,et al.  Cutaneous barrier perturbation stimulates cytokine production in the epidermis of mice. , 1992, The Journal of clinical investigation.

[66]  R. Booth,et al.  Psychological Stress Impairs Early Wound Repair Following Surgery , 2003, Psychosomatic medicine.

[67]  C. Engeland,et al.  Stress, neuroendocrine hormones, and wound healing: Human models , 2007 .

[68]  R. MacCallum,et al.  Stress-related modulation of matrix metalloproteinase expression , 2002, Journal of Neuroimmunology.

[69]  Jie Li,et al.  Pathophysiology of acute wound healing. , 2007, Clinics in dermatology.

[70]  W. Malarkey,et al.  Exercise accelerates wound healing among healthy older adults: a preliminary investigation. , 2005, The journals of gerontology. Series A, Biological sciences and medical sciences.

[71]  D. Carroll,et al.  The effects of physical activity and exercise training on psychological stress and well-being in an adolescent population. , 1992, Journal of psychosomatic research.

[72]  C. Sen,et al.  Wound site neutrophil transcriptome in response to psychological stress in young men. , 2005, Gene expression.

[73]  D. Moser,et al.  Depression, healing, and recovery from coronary artery bypass surgery. , 2005, American journal of critical care : an official publication, American Association of Critical-Care Nurses.

[74]  Tarynn M Witten,et al.  Impaired wound healing. , 2007, Clinics in dermatology.

[75]  D. Margolis,et al.  A multicentre study of percentage change in venous leg ulcer area as a prognostic index of healing at 24 weeks , 2000, The British journal of dermatology.

[76]  C. Potagas,et al.  The impact of stressful life events on risk of relapse in women with multiple sclerosis: A prospective study , 2008, European Psychiatry.

[77]  David A. Padgett,et al.  Experimental Models of Stress and Wound Healing , 2004, World Journal of Surgery.

[78]  L. DiPietro,et al.  Site‐specific production of TGF‐β in oral mucosal and cutaneous wounds , 2008 .

[79]  B. Jobe,et al.  Clinical review: Healing in gastrointestinal anastomoses, Part I , 2006, Microsurgery.

[80]  M. Dyson,et al.  Perceived stress and cortisol levels predict speed of wound healing in healthy male adults , 2004, Psychoneuroendocrinology.

[81]  W. Malarkey,et al.  Slowing of wound healing by psychological stress , 1995, The Lancet.