ESTRÉS Y ENFERMEDAD. Enfoque psiconeuroinmunoendocrino
Palabras clave:
strés, CRH, cortisol, epinefrina, serotonina, hipocampo, hipotálamo, sistema inmune, enfermedades psicosomáticas, depresión, Stress, epinephrine, serotonin, hippocampus, hypothalamus, Immune system, psychosomatic diseases, depressionResumen
ResumenObjetivo: hacer una revisión de los mecanismos moleculares del estrés y del papel que en él juegan sistemas reguladores como el hormonal, el neuropsicológico y el inmunológico.
Métodos: Aunque no se hizo una búsqueda exhaustiva, sí se consultó la bibliografía más citada por autores de trayectoria investigativa en el tema.
Resultados: Se seleccionaron los 50 artículos más relevantes sobre el estrés y enfermedad que se relacionaran con el enfoque psiconeuroinmunoendocrino.
Discusión: El “síndrome de adaptación general” como respuesta al estrés descrito por Selye en 1936, ha sido estudiado desde entonces para comprender mecanismos y sistemas involucrados. En las situaciones de estrés –agudo como crónico- se activan los sistemas endocrino, nervioso autónomo e inmunológico para responder a una amenaza real o imaginaria, generando cambios neuropsicológicos, cardiovasculares y metabólicos. Dicha respuesta al estrés comienza en el sistema límbico con la liberación de la hormona hipotalámica CRH, que estimula la producción de ACTH y de cortisol, mientras que el sistema neurovegetativo libera epinefrina.
En el estrés crónico, el sistema permanece activo con niveles altos o bajos de cortisol en sangre, lo que podría llevar a depresión, ataques de pánico, estrés postraumático, ataques de asma, hipertiroidismo, trastornos menstruales o exacerbación de una artritis reumatoide y muchas otras patologías. La región promotora del gen transportador de la serotonina modera la influencia de los eventos estresantes de la vida en la depresión en los humanos.
Un estilo de vida inadecuado y el estrés crónico generan numerosas patologías de la vida moderna y llevan a una cotidianidad disfuncional. Para mejorar esta situación hay nuevos procedimientos diagnósticos, se han elaborado fármacos y se han diseñado estrategias para controlar la sobrecarga alostática.
Palabras clave: Estrés, CRH, cortisol, epinefrina, serotonina, hipocampo, hipotálamo, sistema inmune, enfermedades psicosomáticas, depresión.
STRESS AND DISEASE, A PSYCHONEUROIMMUNOENDOCRINE APPROACH
AbstractObjective: To make a review of both molecular mechanisms of stress and the role played by regulatory systems such as the endocrine, neuropsychological and immune.
Methods: We checked references by well known investigators, although this review was not systematic.
Results: 50 more relevant papers on the subject were selected.
Discussion. Since Selye described in 1936 the “general adaptation syndrome” in response to stress, a large volume of research have been done to understand mechanisms and to study systems involved. During acute stress, endocrine, neurovegetative and immune systems are activated in response to a threat, inducing neuropsychological, cardiovascular and metabolic derangements. Failure of a living organism to respond appropriately to emotional or physical threats, whether actual or imagined, starts with fear generated in the limbic system and production of a key peptide in the hypothalamus, corticotrophin releasing hormone (CRH), with the initiation of a cascade of changes such as release of ACTH, cortisol, epinephrine, acting on the immune system, generating neuropsychiatric symptoms and involvement of other hormones and tissues. Coronary heart disease, obesity, hypertension, diabetes and metabolic syndrome ensue. Excess of antibodies trigger the appearance of collagen diseases such as rheumatoid arthritis or other pathology like chronic autoimmune thyroiditis.
Suppression of the immune system due to hypercortisolism favors infections. Abnormal cortisol secretion influence specific receptors in the hippocampus, leading to atrophic changes. Memory dysfunction and depression could be a result of this continued cortisol stimulation. A key brain neurotransmitter –serotonin- and the promoting region of the serotonin transporter gene moderate stress influences in depressed subjects. An inadequate life style and chronic stress cause numerous modern life pathologies and lead to a dysfunctional daily living. New diagnostic procedures, modern medicines and non-pharmacologic measures have been devised to counteract allostatic overload.
Key words: Stress, CRH, cortisol, epinephrine, serotonin, hippocampus, hypothalamus, Immune system, psychosomatic diseases, depression.
Biografía del autor/a
Alfredo Jácome Roca, Academia Nacional de Medicina
Referencias bibliográficas
Selye H. Syndrome produced by diverse nocious agents. Nature 1936; 138:32.
Prolo P, Chiappelli F, Fiorucci A, Dovio A, Sartori ML, Angeli A. Psychoneuroimmunology: new avenues of research for the twenty-first century. Ann N Y Acad Sci. 2002; 966: 400-408
Flores M, Ontiveros MP. Hormonas gonadales y depresión en la perimenopausia. Rev Col Psiquiat 2008; 37(2): 236-246
Young EA, Midgley AR, Carlson NE, Brown MB. Alteration in the hypothalamic-pituitary-ovarian axis in depressed women. Arch Gen Psychiatry 2000;57: 1157-62
Salvador J. Neuroendocrinología del estrés. 8º Congreso Colombiano de Endocrinología, “De la biología molecular a la práctica clínica”, 2005. Bogotá
Tsuru J, Akiyoshi J et al. Social support and enhanced suppression of adrenocorticotropic hormone and cortisol responses to hypothalamic-pituitary-adrenal function and thyrotropin-releasing hormone tests in patients with major depressive disorder. Biol Psychol. 2008; 78(2): 159-63
Trucco M. Estrés y trastornos mentales, aspectos neurobiológicos y psicosociales. Rev Chil Neuropsiquiatr 2002; 40 (S2): 8-19
McEwen BS. Stressed or stressed out: what is the difference? J Psychiatry Neurosci 2005; 30: 315-318
Belmaker RH, Agam G. Major Depressive Disorder. N Engl J Med 2008; 358:55-68
Swaab DF,Bao AM, Lucassen PJ. The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev 2005; 4: 141-194
Tanaka M, Telegdy G. Antidepressant-like effects of the CRF family peptides, urocortin 1, urocortin 2 and urocortin 3 in a modified forced swimming test in mice. Brain Res Bull. 2008; 75(5):509-512
Chen C. Recent advances in small molecule antagonists of the corticotropin-releasing factor type-1 receptor-focus on pharmacology and pharmacokinetics. Curr Med Chem. 2006; 13: 1261-82
Weniger SC et al. Stress-induced behaviours require the corticotrophin-releasing-hormone (CRH) receptor but not CRH. Proc Natl Acad Sci 1999.
Cao J et al. Human mast cells express corticotrophinreleasing hormone (CRH) receptors and CRH leads to selective secretion of vascular endothelial growth factor. J Immunol 2005; 174. 7665-7675
Speert DB, Seasholtz AF. Corticotrophin-releasing hormone receptors and ligands in stress: who’s on first? Curr Op Endocrinol & Diab 2001; 8: 161-165
Van Houdenhove B, Van Den Eede F, Luyten P Does hypothalamic-pituitary-adrenal axis hypofunction in chronic fatigue syndrome reflect a ‘crash’ in the stress system?.Med Hypotheses. 2009 Jun;72(6):701-5.
Mesquita AR, Wegerich Y, Patchev AV, Oliveira M, Leão P, Sousa N, Almeida OF. Glucocorticoids and neuro- and behavioural development.. Semin Fetal Neonatal Med. 2009 Jun;14(3):130
Ball TM. Cortisol circadian rhythms and stress responses in infants at risk of allergic disease. Neuroimmunomodulation. 2006;13(5-6):294-300.
Taché Y, Bonaz B. Cortisol circadian rhythms and stress responses in infants at risk of allergic disease J Clin Invest. 2007 Jan;117(1):33-40.
Monteleone P, Martiadis V, Maj M.Circadian rhythms and treatment implications in depression. M. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Aug 5.
Westrich L, Sprouse J. Circadian rhythm dysregulation in bipolar disorder. Curr Opin Investig Drugs. 2010 Jul;11(7):779-87. Review.
Boyce P, Barriball E. Circadian rhythms and depression. Aust Fam Physician. 2010 May;39(5):307-10. Review.
Virk G, Reeves G, Rosenthal NE, Sher L, Postolache TT. Short exposure to light treatment improves depression scores in patients with seasonal affective disorder: A brief report. Int J Disabil Hum Dev. 2009 Jul;8(3):283-286.
Calcagni E, Elenkov I. Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases. Ann N Y Acad Sci. 2006;1069: 62-76
Elenkov IJ, Lezzoni DG, Daly A, Harris AG, Chrousos GP. Cytokine dysregulation, inflammation and wellbeing. Neuroimmunomodulation. 2005; 12: 255-69
Schiepers OJ et al. Cytoquines and major depression. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 201-217
Bazzichi L, Rossi A et al. Association between thyroid autoimmunity and fibromyalgic disease severity. Clin Rheumatol. 2007; 26: 2115-2120
Davis JD, Tremont G. Neuropsychiatric aspects of hypothyroidism and treatment reversibility. Minerva Endocrinol. 2007; 32: 49-65
Carta MG, Loviselli A, Hardoy MC et al. The link between thyroid autoimmunity (antithyroid peroxidase autoantibodies) with anxiety and mood disorders in the community: a field of interest for public health in the future. BMC Psychiatry. 2004; 4: 25
Oomen HA, Schipperijn AJ, Drexhage HA. The prevalence of affective disorder and in particular of a rapid cycling of bipolar disorder in patients with abnormal thyroid function tests. Clin Endocrinol (Oxf). 1996; 45: 215-23
Bokhari R, Bhatara VS, Bandettini F, McMillin JM. Postpartum psychosis and postpartum thyroiditis. Psychoneuroendocrinology. 1998; 23: 643-50
Gill JM, Szanton SL, Page GG Biological underpinnings of health alterations in women with PTSD: a sex disparity .Biol Res Nurs. 2005; 7:44-54.
Nemeroff CB, Simon JS, Haggerty JJ Jr, Evans DL. Antithyroid antibodies in depressed patients. Am J Psychiatry. 1985; 142: 840-3
Carta MG, Hardoy MC et al. Association between panic disorder, major depressive disorder and celiac disease: a possible role of thyroid autoimmunity. J Psychosom Res. 2002; 53: 789-93
Guimarães JM, de Souza Lopes C, Baima J, Sichieri R. Depression symptoms and hypothyroidism in a population-based study of middle-aged Brazilian women. Affect Disord. 2009 Jan 23
Fountoulakis KN et al. Thyroid function in clinical subtypes of major depression, an exploratory study. BMC Psychiatry 2004; www.biomedcentral. com/1471-244X/4/6
Lizcano F, Rodríguez JS. Efectos del tratamiento del hipertiroidismo e hipotiroidismo sobre la actividad del sistema del estrés. Acta Med Colomb 2007; 32: 39-46
Ackerman LS. Sex hormones and the genesis of autoimmunity. Arch Dermatol 2006; 142: 371-376
Lindqvist D, Isaksson A, Träskman-Bendz L, Brundin L. Salivary cortisol and suicidal behavior—a follow-up study. Psychoneuroendocrinology. 2008; 33 (8): 1061-80
Swaab DF, Bao AM, Lucassen PJ. The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev. 2005; 4:141-94.
Land BB, Bruchas MR et al. The dysphoric component of stress is encoded by activation of the dynorphin kappa-opioid system . J Neurosci. 2008; 28(2):407-414
Schüle C, Baghai TC et al. The combined dexamethasone/ CRH Test (DEX/CRH test) and prediction of acute treatment response in major depression. PLoS ONE. 2009; 4: e4324.
Rosembaum JF. Antidepressant treatment and the biology of depression. 2001. www.medscape.com
Di Marco F, Santus P, Centanni S. Anxiety and depression in asthma..Curr Opin Pulm Med. 2010 Oct.
McEwen BS, Gianaros PJ.. Frontiers in the use of biomarkers of health in research on stress and aging. Ann N Y Acad Sci. 2010 Feb;1186:190-222
Nautiyal KM, Ribeiro AC, Pfaff DW, Silver R. Brain mast cells link the immune system to anxietylike behavio Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):18053-7. Epub 2008 Nov 11.
Cerqueira JJ, Almeida OF, Sousa N. The stressed prefrontal cortex. Left? Right! Brain Behav Immun. 2008 Jul;22(5):630-8.
Reiche EM, Nunes SO, Morimoto HK Stress, depression, the immune system, and cancer.Lancet Oncol. 2004 Oct;5(10):617-25. Review.
Spiegel D, Sephton SE. Psychoneuroimmune and endocrine pathways in cancer: effects of stress and support. Semin Clin Neuropsychiatry. 2001 Oct;6(4):252-65.
McEwen BS, Gianaros PJ. Central role of the brain in stress and adaptation: links to socioeconomic status, health, and disease. Ann N Y Acad Sci. 2010 Feb;1186:190-222
Cómo citar
Descargas
Descargas
Publicado
Número
Sección
Licencia
Copyright
ANM de Colombia
Los autores deben declarar revisión, validación y aprobación para publicación del manuscrito, además de la cesión de los derechos patrimoniales de publicación, mediante un documento que debe ser enviado antes de la aparición del escrito. Puede solicitar el formato a través del correo revistamedicina@anmdecolombia.org.co o descargarlo directamente Documento Garantías y cesión de derechos.docx
Copyright
ANM de Colombia
Authors must state that they reviewed, validated and approved the manuscript's publication. Moreover, they must sign a model release that should be sent.
