Depressão e estresse: existe um endofenótipo?
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OBJETIVO: Revisar os achados recentes sobre a relação entre estresse, eixo hipotálamo-pituitária-adrenal e depressão, na tentativa de explicar um endofenótipo de vulnerabilidade para o desenvolvimento da depressão. MÉTODO: Revisão não sistemática da literatura baseada na hipótese de endofenótipo. RESULTADOS: A depressão está relacionada à hipercortisolemia em muitos pacientes; porém, nem todos os deprimidos apresentam esta alteração na função hipotálamo-pituitária-adrenal. Os primeiros estudos publicados observaram esta hiperativação do eixo hipotálamo-pituitária-adrenal por meio do teste de supressão da dexametasona. Estes resultados não foram largamente replicados em grande parte devido à falta de acurácia desse teste. A hipercortisolemia ocorre freqüentemente em pacientes com depressão grave, do tipo melancólico, psicóticos ou não. Está relacionada a um polimorfismo específico do gene do transportador da serotonina; a história de abuso ou negligência durante a infância ou perda parental precoce; e ao temperamento que resulta em alterações na resposta ao estresse. CONCLUSÕES: As alterações do eixo hipotálamo-pituitária-adrenal dependem de diversos fatores, como gravidade e tipo de depressão, genótipo, história de trauma na infância, temperamento e, provavelmente, resiliência. Todas essas variáveis se relacionam a um endofenótipo vulnerável ao desenvolvimento de depressão.
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Hyperactive HPA axis in patients with major depression is one of the important reasons for its onset.
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Cites
Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A., et al. (2003) · Science · doi:10.1126/science.1083968 · Cited by 8,120 · see citing works
Heim, C., & Nemeroff, C. B. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01157-x · Cited by 2,791 · see citing works
The Corticosteroid Receptor Hypothesis of Depression
Holsboer, F. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00159-7 · Cited by 2,181 · see citing works
Heim, C. (2000) · JAMA · doi:10.1001/jama.284.5.592 · Cited by 1,968 · see citing works
Psychopharmacology: The Fourth Generation of Progress
Brophy, J. J. (1995) · JAMA · doi:10.1001/jama.1995.03530220079046 · Cited by 1,582 · see citing works
The Physiology and Psychology of Behavioral Inhibition in Children
Kagan, J., Reznick, J. S., & Snidman, N. C. (1987) · Child Development · doi:10.2307/1130685 · Cited by 1,339 · see citing works
Depression and cortisol responses to psychological stress: A meta-analysis
Burke, H. M., Davis, M. C., Otte, C., & Mohr, D. C. (2005) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2005.02.010 · Cited by 1,194 · see citing works
Discovering Endophenotypes for Major Depression
Hasler, G., Drevets, W. C., Manji, H. K., & Charney, D. S. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300506 · Cited by 1,123 · see citing works
Behavioral Inhibition: Linking Biology and Behavior within a Developmental Framework
Fox, N. A., Henderson, H. A., Marshall, P. J., Nichols, K. E., & Ghera, M. M. (2005) · Annual Review of Psychology · doi:10.1146/annurev.psych.55.090902.141532 · Cited by 1,040 · see citing works
Kendler, K. S., Hettema, J. M., Butera, F., Gardner, C. O., & Prescott, C. A. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.8.789 · Cited by 966 · see citing works
Antidepressants and Hypothalamic-Pituitary-Adrenocortical Regulation
HOLSBOER, F., & Barden, N. (1996) · Endocrine Reviews · doi:10.1210/edrv-17-2-187 · Cited by 851 · see citing works
Nemeroff, C. B., Heim, C. M., Thase, M. E., Klein, D. N., Rush, A. J., Schatzberg, A. F., Ninan, P. T., McCullough, J. P., Weiss, P. M., Dunner, D. L., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2336126100 · Cited by 829 · see citing works
Social supports and serotonin transporter gene moderate depression in maltreated children
Kaufman, J., Yang, B., Douglas-Palumberi, H., Houshyar, S., Lipschitz, D. S., Krystal, J. H., & Gelernter, J. E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404376101 · Cited by 801 · see citing works
Kendler, K. S., Kuhn, J., & Prescott, C. A. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.4.631 · Cited by 799 · see citing works
Sen, S., Burmeister, M., & Ghosh, D. (2004) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.20158 · Cited by 740 · see citing works
Kendler, K. S., Kuhn, J. W., Vittum, J., Prescott, C. A., & Riley, B. P. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.5.529 · Cited by 669 · see citing works
Gene–environment interaction analysis of serotonin system markers with adolescent depression
Eley, T. C., Sugden, K., Corsico, A., Gregory, A. M., Sham, P., McGuffin, P., Plomin, R., & Craig, I. W. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001546 · Cited by 663 · see citing works
Neuroendocrine Regulation in Depression
Carroll, B. J. (1976) · Archives of General Psychiatry · doi:10.1001/archpsyc.1976.01770090041003 · Cited by 638 · see citing works
Psychiatric morbidity in adult inpatients with childhood histories of sexual and physical abuse
Brown, G. R., & Anderson, B. J. (1991) · American Journal of Psychiatry · doi:10.1176/ajp.148.1.55 · Cited by 596 · see citing works
Stable behavioral inhibition and its association with anxiety disorder
HIRSHFELD, D. R., ROSENBAUM, J. F., BIEDERMAN, J., BOLDUC, E. A., FARAONE, S. V., SNIDMAN, N., REZNICK, J. S., & KAGAN, J. (1992) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199201000-00016 · Cited by 491 · see citing works
Taylor, S. E., Way, B. M., Welch, W. T., Hilmert, C. J., Lehman, B. J., & Eisenberger, N. I. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.04.019 · Cited by 432 · see citing works
Premorbid Personality Assessments of First Onset of Major Depression
Hirschfeld, R. M. A. (1989) · Archives of General Psychiatry · doi:10.1001/archpsyc.1989.01810040051008 · Cited by 428 · see citing works
Shea, A., Walsh, C., MacMillan, H., & Steiner, M. (2005) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2004.07.001 · Cited by 378 · see citing works
Zalsman, G., Huang, Y.-Y., Oquendo, M. A., Burke, A. K., Hu, X.-Z., Brent, D. A., Ellis, S. P., Goldman, D., & Mann, J. J. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.9.1588 · Cited by 371 · see citing works
Does Shy-Inhibited Temperament in Childhood Lead to Anxiety Problems in Adolescence?
Prior, M. R., Smart, D., Sanson, A. V., & Oberklaid, F. (2000) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200004000-00015 · Cited by 369 · see citing works
Zobel, A. W., Nickel, T., Sonntag, A., Uhr, M., Holsboer, F., & Ising, M. (2001) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(01)00013-9 · Cited by 354 · see citing works
Hypothalamic-pituitary-adrenal axis function in patients with bipolar disorder
Watson, S., Gallagher, P., Ritchie, J. C., Ferrier, I. N., & Young, A. H. (2004) · British Journal of Psychiatry · doi:10.1192/bjp.184.6.496 · Cited by 343 · see citing works
The DST as a predictor of outcome in depression: a meta-analysis
Ribeiro, S. C. M., Tandon, R., Grunhaus, L. J., & Greden, J. F. (1993) · American Journal of Psychiatry · doi:10.1176/ajp.150.11.1618 · Cited by 321 · see citing works
Life events, first depression onset and the serotonin transporter gene
Wilhelm, K. A., Mitchell, P. B., Niven, H., Finch, A. W., Wedgwood, L., Scimone, A., Blair, I. P., Parker, G. B., & Schofield, P. R. (2006) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.105.009522 · Cited by 309 · see citing works
Gillespie, N. A., Whitfield, J. B., WILLIAMS, B., Heath, A. C., & Martin, N. G. (2004) · Psychological Medicine · doi:10.1017/s0033291704002727 · Cited by 295 · see citing works
Behavioral Inhibition in Children of Parents With Panic Disorder and Agoraphobia
Rosenbaum, J. F. (1988) · Archives of General Psychiatry · doi:10.1001/archpsyc.1988.01800290083010 · Cited by 293 · see citing works
Rapid Reversal of Psychotic Depression Using Mifepristone
Belanoff, J. K., Flores, B. H., Kalezhan, M., Sund, B., & Schatzberg, A. F. (2001) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-200110000-00009 · Cited by 282 · see citing works
Grabe, H.-J., Lange, M., Wolff, B., Völzke, H., Lucht, M. J., Freyberger, H. J., John, U., & Cascorbi, I. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001555 · Cited by 279 · see citing works
Angst, J., & Clayton, P. J. (1986) · Comprehensive Psychiatry · doi:10.1016/0010-440x(86)90055-6 · Cited by 270 · see citing works
Social Adversity, the Serotonin Transporter (5-HTTLPR) Polymorphism and Major Depressive Disorder
Surtees, P. G., Wainwright, N. W. J., Willis-Owen, S. A. G., Luben, R., Day, N. E., & Flint, J. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.07.014 · Cited by 265 · see citing works
Bifulco, A. T., Moran, P. M., Baines, R., Bunn, A., & Stanford, K. (2002) · Bulletin of the Menninger Clinic · doi:10.1521/bumc.66.3.241.23366 · Cited by 228 · see citing works
Young, E. A., Abelson, J. L., & Cameron, O. G. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.03.017 · Cited by 228 · see citing works
Cortisol Circadian Rhythm Alterations in Psychotic Major Depression
Keller, J., Flores, B., Gomez, R. G., Solvason, H. B., Kenna, H., Williams, G. H., & Schatzberg, A. F. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.10.014 · Cited by 217 · see citing works
Modell, S. (1998) · Neuropsychopharmacology · doi:10.1016/s0893-133x(97)00144-9 · Cited by 207 · see citing works
Juruena, M. F., Cleare, A. J., & Pariante, C. M. (2004) · Brazilian Journal of Psychiatry · doi:10.1590/s1516-44462004000300009 · Cited by 181 · see citing works
Self-citationSchmider, J., Lammers, C.-H., Gotthardt, U., Dettling, M., Holsboer, F., & Heuser, I. J. E. (1995) · Biological Psychiatry · doi:10.1016/0006-3223(95)00064-x · Cited by 179 · see citing works
Textbook of Psychopharmacology
(1995) · Nature Medicine · doi:10.1038/nm0895-834 · Cited by 178 · see citing works
Nonhuman Primate Models to Study Anxiety, Emotion Regulation, and Psychopathology
Kalin, N. H., & SHELTONA, S. E. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1301.021 · Cited by 171 · see citing works
Update on stress and depression: the role of the hypothalamic-pituitary-adrenal (HPA) axis
Mello, A. F., Mello, M. F., Carpenter, L. L., & Price, L. H. (2003) · Brazilian Journal of Psychiatry · doi:10.1590/s1516-44462003000400010 · Cited by 169 · see citing works
Self-citationThe dexamethasone suppression test: identification of subtypes of depression
Schatzberg, A. F., Rothschild, A. J., Stahl, J. B., Bond, T. C., Rosenbaum, A. H., Lofgren, S. B., MacLaughlin, R. A., Sullivan, M. A., & Cole, J. O. (1983) · American Journal of Psychiatry · doi:10.1176/ajp.140.1.88 · Cited by 156 · see citing works
von Bardeleben, U., Holsboer, F., Stalla, G. K., & Müller, O. A. (1985) · Life Sciences · doi:10.1016/0024-3205(85)90480-1 · Cited by 153 · see citing works
McFARLANE, A. C., Clark, C. R., Bryant, R. A., Williams, L. M., NIAURA, R. S., Paul, R. H., Hitsman, B. L., Stroud, L. R., Alexander, D. M., & Gordon, E. (2005) · Journal of Integrative Neuroscience · doi:10.1142/s0219635205000689 · Cited by 152 · see citing works
Different responses to dexamethasone and prednisolone in the same depressed patients
Juruena, M. F., Cleare, A. J., Papadopoulos, A. S., Poon, L., Lightman, S., & Pariante, C. M. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0555-4 · Cited by 147 · see citing works
Self-citationThe neuropsychological profile of psychotic major depression and its relation to cortisol
Gomez, R. G., Fleming, S. H., Keller, J., Flores, B., Kenna, H., DeBattista, C., Solvason, B., & Schatzberg, A. F. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.11.010 · Cited by 127 · see citing works
Neuroendocrine Aspects of PTSD
Yehuda, R. (2005) · Handbook of experimental pharmacology · doi:10.1007/3-540-28082-0_13 · Cited by 117 · see citing works
Nash, M. W. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh239 · Cited by 112 · see citing works
von Bardeleben, U., & Holsboer, F. (1991) · Biological Psychiatry · doi:10.1016/0006-3223(91)90360-x · Cited by 94 · see citing works
Does sexual violence contribute to elevated rates of anxiety and depression in females?
Fergusson, D. M., Swain, N., & Horwood, L. J. (2002) · Psychological Medicine · doi:10.1017/s0033291702005986 · Cited by 84 · see citing works
The dex/CRH test—Is it better than the DST?
Watson, S., Gallagher, P., Smith, M. S., Ferrier, I. N., & Young, A. H. (2006) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2006.03.001 · Cited by 82 · see citing works
Neuroendocrinology of mood disorders.
Mazza, M., Satta, M. A., Bria, P., & Mazza, S. (2004) · PubMed · Cited by 79 · see citing works
Temperament and hypothalamic–pituitary–adrenal axis function in healthy adults
Tyrka, A. R., Mello, A. F., Mello, M. F., Gagné, G. G., Grover, K. E., Anderson, G. M., Price, L. H., & Carpenter, L. L. (2006) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2006.06.004 · Cited by 77 · see citing works
Self-citationA novel prednisolone suppression test for the hypothalamic-pituitary-adrenal axis
Pariante, C. M., Papadopoulos, A. S., Poon, L., Checkley, S. A., English, J., Kerwin, R. W., & Lightman, S. L. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01314-2 · Cited by 74 · see citing works
Self-citationLife events and depression in a community sample of siblings
Rijsdijk, F. V., Sham, P. C., Sterne, A., Purcell, S., McGuffin, P., FARMER, A. E., Goldberg, D., MANN, A. H., Cherny, S. S., Webster, M., et al. (2001) · Psychological Medicine · doi:10.1017/s0033291701003361 · Cited by 68 · see citing works
Superposição entre depressão atípica, doença afetiva sazonal e síndrome da fadiga crônica
Juruena, M. F., & Cleare, A. J. (2007) · Brazilian Journal of Psychiatry · doi:10.1590/s1516-44462007000500005 · Cited by 67 · see citing works
Self-citationHormonal differences between psychotic and non-psychotic melancholic depression
Contreras, F., Menchón, J. M., Urretavizcaya, M., Navarro, M. A., Vallejo, J., & Parker, G. B. (2006) · Journal of Affective Disorders · doi:10.1016/j.jad.2006.09.021 · Cited by 63 · see citing works
Interrelationship of childhood trauma, neuroticism, and depressive phenotype
Moskvina, V., FARMER, A. E., Swainson, V., O'Leary, J., Gunasinghe, C., Owen, M., Craddock, N. J., McGuffin, P., & Korszun, A. (2006) · Depression and Anxiety · doi:10.1002/da.20216 · Cited by 58 · see citing works
Coryell, W. H. (1996) · PubMed · Cited by 12 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Juruena MF, Cleare AJ, Pariante CM. [The hypothalamic pituitary adrenal axis, glucocorticoid receptor function and relevance to depression]. Rev Bras Psiquiatr. 2004;26(3):189-201.
- transporter promoter polymorphism, and depressive symptomatology. Biol Psychiatry. 2006;60(7):671-6.
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“Hyperactive HPA axis in patients with major depression is one of the important reasons for its onset[91].”
BackgroundGlucocorticoid Dysregulations and Their Clinical Correlates: From Receptors to Therapeutics
Marques, A. H., Silverman, M. N., & Sternberg, E. M. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04987.x · Cited by 158 · see citing works
Valiengo, L. L., Soeiro-de-Souza, M. G., Marques, A. H., Moreno, D. H., Juruena, M. F., Andreazza, A. C., Gattaz, W. F., & Machado-Vieira, R. (2012) · Journal of Affective Disorders · doi:10.1016/j.jad.2011.11.046 · Cited by 36 · see citing works
Self-citationAssociation of amygdala volumes with cortisol secretion in unipolar depressed patients
Schuhmacher, A., Mössner, R., Jessen, F., Scheef, L., Block, W., Belloche, A. C., Lennertz, L., Welper, H., Höfels, S., Pfeiffer, U., et al. (2012) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2011.09.007 · Cited by 25 · see citing works
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- Authors
- Mello, A. F., Juruena, M. F., Pariante, C. M., Tyrka, A. R., Price, L. H., Carpenter, L. L., & Del Porto, J. A.
- Affiliations
- Universidade Federal de São Paulo, Brasil
- Institute of Psychiatry
- Brown University (US)
- Venue
- Revista Brasileira de Psiquiatria
- Publisher
- EDITORA SCIENTIFIC
- Published
- 2007-05
- Volume
- 29
- Issue
- suppl 1
- Pages
- s13-s18
- ISSN
- 1516-4446 (ISSN-L)
- PMC
- PMC4467732
- OpenAlex
- W1977515998
- Cited by
- 56
- References
- 62
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 8 · 2019: 1 · 2018: 2 · 2017: 4 · 2015: 3 · 2014: 7 · 2013: 2 · 2012: 3
- FWCI
- 0.76
- Type
- journal article
- Language
- pt
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc
- Locations
- Brazilian Journal of Psychiatry (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Americanae (AECID Library) (submittedVersion, cc-by-nc)
- Americanae (AECID Library) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Portal (King's College London) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- National Institute of Mental Health (R01MH068767)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- depression, endophenotypes, hypothalamic-pituitary-adrenal axis, hypercortisolism, dexamethasone suppression test, serotonin transporter gene polymorphism, childhood abuse and neglect, stress exposure, temperament, resilience, endogenous depression
- MeSH terms
- Adrenocorticotropic Hormone, Corticotropin-Releasing Hormone, Major Depressive Disorder, Dexamethasone, Glucocorticoids, Humans, Hypothalamo-Hypophyseal System, Phenotype, Pituitary-Adrenal System, Polymorphism, Genetic, Stress, Psychological, Temperament, Genetic Predisposition to Disease
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