The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Clinical and Biochemical Manifestations of Depression: Relation to the Neurobiology of Stress
Open accessAbstract
Major depressive disorder (MDD) is a chronic, recurrent, and severe psychiatric disorder with high mortality and medical comorbidities. Stress-related pathways have been directly involved in the pathophysiology and treatment of MDD. The present paper provides an overview on the stress system as a model to understand key pathophysiological paradigms in MDD. These mechanisms involve behavioral, cognitive, and systemic manifestations and are also associated with the mechanisms of action of effective antidepressants. Aspects such as depression subtypes, inflammation, insulin resistance, oxidative stress, and prothrombotic states in critical brain circuits and periphery are critically appraised. Finally, new strategies for approaching treatment-resistant major depression and potential adverse effects associated with this complex and intricate network are highlighted. The authors used PubMed as the database for this review. Each author extracted relevant data and assessed the methodological quality of each study.
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“Hypercortisolism is one of the relevant mechanisms involved in response to stress and is present in many people with MDD and in animals subjected to stress in the laboratory.”
From Stress and serum cortisol levels in major depressive disorder: a cross-sectional study (2020) · cites this paper as [9]
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“Chronic stress throughout life involves several biological changes, which are underlying MDD in many patients and in laboratory animals [4],[6],[9].”
From Stress and serum cortisol levels in major depressive disorder: a cross-sectional study (2020) · cites this paper as [9]
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“Insulin resistance and inflammation can cause anxiety [47]”
From The Effect of Anxiety and Nutritional Habits on the Body Distortion of Athletes. (2025) · cites this paper as [47]
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“Experiential avoidance seeks to control the way or frequency of aversive private experiences [37] and has been associated with anxiety [38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54].”
From The Effect of Anxiety and Nutritional Habits on the Body Distortion of Athletes. (2025) · cites this paper as [47]
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Citations
Cites
Kessler, R. C. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950010008002 · Cited by 12,370
A Neurotrophic Model for Stress-Related Mood Disorders
Duman, R. S., & Monteggia, L. M. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.02.013 · Cited by 3,375
The molecular neurobiology of depression
Krishnan, V., & Nestler, E. J. (2008) · Nature · doi:10.1038/nature07455 · Cited by 2,889
Subgenual prefrontal cortex abnormalities in mood disorders
Drevets, W. C., Price, J. L., Simpson, J. R., Todd, R. D., Reich, T., Vannier, M., & Raichle, M. E. (1997) · Nature · doi:10.1038/386824a0 · Cited by 2,693
The Concepts of Stress and Stress System Disorders: Overview of Physical and Behavioral Homeostasis
Chrousos, G. P. (1992) · JAMA · doi:10.1001/jama.1992.03480090092034 · Cited by 2,689
Evidence-based health policy—lessons from the Global Burden of Disease Study
Murray, C. J. L., & Lopez, A. D. (1996) · Science · doi:10.1126/science.274.5288.740 · Cited by 2,178
LeDoux, J. E. (1995) · Annual Review of Psychology · doi:10.1146/annurev.ps.46.020195.001233 · Cited by 1,646
Mechanisms of emotional arousal and lasting declarative memory.
Cahill, L., & McGaugh, J. L. (1998) · Trends in Neurosciences · doi:10.1016/s0166-2236(97)01214-9 · Cited by 1,575
Adult hippocampal neurogenesis buffers stress responses and depressive behaviour
Snyder, J. S., Soumier, A., Brewer, M., Pickel, J., & Cameron, H. A. (2011) · Nature · doi:10.1038/nature10287 · Cited by 1,473
Gold, P. W., & Chrousos, G. P. (2002) · Molecular Psychiatry · doi:10.1038/sj.mp.4001032 · Cited by 1,274
Self-citationPizzagalli, D. A., Holmes, A. J., Dillon, D. G., Goetz, E. L., Birk, J. L., Bogdan, R., Dougherty, D. D., Iosifescu, D. V., Rauch, S. L., & Fava, M. (2009) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2008.08081201 · Cited by 1,232
Diorio, D., Viau, V, & Meaney, M. (1993) · The Journal of Neuroscience · doi:10.1523/jneurosci.13-09-03839.1993 · Cited by 1,151
Stressful life events, genetic liability, and onset of an episode of major depression in women
(1995) · American Journal of Psychiatry · doi:10.1176/ajp.152.6.833 · Cited by 1,063
Clinical and Biochemical Manifestations of Depression
Gold, P. W., Goodwin, F. K., & Chrousos, G. P. (1988) · New England Journal of Medicine · doi:10.1056/nejm198808183190706 · Cited by 1,057
Amygdala activity at encoding correlated with long-term, free recall of emotional information.
Cahill, L. F., Haier, R. J., Fallon, J., Alkire, M. T., Tang, C. Y., Keator, D., Wu, J. C., & McGaugh, J. L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.15.8016 · Cited by 928
Symptoms of depression, acute myocardial infarction, and total mortality in a community sample
Barefoot, J. C., & Schroll, M. (1996) · Circulation · doi:10.1161/01.cir.93.11.1976 · Cited by 850
Neural circuits underlying the pathophysiology of mood disorders
Price, J. L., & Drevets, W. C. (2012) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.12.011 · Cited by 788
Depressed Affect, Hopelessness, and the Risk of Ischemic Heart Disease in a Cohort of U.S. Adults
Anda, R. F., Williamson, D. F., Jones, D., Macera, C., Eaker, E. D., Glassman, A. H., & Marks, J. S. (1993) · Epidemiology · doi:10.1097/00001648-199307000-00003 · Cited by 770
Gold, P. W., Loriaux, D. L., Roy, A., Kling, M. A., Calabrese, J. R., Kellner, C. H., Nieman, L. K., Post, R. M., Pickar, D., Gallucci, W. T., et al. (1986) · New England Journal of Medicine · doi:10.1056/nejm198605223142101 · Cited by 766
Involvement of the amygdala in memory storage: Interaction with other brain systems
McGaugh, J. L., Cahill, L. F., & Roozendaal, B. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13508 · Cited by 747
Demitrack, M. A., Dale, J. K., Straus, S. E., Laue, L., LISTWAK, S. J., Kruesi, M. J. P., Chrousos, G. P., & Gold, P. W. (1991) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-73-6-1224 · Cited by 727
Suicide and Primary Affective Disorders
Guzé, S. B., & Robins, E. (1970) · The British Journal of Psychiatry · doi:10.1192/bjp.117.539.437 · Cited by 724
MacQueen, G., & Frodl, T. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.80 · Cited by 665
Wong, M., Kling, M. A., Munson, P. J., Listwak, S. J., Licinio, J., Prolo, P., Karp, B., McCutcheon, I. E., Geracioti, T. D., DeBellis, M. D., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.1.325 · Cited by 581
Models for the joint effect of genotype and environment on liability to psychiatric illness
Kendler, K. S., & Eaves, L. J. (1986) · American Journal of Psychiatry · doi:10.1176/ajp.143.3.279 · Cited by 549
Clinical and Biochemical Manifestations of Depression
Gold, P. W., Goodwin, F. K., & Chrousos, G. P. (1988) · New England Journal of Medicine · doi:10.1056/nejm198808113190606 · Cited by 547
Amygdala modulation of hippocampal-dependent and caudate nucleus-dependent memory processes
Packard, M. G., Cahill, L., & McGaugh, J. L. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.18.8477 · Cited by 544
Neuroscience of affect: brain mechanisms of pleasure and displeasure
Berridge, K. C., & Kringelbach, M. L. (2013) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2013.01.017 · Cited by 532
Minor and Major Depression and the Risk of Death in Older Persons
Penninx, B. W. J. H., Geerlings, S. W., Deeg, D. J. H., van Eijk, J. T. M., van Tilburg, W., & Beekman, A. T. F. (1999) · Archives of General Psychiatry · doi:10.1001/archpsyc.56.10.889 · Cited by 524
Bone Mineral Density in Women with Depression
Michelson, D., Stratakis, C., Hill, L., Reynolds, J., Galliven, E., Chrousos, G., & Gold, P. (1996) · New England Journal of Medicine · doi:10.1056/nejm199610173351602 · Cited by 471
Self-citationA negative regulator of MAP kinase causes depressive behavior
Duric, V., Banasr, M., Licznerski, P., Schmidt, H. D., Stockmeier, C. A., Simen, A. A., Newton, S. S., & Duman, R. S. (2010) · Nature Medicine · doi:10.1038/nm.2219 · Cited by 412
Makino, S., Gold, P. W., & Schulkin, J. (1994) · Brain Research · doi:10.1016/0006-8993(94)91862-7 · Cited by 400
Self-citationChildhood Parental Loss and Adult Psychopathology in Women
Kendler, K. S. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820020029004 · Cited by 394
Meaney, M. J., Mitchell, J. B., Aitken, D. H., Bhatnagar, S., Bodnoff, S. R., Iny, L. J., & Sarrieau, A. (1991) · Psychoneuroendocrinology · doi:10.1016/0306-4530(91)90072-2 · Cited by 372
Brady, L. S., Whitfield, H. J., Fox, R. J., Gold, P. W., & Herkenham, M. A. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115086 · Cited by 338
The Lifetime History of Major Depression in Women: Reliability of Diagnosis and Heritability
Kendler, K. S. (1993) · Archives of General Psychiatry · doi:10.1001/archpsyc.1993.01820230054003 · Cited by 326
Kendler, K. S. (1996) · Archives of General Psychiatry · doi:10.1001/archpsyc.1996.01830050025004 · Cited by 323
Zola‐Morgan, S., Squire, L. R., Clower, R. P., & Alvarez‐Royo, P. (1991) · Hippocampus · doi:10.1002/hipo.450010208 · Cited by 265 · cited 2×
“The distinct loci for explicit and emotional memory [33] are demonstrated by the phenomenon in which individuals with damage to explicit, fact-laden memories but intact sites for emotional memories respond to someone who had frightened them by crying out, without recognizing the person or the context inwhich theywere…”
BackgroundBrady, L. S., Gold, P. W., Herkenham, M. A., Lynn, A. B., & Whitfield, H. J. (1992) · Brain Research · doi:10.1016/0006-8993(92)90459-m · Cited by 236
Penninx, B. W. J. H., Guralnik, J. M., de Leon, C. F. M., Pahor, M., Visser, M., Corti, M., & Wallace, R. B. (1998) · The American Journal of Cardiology · doi:10.1016/s0002-9149(98)00077-0 · Cited by 201
Maternal separation produces lasting changes in cortisol and behavior in rhesus monkeys
Feng, X., Wang, L., Yang, S., Qin, D., Wang, J., Li, C., Lv, L., Ma, Y., & Hu, X. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010943108 · Cited by 185
Chapter 10 The prefrontal cortex and its relation to behavior
Fuster, J. M. (1991) · Progress in brain research · doi:10.1016/s0079-6123(08)63053-8 · Cited by 184
Viau, V., Sharma, S., Plotsky, P. M., & Meaney, M. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-03-01097.1993 · Cited by 183
Hyponatremia from oxcarbazepine and carbamazepine
Dong, X., Leppik, I. E., White, J., & Rarick, J. O. (2005) · Neurology · doi:10.1212/01.wnl.0000188819.45330.90 · Cited by 170
Wïttchen, H., Knaüper, B., & Kessler, R. C. (1994) · The British Journal of Psychiatry · doi:10.1192/s0007125000293240 · Cited by 164
Joseph-Vanderpool, J. R., Rosenthal, N. E., Chrousos, G. P., Wehr, T. A., Skwerer, R. G., Kasper, S. F., & Gold, P. W. (1991) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-72-6-1382 · Cited by 131
Kling, M. A., Alesci, S., Csako, G., Costello, R., Luckenbaugh, D. A., Bonne, O., Duncko, R., Drevets, W. C., Manji, H. K., Charney, D. S., et al. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.09.033 · Cited by 111
Natural History and Preventative Treatment of Recurrent Mood Disorders
Frank, E., & Thase, M. E. (1999) · Annual Review of Medicine · doi:10.1146/annurev.med.50.1.453 · Cited by 96
Reversed neurovegetative symptoms of depression: a community study of Ontario
Levitan, R. D., LESAGE, A. D., Parikh, S. V., Goering, P. N., & Kennedy, S. H. (1997) · American Journal of Psychiatry · doi:10.1176/ajp.154.7.934 · Cited by 93
Medically serious adverse effects of newer antidepressants
Mago, R., Mahajan, R., & Thase, M. E. (2008) · Current Psychiatry Reports · doi:10.1007/s11920-008-0041-2 · Cited by 34
The neurobiology of stress and its relevance to psychotherapy
Gold, P. W. (2005) · Clinical Neuroscience Research · doi:10.1016/j.cnr.2005.03.006 · Cited by 24
Shapiro, P., Lidagoster, L., & Glassman, A. (1997) · Psychiatric Annals · doi:10.3928/0048-5713-19970501-10 · Cited by 20
Diagnosis and Treatment of a Major Depressive Episode
Thase, M. E. (2009) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.8001cc10c · Cited by 3
Flagged first, then by citations
Research works printed but not linked: 4
- 1994, British Journal of Psychiatry, 165, 16
- 10.1038/sj/mp/4001032 · DOI
- 10.1001/jama.267.9.1244 · DOI · Paper page
- 1992, Emotion and the amygdala, 339
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Sheng, J., Shui, L., Wang, Y., Cui, R., & Zhang, X. (2017) · Neural Plasticity · doi:10.1155/2017/9724371 · Cited by 852
The organization of the stress system and its dysregulation in depressive illness
Gold, P. W. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.163 · Cited by 654
Organization of the Locus Coeruleus-Norepinephrine System
Schwarz, L. A., & Luo, L. (2015) · Current Biology · doi:10.1016/j.cub.2015.09.039 · Cited by 578
The Rodent Forced Swim Test Measures Stress-Coping Strategy, Not Depression-like Behavior
Commons, K. G., Cholanians, A. B., Babb, J. A., & Ehlinger, D. G. (2017) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.7b00042 · Cited by 525
Beck, A. T., & Bredemeier, K. (2016) · Clinical Psychological Science · doi:10.1177/2167702616628523 · Cited by 510
Metadata
- Authors
- Gold, P. W., Machado-Vieira, R., & Pavlatou, M. G.
- Affiliations
- National Institutes of Health (US)
- National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, MD 20892, USA
- Corresponding author
- Gold, Phillip W.
- ORCID
- Pavlatou, Maria G.
- Venue
- Neural Plasticity
- Publisher
- Hindawi Limited
- Published
- 2015
- Volume
- 2015
- Pages
- 1-11
- ISSN
- 1687-5443 (ISSN-L)
- 2090-5904
- PMC
- PMC4387963
- OpenAlex
- W2055457894
- Cited by
- 259
- References
- 53
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 15 · 2023: 17 · 2022: 17 · 2021: 26 · 2020: 24 · 2019: 24 · 2018: 27 · 2017: 29 · 2016: 20 · 2015: 6
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Neural Plasticity (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- major depressive disorder, stress system, neurobiology of stress, depression pathophysiology, antidepressant mechanism, depression subtypes, inflammation, insulin resistance, oxidative stress, hypercoagulability, treatment-resistant depression, antidepressant side effects
- MeSH terms
- Animals, Brain, Depressive Disorder, Homeostasis, Humans, Inflammation, Neuronal Plasticity, Stress, Physiological, Stress, Psychological, Oxidative Stress, Neurogenesis
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