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Cited by 56Stress Responses and CortisolTreatment of Major DepressionHealth and Well-being Studies

Stress and serum cortisol levels in major depressive disorder: a cross-sectional study

Open access
G Bertollo, Amanda, 1 Laboratory of Physiology Pharmacology and Psychopathology, Graduate Program in Biomedical Sciences, Federal University of the Southern Frontier, Chapecó, SC, Brazil, E Grolli, Roberta, E Plissari, Marcos, A Gasparin, Vanessa, Quevedo, João, Z Réus, Gislaine, D Bagatini, Margarete +7 more·2020·AIMS Neuroscience
DOI 10.3934/neuroscience.2020028PMC PMC7701370
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Abstract

Major depressive disorder (MDD) is one of the disorders that most causes disability and affects about 265 million people worldwide, according to the World Health Organization (WHO). Chronic stress is one of the most prevalent factors that trigger MDD. Among the most relevant biological mechanisms that mediate stress and MDD are changes in the hypothalamic-pituitary-adrenal (HPA) axis function. 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. This study aimed to investigate the levels of stress and cortisol in individuals diagnosed with MDD from the Basic Health Unit (BHU) in a small city in the western region of Santa Catarina, Brazil. Depression scores were assessed using Beck's inventory. For the investigation of stress, an adaptation with twenty-four questions of the Checklist-90-R manual was performed. The analysis of the cortisol levels in the individuals' serum was by the chemiluminescence method. Depression and stress scores were significantly higher in individuals with MDD than in control subjects (p < 0.001). Cortisol levels were also significantly higher in individuals with MDD (p < 0.05). Besides, depression scores were positively correlated with stress scores in individuals with MDD (Pearson's "r" = 0.70). Conclusion: Individuals with MDD had higher stress levels and cortisol than control subjects. The positive correlation between the levels of stress and depression in MDD individuals suggests that these conditions are related to a dysregulation of the HPA axis function.

AI snapshot

Written from the paper’s full text.

TL;DR

In a small cross-sectional study in Brazil, individuals with major depressive disorder (MDD) had higher depression, stress, and serum cortisol levels than controls, and depression scores correlated positively with stress scores. The authors suggest chronic stress-related HPA-axis dysregulation may underlie MDD in this sample.

Key findings

  • Beck Depression Inventory scores were significantly higher in MDD individuals than controls (means ± SEM: 24.42 ± 2.86 vs. 9.88 ± 1.65; p < 0.001).
  • Stress scores on the Checklist-90-R adaptation were significantly higher in MDD individuals than controls (50.64 ± 5.37 vs. 22.71 ± 3.70; p < 0.001).
  • Serum cortisol levels were significantly higher in MDD individuals than controls (11.92 ± 1.02 vs. 7.99 ± 0.83 mcg/dL; p < 0.05).
  • Depression scores were positively correlated with stress scores in MDD individuals (Pearson’s r = 0.70), but there was no significant correlation between depression scores and cortisol levels, or between stress scores and cortisol levels.

Methods

  • Cross-sectional study of 17 individuals clinically diagnosed with MDD treated at a Basic Health Unit and 17 control subjects, all over 18 years of age, free of other pathology, and without medication for at least 30 days before the study; conducted in a small municipality in western Santa Catarina, Brazil, with about 5,000 inhabitants.
  • Depression was assessed with Beck’s Depression Inventory; stress was assessed with a 24-item adaptation from the Checklist-90-R; serum cortisol was measured by chemiluminescence using an Immulite 2000.
  • Independent-groups t-tests and Pearson correlation were used, with significance set at p < 0.05; analyses were performed in Statistica.

Limitations

  • The paper states that a probable limitation is the small number of individuals evaluated, while noting that clinically confirmed depression scores and stress/cortisol indicators strengthen the results.
  • Evident from the text: the cross-sectional design cannot establish causality; the sample was predominantly female (controls: 17 F/0 M; MDD: 15 F/2 M) and drawn from one small rural, low-socioeconomic municipality, limiting generalizability.
  • Evident from the text: despite higher group-level cortisol in MDD, cortisol did not significantly correlate with depression or stress scores, which the authors do not explain.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3934/neuroscience.2020028

Cites

38 of 38 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

9 of 21 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Chronic stress throughout life involves biological changes that underlie MDD in many patients and in laboratory animals.

    “Chronic stress throughout life involves several biological changes, which are underlying MDD in many patients and in laboratory animals [4],[6],[9].”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [4] Ignácio ZM, Réus GZ, Abelaira HM, et al., Quetiapine treatment reverses depressive-like behavior and reduces DNA methyltransferase activity induced by maternal deprivation, <em>Behav Brain Res</em> source
    • cites [6] Ignácio ZM, Réus GZ, Abelaira HM, et al., Epigenetic and epistatic interactions between serotonin transporter and brain-derived neurotrophic factor genetic polymorphism: insights in depression, <em>Neuroscience</em> source
    • cites [9] 9. Gold PW, Machado-Vieira R, Pavlatou MG (2015) Clinical and biochemical manifestations of depression: relation to the neurobiology of stress. <em>Neural Plast</em> 2015: 581976. source
  • Premisecitation

    In a recent meta-analysis, cortisol was the only biological marker that increased the odds for both the onset and relapse/recurrence of MDD.

    “It is crucial to highlight the results in a recent meta-analysis, which found that cortisol was the only biological marker that increased the odds for both the onset and relapse/recurrence of MDD [35].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [35] Kennis M, Gerritsen L, Van Dalen M, et al., Prospective biomarkers of major depressive disorder: a systematic review and meta-analysis, <em>Mol Psychiatry</em> source
  • Premisecitation

    Stressful events in childhood, adolescence, or adulthood can trigger psychiatric disorders such as depression.

    “Stressful events in childhood, adolescence, or adulthood are considered villains due to their ability to trigger psychiatric disorders, such as depression or depressive-like behaviors in animals [3],[4].”
    • Also stated in: § Discussion · boosted
      “Exposure to life stressors is one of the most relevant precipitating factors in developing depressive episodes [32].”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [3] Chapman DP, Whitfield CL, Felitti VJ, et al., Adverse childhood experiences and the risk of depressive disorders in adulthood, <em>J Affect Disord</em> source
    • cites [4] Ignácio ZM, Réus GZ, Abelaira HM, et al., Quetiapine treatment reverses depressive-like behavior and reduces DNA methyltransferase activity induced by maternal deprivation, <em>Behav Brain Res</em> source
    • cites [32] Hill MN, Hellemans KG, Verma P, et al., Neurobiology of chronic mild stress: parallels to major depression, <em>Neurosci Biobehav Rev</em> source

      The Introduction (page unavailable) describes life stressors as a precipitating factor for depressive episodes in humans and chronic mild stress as a rodent model of depression. It does not establish the claim for stressful events at each specified life stage—childhood, adolescence, and adulthood—and cautions that stress does not invariably lead to depression. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • Findingown data

    Serum cortisol levels were significantly higher in individuals with MDD than in control subjects (p < 0.05).

    “Regarding serum cortisol, MDD individuals had significantly higher levels than control subjects. Results are expressed as Means ± SEM of micrograms per deciliter of serum (mcg/dL) (Patients = 11.92 ± 1.02; Controls = 7.99 ± 0.83; p < 0.05). (Figure 4).”
    • Also stated in: § Abstract · plain
      “Cortisol levels were also significantly higher in individuals with MDD (p < 0.05).”
    Quote in the paperSubstantial claim
  • Findingown data

    There was no significant correlation between depression scores and cortisol levels in individuals with MDD.

    “Although cortisol levels are significantly higher in MDD individuals, correlation analysis showed no significant correlation between depression scores and cortisol levels.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 6
  • May combine two claims. 7

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The Checklist-90-R is useful in assessing depressive and anxious symptoms.

    “The results suggested a beneficial effect of the therapy, corroborating the scale's usefulness in assessing depressive and anxious symptoms [30].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [30] DiNapoli EA, Pierpaoli CM, Shah A, et al., Effects of Home-Delivered Cognitive Behavioral Therapy (CBT) for Depression on Anxiety Symptoms among Rural, Ethnically Diverse Older Adults, <em>Clin Gerontol</em> source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Low socioeconomic status is a significant risk factor for MDD.

    “Although MDD is present in individuals of various social situations, it seems to increase considerably in poor populations and low socioeconomic status, suggesting that this condition is a significant risk factor for the disorder [7],[16],[17].”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [7] Hasin DS, Sarvet AL, Meyers JL, et al., Epidemiology of Adult DSM-5 Major Depressive Disorder and Its Specifiers in the United States, <em>JAMA Psychiatry</em> source

      The DSM-5 MDD Prevalence and Sociodemographic Correlates section reports greater odds of 12-month MDD in lower household-income categories. The Discussion also identifies an association with low income, but acknowledges that depression-impaired functioning could lead to lower income. The paper therefore supports an association, not the stronger claim that low socioeconomic status is an established risk factor causing MDD. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [16] Lorant V, Deliege D, Eaton W, et al., Socioeconomic inequalities in depression: a meta-analysis, <em>Am J Epidemiol</em> source
    • cites [17] 17. Husain N, Creed F, Tomenson B (2002) Depression and social stress in Pakistan. <em>Psychol Med</em> 30: 395–402.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Some rural populations are highly prone to MDD, and rural residence is associated with high depression rates and high stress.

    “In addition to socio-cultural factors, some research has indicated differences in the proportion of patients and severity of MDD between urban and rural communities, suggesting that some rural populations are highly prone to MDD [18].”
    • Also stated in: § Introduction · plain
      “Šidlauskaitė-Stripeikienė et al. [19] observed a rural community high rate of depression among adults, correlated with a low level of education, low social support, and social network, and high levels of stress.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [18] 18. Probst JC, Laditka S, Moore CG, et al. (2005) Depression in rural populations: Prevalence, effects on life quality and treatment-seeking behavior. <em>South Carolina Rural Health Res Cent,</em> 1–64.

      Not checked in the free run.

    • cites [19] Sidlauskaitė-Stripeikienė I, Zemaitienė N, Klumbienė J, Associations between depressiveness and psychosocial factors in Lithuanian rural population, <em>Medicina</em> source

      The Results and Discussion report high levels of depressiveness among Lithuanian rural adults and an association between depressiveness and perceived stress. They do not establish rates or severity of diagnosed MDD, compare urban and rural communities, or show that rural residence itself is associated with higher depression or stress. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationcitation

    The predominance of individuals in a rural community and low socioeconomic status in the study population are substantial factors underlying chronic stress and vulnerability for MDD development.

    “These conditions are substantial factors underlying chronic stress and vulnerability for MDD development.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [18] 18. Probst JC, Laditka S, Moore CG, et al. (2005) Depression in rural populations: Prevalence, effects on life quality and treatment-seeking behavior. <em>South Carolina Rural Health Res Cent,</em> 1–64.

      Not checked in the free run.

    • cites [19] Sidlauskaitė-Stripeikienė I, Zemaitienė N, Klumbienė J, Associations between depressiveness and psychosocial factors in Lithuanian rural population, <em>Medicina</em> source

      The Abstract reports that lower education and higher stress were associated with depressiveness in a Lithuanian rural sample. The Discussion says the cross-sectional study cannot establish causation. It does not show that rural residence or low socioeconomic status causes chronic stress or vulnerability to major depressive disorder. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Hypercortisolism is a relevant feature associated with melancholic-type depression and is present in many people with MDD and in animals subjected to stress.

    “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.”
    • Also stated in: § Introduction · plain
      “Hypercortisolism is a relevant feature associated with melancholic-type depression [9].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [9] 9. Gold PW, Machado-Vieira R, Pavlatou MG (2015) Clinical and biochemical manifestations of depression: relation to the neurobiology of stress. <em>Neural Plast</em> 2015: 581976. source

      Section 5.1 associates hypercortisolism with major depression with melancholic features, and Section 2 lists it among signs of melancholia. The copy does not establish that it is present in many people with MDD generally or in laboratory animals subjected to stress; Section 8 discusses heightened stress responses in experimental animals without identifying hypercortisolism. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The chemiluminescence cortisol assay was adjusted in four replicates when starting the routine analysis on the device.

    “According to the manufacturer's recommendations, adjustments were made in four replicates when starting the routine chemiluminescence analysis on this device.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    The Beck Depression Inventory has high internal consistency and validity in differentiating between MDD individuals and controls.

    “The Beck depression inventory is one of the most widely used scales worldwide and has high internal consistency and validity in differentiating between MDD individuals and controls [24].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] 24. Gorestein C, Andrade LHSG (1998) Inventário de depressão de Beck: propriedades psicométricas da versão em português. <em>Rev de Psiquiatr Clín</em> 25: 245–250.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    Depression scores through the inventory were clinically confirmed.

    “However, depression scores through the inventory are clinically confirmed.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    In these MDD individuals, stress is involved with hyperactivity of the HPA axis and increased cortisol levels, which may be a mechanism mediating stress and MDD.

    “Thus, the evidence in this study suggests that stress is involved with hyperactivity of the HPA axis, with increased levels of cortisol, which is possibly a relevant mechanism mediating stress and MDD in these individuals.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Serum cortisol level is a valid indicator of HPA axis activity.

  • May combine two claims.

    Interpretationreasoning

    In these MDD individuals, chronic stress is involved in elevated cortisol levels, which appears to be at least in part the underlying mechanism of MDD.

    “These results suggest that chronic stress is involved in elevated cortisol levels, which, at least in part, appears to be the underlying mechanism of MDD in these individuals.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Serum cortisol level is a valid indicator of HPA axis activity.

  • May combine two claims.

    Premisecitation

    Chronic stress can deregulate the HPA axis feedback system, increase cortisol levels, and culminate in glucocorticoid resistance.

    “Although changes in the HPA axis may differ according to the MDD subtype, scientific literature has shown that chronic stress can deregulate the axis feedback system, increase cortisol levels [34], and culminate in a situation of resistance to glucocorticoids [13].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [34] Dean J, Keshavan M, The neurobiology of depression: An integrated view, <em>Asian J Psychiatr</em> source
    • cites [13] Ignácio ZM, Da Silva RS, Plissari ME, et al., Physical Exercise and Neuroinflammation in Major Depressive Disorder, <em>Mol Neurobiol</em> source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    A probable limitation of this study is the small number of individuals evaluated.

    “A probable limitation of this study is related to the small number of individuals evaluated.”
    Quote in the paperNot a substantial claim
12 of 12

  • The paper relies on this without support.

    Serum cortisol level is a valid indicator of HPA axis activity.

    “Thus, the evidence in this study suggests that stress is involved with hyperactivity of the HPA axis, with increased levels of cortisol, which is possibly a relevant mechanism mediating stress and MDD in these individuals.”
1 of 1

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Cortisol sample described as both plasma and serum

    Minor

    The statistical methods say plasma cortisol levels were analyzed, while the results identify the measured cortisol levels as serum. Plasma and serum are different sample types.

1 of 1

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Authors
G Bertollo, A., 1 Laboratory of Physiology Pharmacology and Psychopathology, G. P. I. B. S., E Grolli, R., E Plissari, M., A Gasparin, V., Quevedo, J., Z Réus, G., D Bagatini, M., M Ignácio, Z., 2 Santa Catarina State University, W. H. E. C., 3 Laboratory of Translational Psychiatry, G. P. I. H. S., 4 Center of Excellence on Mood Disorders, F. D. O. P. A. B. S., 5 Translational Psychiatry Program, F. D. O. P. A. B. S., 6 Neuroscience Graduate Program, G. S. O. B. S., & 7 Laboratory of Cell Culture, G. P. I. B. S.
Affiliations
The University of Texas Health Science Center at Houston (US)
ORCID
Quevedo, João
Venue
AIMS Neuroscience
Publisher
American Institute of Mathematical Sciences (AIMS)
Published
2020
Volume
7
Issue
4
Pages
459-469
ISSN
2373-7972 (ISSN-L)
DOI
10.3934/neuroscience.2020028
PMC
PMC7701370
OpenAlex
W3100729513
Semantic Scholar
0371ff2ef9920547129e9a23f58541b57dd1dacc
Cited by
56
References
38
Citations by year
2026: 14 · 2025: 12 · 2024: 8 · 2023: 14 · 2022: 5 · 2021: 3
FWCI
3.07
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • AIMS neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Social Sciences › Psychology › Clinical Psychology › Health and Well-being Studies
Keywords
major depressive disorder, chronic stress, serum cortisol, hypercortisolism, HPA axis dysregulation, primary care patients

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