Plasma cortisol in first episode drug-naive mania: differential levels in euphoric versus irritable mood
Open accessAbstract
Background Dysregulation of HPA axis has been widely described in subjects with bipolar disorder (BD), including changes in cortisol levels during mood episodes and euthymia. However, most of the studies were done with medicated BD patients with variable length of illness, which was shown to interfere on peripheral cortisol levels. Therefore, the present study aims to evaluate plasma cortisol levels in drug-naïve BD subjects during the first manic episode, as well as investigate the relationship between plasma cortisol levels and manic symptomatology.Methods Twenty-six drug-naïve patients were enrolled meeting criteria for a first manic episode in bipolar I disorder. Severity of mania was assessed using the Young Mania Rating Scale (YMRS). The control group included 27 healthy subjects matched by age and gender. Cortisol was quantified using a direct radioimmunoassay.Results Plasma cortisol levels were decreased during first manic episode compared to healthy controls. Higher cortisol levels were positively associated with the presence of irritability (dysphoria), while elated mania showed lower cortisol levels compared to controls.Limitation Data including larger samples are lacking.Conclusion Higher cortisol in dysphoric mania compared to predominantly elated/euphoric mania may indicate a clinical and neurobiological polymorphic phenomenon, potentially involving a higher biological sensitivity to stress in the presence of irritable mood. The present findings highlight the importance to add a dimensional approach to the traditional categorical diagnosis for future neurobiological studies in BD.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Indices of HPA axis function are associated with the severity of symptoms of bipolar disorder.
“indices of HPA axis function are associated with the severity of symptoms of BD (Belvederi Murri et al. 2014;Valiengo et al. 2012)”
From The HPA axis in bipolar disorder: Systematic review and meta-analysis (2016) · cites this paper as Valiengo et al. 2012
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Diagnostic and Statistical Manual of Mental Disorders ( DSM ‐ IV ‐ TR )
Segal, D. L. (2010) · Wiley eBooks · doi:10.1002/9780470479216.corpsy0271 · Cited by 4,683 · see citing works
Hammen, C. (2005) · Annual Review of Clinical Psychology · doi:10.1146/annurev.clinpsy.1.102803.143938 · Cited by 2,979 · see citing works
Davenport, Y. B., Adland, M. L., Gold, P. W., & Goodwin, F. K. (1984) · The Lancet · doi:10.1016/s0140-6736(84)92810-1 · Cited by 2,925 · see citing works
THE EFFECTS OF STRESSFUL LIFE EVENTS ON DEPRESSION
Kessler, R. C. (1997) · Annual Review of Psychology · doi:10.1146/annurev.psych.48.1.191 · Cited by 2,111 · cited 1× · see citing works
“The relationship between stress and mood disorders is well documented (Hammen, 2005; Kessler, 1997).”
BackgroundMcEwen, B. S. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.11.071 · Cited by 1,864 · see citing works
Stress and the hypothalamic pituitary adrenal axis in the developmental course of schizophrenia
Walker, E., Mittal, V., & Tessner, K. (2008) · Annual Review of Clinical Psychology · doi:10.1146/annurev.clinpsy.4.022007.141248 · Cited by 615 · see citing works
Clinical and research implications of the diagnosis of dysphoric or mixed mania or hypomania
McElroy, S. L., Keck, P. E., Pope, H. G., Hudson, J. I., Faedda, G. L., & Swann, A. C. (1992) · American Journal of Psychiatry · doi:10.1176/ajp.149.12.1633 · Cited by 428 · see citing works
Carlson, G. A. (1973) · Archives of General Psychiatry · doi:10.1001/archpsyc.1973.01750320053009 · Cited by 424 · see citing works
Hypothalamic-Pituitary-Adrenal Axis Activity in Depressive Illness
Schlesser, M. A. (1980) · Archives of General Psychiatry · doi:10.1001/archpsyc.1980.01780200015001 · Cited by 387 · 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
Fernandes, P., Ramaswamy, S., Marcil, W., & Petty, F. (2007) · xPharm: The Comprehensive Pharmacology Reference · doi:10.1016/b978-008055232-3.60649-x · Cited by 294 · see citing works
Minireview: Stress-related psychiatric disorders with low cortisol levels: A metabolic hypothesis
Yehuda, R., & Seckl, J. (2011) · Endocrinology · doi:10.1210/en.2011-1218 · Cited by 276 · see citing works
Bradley, A. J., & Dinan, T. G. (2010) · Journal of Psychopharmacology · doi:10.1177/1359786810385491 · Cited by 258 · see citing works
Hypothalamic-pituitary-adrenal axis and bipolar disorder
Daban, C., Vieta, E., Mackin, P., & Young, A. H. (2005) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2005.01.005 · Cited by 245 · see citing works
Incidence and Significance of Mixed Affective States in a Bipolar Population
Himmelhoch, J. M. (1976) · Archives of General Psychiatry · doi:10.1001/archpsyc.1976.01770090052004 · Cited by 230 · see citing works
RYBAKOWSKI, J. K., & Twardowska, K. (1999) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(99)00014-x · Cited by 212 · see citing works
Signs and symptoms of mania in pure and mixed episodes
Cassidy, F., Murry, E., Forest, K., & Carroll, B. J. (1998) · Journal of Affective Disorders · doi:10.1016/s0165-0327(98)00016-0 · Cited by 188 · see citing works
Schmider, 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
Pépin, M.-C., Beaulieu, S., & Barden, N. (1989) · Molecular Brain Research · doi:10.1016/0169-328x(89)90031-4 · Cited by 136 · see citing works
Effect of 5-Hydroxytryptophan on Serum Cortisol Levels in Major Affective Disorders
Meltzer, H. Y. (1984) · Archives of General Psychiatry · doi:10.1001/archpsyc.1984.01790150069010 · Cited by 118 · see citing works
The 24-Hour Profiles of Cortisol, Prolactin, and Growth Hormone Secretion in Mania
Linkowski, P. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950080028004 · Cited by 116 · see citing works
Hypothalamic‐pituitary‐adrenocortical function in mixed and pure mania
Swann, A. C., Stokes, P. E., Casper, R. C., Secunda, S. K., Bowden, C. L., Berman, N., Katz, M. M., & Robins, E. (1992) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1992.tb01468.x · Cited by 101 · see citing works
Abnormal cortisol suppression in bipolar patients with simultaneous manic and depressive symptoms
Krishnan, R. R., Maltbie, A. A., & Davidson, J. R. T. (1983) · American Journal of Psychiatry · doi:10.1176/ajp.140.2.203 · Cited by 79 · see citing works
The dexamethasone suppression test in mixed bipolar disorder
Evans, D. L., & Nemeroff, C. B. (1983) · American Journal of Psychiatry · doi:10.1176/ajp.140.5.615 · Cited by 79 · see citing works
High levels of cortisol among adolescent offspring of parents with bipolar disorder: a pilot study
Ellenbogen, M. A., Hodgins, S., & Walker, C. D. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(02)00135-x · Cited by 77 · see citing works
Rush, A. J., Giles, D. E., Schlesser, M. A., Orsulak, P. J., Weissenburger, J. E., Fulton, C. L., Fairchild, C., & Roffwarg, H. P. (1997) · Biological Psychiatry · doi:10.1016/s0006-3223(97)00148-0 · Cited by 75 · see citing works
The Cortisol Awakening Response in Bipolar Illness: A Pilot Study
Deshauer, D., Duffy, A. C., Alda, M., Grof, E., Albuquerque, J., & Grof, P. (2003) · The Canadian Journal of Psychiatry · doi:10.1177/070674370304800706 · Cited by 65 · see citing works
VIETA, E., MARTÍNEZ-DE-OSABA, M. J., COLOM, F., MARTÍNEZ-ARÁN, A., BENABARRE, A., & GASTÓ, C. (1999) · Psychological Medicine · doi:10.1017/s0033291799008727 · Cited by 62 · see citing works
Bschor, T., Lewitzka, U., Sasse, J., Adli, M., Köberle, U., & Bauer, M. (2003) · Pharmacopsychiatry · doi:10.1055/s-2003-45135 · Cited by 59 · see citing works
Swann, A. C., Stokes, P. E., Secunda, S. K., et al. (1994) · Biological Psychiatry · doi:10.1016/0006-3223(94)91143-6 · Cited by 57 · see citing works
Depressão e estresse: existe um endofenótipo?
Mello, A. F., Juruena, M. F., Pariante, C. M., Tyrka, A. R., Price, L. H., Carpenter, L. L., & Del Porto, J. A. (2007) · Revista Brasileira de Psiquiatria · doi:10.1590/s1516-44462007000500004 · Cited by 56 · see citing works
Self-citationLithium, arginine vasopressin and the dex/CRH test in mood disordered patients
Watson, S., Gallagher, P., Smith, M. S., Young, A. H., & Ferrier, I. N. (2007) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2007.02.010 · Cited by 23 · see citing works
Eroǧlu, L., Atamer-Şimşek, Ş., Yazıcı, O., et al. (1979) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.1979.tb05917.x · Cited by 22 · see citing works
Individual differences in plasma cortisol changes during mania and depression
Joyce, P. R., Donald, R. A., & Elder, P. A. (1987) · Journal of Affective Disorders · doi:10.1016/0165-0327(87)90054-1 · Cited by 18 · see citing works
Increased CSF cortisol levels after neuroleptic treatment in schizophrenia
Gattaz, W. F. (1985) · Psychoneuroendocrinology · doi:10.1016/0306-4530(85)90012-5 · Cited by 13 · see citing works
Self-citationThe dexamethasone suppression test in acute mania
Godwin, C. (1984) · Journal of Affective Disorders · doi:10.1016/0165-0327(84)90049-1 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The HPA axis in bipolar disorder: Systematic review and meta-analysis
Belvederi Murri, M., Prestia, D., Mondelli, V., Pariante, C., Patti, S., Olivieri, B., Arzani, C., Masotti, M., Respino, M., Antonioli, M., et al. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.10.014 · Cited by 391 · see citing works
What is mood? A computational perspective
Clark, J. E., Watson, S., & Friston, K. J. (2018) · Psychological Medicine · doi:10.1017/s0033291718000430 · Cited by 204 · see citing works
Berk, L., Hallam, K. T., Venugopal, K., Lewis, A. J., Austin, D. W., Kulkarni, J., Dodd, S., de Castella, A., Fitzgerald, P. B., & Berk, M. (2017) · Bipolar Disorders · doi:10.1111/bdi.12486 · Cited by 22 · see citing works
- Authors
- 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.
- Affiliations
- National Institutes of Health (US)
- Universidade de São Paulo (BR)
- University of Toronto (CA)
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 138
- Issue
- 1-2
- Pages
- 149-152
- ISSN
- 0165-0327 (ISSN-L)
- PMC
- PMC4479259
- OpenAlex
- W2105519253
- Cited by
- 36
- References
- 37
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2022: 5 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 6 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 6 · 2013: 1
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Fapesp (2009/14891-9)
- Associação Beneficente Alzira Denise Hertzog da Silva (ABADHS)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Personality Disorders and Psychopathology
- Keywords
- plasma cortisol, bipolar I disorder, first manic episode, drug-naive patients, HPA axis dysregulation, irritable mood, dysphoric mania, stress sensitivity, dimensional diagnosis
- MeSH terms
- Adult, Bipolar Disorder, Euphoria, Humans, Hydrocortisone, Irritable Mood, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
