Hypothalamic-Pituitary-Adrenal Axis Function in Chronic Schizophrenia: Association with Clinical Features
Abstract
The function of the hypothalamic-pituitary-adrenal axis (HPA-axis) and its association with clinical features in chronic schizophrenia were investigated. Twenty of 33 chronic schizophrenics exhibited an abnormal diurnal variation of the saliva cortisol level. The patients with abnormal diurnal variation gave higher scores for some negative symptoms than those with normal diurnal variation. On the dexamethasone suppression test (DST) of saliva samples, 13 of 34 chronic schizophrenics were abnormal. The patients with DST nonsuppression were more frequently classified into disorganized type and exhibited low scores of anxiety compared with the patients with normal suppression. The 9 patients who showed abnormal diurnal variation and DST nonsuppression were more frequently classified into disorganized type and showed higher scores of negative symptoms than the 9 patients who did not show any abnormal cortisol data. These results suggest that there might be some disturbance in the function of the HPA-axis in a group of chronic schizophrenics and that these patients might have severe negative symptoms.
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Altered regulation of the HPA axis in schizophrenia is predictive of more severe psychotic and motor symptoms.
“Furthermore, altered regulation of the HPA axis in SZ is predictive of more severe psychotic and motor symptoms159,160.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [160]
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Schizophrenia: A neural diathesis-stress model.
Walker, E. F., & Diforio, D. (1997) · Psychological Review · doi:10.1037//0033-295x.104.4.667 · Cited by 930 · see citing works
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Ryan, M. C. M., Collins, P. B., & Thakore, J. H. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.2.284 · Cited by 828 · see citing works
Koenig, J. I., Elmer, G. I., Shepard, P. D., Lee, P. R., Mayo, C. L., Joy, B., Hercher, E., & Brady, D. L. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.05.030 · Cited by 297 · see citing works
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Elkis, H. (1995) · Archives of General Psychiatry · doi:10.1001/archpsyc.1995.03950210029008 · Cited by 259 · see citing works
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Ryan, M. C. M., & Thakore, J. H. (2002) · Life Sciences · doi:10.1016/s0024-3205(02)01646-6 · Cited by 251 · see citing works
Phillips, L., McGorry, P. D., Garner, B., Thompson, K. N., Pantelis, C., Wood, S. J., & Berger, G. E. (2006) · Australian & New Zealand Journal of Psychiatry · doi:10.1080/j.1440-1614.2006.01877.x · Cited by 230 · see citing works
Zhang, X. Y., Zhou, D. F., Cao, L. Y., Wu, G. Y., & Shen, Y. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300756 · Cited by 208 · see citing works
“…suggest a relationship between HPA activity and symptomatology in SCH. Cortisol secretion has been associated with more severe positive symptoms (Kaneko et al, 1992; Walder et al, 2000), whereas in others it was associated with higher ratings of negative symptoms (Newcomer et al, 1991; Tandon…”
BackgroundGlucocorticoid hormones and early brain development in schizophrenia
Ph.D., J. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00396-7 · Cited by 199 · see citing works
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BackgroundMethodResultInfluentialThe Relationship of Sex Hormones and Cortisol with Cognitive functioning in Schizophrenia
Halari, R., Kumari, V., Mehrotra, R., Wheeler, M., Hines, M., & Sharma, T. (2004) · Journal of Psychopharmacology · doi:10.1177/026988110401800307 · Cited by 82 · see citing works
“There are observations of a positive relationship between cortisol levels and positive (Rybakowski et al., 1991; Kaneko et al., 1992) as well as negative symptom scores (Newcomer et al.”
BackgroundCodoñer‐Franch, P., Gombert, M., Martı́nez-Raga, J., & Cénit, M. C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087579 · Cited by 69 · see citing works
“In addition, the altered regulation of the hypothalamic–pituitary–adrenal (HPA) axis in SCZ appears to be predictive of more severe psychotic and motor symptoms [86].”
BackgroundZhang, C., Xu, D., Luo, H., Lü, J., Liu, L., Ping, J., & Wang, H. (2014) · Toxicology · doi:10.1016/j.tox.2014.08.015 · Cited by 60 · see citing works
Sexual Function in Women with Epilepsy
Duncan, S., Blacklaw, J., Beastall, G. H., & Brodie, M. J. (1997) · Epilepsia · doi:10.1111/j.1528-1157.1997.tb01196.x · Cited by 59 · see citing works
Mitropoulou, V., Goodman, M. S., Sevy, S. M., Elman, I., New, A. S., Iskander, E. G., Silverman, J. M., Breier, A. F., & Siever, L. J. (2003) · Schizophrenia Research · doi:10.1016/j.schres.2003.10.008 · Cited by 51 · see citing works
Enlarged hypothalamic volumes in schizophrenia
Tognin, S., Rambaldelli, G., Perlini, C., Bellani, M., Marinelli, V., Zoccatelli, G., Alessandrini, F., Pizzini, F. B., Beltramello, A., Terlevic, R., et al. (2012) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2012.10.006 · Cited by 47 · see citing works
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Kiss, A., Bundzikova, J., Pirník, Z., & Mikkelsen, J. D. (2009) · Journal of Neuroscience Research · doi:10.1002/jnr.22226 · Cited by 43 · see citing works
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BackgroundResultInfluentialKelly, D. L., Rowland, L. M., Patchan, K. M., Sullivan, K. M., Earl, A. K., Raley, H., Liu, F., Feldman, S., & McMahon, R. P. (2016) · Child and Adolescent Psychiatry and Mental Health · doi:10.1186/s13034-016-0092-9 · Cited by 42 · see citing works
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Neuropeptide Systems and Schizophrenia
LaCrosse, A., & Olive, M. F. (2013) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527311312050010 · Cited by 39 · see citing works
“, the dexamethasone suppression test), and this non-suppression is correlated with increased negative and cognitive symptoms, poorer prognosis, and ventricular enlargement [76-80].”
BackgroundDisrupted circadian rhythms and mental health
Walker, W. H., Walton, J. C., & Nelson, R. J. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-819975-6.00016-9 · Cited by 45 · see citing works
Some biological correlates of drug resistance in schizophrenia: A multidimensional approach
Altamura, A. C., Bassetti, R., Cattaneo, E., & Vismara, S. (2005) · The World Journal of Biological Psychiatry · doi:10.1080/15622970510030027 · Cited by 37 · see citing works
“In some of them cortisol secretion was associated with more severe positive symptoms (Kaneko et al. 1992; Walder et al. 2000), whereas in others it was associated with higher ratings of negative symptoms (Newcomer et al. 1991; Tandon et al. 1991).”
BackgroundThe developmental pathways to schizophrenia: Potential moderating effects of stress
Walker, E. F., Neumann, C. C., Baum, K. M., Davis, D. M., Diforio, D., & Bergman, A. J. (1996) · Development and Psychopathology · doi:10.1017/s0954579400007343 · Cited by 37 · see citing works
“After the first year, how- later-day decline (Kaneko et al., 1992; Van ever, cortisol levels gradually increase, then Cauter et al., 1991).”
BackgroundEvaluation of a salivary based combined dexamethasone/CRH test in patients with major depression
Baghai, T. C., Schüle, C., Zwanzger, P., Minov, C., Holme, C., Padberg, F., Bidlingmaier, M., Strasburger, C. J., & Rupprecht, R. (2002) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(01)00060-9 · Cited by 36 · see citing works
“, 1987), schizophrenia (Kaneko et al., 1992), premenstrual syndrome (Odber et al.”
BackgroundMotor dysfunction in schizotypal personality disorder
Neumann, C. S., & Walker, E. F. (1999) · Schizophrenia Research · doi:10.1016/s0920-9964(99)00011-0 · Cited by 32 · see citing works
Increased prefrontal sulcal prominence in relatively young patients with unipolar major depression
Elkis, H., Friedman, L., Buckley, P. F., Lee, H. S., Lys, C., Kaufman, B., & Meltzer, H. Y. (1996) · Psychiatry Research Neuroimaging · doi:10.1016/0925-4927(96)02744-8 · Cited by 27 · see citing works
D'Reaux, R. A., Neumann, C. S., & Rhymer, K. N. (2000) · Schizophrenia Research · doi:10.1016/s0920-9964(99)00196-6 · Cited by 24 · see citing works
Stress axis dysfunction in schizophrenia
Yeap, S., & Thakore, J. H. (2005) · European Psychiatry · doi:10.1016/s0924-9338(05)80181-6 · Cited by 22 · see citing works
Zorrilla, E. P., Cannon, T. D., Kessler, J., & Gur, R. E. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(97)00358-2 · Cited by 21 · see citing works
The biochemical womb of schizophrenia: A review
Gaur, N., Gautam, S., Gaur, M. C., Sharma, P., Dadheech, G., & Mishra, S. (2008) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-008-0071-x · Cited by 20 · see citing works
Ho, R. T. H., Fong, T. C. T., Wan, A. H. Y., Au-Yeung, F. S. W., Chen, E. Y. H., & Spiegel, D. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.06.014 · Cited by 19 · see citing works
LI, X., & Xu, H. (2006) · International review of neurobiology · doi:10.1016/s0074-7742(06)77004-0 · Cited by 18 · see citing works
Hypothalamic‐Pituitary‐Adrenocortical Axis: Neuropsychiatric Aspects
Jacobson, L. (2014) · Comprehensive physiology · doi:10.1002/j.2040-4603.2014.tb00561.x · Cited by 17 · see citing works
“Where HPA hyperactivity or dexamethasone nonsuppression was observed, it was difficult to relate to negative (withdrawal) or positive (hallucination) symptoms, although there may be a better correlation with negative symptoms in long-standing schizophrenia (39,202,369,461).”
Pituitary volume in schizophrenia spectrum disorders
Romo‐Nava, F., Hoogenboom, W. S., Pelavin, P. E., Alvarado, J. L., Bobrow, L., MacMaster, F. P., Keshavan, M. S., McCarley, R. W., & Shenton, M. E. (2013) · Schizophrenia Research · doi:10.1016/j.schres.2013.02.024 · Cited by 16 · see citing works
“More specifically, the HPA axis has been associated with stress responsivity, and there is also evidence that these two systems are closely related in schizophrenia (Kaneko et al., 1992; Walker and Diforio, 1997).”
BackgroundSchizophrénie, diabète et antipsychotiques
Gury, C. (2004) · L Encéphale · doi:10.1016/s0013-7006(04)95452-8 · Cited by 16 · see citing works
Salinity History of Coastal Marshes Reconstructed from Diatom Remains
Parsons, M. L., Dortch, Q., Turner, R. E., et al. (1999) · Estuaries · doi:10.2307/1353085 · Cited by 15 · see citing works
Feroz, F. S., Leicht, G., Rauh, J., & Mulert, C. (2018) · Brain Topography · doi:10.1007/s10548-018-0677-0 · Cited by 13 · see citing works
Plasma cortisol levels and illness appraisal in deficit syndrome schizophrenia
White, R. G., Lysaker, P. H., Gumley, A. I., McLeod, H. J., McCleery, M., O’Neill, D., MacBeth, A. M., Giurgi-Oncu, C., & Mulholland, C. C. (2014) · Psychiatry Research · doi:10.1016/j.psychres.2014.08.043 · Cited by 8 · see citing works
“Peralta et al. (2014) recently found no significant difference in levels of depression between individuals with deficit syndrome compared to non-deficit syndrome.”
Goldman, M. B., & Wood, G. J. (2000) · Neuroendocrinology · doi:10.1159/000054560 · Cited by 8 · see citing works
Babinkostova, Z., Stefanovski, B., Janićević-Ivanovska, D., & Samardziska, V. (2015) · Open Access Macedonian Journal of Medical Sciences · doi:10.3889/oamjms.2015.018 · Cited by 7 · see citing works
“The neuroendocrinologic system, particularly the HPA axis, has been a focus of interest for neurobiological studies aiming at elucidating the cause of schizophrenia [1].”
BackgroundWoldesenbet, Y. M., Alenko, A., Tadesse, I., Gedefaw, L., & Fikru, C. (2021) · SAGE Open Medicine · doi:10.1177/20503121211056216 · Cited by 7 · see citing works
Gallagher, P., & Ritsner, M. S. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9838-3_3 · Cited by 5 · see citing works
Babinkostova, Z., Stefanovski, B., Janićević-Ivanovska, D., Samardziska, V., & Stojanovska, L. (2015) · PubMed · Cited by 5 · see citing works
At-risk mental state and prediction
Yung, A. R., Klosterkötter, J., Cornblatt, B. A., & Schultze‐Lutter, F. (2009) · Cambridge University Press eBooks · doi:10.1017/cbo9780511576287.007 · Cited by 5 · see citing works
Schizophrenia and Immune Responses
Gaughran, F., & Welch, J. (2007) · Springer eBooks · doi:10.1007/978-0-387-30398-7_21 · Cited by 4 · see citing works
Bioactive Compounds of Tucuma (Astrocaryum aculeatum G. Mey.)
da Cruz, I. B. M., Barbisan, F., & Ribeiro, E. E. (2019) · Reference series in phytochemistry · doi:10.1007/978-3-030-06120-3_13-1 · Cited by 3 · see citing works
Antipsychotic natural products
Skalicka‐Woźniak, K., & Gertsch, J. (2020) · Annual reports in medicinal chemistry · doi:10.1016/bs.armc.2020.03.004 · Cited by 3 · see citing works
The impact of social isolation on rat behaviour
Porkess, V. (2008) · Nottingham ePrints (University of Nottingham) · Cited by 3 · see citing works
The Neuroimmune System in Psychiatric Disorders
Leyrer‐Jackson, J. M., DeKrey, G. K., & Thomas, M. P. (2016) · Springer eBooks · doi:10.1007/978-3-319-44022-4_39 · Cited by 2 · see citing works
Babinkostova, Z., Stefanovski, B., Janićević-Ivanovska, D., Samardziska, V., & Stojanovska, L. (2015) · PRILOZI · doi:10.1515/prilozi-2015-0042 · Cited by 5 · see citing works
“In some studies cortisol secretion was primarily associated with more severe positive symptoms [2, 5, 25], whereas in others it was associated with higher ratings of negative symptoms [7, 17, 26].”
BackgroundResultThe Neuroimmune System in Psychiatric Disorders
Murrin, L. C., & Thomas, M. P. (2008) · Springer eBooks · doi:10.1007/978-0-387-72573-4_34 · Cited by 2 · see citing works
Κωνσταντοπούλου, Γ., Ioakeimidi, M., Assimakopoulos, K., & Tsermpini, E. E. (2021) · International Journal of Medical Science and Clinical Research Studies · doi:10.47191/ijmscrs/v1-i9-05 · Cited by 1 · see citing works
Reynolds, F. D. (2004) · doi:10.12794/metadc4492 · Cited by 1 · see citing works
Diabetes‐Associated Comorbidities
(2011) · Wiley eBooks · doi:10.1002/9781119950424.ch9
Antiepileptika und Hormone bei Frauen
Schmitz, B. (2006) · Clinical Epileptology · doi:10.1007/s10309-006-0212-2
Toward a Unified Model of Neurogenetics
Tankou, S. K., & Sawa, A. (2007) · CRC Press eBooks · doi:10.3109/9781420019544-10
Fathy, H., Hamed, H., & Ali, K. M. (2015) · Middle East Current Psychiatry · doi:10.1097/01.xme.0000457454.30741.61
Toward a Unified Model of Neurogenetics
Tankou, S. K., & Sawa, A. (2007) · Medical psychiatry · doi:10.3109/9781420019544.007
Shahini, N., derakhshanopour, F., Chalakinia, N., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3596339/v1
- Authors
- Kaneko, M., Yokoyama, F., Hoshino, Y., Takahagi, K., Murata, S., Watanabe, M., & Kumashiro, H.
- Affiliations
- Fukushima Medical University (JP)
- Venue
- Neuropsychobiology
- Publisher
- S. Karger AG
- Published
- 2008-02-21
- Volume
- 25
- Issue
- 1
- Pages
- 1-7
- ISSN
- 0302-282X (ISSN-L)
- 1423-0224
- OpenAlex
- W2075611022
- Cited by
- 70
- References
- 0
- Citations by year
- 2023: 2 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 1 · 2016: 3 · 2015: 4 · 2014: 5 · 2013: 2 · 2012: 1
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropsychobiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- hypothalamic-pituitary-adrenal axis, chronic schizophrenia, diurnal cortisol rhythm, salivary cortisol, dexamethasone suppression test, negative symptoms, anxiety, HPA axis dysregulation
- MeSH terms
- Adult, Aged, Chronic Disease, Circadian Rhythm, Cognition Disorders, Dexamethasone, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Male, Middle Aged, Pituitary-Adrenal System, Psychiatric Status Rating Scales, Saliva, Schizophrenia, Antipsychotic Agents, Comorbidity
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