Changes in steroidogenesis in psychoneurological diseases as a pathological aspect of the development of clinical phenomena
Keywords:
steroid hormones, neurosteroids, adrenal glands, stress, psychoneurological diseases, neurodegeneration, autism
Abstract
The review focuses on the function of steroid hormones as an important component of the neuroimmunoendocrine regulatory system responsible for adaptation of the body both at the physiological and behavioral levels. The authors address the neurobiological effects of steroid hormones, their contribution as trophic and immunoregulatory factors, and as modulators of neuronal excitability in maintaining normal functioning of the central nervous system, including their role in its adaptation to stress triggers. Neurosteroidogenesis is described as a mechanism for the production of auto- and paracrine regulators in the central nervous system, along with individual neurobiological effects of glucocorticoids and sex steroids. Changes in the production of steroids with neuroactive properties, primarily caused by stress-induced hypothalamic-pituitary-adrenal axis dysregulation, are considered as a factor of the development and progression of central pathology. The review discusses the involvement of steroid changes in adult and pediatric neuropsychiatric diseases, including affective, anxiety, and behavioral disorders, neuroinflammatory and neurodegenerative diseases, neurodevelopmental delays and disorders. A possibility is shown of modulating the endocrine axes, specifically the hypothalamic-pituitary-adrenal axis, with hormonal agents in the treatment of patients.
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References
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[24] Chew L, Sun KL, Sun W, Wang Z, Rajadas J, Flores RE, Arnold E, Jo B, Fung LK. Association of serum allopregnanolone with restricted and repetitive behaviors in adult males with autism. Psychoneuroendocrinology. 2021;123:105039. https://doi.org/10.1016/j.psyneuen.2020.105039
[25] Al-Zaid F. S., Alhader A. F. A., Al-Ayadhi L. Y. A potential role for the adrenal gland in autism. Scientific Reports. 2021;11(1):17743. https://doi.org/10.1038/s41598-021-97266-8
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[27] Spratt EG, Nicholas JS, Brady KT, et al. Enhanced cortisol response to stress in children in autism. J Autism Dev Disord. 2012;42(1):75-81. https://doi.org/10.1007/s10803-011-1214-0
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[29] de Vaan Gitta , Beijers Roseriet , Vervloed Mathijs P. J. , Knoors Harry , Bloeming-Wolbrink Kitty A. , de Weerth Carolina , Verhoeven Ludo Associations between cortisol stress levels and autism symptoms in people with sensory and intellectual disabilities. Frontiers in Education. 2020;5:540387. https://doi.org/10.3389/feduc.2020.540387
[30] Lin J. et al. Cholesterol metabolism pathway in autism spectrum disorder: From animal models to clinical observations. Pharmacology Biochemistry and Behavior. 2023;223:173522. https://doi.org/10.1016/j.pbb.2023.173522
[31] Gillberg C. et al. The role of cholesterol metabolism and various steroid abnormalities in autism spectrum disorders: A hypothesis paper. Autism Research. 2017;10(6):1022-1044. https://doi.org/10.1002/aur.1777
[32] Boero G., Porcu P., Morrow A. L. Pleiotropic actions of allopregnanolone underlie therapeutic benefits in stress-related disease. Neurobiology of stress. 2020;12:100203. https://doi.org/10.1016/j.ynstr.2019.100203
[33] Reddy D. S., Estes W. A. Clinical potential of neurosteroids for CNS disorders. Trends in pharmacological sciences. 2016;37(7):543-561. https://doi.org/10.1016/j.tips.2016.04.003
[34] Maguire J. L., Mennerick S. Neurosteroids: mechanistic considerations and clinical prospects. Neuropsychopharmacology. 2024;49(1):73-82. https://doi.org/10.1038/s41386-023-01626-z
[35] Grimm A. et al. Improvement of neuronal bioenergetics by neurosteroids: implications for age-related neurodegenerative disorders. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2014;1842(12):2427-2438. https://doi.org/10.1016/j.bbadis.2014.09.013
[36] Balan I. et al. Brexanolone therapeutics in post-partum depression involves inhibition of systemic inflammatory pathways. EBioMedicine. 2023;89:104473. https://doi.org/10.1016/j.ebiom.2023. 104473
[37] Fung L. K. et al. Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder. Journal of autism and developmental disorders. 2014;44:2971-2977. https://doi.org/10.1007/s10803-014-2144-4
[1] Yilmaz C. et al. Neurosteroids as regulators of neuroinflammation. Frontiers in Neuroendocrinology. 2019;55:100788. https://doi.org/10.1016/j.yfrne.2019.100788
[2] Lloyd-Evans E., Waller-Evans H. Biosynthesis and signalling functions of central and peripheral nervous system neurosteroids in health and disease. Essays in Biochemistry. 2020;64(3);591-606. https://doi.org/10.1042/EBC20200043
[3] Maninger N. et al. Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). Frontiers in neuroendocrinology. 2009;30(1):65-91. https://doi.org/10.1016/j.yfrne.2008.11.002
[4] Kamin H. S., Kertes D. A. Cortisol and DHEA in development and psychopathology. Hormones and behavior. 2017;89:69-85. https://doi.org/10.1016/j.yhbeh.2016.11.018
[5] Ouanes S., Popp J. High cortisol and the risk of dementia and Alzheimer’s disease: a review of the literature. Front Aging Neurosci. 2019;11:43. https://doi.org/10.3389/fnagi.2019.00043
[6] Bao A. M., Meynen G., Swaab D. F. The stress system in depression and neurodegeneration: focus on the human hypothalamus. Brain research reviews. 2008;57(2):531-553. https://doi.org/10.1016/j.brainresrev.2007.04.005
[7] Kim B. K. et al. Composite contributions of cerebrospinal fluid GABAergic neurosteroids, neuropeptide Y and interleukin-6 to PTSD symptom severity in men with PTSD. Neurobiology of Stress. 2020;12:100220. https://doi.org/10.1016/j.ynstr.2020.100220
[8] Pineles S. L. et al. Associations between PTSD-Related extinction retention deficits in women and plasma steroids that modulate brain GABAA and NMDA receptor activity. Neurobiology of Stress. 2020;13:100225. https://doi.org/10.1016/j.ynstr.2020.100225
[9] Aldred S., Mecocci P. Decreased dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) concentrations in plasma of Alzheimer's disease (AD) patients. Archives of gerontology and geriatrics. 2010;51(1):e16-e18. https://doi.org/10.1016/j.archger.2009.07.001
[10] Bianchi V. E. et al. Androgen therapy in neurodegenerative diseases. Journal of the Endocrine Society. 2020;4(11):bvaa120. https://doi.org/10.1210/jendso/bvaa120
[11] Strous R. D. et al. Analysis of neurosteroid levels in attention deficit hyperactivity disorder. International Journal of Neuropsychopharmacology. 2001;4(3):259-264. https://doi.org/10.1017/S1461145701002462
[12] Chang, J.PC., Su, KP., Mondelli, V. et al. Cortisol and inflammatory biomarker levels in youths with attention deficit hyperactivity disorder (ADHD): evidence from a systematic review with meta-analysis. Transl Psychiatry. 2021;11(1):430. https://doi.org/10.1038/s41398-021-01550-0
[13] Zheng H. F. et al. Neuroactive steroids and related steroids in autism spectrum disorders. Neuropsychiatry. 2018;8(2):468-476. https://doi.org/10.4172/Neuropsychiatry.1000368
[14] Auyeung B. et al. Prenatal versus postnatal sex steroid hormone effects on autistic traits in children at 18 to 24 months of age. Molecular autism. – 2012;3:1-5. https://doi.org/10.1186/2040-2392-3-17
[15] Coscini N. et al. Association between early androgens and autistic traits: A systematic review and meta-analysis. Research in Autism Spectrum Disorders. 2021;85:101789. https://doi.org/10.1016/j.rasd.2021.101789
[16] Wang Z, Zhang B, Mu C, Qiao D, Chen H, Zhao Y, Cui H, Zhang R, Li S. Androgen levels in autism spectrum disorders: a systematic review and meta-analysis. Front Endocrinol. 2024;15:1371148. https://doi.org/10.3389/fendo.2024.1371148
[17] He Q., Wang Y., Liu Z. et al. Analysis of salivary steroid hormones in boys with autism spectrum disorder. BMC Psychiatry. 2023;23(1):105. https://doi.org/10.1186/s12888-023-04586-2
[18] Majewska M. D. et al. Marked elevation of adrenal steroids, especially androgens, in saliva of prepubertal autistic children. European child & adolescent psychiatry. 2014;23:485-498. https://doi.org/10.1007/s00787-013-0472-0
[19] Janšáková K. et al. Alteration of the steroidogenesis in boys with autism spectrum disorders. Translational Psychiatry. 2020;10(1):340. https://doi.org/10.1038/s41398-020-01017-8
[20] Gasser BA, Kurz J, Dick B, Mohaupt MG. Steroid Metabolites Support Evidence of Autism as a Spectrum. Behav Sci (Basel). 2019;9(5):52. https://doi.org/10.3390/bs9050052
[21] Gasser B, Kurz J, Escher G, Mistry HD, Mohaupt MG. Androgens Tend to Be Higher, but What about Altered Progesterone Metabolites in Boys and Girls with Autism?. Life (Basel). 2022;12(7):1004. https://doi.org/10.3390/life12071004
[22] Strous R. D. et al. Lowered DHEA-S plasma levels in adult individuals with autistic disorder. European Neuropsychopharmacology. 2005;15(3):305-309. https://doi.org/10.1016/j.euroneuro.2004.12.004
[23] Croonenberghs J. et al. Serum testosterone concentration in male autistic youngsters. Neuroendocrinology Letters. 2010;31(4):483.
[24] Chew L, Sun KL, Sun W, Wang Z, Rajadas J, Flores RE, Arnold E, Jo B, Fung LK. Association of serum allopregnanolone with restricted and repetitive behaviors in adult males with autism. Psychoneuroendocrinology. 2021;123:105039. https://doi.org/10.1016/j.psyneuen.2020.105039
[25] Al-Zaid F. S., Alhader A. F. A., Al-Ayadhi L. Y. A potential role for the adrenal gland in autism. Scientific Reports. 2021;11(1):17743. https://doi.org/10.1038/s41598-021-97266-8
[26] Gao J. et al. Alteration of peripheral cortisol and autism spectrum disorder: A meta-analysis. Frontiers in psychiatry. 2022;13:928188. https://doi.org/10.3389/fpsyt.2022.928188
[27] Spratt EG, Nicholas JS, Brady KT, et al. Enhanced cortisol response to stress in children in autism. J Autism Dev Disord. 2012;42(1):75-81. https://doi.org/10.1007/s10803-011-1214-0
[28] Corbett BA, Schupp CW, Lanni KE. Comparing biobehavioral profiles across two social stress paradigms in children with and without autism spectrum disorders. Mol Autism. 2012;3(1):13. https://doi.org/10.1186/2040-2392-3-13
[29] de Vaan Gitta , Beijers Roseriet , Vervloed Mathijs P. J. , Knoors Harry , Bloeming-Wolbrink Kitty A. , de Weerth Carolina , Verhoeven Ludo Associations between cortisol stress levels and autism symptoms in people with sensory and intellectual disabilities. Frontiers in Education. 2020;5:540387. https://doi.org/10.3389/feduc.2020.540387
[30] Lin J. et al. Cholesterol metabolism pathway in autism spectrum disorder: From animal models to clinical observations. Pharmacology Biochemistry and Behavior. 2023;223:173522. https://doi.org/10.1016/j.pbb.2023.173522
[31] Gillberg C. et al. The role of cholesterol metabolism and various steroid abnormalities in autism spectrum disorders: A hypothesis paper. Autism Research. 2017;10(6):1022-1044. https://doi.org/10.1002/aur.1777
[32] Boero G., Porcu P., Morrow A. L. Pleiotropic actions of allopregnanolone underlie therapeutic benefits in stress-related disease. Neurobiology of stress. 2020;12:100203. https://doi.org/10.1016/j.ynstr.2019.100203
[33] Reddy D. S., Estes W. A. Clinical potential of neurosteroids for CNS disorders. Trends in pharmacological sciences. 2016;37(7):543-561. https://doi.org/10.1016/j.tips.2016.04.003
[34] Maguire J. L., Mennerick S. Neurosteroids: mechanistic considerations and clinical prospects. Neuropsychopharmacology. 2024;49(1):73-82. https://doi.org/10.1038/s41386-023-01626-z
[35] Grimm A. et al. Improvement of neuronal bioenergetics by neurosteroids: implications for age-related neurodegenerative disorders. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2014;1842(12):2427-2438. https://doi.org/10.1016/j.bbadis.2014.09.013
[36] Balan I. et al. Brexanolone therapeutics in post-partum depression involves inhibition of systemic inflammatory pathways. EBioMedicine. 2023;89:104473. https://doi.org/10.1016/j.ebiom.2023. 104473
[37] Fung L. K. et al. Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder. Journal of autism and developmental disorders. 2014;44:2971-2977. https://doi.org/10.1007/s10803-014-2144-4
Published
2025-06-22
How to Cite
Alexandrenkova A. N., Generalov V. O., Obodzinskaya T. E., Klyushnik T. P., Morozov S. G. Changes in steroidogenesis in psychoneurological diseases as a pathological aspect of the development of clinical phenomena // Patologicheskaya Fiziologiya i Eksperimental’naya Terapiya (Pathological physiology and experimental therapy). 2025. VOL. 69. № 2. PP. 108–116.
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