Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications
Neurosteroids are a group of important endogenous molecules affecting many neural functions in the brain. Increasing evidence suggests a possible role of these neurosteroids in the pathology and symptomatology of schizophrenia (SZ) and other mental disorders. The aim of this review is to summarize t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-03-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fpsyt.2018.00073/full |
| _version_ | 1828808468850540544 |
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| author | HuaLin Cai HuaLin Cai Ting Cao Ting Cao Xiang Zhou Xiang Zhou Jeffrey K. Yao Jeffrey K. Yao Jeffrey K. Yao |
| author_facet | HuaLin Cai HuaLin Cai Ting Cao Ting Cao Xiang Zhou Xiang Zhou Jeffrey K. Yao Jeffrey K. Yao Jeffrey K. Yao |
| author_sort | HuaLin Cai |
| collection | DOAJ |
| description | Neurosteroids are a group of important endogenous molecules affecting many neural functions in the brain. Increasing evidence suggests a possible role of these neurosteroids in the pathology and symptomatology of schizophrenia (SZ) and other mental disorders. The aim of this review is to summarize the current knowledge about the neural functions of neurosteroids in the brain, and to evaluate the role of the key neurosteroids as candidate modulators in the etiology and therapeutics of SZ. The present paper provides a brief introduction of neurosteroid metabolism and distribution, followed by a discussion of the mechanisms underlying neurosteroid actions in the brain. The content regarding the modulation of the GABAA receptor is elaborated, given the considerable knowledge of its interactions with other neurotransmitter and neuroprotective systems, as well as its ameliorating effects on stress that may play a role in the SZ pathophysiology. In addition, several preclinical and clinical studies suggested a therapeutic benefit of neurosteroids in SZ patients, even though the presence of altered neurosteroid pathways in the circulating blood and/or brain remains debatable. Following treatment of antipsychotic drugs in SZ, therapeutic benefits have also been linked to the regulation of neurosteroid signaling. Specifically, the neurosteroids such as pregnenolone and dehydroepiandrosterone affect a broad spectrum of behavioral functions through their unique molecular characteristics and may represent innovative therapeutic targets for SZ. Future investigations in larger cohorts with long-term follow-ups will be required to ascertain the neuropsychopharmacological role of this yet unexploited class of neurosteroid agents. |
| first_indexed | 2024-12-12T08:42:08Z |
| format | Article |
| id | doaj.art-108358a87b5d41efb834824adf6f5e1c |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-12-12T08:42:08Z |
| publishDate | 2018-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-108358a87b5d41efb834824adf6f5e1c2022-12-22T00:30:45ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402018-03-01910.3389/fpsyt.2018.00073321928Neurosteroids in Schizophrenia: Pathogenic and Therapeutic ImplicationsHuaLin Cai0HuaLin Cai1Ting Cao2Ting Cao3Xiang Zhou4Xiang Zhou5Jeffrey K. Yao6Jeffrey K. Yao7Jeffrey K. Yao8Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, ChinaThe Institute of Clinical Pharmacy, Central South University, Changsha, ChinaDepartment of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, ChinaThe Institute of Clinical Pharmacy, Central South University, Changsha, ChinaMedical Research Service, VA Pittsburgh Healthcare System, Pittsburgh, PA, United StatesDepartment of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, United StatesMedical Research Service, VA Pittsburgh Healthcare System, Pittsburgh, PA, United StatesDepartment of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, United StatesDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, United StatesNeurosteroids are a group of important endogenous molecules affecting many neural functions in the brain. Increasing evidence suggests a possible role of these neurosteroids in the pathology and symptomatology of schizophrenia (SZ) and other mental disorders. The aim of this review is to summarize the current knowledge about the neural functions of neurosteroids in the brain, and to evaluate the role of the key neurosteroids as candidate modulators in the etiology and therapeutics of SZ. The present paper provides a brief introduction of neurosteroid metabolism and distribution, followed by a discussion of the mechanisms underlying neurosteroid actions in the brain. The content regarding the modulation of the GABAA receptor is elaborated, given the considerable knowledge of its interactions with other neurotransmitter and neuroprotective systems, as well as its ameliorating effects on stress that may play a role in the SZ pathophysiology. In addition, several preclinical and clinical studies suggested a therapeutic benefit of neurosteroids in SZ patients, even though the presence of altered neurosteroid pathways in the circulating blood and/or brain remains debatable. Following treatment of antipsychotic drugs in SZ, therapeutic benefits have also been linked to the regulation of neurosteroid signaling. Specifically, the neurosteroids such as pregnenolone and dehydroepiandrosterone affect a broad spectrum of behavioral functions through their unique molecular characteristics and may represent innovative therapeutic targets for SZ. Future investigations in larger cohorts with long-term follow-ups will be required to ascertain the neuropsychopharmacological role of this yet unexploited class of neurosteroid agents.http://journal.frontiersin.org/article/10.3389/fpsyt.2018.00073/fullneurosteroidsGABAA receptormetabolismclinical trial as topicschizophrenia |
| spellingShingle | HuaLin Cai HuaLin Cai Ting Cao Ting Cao Xiang Zhou Xiang Zhou Jeffrey K. Yao Jeffrey K. Yao Jeffrey K. Yao Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications Frontiers in Psychiatry neurosteroids GABAA receptor metabolism clinical trial as topic schizophrenia |
| title | Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications |
| title_full | Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications |
| title_fullStr | Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications |
| title_full_unstemmed | Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications |
| title_short | Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications |
| title_sort | neurosteroids in schizophrenia pathogenic and therapeutic implications |
| topic | neurosteroids GABAA receptor metabolism clinical trial as topic schizophrenia |
| url | http://journal.frontiersin.org/article/10.3389/fpsyt.2018.00073/full |
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