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Li J, Pang L, Liu F, Lu Z, Zhang Y, Yang Y, Li X, Hu Q, Su K, Chen Y, Zhang Y, Zhao F, Song X, Hei G. Disentangling the topological symptom structure of schizophrenia: A network analysis. Schizophr Res 2025; 275:115-122. [PMID: 39701019 DOI: 10.1016/j.schres.2024.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 10/23/2024] [Accepted: 12/08/2024] [Indexed: 12/21/2024]
Abstract
BACKGROUND AND HYPOTHESIS The Positive and Negative Syndrome Scale (PANSS), comprehensively assesses schizophrenia severity. While network analyses of schizophrenic symptoms have yielded inconsistent results, components of disorganized thought consistently rank high in centrality. The present study aims to explore the centrality of disorganized thought across patient subgroups and its potential as a treatment target. We hypothesize that disorganized thought will emerge as a central feature in the symptom network across different patient populations. STUDY DESIGN We conducted a network psychometric analysis on data from 1435 schizophrenia patients, stratified into four groups based on family history and sex. Local and global network properties, including centrality, clustering coefficient, degree, density, and community detection, were investigated. Network comparisons were performed across groups, and results were validated using an independent dataset. STUDY RESULTS Disorganized thought emerged as the most central factor in Marder 5-factor model, maintaining stability across family history and sex differences. While family history did not significantly impact symptom structures (Females: M = 0.2, P = 0.4; S = 0.4, P = 0.7; Males: M = 0.2, P = 0.7; S = 0.1, P = 0.9), significant differences were observed between male and female symptom structures (Positive family history: M = 0.3, P < 0.05; Negative family history: M = 0.3, P < 0.01). The centrality and high stability of disorganized thought were further confirmed in the validation dataset. CONCLUSIONS The consistent centrality of disorganized thought across different patient subgroups suggests its potential as a key treatment target for schizophrenia.
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Affiliation(s)
- Jingjing Li
- Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan International Joint Laboratory of Biological Psychiatry, Zhengzhou University, Zhengzhou, China; Henan Psychiatric Transformation Research Key Laboratory, Zhengzhou University, Zhengzhou, China
| | - Lijuan Pang
- Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan International Joint Laboratory of Biological Psychiatry, Zhengzhou University, Zhengzhou, China; Henan Psychiatric Transformation Research Key Laboratory, Zhengzhou University, Zhengzhou, China
| | - Fang Liu
- Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Department of Operations Management, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhe Lu
- Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, China
| | - Yu Zhang
- Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan International Joint Laboratory of Biological Psychiatry, Zhengzhou University, Zhengzhou, China; Henan Psychiatric Transformation Research Key Laboratory, Zhengzhou University, Zhengzhou, China
| | - Yongfeng Yang
- Henan International Joint Laboratory of Biological Psychiatry, Zhengzhou University, Zhengzhou, China; Department of Psychiatry, Henan Mental Hospital, the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Xue Li
- Henan International Joint Laboratory of Biological Psychiatry, Zhengzhou University, Zhengzhou, China; Department of Psychiatry, Henan Mental Hospital, the Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Qiushi Hu
- Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan International Joint Laboratory of Biological Psychiatry, Zhengzhou University, Zhengzhou, China; Henan Psychiatric Transformation Research Key Laboratory, Zhengzhou University, Zhengzhou, China
| | - Keju Su
- Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan International Joint Laboratory of Biological Psychiatry, Zhengzhou University, Zhengzhou, China; Henan Psychiatric Transformation Research Key Laboratory, Zhengzhou University, Zhengzhou, China
| | - Yishao Chen
- Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan International Joint Laboratory of Biological Psychiatry, Zhengzhou University, Zhengzhou, China; Henan Psychiatric Transformation Research Key Laboratory, Zhengzhou University, Zhengzhou, China
| | - Yan Zhang
- Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan International Joint Laboratory of Biological Psychiatry, Zhengzhou University, Zhengzhou, China; Henan Psychiatric Transformation Research Key Laboratory, Zhengzhou University, Zhengzhou, China
| | - Fangfang Zhao
- Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan International Joint Laboratory of Biological Psychiatry, Zhengzhou University, Zhengzhou, China; Henan Psychiatric Transformation Research Key Laboratory, Zhengzhou University, Zhengzhou, China
| | - Xueqin Song
- Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan International Joint Laboratory of Biological Psychiatry, Zhengzhou University, Zhengzhou, China; Henan Psychiatric Transformation Research Key Laboratory, Zhengzhou University, Zhengzhou, China.
| | - Gangrui Hei
- Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan International Joint Laboratory of Biological Psychiatry, Zhengzhou University, Zhengzhou, China; Henan Psychiatric Transformation Research Key Laboratory, Zhengzhou University, Zhengzhou, China.
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Seeman MV. Sex/Gender differences in schizophrenia: Thinking back and thinking forward. Psychiatry Res 2022; 316:114738. [PMID: 35905691 DOI: 10.1016/j.psychres.2022.114738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 07/17/2022] [Accepted: 07/21/2022] [Indexed: 10/16/2022]
Abstract
This commentary summarizes my view of my life's work in psychiatry, which has mainly been devoted to my obsessive interest in sex and gender differences in schizophrenia. I summarize the influences that guided my research and I take the opportunity to make some personal recommendations to future researchers.
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Affiliation(s)
- Mary V Seeman
- Professor Emerita, Department of Psychiatry, University of Toronto, #605 260 Heath Street West, Toronto, Ontario, Canada, M5P 3L6.
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Gui Y, Zhou X, Wang Z, Zhang Y, Wang Z, Zhou G, Zhao Y, Liu M, Lu H, Zhao H. Sex-specific genetic association between psychiatric disorders and cognition, behavior and brain imaging in children and adults. Transl Psychiatry 2022; 12:347. [PMID: 36028495 PMCID: PMC9418275 DOI: 10.1038/s41398-022-02041-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 06/22/2022] [Accepted: 06/29/2022] [Indexed: 11/09/2022] Open
Abstract
Although there are pronounced sex differences for psychiatric disorders, relatively little has been published on the heterogeneity of sex-specific genetic effects for these traits until very recently for adults. Much less is known about children because most psychiatric disorders will not manifest until later in life and existing studies for children on psychiatric traits such as cognitive functions are underpowered. We used results from publicly available genome-wide association studies for six psychiatric disorders and individual-level data from the Adolescent Brain Cognitive Development (ABCD) study and the UK Biobank (UKB) study to evaluate the associations between the predicted polygenic risk scores (PRS) of these six disorders and observed cognitive functions, behavioral and brain imaging traits. We further investigated the mediation effects of the brain structure and function, which showed heterogeneity between males and females on the correlation between genetic risk of schizophrenia and fluid intelligence. There was significant heterogeneity in genetic associations between the cognitive traits and psychiatric disorders between sexes. Specifically, the PRSs of schizophrenia of boys showed stronger correlation with eight of the ten cognitive functions in the ABCD data set; whereas the PRSs of autism of females showed a stronger correlation with fluid intelligence in the UKB data set. Besides cognitive traits, we also found significant sexual heterogeneity in genetic associations between psychiatric disorders and behavior and brain imaging. These results demonstrate the underlying early etiology of psychiatric disease and reveal a shared and unique genetic basis between the disorders and cognition traits involved in brain functions between the sexes.
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Affiliation(s)
- Yuanyuan Gui
- grid.16821.3c0000 0004 0368 8293State Key Laboratory of Microbial metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China ,grid.16821.3c0000 0004 0368 8293SJTU-Yale Joint Center for Biostatistics and Data Science, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaocheng Zhou
- grid.16821.3c0000 0004 0368 8293State Key Laboratory of Microbial metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China ,grid.16821.3c0000 0004 0368 8293SJTU-Yale Joint Center for Biostatistics and Data Science, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Zixin Wang
- grid.16821.3c0000 0004 0368 8293State Key Laboratory of Microbial metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China ,grid.16821.3c0000 0004 0368 8293SJTU-Yale Joint Center for Biostatistics and Data Science, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Yiliang Zhang
- grid.47100.320000000419368710Department of Biostatistics, Yale School of Public Health, New Haven, CT USA
| | - Zhaobin Wang
- grid.16821.3c0000 0004 0368 8293State Key Laboratory of Microbial metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China ,grid.16821.3c0000 0004 0368 8293SJTU-Yale Joint Center for Biostatistics and Data Science, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
| | - Geyu Zhou
- grid.47100.320000000419368710Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT USA
| | - Yize Zhao
- grid.47100.320000000419368710Department of Biostatistics, Yale School of Public Health, New Haven, CT USA
| | - Manhua Liu
- grid.16821.3c0000 0004 0368 8293MoE Key Laboratory of Artificial Intelligence, AI Institute, Shanghai Jiao Tong University, Shanghai, China
| | - Hui Lu
- State Key Laboratory of Microbial metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. .,SJTU-Yale Joint Center for Biostatistics and Data Science, Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
| | - Hongyu Zhao
- Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA. .,Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.
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Shinn AK, Carol EE. The Importance of Context in Identifying the Recovery Needs of Women With Psychosis. J Clin Psychiatry 2021; 82:21com13936. [PMID: 34010523 PMCID: PMC8759245 DOI: 10.4088/jcp.21com13936] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Stam N, Taipale H, Tanskanen A, Isphording L, Okhuijsen‐Pfeifer C, Schuiling‐Veninga CC, Bos JH, Bijker BJ, Tiihonen J, Luykx JJ. Persistence of Antipsychotic Use After Clozapine Discontinuation: A Real-World Study Across Antipsychotics. Clin Transl Sci 2020; 13:1170-1177. [PMID: 32441836 PMCID: PMC7719358 DOI: 10.1111/cts.12801] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 04/07/2020] [Indexed: 01/08/2023] Open
Abstract
Although clozapine treatment is often discontinued due to limited efficacy or low tolerability, there is a lack of guidelines and evidence on treatment options after discontinuation of clozapine in patients with schizophrenia. Persistence has proven to be an adequate indicator for treatment effectiveness in patients with schizophrenia. The aim of this study was, therefore, to compare persistence of antipsychotic use between antipsychotic treatment options in patients after stopping clozapine treatment. Registry data from a prescription database representative of the Dutch population (1996-2017) was collected to investigate persistence in patients with schizophrenia who had been using clozapine for ≥ 90 days. Persistence with antipsychotics after clozapine discontinuation was analyzed using Cox-proportional hazard regression models. Our study population consisted of 321 participants, of whom 138 re-initiated clozapine and 183 started some other antipsychotic in the year after clozapine discontinuation (N = 518 antipsychotic use periods, N = 9,178 months). Second-generation antipsychotics (SGAs) as a group were associated with better persistence compared to first-generation antipsychotics (adjusted hazard ratio (aHR), 0.73; 95% confidence interval (CI) 0.57-0.93; P = 0.011). Compared with other antipsychotics, the following oral monotherapy antipsychotics were associated with significantly better persistence: restarting clozapine (aHR 0.48; 95% CI 0.32-0.71; P < 0.001) and switching to risperidone (aHR 0.52; 95% CI 0.32-0.84; P = 0.008) or olanzapine (aHR 0.55; 95% CI 0.35-0.87; P = 0.010). Sensitivity analyses confirmed the results. In conclusion, oral SGAs are associated with better persistence than alternative antipsychotic treatment options in patients discontinuing clozapine for undefined reasons. Especially clozapine (except in those with previous serious adverse reactions to clozapine), olanzapine and risperidone should be considered as oral monotherapy for these patients.
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Affiliation(s)
- Noraly Stam
- Department of PsychiatryUMC Utrecht Brain CenterUniversity Medical Center UtrechtUtrecht UniversityUtrechtThe Netherlands
| | - Heidi Taipale
- Department of Clinical NeuroscienceKarolinska InstitutetStockholmSweden
- Department of Forensic PsychiatryUniversity of Eastern FinlandNiuvanniemi HospitalKuopioFinland
- School of PharmacyUniversity of Eastern FinlandKuopioFinland
| | - Antti Tanskanen
- Department of Clinical NeuroscienceKarolinska InstitutetStockholmSweden
- Department of Forensic PsychiatryUniversity of Eastern FinlandNiuvanniemi HospitalKuopioFinland
- Public Health SolutionsNational Institute for Health and WelfareHelsinkiFinland
| | - Luka Isphording
- Department of PsychiatryUMC Utrecht Brain CenterUniversity Medical Center UtrechtUtrecht UniversityUtrechtThe Netherlands
| | - Cynthia Okhuijsen‐Pfeifer
- Department of PsychiatryUMC Utrecht Brain CenterUniversity Medical Center UtrechtUtrecht UniversityUtrechtThe Netherlands
| | - Catharina C.M. Schuiling‐Veninga
- Department of Pharmacotherapy, Epidemiology, and EconomicsFaculty of Science and EngineeringUniversity of GroningenGroningenThe Netherlands
| | - Jens H.J. Bos
- Department of Pharmacotherapy, Epidemiology, and EconomicsFaculty of Science and EngineeringUniversity of GroningenGroningenThe Netherlands
| | - Bert J. Bijker
- Department of Pharmacotherapy, Epidemiology, and EconomicsFaculty of Science and EngineeringUniversity of GroningenGroningenThe Netherlands
| | - Jari Tiihonen
- Department of Clinical NeuroscienceKarolinska InstitutetStockholmSweden
- Department of Forensic PsychiatryUniversity of Eastern FinlandNiuvanniemi HospitalKuopioFinland
- Center for Psychiatric ResearchStockholm City CouncilStockholmSweden
| | - Jurjen J. Luykx
- Department of PsychiatryUMC Utrecht Brain CenterUniversity Medical Center UtrechtUtrecht UniversityUtrechtThe Netherlands
- Department of Translational NeuroscienceUMC Utrecht Brain CenterUniversity Medical Center UtrechtUtrecht UniversityUtrechtThe Netherlands
- GGNet Mental HealthApeldoornThe Netherlands
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6
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Zhang Z, Li Y, He F, Cui Y, Zheng Y, Li R. Sex differences in circulating neuregulin1-β1 and β-secretase 1 expression in childhood-onset schizophrenia. Compr Psychiatry 2020; 100:152176. [PMID: 32430144 DOI: 10.1016/j.comppsych.2020.152176] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Revised: 04/10/2020] [Accepted: 04/13/2020] [Indexed: 02/01/2023] Open
Abstract
OBJECTIVE Early-onset schizophrenia is a severe and rare form of schizophrenia that is clinically and neurobiologically continuous with the adult form of schizophrenia. Neuregulin1 (NRG1)-mediated signaling is crucial for early neurodevelopment, which exerts its function by limited β-secretase 1 (BACE1) proteolysis processing. However, circulating neuregulin1-β1 (NRG1-β1), an isoform of NRG1, and its cleavage enzyme BACE1 have not been studied in early-onset patients with schizophrenia. METHODS In this study, we collected plasma and clinical information from 71 young patients (7 ≤ age years ≤20) with schizophrenia and 53 age- and sex-matched healthy controls. Immunoassay was used to test levels of circulating NRG1-β1 and BACE1 expression. We further analyzed the relationship of disease-onset age and gender with NRG1-β1 and BACE1 levels. RESULTS We found that circulating plasma levels of NRG1-β1 were significantly decreased in young patients with early-onset schizophrenia. In males with childhood onset schizophrenia (COS), NRG1-β1 was reduced and was inversely correlated with positive symptom of PANSS; moreover, these male patients with higher plasma BACE1 levels showed more severe general symptoms of PANSS and defective social functioning; whereas, no aforementioned results were found in adolescent-onset schizophrenia (AOS). Notably, young female patients with COS and AOS had no significant change in NRG1-β1 and BACE1, which demonstrated a sex-dependent effect in early-onset schizophrenia. CONCLUSION Our results suggest that decreased levels of NRG1-β1 and its cleavage enzyme BACE1 contribute to increased risk of etiology of schizophrenia. Synthetic biomarkers may have clinical applications for the early diagnosis of male COS.
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Affiliation(s)
- Zhengrong Zhang
- National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China
| | - Yuhong Li
- Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China
| | - Fan He
- National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China
| | - Yonghua Cui
- National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China
| | - Yi Zheng
- National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China.
| | - Rena Li
- National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China; Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China.
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7
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Seeman MV. Women who suffer from schizophrenia: Critical issues. World J Psychiatry 2018; 8:125-136. [PMID: 30425943 PMCID: PMC6230925 DOI: 10.5498/wjp.v8.i5.125] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 08/24/2018] [Accepted: 10/11/2018] [Indexed: 02/05/2023] Open
Abstract
Many brain diseases, including schizophrenia, affect men and women unequally - either more or less frequently, or at different times in the life cycle, or to varied degrees of severity. With updates from recent findings, this paper reviews the work of my research group over the last 40 years and underscores issues that remain critical to the optimal care of women with schizophrenia, issues that overlap with, but are not identical to, the cares and concerns of men with the same diagnosis. Clinicians need to be alert not only to the overarching needs of diagnostic groups, but also to the often unique needs of women and men.
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Affiliation(s)
- Mary V Seeman
- Department of Psychiatry, University of Toronto, Institute of Medical Science, Toronto, ON M5P 3L6, Canada
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Monte AS, Mello BSF, Borella VCM, da Silva Araujo T, da Silva FER, Sousa FCFD, de Oliveira ACP, Gama CS, Seeman MV, Vasconcelos SMM, Lucena DFD, Macêdo D. Two-hit model of schizophrenia induced by neonatal immune activation and peripubertal stress in rats: Study of sex differences and brain oxidative alterations. Behav Brain Res 2017; 331:30-37. [PMID: 28527693 DOI: 10.1016/j.bbr.2017.04.057] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Revised: 04/09/2017] [Accepted: 04/10/2017] [Indexed: 02/06/2023]
Abstract
Schizophrenia is considered to be a developmental disorder with distinctive sex differences. Aiming to simulate the vulnerability of the third trimester of human pregnancy to the developmental course of schizophrenia, an animal model was developed, using neonatal poly(I:C) as a first-hit, and peripubertal stress as a second-hit, i.e. a two-hit model. Since, to date, there have been no references to sex differences in the two-hit model, our study sought to determine sex influences on the development of behavior and brain oxidative change in adult rats submitted to neonatal exposure to poly(I:C) on postnatal days 5-7 as well as peripubertal unpredictable stress (PUS). Our results showed that adult two-hit rats present sex-specific behavioral alterations, with females showing more pronounced deficits in prepulse inhibition of the startle reflex and hyperlocomotion, while males showing more deficits in social interaction. Male and female animals exhibited similar working memory deficits. The levels of the endogenous antioxidant, reduced glutathione, were decreased in the prefrontal cortex (PFC) of both male and female animals exposed to both poly(I:C) and poly(I:C)+PUS. Only females presented decrements in GSH levels in the striatum. Nitrite levels were increased in the PFC of male and in the striatum of female poly(I:C)+PUS rats. Increased lipid peroxidation was observed in the PFC of females and in the striatum of males and females exposed to poly(I:C) and poly(I:C)+PUS. Thus, the present study presents evidence for sex differences in behavior and oxidative brain change induced by a two-hit model of schizophrenia.
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Affiliation(s)
- Aline Santos Monte
- Drug Research and Development Center, Department of Physiology and Pharmacology, Universidade Federal do Ceará, Fortaleza, CE, Brazil.
| | - Bruna Stefânia Ferreira Mello
- Drug Research and Development Center, Department of Physiology and Pharmacology, Universidade Federal do Ceará, Fortaleza, CE, Brazil.
| | - Vládia Célia Moreira Borella
- Drug Research and Development Center, Department of Physiology and Pharmacology, Universidade Federal do Ceará, Fortaleza, CE, Brazil.
| | - Tatiane da Silva Araujo
- Drug Research and Development Center, Department of Physiology and Pharmacology, Universidade Federal do Ceará, Fortaleza, CE, Brazil.
| | | | - Francisca Cléa F de Sousa
- Drug Research and Development Center, Department of Physiology and Pharmacology, Universidade Federal do Ceará, Fortaleza, CE, Brazil.
| | | | - Clarissa Severino Gama
- Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Programa de Pós-Graduação em Psiquiatria e Ciências do Comportamento, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
| | - Mary V Seeman
- Departament of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
| | | | - David Freitas De Lucena
- Drug Research and Development Center, Department of Physiology and Pharmacology, Universidade Federal do Ceará, Fortaleza, CE, Brazil; National Institute for Developmental Psychiatry (INCT - INPD, CNPq), Brazil.
| | - Danielle Macêdo
- Drug Research and Development Center, Department of Physiology and Pharmacology, Universidade Federal do Ceará, Fortaleza, CE, Brazil; National Institute for Translational Medicine (INCT-TM, CNPq), Brazil.
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Abstract
OBJECTIVE The aim of this review is to examine three questions: What are the risks and benefits of treating women with schizophrenia with hormone therapy (HT) at menopause? Should the antipsychotic regimen be changed at menopause? Do early- and late-onset women with schizophrenia respond differently to HT at menopause? METHODS MEDLINE databases for the years 1990 to 2016 were searched using the following interactive terms: schizophrenia, gender, menopause, estrogen, and hormones. The selected articles (62 out of 800 abstracts) were chosen on the basis of their applicability to the objectives of this targeted narrative review. RESULTS HT during the perimenopause in women with schizophrenia ameliorates psychotic and cognitive symptoms, and may also help affective symptoms. Vasomotor, genitourinary, and sleep symptoms are also reduced. Depending on the woman's age and personal risk factors and antipsychotic side effects, the risk of breast cancer and cardiovascular disease may be increased. Antipsychotic types and doses may need to be adjusted at menopause, as may be the mode of administration. CONCLUSIONS Both HT and changes in antipsychotic management should be considered for women with schizophrenia at menopause. The question about differences in response between early- and late-onset women cannot yet be answered.
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Affiliation(s)
- Amnon Brzezinski
- 1Department of Obstetrics and Gynecology, The Hebrew University-Hadasssah Medical Center, Jerusalem, Israel 2Ben-Gurion University Medical School, Beer-Sheba, Israel 3Department of Psychiatry, University of Toronto, Canada
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Abstract
Interest in the negative symptoms of schizophrenia has increased rapidly over the last several decades, paralleling a growing interest in functional, in addition to clinical, recovery, and evidence underscoring the importance negative symptoms play in the former. Efforts continue to better define and measure negative symptoms, distinguish their impact from that of other symptom domains, and establish effective treatments as well as trials to assess these. Multiple interventions have been the subject of investigation, to date, including numerous pharmacological strategies, brain stimulation, and non-somatic approaches. Level and quality of evidence vary considerably, but to this point, no specific treatment can be recommended. This is particularly problematic for individuals burdened with negative symptoms in the face of mild or absent positive symptoms. Presently, clinicians will sometimes turn to interventions that are seen as more “benign” and in line with routine clinical practice. Strategies include use of atypical antipsychotics, ensuring the lowest possible antipsychotic dose that maintains control of positive symptoms (this can involve a shift from antipsychotic polypharmacy to monotherapy), possibly an antidepressant trial (given diagnostic uncertainty and the frequent use of these drugs in schizophrenia), and non-somatic interventions (e.g., cognitive behavioral therapy, CBT). The array and diversity of strategies currently under investigation highlight the lack of evidence-based treatments and our limited understanding regarding negative symptoms underlying etiology and pathophysiology. Their onset, which can precede the first psychotic break, also means that treatments are delayed. From this perspective, identification of biomarkers and/or endophenotypes permitting earlier diagnosis and intervention may serve to improve treatment efficacy as well as outcomes.
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11
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Paine MF, Smith BP. Movember Is Mustache Month. Clin Pharmacol Ther 2016; 98:562-4. [PMID: 26768983 DOI: 10.1002/cpt.262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Accepted: 09/08/2015] [Indexed: 11/09/2022]
Affiliation(s)
- M F Paine
- Washington State University, Spokane, Washington, USA
| | - B P Smith
- Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA
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