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Sargazi S, Mirani Sargazi F, Heidari Nia M, Sheervalilou R, Saravani R, Mirinejad S, Shakiba M. Functional Variants of miR-143 Are Associated with Schizophrenia Susceptibility: A Preliminary Population-Based Study and Bioinformatics Analysis. Biochem Genet 2021; 60:868-881. [PMID: 34515927 DOI: 10.1007/s10528-021-10133-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Accepted: 09/04/2021] [Indexed: 12/19/2022]
Abstract
Single nucleotide polymorphisms within genes encoding microRNAs may alter the expression of microRNAs and their target genes, contributing to the etiology of psychiatric disorders. We aimed to investigate the link between rs4705342T/C and rs4705343T/C polymorphisms in the promoter region of miR-143 and the risk of schizophrenia (SCZ) in a sample of an Iranian population. In this experimental study, a total of 398 subjects were recruited. Genotyping carried out using allele-specific PCR (AS-PCR) method. Different bioinformatics databases and Cytoscape V3.4.0 software were used for the analysis of the gene-miRNA interaction network. The genotypic analysis of rs4705342C/T showed that CC genotype in the co-dominant model significantly decreased the risk of SCZ (p < 0.001). Also, a significantly reduced risk of SCZ was observed under allelic (p < 0.001), dominant (p = 0.007), and recessive (p = 0.001) models of this variant. As regards rs4705343T/C, significantly enhanced risk of SCZ was found under the co-dominant CC (p = 0.01) and recessive (p = 0.007) contrasted genetic models. For this variant, the C allele conferred an increased risk of SCZ by 1.41 fold. Haplotype analysis showed that the Crs4705342 Trs4705343 haplotype significantly diminished SCZ susceptibility. The result of the bioinformatics analysis showed that miR-143, as a critical miRNA, targets ERK5, ERBB3, HK2, and PKCε, the four major genes involved in SCZ development. Our findings suggest that these two polymorphisms might affect SCZ susceptibility. Elucidating the precise regulatory mechanisms of gene expression in the development of SCZ will help researchers discover a novel target for therapeutic interventions.
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Affiliation(s)
- Saman Sargazi
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Fariba Mirani Sargazi
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Milad Heidari Nia
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | | | - Ramin Saravani
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran. .,Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
| | - Shekoufeh Mirinejad
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Mansoor Shakiba
- Department of Psychiatry, Zahedan University of Medical Sciences, Zahedan, Iran
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2
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Teigset CM, Mohn C, Rund BR. Perinatal complications and executive dysfunction in early-onset schizophrenia. BMC Psychiatry 2020; 20:103. [PMID: 32131788 PMCID: PMC7057649 DOI: 10.1186/s12888-020-02517-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Accepted: 02/26/2020] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The present study examined the association between perinatal obstetric complications and executive dysfunction in early-onset schizophrenia (EOS), compared to healthy controls. Higher incidences of obstetric complications and more severe executive dysfunctions characterize EOS. Research shows extensive brain maturation in newborns, suggesting them to be particularly vulnerable for perinatal insults. Executive function is mainly mediated by the prefrontal cortex, an area that matures last during pregnancy. Thus, exposure to perinatal complications may influence executive dysfunction in EOS. METHODS The participants were 19 EOS patients and 54 healthy controls. Executive function was assessed with the D-KEFS Color Word Interference Test and the Wisconsin Card Sorting Test. Information on perinatal obstetric complications and Apgar 5-min scores were obtained from the Norwegian Medical Birth Registry. Associations between perinatal conditions and executive function were studied using stepwise regression analyses. RESULTS Perinatal complications, and especially shorter gestational lengths, were significantly associated with significant executive dysfunctions in EOS. Perinatal complications did not affect executive function among healthy controls. A significant relationship between lower Apgar 5-min scores and executive dysfunction was found among both EOS patients and healthy controls. CONCLUSIONS Exposure to perinatal complications, and particularly a shorter gestational length, was associated with increased executive dysfunction in EOS. Exposed healthy controls did not exhibit similar executive difficulties, suggesting that the EOS patients seemed especially vulnerable for executive deficits due to perinatal insults. The findings indicate that EOS youths learn more slowly and experience more difficulty with problem-solving, which carry important implications for clinical practice. Lower Apgar 5-min scores were associated with executive dysfunction in both groups. Low Apgar score at 5 min may therefore be an important early indicator of executive difficulties among adolescents, independent of diagnosis.
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Affiliation(s)
- Charlotte M. Teigset
- grid.459157.b0000 0004 0389 7802Vestre Viken Hospital Trust, Research Department, Wergelands gate 10, 3004 Drammen, Norway
| | - Christine Mohn
- grid.459157.b0000 0004 0389 7802Vestre Viken Hospital Trust, Research Department, Wergelands gate 10, 3004 Drammen, Norway ,grid.5510.10000 0004 1936 8921NORMENT Norwegian Centre for Mental Disorders Research, Institute of Clinical Medicine, Postboks 4956 Nydalen, 0424 Oslo, Norway
| | - Bjørn Rishovd Rund
- grid.459157.b0000 0004 0389 7802Vestre Viken Hospital Trust, Research Department, Wergelands gate 10, 3004 Drammen, Norway ,grid.5510.10000 0004 1936 8921Department of Psychology, University of Oslo, Postboks 1094 Blindern, 0317 Oslo, Norway
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Qian K, Sun L, Zhou G, Ge H, Meng Y, Li J, Li X, Fang X. Trifluoperazine as an alternative strategy for the inhibition of tumor growth of colorectal cancer. J Cell Biochem 2019; 120:15756-15765. [PMID: 31081173 DOI: 10.1002/jcb.28845] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Revised: 01/29/2019] [Accepted: 02/04/2019] [Indexed: 12/27/2022]
Abstract
The development of cancer in patients with schizophrenia is affected by genetic and environmental factors and antipsychotic medication. Several studies found that schizophrenia was associated with decreased risk of some cancers, and the neuroleptic medication might help to reduce the risk of colorectal cancer (CRC). Phenothiazine drugs including trifluoperazine (TFP) are widely used antipsychotic drugs and showed some antitumor effects, we here investigated the potential application of TFP in the treatment of colon cancer. A series doses of TFP were treated to the colon cancer cell line HCT116 and the inhibitory concentration (IC50 ) of TFP for HCT116 was determined by cell counting kit-8. The results indicated that the treatment of TFP impaired the cell vitality of HCT116 in a dose- and time-dependent manner. Meanwhile, the Edu assay demonstrated that the proliferation was also inhibited by TFP, which was accompanied with the induction of apoptosis and autophagy. The expression of CCNE1, CDK4, and antiapoptosis factor BCL-2 was downregulated but the proapoptosis factor BAX was upregulated. The autophagy inhibitor chloroquine could significantly reverse the TFP-induced apoptosis. Moreover, the ability of migration and invasion of HCT116 was found to be suppressed by TFP, which was associated with the inhibition of epithelial-mesenchymal transition (EMT). The function of TFP in vivo was further confirmed. The results showed that the administration of TFP remarkably abrogated the tumor growth with decreased tumor volume and proliferation index Ki-67 level in tumor tissues. The EMT phenotype was also confirmed to be inhibited by TFP in vivo, suggesting the promising antitumor effects of TFP in CRC.
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Affiliation(s)
- Kun Qian
- College of Life Sciences, Huzhou University, Huzhou, Zhejiang, People's Republic of China
| | - Laiyu Sun
- College of Life Sciences, Huzhou University, Huzhou, Zhejiang, People's Republic of China
| | - Guoqing Zhou
- College of Life Sciences, Huzhou University, Huzhou, Zhejiang, People's Republic of China
| | - Haixia Ge
- College of Life Sciences, Huzhou University, Huzhou, Zhejiang, People's Republic of China
| | - Yue Meng
- College of Life Sciences, Huzhou University, Huzhou, Zhejiang, People's Republic of China
| | - Jingfen Li
- College of Life Sciences, Huzhou University, Huzhou, Zhejiang, People's Republic of China
| | - Xiao Li
- College of Life Sciences, Huzhou University, Huzhou, Zhejiang, People's Republic of China
| | - Xinqiang Fang
- College of Life Sciences, Huzhou University, Huzhou, Zhejiang, People's Republic of China
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Xu C, Tian G, Jiang C, Xue H, Kuerbanjiang M, Sun L, Gu L, Zhou H, Liu Y, Zhang Z, Xu Q. NPTX2 promotes colorectal cancer growth and liver metastasis by the activation of the canonical Wnt/β-catenin pathway via FZD6. Cell Death Dis 2019; 10:217. [PMID: 30833544 PMCID: PMC6399240 DOI: 10.1038/s41419-019-1467-7] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 02/04/2019] [Accepted: 02/12/2019] [Indexed: 12/21/2022]
Abstract
Accumulating evidence from clinical and epidemiological studies has highlighted the close correlation between the individual risk of cancer and nervous system diseases. The expression of neuronal pentraxin 2 (NPTX2) is absent in Alzheimer's disease, anxiety, and depression. Herein, we found that NPTX2 mRNA and protein expression was significantly upregulated in colorectal carcinoma (CRC). NPTX2 expression level gradually increased with CRC progression and was closely associated with poor prognosis. In vitro and in vivo studies demonstrated that NPTX2 promoted CRC proliferation and metastasis through the activation of the Wnt/β-catenin signaling pathway. As NPTX2 receptors are absent on CRC cells, NPTX2 was shown to physically interact with frizzled class receptor 6 (FZD6) to promote β-catenin translocation into the cell nucleus, resulting in an increase in the expression of MYC, cyclin D1, snail, and N-cadherin along with a decrease in the expression of E-cadherin. Knockdown of FZD6 expression with a small-interfering RNA almost completely reversed the proliferative effects of NPTX2 on CRC development. In conclusion, NPTX2, a molecule related to nervous system diseases, promotes CRC cell proliferation and metastasis through the activation of the Wnt/β-catenin pathway via direct interaction with FZD6.
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Affiliation(s)
- Chunjie Xu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, P.R. China
| | - Guangang Tian
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P.R. China
| | - Chunhui Jiang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, P.R. China
| | - Hanbing Xue
- Division of Gastroenterology and Hepatology; Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, P.R. China
| | - Manzila Kuerbanjiang
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, P.R. China
| | - Longci Sun
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, P.R. China
| | - Lei Gu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, P.R. China
| | - Hong Zhou
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, P.R. China
| | - Ye Liu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, P.R. China
| | - Zhigang Zhang
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, P.R. China.
| | - Qing Xu
- Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, P.R. China.
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5
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Gao X, Mi Y, Guo N, Xu H, Jiang P, Zhang R, Xu L, Gou X. Glioma in Schizophrenia: Is the Risk Higher or Lower? Front Cell Neurosci 2018; 12:289. [PMID: 30233327 PMCID: PMC6129591 DOI: 10.3389/fncel.2018.00289] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Accepted: 08/13/2018] [Indexed: 12/17/2022] Open
Abstract
Whether persons with schizophrenia have a higher or lower incidence of cancer has been discussed for a long time. Due to the complex mechanisms and characteristics of different types of cancer, it is difficult to evaluate the exact relationship between cancers and schizophrenia without considering the type of tumor. Schizophrenia, a disabling mental illness that is now recognized as a neurodevelopmental disorder, is more correlated with brain tumors, such as glioma, than other types of tumors. Thus, we mainly focused on the relationship between schizophrenia and glioma morbidity. Glioma tumorigenesis and schizophrenia may share similar mechanisms; gene/pathway disruption would affect neurodevelopment and reduce the risk of glioma. The molecular defects of disrupted-in-schizophrenia-1 (DISC1), P53, brain-derived neurotrophic factor (BDNF) and C-X-C chemokine receptors type 4 (CXCR4) involved in schizophrenia pathogenesis might play opposite roles in glioma development. Many microRNAs (miRNAs) such as miR-183, miR-9, miR-137 and miR-126 expression change may be involved in the cross talk between glioma prevalence and schizophrenia. Finally, antipsychotic drugs may have antitumor effects. All these factors show that persons with schizophrenia have a decreased incidence of glioma; therefore, epidemiological investigation and studies comparing genetic and epigenetic aberrations involved in both of these complex diseases should be performed. These studies can provide more insightful knowledge about glioma and schizophrenia pathophysiology and help to determine the target/strategies for the prevention and treatment of the two diseases.
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Affiliation(s)
- Xingchun Gao
- Shaanxi Key Laboratory of Brain Disorders & Institute of Basic Medical Sciences & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China.,State Key Laboratory of Military Stomatology, Department of Anesthesiology, School of Stomatology, The Fourth Military Medical University, Xi'an, China
| | - Yajing Mi
- Shaanxi Key Laboratory of Brain Disorders & Institute of Basic Medical Sciences & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China
| | - Na Guo
- Shaanxi Key Laboratory of Brain Disorders & Institute of Basic Medical Sciences & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China
| | - Hao Xu
- Shaanxi Key Laboratory of Brain Disorders & Institute of Basic Medical Sciences & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China.,State Key Laboratory of Military Stomatology, Department of Anesthesiology, School of Stomatology, The Fourth Military Medical University, Xi'an, China
| | - Pengtao Jiang
- Shaanxi Key Laboratory of Brain Disorders & Institute of Basic Medical Sciences & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China
| | - Ruisan Zhang
- Shaanxi Key Laboratory of Brain Disorders & Institute of Basic Medical Sciences & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China
| | - Lixian Xu
- Shaanxi Key Laboratory of Brain Disorders & Institute of Basic Medical Sciences & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China.,State Key Laboratory of Military Stomatology, Department of Anesthesiology, School of Stomatology, The Fourth Military Medical University, Xi'an, China
| | - Xingchun Gou
- Shaanxi Key Laboratory of Brain Disorders & Institute of Basic Medical Sciences & Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China
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6
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Jiang J, Huang Z, Chen X, Luo R, Cai H, Wang H, Zhang H, Sun T, Zhang Y. Trifluoperazine Activates FOXO1-Related Signals to Inhibit Tumor Growth in Hepatocellular Carcinoma. DNA Cell Biol 2017; 36:813-821. [PMID: 28876084 DOI: 10.1089/dna.2017.3790] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Schizophrenic patients tend to have reduced incidence of some cancers due to the treatment of antipsychotic drugs with antitumor effects, such as chlorpromazine and trifluoperazine (TFP). Forkhead Box O1 (FOXO1) as tumor suppressor in many malignancies is often inactivated by nuclear export, which could be inhibited by TFP. However, the antitumor efficiency of TFP and related role of FOXO1 in hepatocellular carcinoma (HCC) are unclear. Thus, two HCC cell lines SMMC-7721 and Bel-7402 were treated with different concentrations of TFP and the IC50 was determined. We found that TFP could inhibit the vitality of two cell lines and induce cell cycle arrest at G0/G1. Meanwhile, the apoptosis was also increased and the ability of migration or invasion was found to be impaired by TFP. Interestingly, TFP reversed the cytoplasmic localization of FOXO1 to nuclear and increased its expression in nuclear, and increased the ratio of Bax/Bcl-2. However, knockdown of FOXO1 significantly abrogated the TFP-induced
apoptosis by decreasing the Bcl-2 expression [corrected]. Furthermore, we found that TFP in vivo could effectively restrict the angiogenesis and tumor growth with reduced expression of VEGF, Bcl-2, and PCNA, and increased the nuclear localization of FOXO1, which indicated its antitumor role in HCC.
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Affiliation(s)
- Jingwen Jiang
- 1 Department of Medical Oncology, Hainan Province Hospital of Traditional Chinese Medicine , Haikou, China
| | - Zhongxi Huang
- 2 Guangdong Provincial Key Laboratory of Cancer Immunotherapy, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical Sciences, Southern Medical University , Guangzhou, China
| | - Xuewu Chen
- 1 Department of Medical Oncology, Hainan Province Hospital of Traditional Chinese Medicine , Haikou, China
| | - Rongcheng Luo
- 3 TCM-Integrated Cancer Center, Southern Medical University , Guangzhou, China
| | - Hongbin Cai
- 4 Department of Medical Oncology, TCM-Integrated Cancer Center of Southern Medical University , Guangzhou, China
| | - Hairu Wang
- 5 Department of Surgical Oncology, Haikou People's Hospital , Haikou, China
| | - Hui Zhang
- 1 Department of Medical Oncology, Hainan Province Hospital of Traditional Chinese Medicine , Haikou, China
| | - Tao Sun
- 6 College of Traditional Chinese Medicine, Hainan Medical University , Haikou, Hainan, China
| | - Yunfang Zhang
- 1 Department of Medical Oncology, Hainan Province Hospital of Traditional Chinese Medicine , Haikou, China
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7
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Chou FHC, Tsai KY, Wu HC, Shen SP. Cancer in patients with schizophrenia: What is the next step? Psychiatry Clin Neurosci 2016; 70:473-488. [PMID: 27392126 DOI: 10.1111/pcn.12420] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Revised: 06/12/2016] [Accepted: 06/22/2016] [Indexed: 12/15/2022]
Abstract
People with schizophrenia, who constitute approximately 0.3-1% of the general population, have a nearly 20% shorter life expectancy than the general population. The incidence of varied types of cancers in patients with schizophrenia is controversial. The majority of previous research has demonstrated that patients who have schizophrenia and cancer have early mortality compared to the general population with cancer. The causes of early mortality in patients with schizophrenia and cancer might be attributed to a lower cancer screening rate and lack of effective treatment, including: (i) patient factors, such as poor lifestyle, passive attitude toward treatment, or comorbidity; (ii) physician factors, such as physician bias, which may decrease the delivery of care for individuals with mental disorders; and (iii) hospital administration factors, such as stigma and discrimination. Additional studies on patients with schizophrenia and cancer are warranted and should include the following: a comprehensive review of previous studies; a focus on differentiating the specific types of cancer; and methods for improvement. To decrease the early mortality of patients with schizophrenia, the following measures are proposed: (i) enhance early detection and early treatment, such as increasing the cancer screening rate for patients with schizophrenia; (ii) provide effective, timely treatment and rehabilitation; (iii) improve patients' psychiatric symptoms and cognitive impairment; (iv) promote healthy behavior in the general population and emphasize healthy lifestyles in vulnerable populations; and (v) remove the stigma of schizophrenia. To reduce disparities in physical health, public health strategies and welfare policies must continue to focus on this group of patients.
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Affiliation(s)
- Frank H-C Chou
- Department of Community Psychiatry, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan.,Graduate Institute of Health Care, Meiho University, Ping-Tong County, Taiwan
| | - Kuan-Yi Tsai
- Department of Community Psychiatry, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan
| | - Hung-Chi Wu
- Department of Community Psychiatry, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan
| | - Shih-Pei Shen
- Department of Community Psychiatry, Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung, Taiwan.,Department of Public Health, China Medical University, Taichung, Taiwan
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8
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Rizos E, Siafakas N, Skourti E, Papageorgiou C, Tsoporis J, Parker TH, Christodoulou DI, Spandidos DA, Katsantoni E, Zoumpourlis V. miRNAs and their role in the correlation between schizophrenia and cancer (Review). Mol Med Rep 2016; 14:4942-4946. [PMID: 27748930 PMCID: PMC5355746 DOI: 10.3892/mmr.2016.5853] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Accepted: 09/30/2016] [Indexed: 02/06/2023] Open
Abstract
Schizophrenia (SZ) and cancer (Ca) have a broad spectrum of clinical phenotypes and a complex biological background, implicating a large number of genetic and epigenetic factors. SZ is a chronic neurodevelopmental disorder signified by an increase in the expression of apoptotic molecular signals, whereas Ca is conversely characterized by an increase in appropriate molecular signaling that stimulates uncontrolled cell proliferation. The rather low risk of developing Ca in patients suffering from SZ is a hypothesis that is still under debate. Recent evidence has indicated that microRNAs (miRNAs or miRs), a large group of small non-coding oligonoucleotides, may play a significant role in the development of Ca and major psychiatric disorders, such as SZ, bipolar disorder, autism spectrum disorders, suicidality and depression, through their interference with the expression of multiple genes. For instance, the possible role of let-7, miR-98 and miR-183 as biomarkers for Ca and SZ was investigated in our previous research studies. Therefore, further investigations on the expression profiles of these regulatory, small RNA molecules and the molecular pathways through which they exert their control may provide a plausible explanation as to whether there is a correlation between psychiatric disorders and low risk of developing Ca.
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Affiliation(s)
- E Rizos
- 2nd Department of Psychiatry, National and Kapodistrian University of Athens, School of Medicine, University General Hospital 'ATTIKON', Athens 124 62, Greece
| | - N Siafakas
- Laboratory of Clinical Microbiology, National and Kapodistrian University of Athens, School of Medicine, University General Hospital 'ATTIKON', Athens 124 62, Greece
| | - E Skourti
- Unit of Biomedical Applications, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens 116 35, Greece
| | - C Papageorgiou
- 1st Department of Psychiatry, National and Kapodistrian University of Athens, School of Medicine, 'Eginition' Hospital, Athens 115 28, Greece
| | - J Tsoporis
- Keenan Research Centre, Li Ka Shing Knowledge Centre, Institute of Biomedical Science, St. Michael's Hospital, Toronto, ON M5B 1W8, Canada
| | - T H Parker
- Keenan Research Centre, Li Ka Shing Knowledge Centre, Institute of Biomedical Science, St. Michael's Hospital, Toronto, ON M5B 1W8, Canada
| | - D I Christodoulou
- Unit of Biomedical Applications, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens 116 35, Greece
| | - D A Spandidos
- Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion 71003, Greece
| | - E Katsantoni
- Biomedical Research Foundation, Academy of Athens, Hematology‑Oncology Division, Athens 115 27, Greece
| | - V Zoumpourlis
- Unit of Biomedical Applications, Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, Athens 116 35, Greece
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9
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Kosten L, Verhaeghe J, Verkerk R, Thomae D, De Picker L, Wyffels L, Van Eetveldt A, Dedeurwaerdere S, Stroobants S, Staelens S. Multiprobe molecular imaging of an NMDA receptor hypofunction rat model for glutamatergic dysfunction. Psychiatry Res Neuroimaging 2016; 248:1-11. [PMID: 26803479 DOI: 10.1016/j.pscychresns.2016.01.013] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Revised: 12/23/2015] [Accepted: 01/07/2016] [Indexed: 12/21/2022]
Abstract
There are many indications of a connection between abnormal glutamate transmission through N-methyl-d-aspartate (NMDA) receptor hypofunction and the occurrence of schizophrenia. The importance of metabotropic glutamate receptor subtype 5 (mGluR5) became generally recognized due to its physical link through anchor proteins with NMDAR. Neuroinflammation as well as the kynurenine (tryptophan catabolite; TRYCAT) pathway are equally considered as major contributors to the pathology. We aimed to investigate this interplay between glutamate release, neuronal activation and inflammatory markers, by using small-animal positron emission tomography (PET) in a rat model known to induce schizophrenia-like symptoms. Daily intraperitoneal injection of MK801 or saline were administered to induce the model together with N-Acetyl-cysteine (NAc) or saline as the treatment in 24 male Sprague Dawley rats for one month. Biweekly in vivo [(11)C]-ABP688 microPET was performed together with mGluR5 immunohistochemistry. Simultaneously, weekly in vivo [(18)F]-FDG microPET imaging data for glucose metabolism was acquired and microglial activation was investigated with biweekly in vivo [(18)F]-PBR111 scans versus OX42 immunohistochemistry. Finally, plasma samples were analyzed for TRYCAT metabolites. We show that chronic MK801 administration (and thus elevated endogenous glutamate) causes significant tissue loss in rat brain, enhances neuroinflammatory pathways and may upregulate mGluR5 expression.
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Affiliation(s)
- Lauren Kosten
- Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium
| | - Jeroen Verhaeghe
- Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium
| | - Robert Verkerk
- Laboratory of Medical Biochemistry, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium
| | - David Thomae
- Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium; Department of Nuclear Medicine, University Hospital Antwerp, Antwerp, Belgium
| | - Livia De Picker
- Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Antwerp, Belgium
| | - Leonie Wyffels
- Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium; Department of Nuclear Medicine, University Hospital Antwerp, Antwerp, Belgium
| | | | | | - Sigrid Stroobants
- Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium; Department of Nuclear Medicine, University Hospital Antwerp, Antwerp, Belgium
| | - Steven Staelens
- Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.
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10
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Obstetric complications in early psychosis: relation with family history of psychosis. Psychiatry Res 2012; 200:708-14. [PMID: 22868179 DOI: 10.1016/j.psychres.2012.07.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2011] [Revised: 07/12/2012] [Accepted: 07/15/2012] [Indexed: 10/28/2022]
Abstract
The people classified as being at ultra-high risk (UHR) of developing psychosis are expected to share many risk factors for psychosis with the patients diagnosed with schizophrenia, including an enhanced incidence of obstetric complications (OCs). This study set out to investigate the incidence and correlates of OCs in a sample of patients accessing an early intervention center. Patients' mothers were asked whether they had suffered from any somatic complication during pregnancy from a list of OCs with potential direct relevance to the physical wellbeing of the offspring. Out of 86 patients diagnosed with first-episode psychosis, 20 (23%) cases were positive for the occurrence of severe OCs, as reported by their mothers during an interview; out of 83 UHR patients, 21 (25%) cases were positive for OCs. OCs were more common in individuals with a family history of psychosis than in those without such a history. OCs might interact with genetic vulnerability to increase the risk of psychosis. Lack of comparison to healthy controls is a limitation that decreases the value of these findings.
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Psychotic-like or unusual subjective experiences? The role of certainty in the appraisal of the subclinical psychotic phenotype. Psychiatry Res 2012; 200:669-73. [PMID: 22862912 DOI: 10.1016/j.psychres.2012.07.014] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2011] [Revised: 07/12/2012] [Accepted: 07/14/2012] [Indexed: 11/21/2022]
Abstract
The multi-dimensional features of Unusual Subjective Experiences (USEs) may be more accurate indicators of psychosis-proneness than simple frequency count. We tested whether subjective certainty or uncertainty of the occurrence of USEs can influence perceived wellbeing. Five hundred and four undergraduate students completed measures of delusion- and hallucination-proneness, general health and emotional processing. Participants' responses on the delusion- and hallucination-proneness scales were dichotomized on the basis of their certainty level. Results showed that, USEs rated with certainty were associated with poor self-perceived health and difficult emotional processing, while those rated with uncertainty were not. Certainty of USEs was associated with increased distress and may be important in characterizing psychopathological significance. Specific characteristics associated with USEs may be more important than their frequency in predicting psychosis risk.
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