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Li J, Hu R, Luo H, Guo Y, Zhang Z, Luo Q, Xia P. Associations between dietary habits and bipolar disorder: a diet-wide mendelian randomization study. Front Psychiatry 2024; 15:1388316. [PMID: 38800064 PMCID: PMC11116565 DOI: 10.3389/fpsyt.2024.1388316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 04/29/2024] [Indexed: 05/29/2024] Open
Abstract
Background Diet/nutrition is critically important in the pathogenesis, progression, and treatment outcomes of various mental disorders. Current research predominantly focuses on the role of diet in the development and treatment of depression, with less attention given to the relationship between diet and Bipolar Disorder (BD). Method We employed Mendelian Randomization (MR) to investigate the relationship between 28 dietary habits and BD. An analysis was conducted using publicly available genome-wide association study data from the UK Biobank dataset. Various dietary habits were analyzed as exposures with BD as the outcome, mainly using the Inverse Variance Weighted (IVW) method. Results Intake of non-oily fish and sponge pudding both have a positive association with BD. Oily fish, dried fruit, apples, salt, and cooked vegetables intake also appeared potentially risky for BD, although the possibility of false positives cannot be ruled out. Sensitivity analysis further confirmed the robustness of these findings. Conclusion Our research provides evidence of a relationship between various dietary habits and BD. It underscores the need for careful dietary management and balance to reduce the risk of BD, suggesting caution with dietary preferences for fish and sponge pudding. Furthermore, more detailed studies are needed to further understand the potential impacts of high-sugar and high-protein diets on BD development.
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Affiliation(s)
- Junyao Li
- Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Renqin Hu
- Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Huirong Luo
- Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yanwei Guo
- Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zheng Zhang
- Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qinghua Luo
- Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Pingyou Xia
- Yongchuan District Mental Health Center, Chongqing, China
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Imtiaz T, Nanayakkara J, Fang A, Jomaa D, Mayotte H, Damiani S, Javed F, Jones T, Kaczmarek E, Adebayo FO, Imtiaz U, Li Y, Zhang R, Mousavi P, Renwick N, Tyryshkin K. A user-driven machine learning approach for RNA-based sample discrimination and hierarchical classification. STAR Protoc 2023; 4:102661. [PMID: 39491552 PMCID: PMC10751557 DOI: 10.1016/j.xpro.2023.102661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 08/18/2023] [Accepted: 10/02/2023] [Indexed: 11/05/2024] Open
Abstract
RNA-based sample discrimination and classification can be used to provide biological insights and/or distinguish between clinical groups. However, finding informative differences between sample groups can be challenging due to the multidimensional and noisy nature of sequencing data. Here, we apply a machine learning approach for hierarchical discrimination and classification of samples with high-dimensional miRNA expression data. Our protocol comprises data preprocessing, unsupervised learning, feature selection, and machine-learning-based hierarchical classification, alongside open-source MATLAB code.
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Affiliation(s)
- Tashifa Imtiaz
- Laboratory of Translational RNA Biology, Department of Pathology and Molecular Medicine, Queen's University, 88 Stuart St, Kingston, ON K7L 3N6, Canada.
| | - Jina Nanayakkara
- Laboratory of Translational RNA Biology, Department of Pathology and Molecular Medicine, Queen's University, 88 Stuart St, Kingston, ON K7L 3N6, Canada
| | - Alexis Fang
- Laboratory of Translational RNA Biology, Department of Pathology and Molecular Medicine, Queen's University, 88 Stuart St, Kingston, ON K7L 3N6, Canada
| | - Danny Jomaa
- School of Medicine, Faculty of Health Sciences, Queen's University, 80 Barrie St, Kingston, ON K7L 3N6, Canada
| | - Harrison Mayotte
- Laboratory of Translational RNA Biology, Department of Pathology and Molecular Medicine, Queen's University, 88 Stuart St, Kingston, ON K7L 3N6, Canada
| | - Simona Damiani
- Laboratory of Translational RNA Biology, Department of Pathology and Molecular Medicine, Queen's University, 88 Stuart St, Kingston, ON K7L 3N6, Canada
| | - Fiza Javed
- Laboratory of Translational RNA Biology, Department of Pathology and Molecular Medicine, Queen's University, 88 Stuart St, Kingston, ON K7L 3N6, Canada
| | - Tristan Jones
- Laboratory of Translational RNA Biology, Department of Pathology and Molecular Medicine, Queen's University, 88 Stuart St, Kingston, ON K7L 3N6, Canada
| | - Emily Kaczmarek
- Medical Informatics Laboratory, School of Computing, Queen's University, 557 Goodwin Hall, Kingston, ON K7L 2N8, Canada
| | - Flourish Omolara Adebayo
- Medical Informatics Laboratory, School of Computing, Queen's University, 557 Goodwin Hall, Kingston, ON K7L 2N8, Canada
| | - Uroosa Imtiaz
- School of Computing, Queen's University, 557 Goodwin Hall, Kingston, ON K7L 2N8, Canada
| | - Yiheng Li
- School of Computing, Queen's University, 557 Goodwin Hall, Kingston, ON K7L 2N8, Canada
| | - Richard Zhang
- Laboratory of Translational RNA Biology, Department of Pathology and Molecular Medicine, Queen's University, 88 Stuart St, Kingston, ON K7L 3N6, Canada
| | - Parvin Mousavi
- Medical Informatics Laboratory, School of Computing, Queen's University, 557 Goodwin Hall, Kingston, ON K7L 2N8, Canada
| | - Neil Renwick
- Laboratory of Translational RNA Biology, Department of Pathology and Molecular Medicine, Queen's University, 88 Stuart St, Kingston, ON K7L 3N6, Canada
| | - Kathrin Tyryshkin
- Laboratory of Translational RNA Biology, Department of Pathology and Molecular Medicine, Queen's University, 88 Stuart St, Kingston, ON K7L 3N6, Canada; School of Computing, Queen's University, 557 Goodwin Hall, Kingston, ON K7L 2N8, Canada.
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Nascimento C, Kyunghee Kim H, Villela Nunes P, Paraiso Leite RE, Katia Cristina DO, Barbosa A, Bernardi Bertonha F, Moreira-Filho CA, Jacob-Filho W, Nitrini R, Pasqualucci CA, Tenenholz Grinberg L, Kimie Suemoto C, Brentani HP, Lafer B. Gene expression alterations in the postmortem hippocampus from older patients with bipolar disorder - A hypothesis generating study. J Psychiatr Res 2023; 164:329-334. [PMID: 37393798 DOI: 10.1016/j.jpsychires.2023.06.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 05/23/2023] [Accepted: 06/14/2023] [Indexed: 07/04/2023]
Abstract
Bipolar disorder (BD) presents with a progressive course in a subset of patients. However, our knowledge of molecular changes in older BD is limited. In this study, we examined gene expression changes in the hippocampus of BD from the Biobank of Aging Studies to identify genes of interest that warrant further exploration. RNA was extracted from the hippocampus from 11 subjects with BD and 11 age and sex-matched controls. Gene expression data was generated using the SurePrint G3 Human Gene Expression v3 microarray. Rank feature selection was performed to identify a subset of features that can optimally differentiate BD and controls. Genes ranked in the top 0.1% with log2 fold change >1.2 were identified as genes of interest. Average age of the subjects was 64 years old; duration of disease was 21 years and 82% were female. Twenty-five genes were identified, of which all but one was downregulated in BD. Of these, CNTNAP4, MAP4, SLC4A1, COBL, and NEURL4 had been associated with BD and other psychiatric conditions in previous studies. We believe our findings have identified promising targets to inform future studies aiming to understand the pathophysiology of BD in later life.
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Affiliation(s)
- Camila Nascimento
- Bipolar Disorder Program, Department of Psychiatry, University of Sao Paulo Medical School, SP, Brazil; Department of Psychiatry, University of Sao Paulo Medical School, SP, Brazil.
| | | | - Paula Villela Nunes
- Bipolar Disorder Program, Department of Psychiatry, University of Sao Paulo Medical School, SP, Brazil; Department of Psychiatry, University of Sao Paulo Medical School, SP, Brazil.
| | | | | | - André Barbosa
- Department of Psychiatry, University of Sao Paulo Medical School, SP, Brazil.
| | | | | | - Wilson Jacob-Filho
- Division of Geriatrics, University of Sao Paulo Medical School, SP, Brazil.
| | - Ricardo Nitrini
- Department of Neurology, University of Sao Paulo Medical School, SP, Brazil.
| | | | - Lea Tenenholz Grinberg
- Department of Pathology, University of Sao Paulo Medical School, SP, Brazil; Memory and Aging Center University of California, San Francisco, USA.
| | | | | | - Beny Lafer
- Bipolar Disorder Program, Department of Psychiatry, University of Sao Paulo Medical School, SP, Brazil; Department of Psychiatry, University of Sao Paulo Medical School, SP, Brazil.
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Gerolami J, Wong JJM, Zhang R, Chen T, Imtiaz T, Smith M, Jamaspishvili T, Koti M, Glasgow JI, Mousavi P, Renwick N, Tyryshkin K. A Computational Approach to Identification of Candidate Biomarkers in High-Dimensional Molecular Data. Diagnostics (Basel) 2022; 12:diagnostics12081997. [PMID: 36010347 PMCID: PMC9407361 DOI: 10.3390/diagnostics12081997] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 08/16/2022] [Accepted: 08/17/2022] [Indexed: 12/13/2022] Open
Abstract
Complex high-dimensional datasets that are challenging to analyze are frequently produced through ‘-omics’ profiling. Typically, these datasets contain more genomic features than samples, limiting the use of multivariable statistical and machine learning-based approaches to analysis. Therefore, effective alternative approaches are urgently needed to identify features-of-interest in ‘-omics’ data. In this study, we present the molecular feature selection tool, a novel, ensemble-based, feature selection application for identifying candidate biomarkers in ‘-omics’ data. As proof-of-principle, we applied the molecular feature selection tool to identify a small set of immune-related genes as potential biomarkers of three prostate adenocarcinoma subtypes. Furthermore, we tested the selected genes in a model to classify the three subtypes and compared the results to models built using all genes and all differentially expressed genes. Genes identified with the molecular feature selection tool performed better than the other models in this study in all comparison metrics: accuracy, precision, recall, and F1-score using a significantly smaller set of genes. In addition, we developed a simple graphical user interface for the molecular feature selection tool, which is available for free download. This user-friendly interface is a valuable tool for the identification of potential biomarkers in gene expression datasets and is an asset for biomarker discovery studies.
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Affiliation(s)
- Justin Gerolami
- School of Computing, Queen’s University, Kingston, ON K7L 3N6, Canada
| | - Justin Jong Mun Wong
- Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON K7L 3N6, Canada
| | - Ricky Zhang
- School of Computing, Queen’s University, Kingston, ON K7L 3N6, Canada
| | - Tong Chen
- School of Computing, Queen’s University, Kingston, ON K7L 3N6, Canada
| | - Tashifa Imtiaz
- Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON K7L 3N6, Canada
| | - Miranda Smith
- School of Computing, Queen’s University, Kingston, ON K7L 3N6, Canada
| | - Tamara Jamaspishvili
- Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON K7L 3N6, Canada
- Department of Pathology & Laboratory Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, USA
| | - Madhuri Koti
- Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON K7L 3N6, Canada
| | | | - Parvin Mousavi
- School of Computing, Queen’s University, Kingston, ON K7L 3N6, Canada
| | - Neil Renwick
- Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON K7L 3N6, Canada
| | - Kathrin Tyryshkin
- School of Computing, Queen’s University, Kingston, ON K7L 3N6, Canada
- Department of Pathology and Molecular Medicine, Queen’s University, Kingston, ON K7L 3N6, Canada
- Correspondence: ; Tel.: +1-613-533-2345
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Gabriel FC, Oliveira M, Martella BDM, Berk M, Brietzke E, Jacka FN, Lafer B. Nutrition and bipolar disorder: a systematic review. Nutr Neurosci 2022; 26:637-651. [PMID: 35608150 DOI: 10.1080/1028415x.2022.2077031] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Individuals with bipolar disorder (BD) have higher rates of unhealthy lifestyles and risk for medical comorbidities Research currently suggests that dietary factors may play a role in the development of depression and anxiety. Therefore, nutritional approaches are potential strategies for the treatment of BD. The aim of this review is to summarize the available evidence on nutrition and BD. MATERIALS AND METHODS The paper was developed based on PRISMA 2020 guidelines. The search was conducted in Sep-2021 using PubMed and Cochrane Library, augmented by manually checked references lists. The search found 986 studies, of which 47 were included, combined with 13 from reference lists, totaling 60 studies. RESULTS There were 33 observational trials, of which 15 focused on fatty acids, 9 on micronutrients, 5 on specific foods, 4 on macro and micronutrients. The 27 interventional studies mainly focused on fatty acids, micronutrients and N-acetylcysteine (NAC). DISCUSSION Dietary intake or supplementation of unsaturated fatty acids, mainly Omega-3 seems to be associated with improved BD symptoms, along with seafood, folic acid and zinc. Studies found variable, mainly non-significant impacts of creatine, carnitine, vitamin D, inositol or NAC supplementation on BD. There are promising results associated with Coenzyme Q10 (Coq10) and probiotics. Taken together, these preliminary findings suggest that dietetic approaches might be included as part of BD treatment. Also considering the high risk of metabolic disorders in individuals with BD, they should be encouraged to choose healthy dietary lifestyles, including daily intake of fruits, vegetables, seafood and whole grains.
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Affiliation(s)
- Fernanda C Gabriel
- Bipolar Research Program, Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil
| | - Manoela Oliveira
- Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL, USA
| | - Bruna De M Martella
- Bipolar Research Program, Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil
| | - Michael Berk
- IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Australia.,Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, The University of Melbourne, Melbourne, Australia
| | - Elisa Brietzke
- Department of Psychiatry, Queen's University School of Medicine, Kingston, Canada.,Centre for Neuroscience Studies (CNS), Queen's University, Kingston, Canada
| | - Felice N Jacka
- The Food & Mood Centre, IMPACT (the Institute for Mental and Physical Health and Clinical Translation), School of Medicine, Barwon Health, Deakin University, Geelong, Australia
| | - Beny Lafer
- Bipolar Research Program, Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil
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Valdés-Tovar M, Rodríguez-Ramírez AM, Rodríguez-Cárdenas L, Sotelo-Ramírez CE, Camarena B, Sanabrais-Jiménez MA, Solís-Chagoyán H, Argueta J, López-Riquelme GO. Insights into myelin dysfunction in schizophrenia and bipolar disorder. World J Psychiatry 2022; 12:264-285. [PMID: 35317338 PMCID: PMC8900585 DOI: 10.5498/wjp.v12.i2.264] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 08/10/2021] [Accepted: 01/17/2022] [Indexed: 02/06/2023] Open
Abstract
Schizophrenia and bipolar disorder are disabling psychiatric disorders with a worldwide prevalence of approximately 1%. Both disorders present chronic and deteriorating prognoses that impose a large burden, not only on patients but also on society and health systems. These mental illnesses share several clinical and neurobiological traits; of these traits, oligodendroglial dysfunction and alterations to white matter (WM) tracts could underlie the disconnection between brain regions related to their symptomatic domains. WM is mainly composed of heavily myelinated axons and glial cells. Myelin internodes are discrete axon-wrapping membrane sheaths formed by oligodendrocyte processes. Myelin ensheathment allows fast and efficient conduction of nerve impulses through the nodes of Ranvier, improving the overall function of neuronal circuits. Rapid and precisely synchronized nerve impulse conduction through fibers that connect distant brain structures is crucial for higher-level functions, such as cognition, memory, mood, and language. Several cellular and subcellular anomalies related to myelin and oligodendrocytes have been found in postmortem samples from patients with schizophrenia or bipolar disorder, and neuroimaging techniques have revealed consistent alterations at the macroscale connectomic level in both disorders. In this work, evidence regarding these multilevel alterations in oligodendrocytes and myelinated tracts is discussed, and the involvement of proteins in key functions of the oligodendroglial lineage, such as oligodendrogenesis and myelination, is highlighted. The molecular components of the axo-myelin unit could be important targets for novel therapeutic approaches to schizophrenia and bipolar disorder.
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Affiliation(s)
- Marcela Valdés-Tovar
- Departamento de Farmacogenética, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City 14370, Mexico
| | | | - Leslye Rodríguez-Cárdenas
- Departamento de Farmacogenética, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City 14370, Mexico
| | - Carlo E Sotelo-Ramírez
- Departamento de Farmacogenética, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City 14370, Mexico
- Doctorado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City 09340, Mexico
| | - Beatriz Camarena
- Departamento de Farmacogenética, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City 14370, Mexico
| | | | - Héctor Solís-Chagoyán
- Laboratorio de Neurofarmacología, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City 14370, Mexico
| | - Jesús Argueta
- Doctorado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City 09340, Mexico
- Laboratorio de Neurofarmacología, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City 14370, Mexico
| | - Germán Octavio López-Riquelme
- Laboratorio de Socioneurobiología, Centro de Investigación en Ciencias Cognitivas, Universidad del Estado de Morelos, Cuernavaca 62209, Morelos, Mexico
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A Comprehensive Review on the Role of Non-Coding RNAs in the Pathophysiology of Bipolar Disorder. Int J Mol Sci 2021; 22:ijms22105156. [PMID: 34068138 PMCID: PMC8152970 DOI: 10.3390/ijms22105156] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 05/06/2021] [Accepted: 05/07/2021] [Indexed: 01/02/2023] Open
Abstract
Aim: Bipolar disorder is a multifactorial disorder being linked with dysregulation of several genes. Among the recently acknowledged factors in the pathophysiology of bipolar disorder are non-coding RNAs (ncRNAs). Methods: We searched PubMed and Google Scholar databases to find studies that assessed the expression profile of miRNAs, lncRNAs and circRNAs in bipolar disorder. Results: Dysregulated ncRNAs in bipolar patients have been enriched in several neuron-related pathways such as GABAergic and glutamatergic synapses, morphine addiction pathway and redox modulation. Conclusion: Altered expression of these transcripts in bipolar disorder provides clues for identification of the pathogenesis of this disorder and design of targeted therapies for the treatment of patients.
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Wingo TS, Yang J, Fan W, Min Canon S, Gerasimov ES, Lori A, Logsdon B, Yao B, Seyfried NT, Lah JJ, Levey AI, Boyle PA, Schneider JA, De Jager PL, Bennett DA, Wingo AP. Brain microRNAs associated with late-life depressive symptoms are also associated with cognitive trajectory and dementia. NPJ Genom Med 2020; 5:6. [PMID: 32047652 PMCID: PMC7004995 DOI: 10.1038/s41525-019-0113-8] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Accepted: 12/20/2019] [Indexed: 12/11/2022] Open
Abstract
Late-life depression is associated with an increased risk for dementia but we have limited knowledge of the molecular mechanisms underlying this association. Here we investigated whether brain microRNAs, important posttranscriptional regulators of gene expression, contribute to this association. Late-life depressive symptoms were assessed annually in 300 participants of the Religious Orders Study and Rush Memory and Aging Project for a mean of 7 years. Participants underwent annual cognitive testing, clinical assessment of cognitive status, and uniform neuropathologic examination after death. microRNAs were profiled from the prefrontal cortex using NanoString platform in the discovery cohort and small RNA sequencing in the replication cohort. A global microRNA association study of late-life depressive symptoms was performed using linear mixed model adjusting for the potential confounding factors. Four brain microRNAs were associated with late-life depressive symptoms at adjusted p < 0.05: miR-484, miR-26b-5p, miR-30d-5p, and miR-197-3p. Lower expression levels of these miRNAs were associated having greater depressive symptoms. Furthermore, lower levels of miR-484 and miR-197-3p were associated with faster decline of cognition over time. Moreover, lower miR-484 level was associated with higher probability of having Alzheimer's dementia. Importantly, the associations between miR-484 and depressive symptoms and Alzheimer's dementia, respectively, were replicated in an independent cohort. Lastly, the predicted targets of miR-484 were enriched in a brain protein co-expression module involving synaptic transmission and regulation of synaptic plasticity. This study identified four brain microRNAs associated with late-life depressive symptoms assessed longitudinally. In addition, we found a molecular connection between late-life depression and dementia through miR-484.
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Affiliation(s)
- Thomas S. Wingo
- Department of Neurology, Emory University School of Medicine, Atlanta, GA USA
| | - Jingjing Yang
- Department of Human Genetics, Emory University School of Medicine, Atlanta, GA USA
| | - Wen Fan
- Department of Neurology, Emory University School of Medicine, Atlanta, GA USA
| | - Se Min Canon
- Department of Neurology, Emory University School of Medicine, Atlanta, GA USA
| | | | - Adriana Lori
- Department of Psychiatry, Emory University School of Medicine, Atlanta, GA USA
| | | | - Bing Yao
- Department of Human Genetics, Emory University School of Medicine, Atlanta, GA USA
| | - Nicholas T. Seyfried
- Department of Biochemistry, Emory University School of Medicine, Atlanta, GA USA
| | - James J. Lah
- Department of Neurology, Emory University School of Medicine, Atlanta, GA USA
| | - Allan I. Levey
- Department of Neurology, Emory University School of Medicine, Atlanta, GA USA
| | - Patricia A. Boyle
- Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL USA
| | - Julia A. Schneider
- Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL USA
| | - Philip L. De Jager
- Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY USA
| | - David A. Bennett
- Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, IL USA
| | - Aliza P. Wingo
- Department of Psychiatry, Emory University School of Medicine, Atlanta, GA USA
- Division of Mental Health, Atlanta VA Medical Center, Decatur, GA USA
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Ceylan D, Tufekci KU, Keskinoglu P, Genc S, Özerdem A. Circulating exosomal microRNAs in bipolar disorder. J Affect Disord 2020; 262:99-107. [PMID: 31726266 DOI: 10.1016/j.jad.2019.10.038] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 09/23/2019] [Accepted: 10/27/2019] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Emerging evidence suggests central roles of miRNAs in the pathogenesis of bipolar disorder (BD). Exosomes are membrane-bound vesicles acting as "biological cargo carriers" of various types of molecules including microRNAs. In this study, we aimed to investigate circulating exosomal microRNAs as potential diagnostic biomarkers for BD. METHODS The exosomes were precipitated from plasma samples of patients with BD (n = 69; 15 depressed, 27 manic, 27 euthymic) and healthy controls (n = 41). Total RNA was extracted from the exosomes and the levels of miRNAs were assayed by qPCR. Dysregulated miRNAs were subjected to Kyoto Encyclopedia of Genes and Genomes" (KEGG) pathway analysis by DIANA-miRPath v3.0 to identify the predicted targets and the related pathways. RESULTS Thirteen miRNAs showed significant differences between patients with BD and healthy individuals; among these, MiR-484, -652-3p, -142-3p remained significantly downregulated and miR-185-5p remained significantly upregulated after accounting for multiple comparisons and adjustments for potential confounders. There were no significant alterations among different states of BD. The KEEG analysis of four dysregulated miRNAs highlighted several target pathways including PI3K/Akt signaling, fatty acid biosynthesis/metabolism, extracellular matrix and adhesion pathways. CONCLUSION Our findings suggest that dysregulation of miRNAs might be involved in the underlying pathophysiology of BD through several biological pathways; and highlight the importance of the exosomal miRNAs for biomarker research in BD. Further longitudinal studies may clarify the roles of exosomal miRNAs and their targets in the neurobiology of BD.
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Affiliation(s)
- Deniz Ceylan
- Izmir University of Economics, Faculty of Medicine, Department of Psychiatry, Izmir, Turkey
| | - Kemal Ugur Tufekci
- Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir, Turkey
| | - Pembe Keskinoglu
- Department of Biostatistics and Medical Informatics, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey
| | - Sermin Genc
- Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir, Turkey; Department of Neuroscience, Institute of Health Sciences, Dokuz Eylul University Health Campus, Izmir, Turkey
| | - Ayşegül Özerdem
- Department of Neuroscience, Institute of Health Sciences, Dokuz Eylul University Health Campus, Izmir, Turkey; Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA; Department of Psychiatry, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey.
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Symons LK, Miller JE, Tyryshkin K, Monsanto SP, Marks RM, Lingegowda H, Vanderbeck K, Childs T, Young SL, Lessey BA, Koti M, Tayade C. Neutrophil recruitment and function in endometriosis patients and a syngeneic murine model. FASEB J 2019; 34:1558-1575. [PMID: 31914688 DOI: 10.1096/fj.201902272r] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 11/08/2019] [Accepted: 11/15/2019] [Indexed: 02/06/2023]
Abstract
Endometriosis is a chronic inflammatory, gynecological disease characterized by the presence of endometrial-like tissue lesions outside of the uterus. Neutrophils are elevated in the systemic circulation and peritoneal fluid of endometriosis patients; however, whether and how neutrophils contribute to endometriosis pathophysiology remain poorly understood. With emerging roles for neutrophils in chronic and sterile inflammatory conditions, we sought to provide in-depth characterization of neutrophil involvement in endometriosis. We demonstrate that neutrophils reside within patient endometriotic lesions and that patient lesions possess a microenvironment that may influence neutrophil recruitment and function. We also provide the first evidence that systemic circulating neutrophils from endometriosis patients display distinct transcriptomic differences compared neutrophils from healthy control subjects. Time course characterization of our syngeneic, immunocompetent mouse model of endometriosis revealed that neutrophils are rapidly recruited to the peritoneal environment early after endometriotic lesion establishment and remain present in murine lesions long term. In vivo neutrophil depletion altered the systemic and peritoneal immune microenvironment of mice with endometriosis as demonstrated by changes in pro-inflammatory and angiogenic mediators. Taken together, these findings highlight a novel role for neutrophils in early events such as angiogenesis and modulation of the local inflammatory environment associated with endometriosis pathogenesis.
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Affiliation(s)
- Lindsey K Symons
- Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada
| | - Jessica E Miller
- Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada
| | - Kathrin Tyryshkin
- Department of Pathology and Molecular Medicine, Kingston Health Sciences Center, Kingston, ON, Canada
| | - Stephany P Monsanto
- Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada
| | - Ryan M Marks
- Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada
| | | | - Kaitlin Vanderbeck
- Department of Pathology and Molecular Medicine, Kingston Health Sciences Center, Kingston, ON, Canada
| | - Timothy Childs
- Department of Pathology and Molecular Medicine, Kingston Health Sciences Center, Kingston, ON, Canada
| | - Steven L Young
- Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC, USA
| | | | - Madhuri Koti
- Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.,Department of Obstetrics and Gynecology, Kingston Health Sciences Center, Kingston, ON, Canada.,Division of Cancer Biology and Genetics, Queen's University, Kingston, ON, Canada
| | - Chandrakant Tayade
- Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada
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