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Wakonigg Alonso C, McElhatton F, O'Mahony B, Campbell M, Pollak TA, Stokes PRA. The blood-brain barrier in bipolar disorders: A systematic review. J Affect Disord 2024; 361:434-444. [PMID: 38897301 DOI: 10.1016/j.jad.2024.06.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 05/13/2024] [Accepted: 06/13/2024] [Indexed: 06/21/2024]
Abstract
BACKGROUND Bipolar disorders (BD) are chronic, debilitating disorders. The blood-brain barrier (BBB) has been increasingly investigated in BD. This systematic review aimed to assess the available evidence on the relationship between BD and markers of BBB dysfunction. METHODS A systematic search in PubMed, Embase, PsycINFO, CINAHL and Web of Science was run where the primary outcomes were BBB markers such as S100B, albumin ratio, matrix metalloproteinase (MMP), cell adhesion molecule (CAM), and tight junction proteins. Techniques included blood, cerebrospinal fluid (CSF), post-mortem, genetic and imaging methods in BD compared to healthy controls. RESULTS 55 studies were identified, 38 of which found an association between BD and markers of BBB dysfunction. 16/29 studies found increased blood/CSF albumin ratio, S100B, CAMs or MMP levels in BD participants compared to controls. 5/19 post-mortem studies found increased levels of chondroitin sulphate proteoglycans, intercellular CAM, neurexin or claudin-5 mRNA in distinct locations throughout the brain in BD compared to controls. One imaging study identified extensive BBB leakage in 30 % of BD participants, compared to 0 % in controls. LIMITATIONS The diversity in methodologies used in the included studies makes direct comparison of results challenging. Furthermore, imaging methods are the gold standard, but only one study used them. Other markers are only indicative of BBB permeability. CONCLUSIONS This review suggests an association between BD and BBB dysfunction. Further research is needed to provide definite answers considering the existing literature's limitations, and to clarify whether this association provides a pathogenic mechanism, or is an epiphenomenon of BD.
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Affiliation(s)
- Clara Wakonigg Alonso
- Institute of Psychiatry & Psychology and Neuroscience, King's College London,United Kingdom.
| | - Frances McElhatton
- Institute of Psychiatry & Psychology and Neuroscience, King's College London,United Kingdom
| | - Brian O'Mahony
- Institute of Psychiatry & Psychology and Neuroscience, King's College London,United Kingdom
| | - Matthew Campbell
- Smurfit Institute of Genetics, Trinity College Dublin, Lincoln Place Gate, Dublin 2, Ireland
| | - Thomas A Pollak
- Dept of Psychosis Studies, Institute of Psychiatry & Psychology and Neuroscience, King's College London, United Kingdom; South London and Maudsley NHS Foundation Trust,Bethlem Royal Hospital, Monks Orchard Road, Beckenham, Kent, BR3 3BX, United Kingdom
| | - Paul R A Stokes
- South London and Maudsley NHS Foundation Trust,Bethlem Royal Hospital, Monks Orchard Road, Beckenham, Kent, BR3 3BX, United Kingdom; Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry & Psychology and Neuroscience, King's College London,United Kingdom
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2
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Pantovic-Stefanovic M, Petronijevic N, Dunjic-Kostic B, Velimirovic M, Jurisic V, Nikolic T, Dodic S, Ivkovic M. Differentiating Stages of Bipolar and Unipolar Depression-The Possible Role of sICAM-1 and sVCAM-1. Cells 2024; 13:1213. [PMID: 39056795 PMCID: PMC11274993 DOI: 10.3390/cells13141213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Revised: 06/27/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
Increased immune-inflammatory activation has been repeatedly linked to etiopathogenesis and the progression of both major depressive disorder (MDD) and bipolar depression (BD). We explore the role of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in diagnostic differentiation and disorder progression in patients with MDD and BD. Serum levels of sICAM-1 and sVCAM-1 were measured in 137 patients (MDD = 93 and BD = 44) and compared with 73 healthy controls. The severity of psychopathology was assessed using the Hamilton Depression Rating Scale and Clinical Global Impression Scale. After adjustment for multiple confounders, we noticed significant downregulation of sVCAM-1 and upregulation of sICAM-1 levels in both patient groups. Decreased sVCAM-1 levels were detected in patients with acute episodes of BD when compared to MDD. Immune mediators were related to indicators of progression in both mood disorders. They also followed different post-treatment normalization patterns in MDD and BD and in relation to the stage of each disorder. Adhesion molecules could potentially be useful in discriminating between patients with MDD and BD and determining the possible progression of the disorders. Future nosological methods should include time-dependent pathoplasticity and biological correlates, at least for affective disorders.
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Affiliation(s)
- Maja Pantovic-Stefanovic
- Department of Bipolar Disorders, Clinic for Psychiatry, University Clinical Centre of Serbia, Pasterova 2, 11000 Belgrade, Serbia; (M.P.-S.)
- School of Medicine, University of Belgrade, Dr Subotica 8 st., 11000 Belgrade, Serbia; (N.P.)
| | - Natasa Petronijevic
- School of Medicine, University of Belgrade, Dr Subotica 8 st., 11000 Belgrade, Serbia; (N.P.)
- Institute of Clinical and Medical Biochemistry, Pasterova 2, 11000 Belgrade, Serbia
| | - Bojana Dunjic-Kostic
- Department of Bipolar Disorders, Clinic for Psychiatry, University Clinical Centre of Serbia, Pasterova 2, 11000 Belgrade, Serbia; (M.P.-S.)
- School of Medicine, University of Belgrade, Dr Subotica 8 st., 11000 Belgrade, Serbia; (N.P.)
| | - Milica Velimirovic
- School of Medicine, University of Belgrade, Dr Subotica 8 st., 11000 Belgrade, Serbia; (N.P.)
- Institute of Clinical and Medical Biochemistry, Pasterova 2, 11000 Belgrade, Serbia
| | - Vladimir Jurisic
- Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 11000 Kragujevac, Serbia
| | - Tatjana Nikolic
- School of Medicine, University of Belgrade, Dr Subotica 8 st., 11000 Belgrade, Serbia; (N.P.)
- Institute of Clinical and Medical Biochemistry, Pasterova 2, 11000 Belgrade, Serbia
| | - Sara Dodic
- Department of Bipolar Disorders, Clinic for Psychiatry, University Clinical Centre of Serbia, Pasterova 2, 11000 Belgrade, Serbia; (M.P.-S.)
- School of Medicine, University of Belgrade, Dr Subotica 8 st., 11000 Belgrade, Serbia; (N.P.)
| | - Maja Ivkovic
- Department of Bipolar Disorders, Clinic for Psychiatry, University Clinical Centre of Serbia, Pasterova 2, 11000 Belgrade, Serbia; (M.P.-S.)
- School of Medicine, University of Belgrade, Dr Subotica 8 st., 11000 Belgrade, Serbia; (N.P.)
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Sheikh MA, O'Connell KS, Lekva T, Szabo A, Akkouh IA, Osete JR, Agartz I, Engh JA, Andreou D, Boye B, Bøen E, Elvsåshagen T, Hope S, Frogner Werner MC, Joa I, Johnsen E, Kroken RA, Lagerberg TV, Melle I, Drange OK, Morken G, Nærland T, Sørensen K, Vaaler AE, Weibell MA, Westlye LT, Aukrust P, Djurovic S, Steen NE, Andreassen OA, Ueland T. Systemic Cell Adhesion Molecules in Severe Mental Illness: Potential Role of Intercellular CAM-1 in Linking Peripheral and Neuroinflammation. Biol Psychiatry 2023; 93:187-196. [PMID: 36182530 DOI: 10.1016/j.biopsych.2022.06.029] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 06/14/2022] [Accepted: 06/14/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND Cell adhesion molecules (CAMs) orchestrate leukocyte trafficking and could link peripheral and neuroinflammation in patients with severe mental illness (SMI), by promoting inflammatory and immune-mediated responses and mediating signals across blood-brain barrier. We hypothesized that CAMs would be dysregulated in SMI and evaluated plasma levels of different vascular and neural CAMs. Dysregulated CAMs in plasma were further evaluated in vivo in leukocytes and brain tissue and in vitro in induced pluripotent stem cells. METHODS We compared plasma soluble levels of different vascular (VCAM-1, ICAM-1, P-SEL) and neural (JAM-A, NCAD) CAMs in circulating leukocytes in a large SMI sample of schizophrenia (SCZ) spectrum disorder (n = 895) and affective disorder (n = 737) and healthy control participants (n = 1070) controlling for age, sex, body mass index, C-reactive protein, and freezer storage time. We also evaluated messenger RNA expression of ICAM1 and related genes encoding ICAM-1 receptors in leukocytes using microarray (n = 842) and in available RNA sequencing data from the CommonMind Consortium (CMC) in postmortem samples from the dorsolateral prefrontal cortex (n = 474). The regulation of soluble ICAM-1 in induced pluripotent stem cell-derived neurons and astrocytes was assessed in patients with SCZ and healthy control participants (n = 8 of each). RESULTS Our major findings were 1) increased soluble ICAM-1 in patients with SMI compared with healthy control participants; 2) increased ITGB2 messenger RNA, encoding the beta chain of the ICAM-1 receptor, in circulating leukocytes from patients with SMI and increased prefrontal cortex messenger RNA expression of ICAM1 in SCZ; and 3) enhanced soluble ICAM-1 release in induced pluripotent stem cell-derived neurons from patients with SCZ. CONCLUSIONS Our results support a systemic and cerebral dysregulation of soluble ICAM-1 expression in SMI and especially in patients with SCZ.
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Affiliation(s)
- Mashhood A Sheikh
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
| | - Kevin S O'Connell
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
| | - Tove Lekva
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
| | - Attila Szabo
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
| | - Ibrahim A Akkouh
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
| | - Jordi Requena Osete
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
| | - Ingrid Agartz
- NORMENT, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
| | - John A Engh
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Vestfold Hospital Trust, Division of Mental Health and Addiction, Tønsberg, Norway
| | - Dimitrios Andreou
- NORMENT, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
| | | | | | - Torbjørn Elvsåshagen
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
| | - Sigrun Hope
- Department of Neuro Habilitation, Oslo University Hospital Ullevål, Oslo, Norway
| | - Maren Caroline Frogner Werner
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
| | - Inge Joa
- Network for Clinical Psychosis Research, Division of Psychiatry, Stavanger University Hospital, Stavanger, Norway; Network for Medical Sciences, Faculty of Health, University of Stavanger, Stavanger, Norway
| | - Erik Johnsen
- Division of Psychiatry, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway; NORMENT Centre of Excellence, Bergen, Norway
| | - Rune A Kroken
- Division of Psychiatry, Haukeland University Hospital, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway; NORMENT Centre of Excellence, Bergen, Norway
| | - Trine Vik Lagerberg
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
| | - Ingrid Melle
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; NORMENT, University of Oslo, Oslo, Norway
| | - Ole Kristian Drange
- Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway; Department of Østmarka, Division of Mental Health, St. Olavs University Hospital, Trondheim, Norway; Department of Psychiatry, Sørlandet Hospital HF, Kristiansand, Norway
| | - Gunnar Morken
- Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway
| | | | - Kjetil Sørensen
- Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway
| | - Arne E Vaaler
- Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway; Department of Østmarka, Division of Mental Health, St. Olavs University Hospital, Trondheim, Norway
| | - Melissa Authen Weibell
- Network for Clinical Psychosis Research, Division of Psychiatry, Stavanger University Hospital, Stavanger, Norway; Network for Medical Sciences, Faculty of Health, University of Stavanger, Stavanger, Norway
| | - Lars T Westlye
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Pål Aukrust
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Srdjan Djurovic
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; K.G. Jebsen Center for Neurodevelopmental Disorders, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Nils Eiel Steen
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; NORMENT, University of Oslo, Oslo, Norway
| | - Ole A Andreassen
- Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; NORMENT, University of Oslo, Oslo, Norway
| | - Thor Ueland
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway.
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Tsai SY, Kuo CJ, Sajatovic M, Huang YJ, Chen PH, Chung KH. Lithium exposure and chronic inflammation with activated macrophages and monocytes associated with atherosclerosis in bipolar disorder. J Affect Disord 2022; 314:233-240. [PMID: 35878826 DOI: 10.1016/j.jad.2022.07.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 05/09/2022] [Accepted: 07/17/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Atherosclerosis accounts for cardiovascular diseases (CVDs). This study aimed to explore the association between carotid intima-media thickness (CIMT), psycho-pharmacotherapy, and inflammatory markers along with other molecules related to atherosclerosis in bipolar disorder (BD). METHODS The euthymic patients with bipolar I disorder (BD-I) aged over 20 years were recruited to measure CIMT through ultrasound and the blood levels of lipid profiles, soluble tumor necrosis factor receptor-1 (sTNF-R1), soluble interleukin-6 receptor (sIL-6R), monocyte chemoattractant protein-1, chitinase 3-like 1, endothelial adhesive proteins, and thrombin-antithrombin complex. RESULTS Participants were 103 BD-I patients with mean 44.3 years old. The ratio of lithium exposure in relation to illness chronicity and the current daily dosage of lithium therapy exhibited an inverse relationship with CIMT in the entire sample. After controlling for age and BMI, multivariate regression indicated that a higher lithium level was significantly associated with decreased CIMT in the entire sample, high-risk (those with CVDs or endocrine diseases, N = 48), middle-risk (those without CVDs and endocrine diseases, N = 55), and low-risk (those aged <45 years in the middle-risk subgroup, N = 43) subgroups. Furthermore, higher levels of sTNF-R1 in the entire sample and high-risk subgroup and sIL-6R in the middle- and low-risk subgroups were statistically associated with greater CIMT. LIMITATION The age range was too wide to control for the effect of age on CIMT and medication. CONCLUSIONS Lithium exposure may be a protective factor for atherosclerosis progression in BD-I. The chronic inflammation in BD-I with activated macrophages and monocytes may link with the atherosclerosis development over time.
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Affiliation(s)
- Shang-Ying Tsai
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
| | - Chian-Jue Kuo
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan
| | - Martha Sajatovic
- Department of Psychiatry, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Yu-Jui Huang
- Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
| | - Pao-Huan Chen
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
| | - Kuo-Hsuan Chung
- Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Psychiatry and Psychiatric Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
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Elkjaer Greenwood Ormerod MB, Ueland T, Frogner Werner MC, Hjell G, Rødevand L, Sæther LS, Lunding SH, Johansen IT, Ueland T, Lagerberg TV, Melle I, Djurovic S, Andreassen OA, Steen NE. Composite immune marker scores associated with severe mental disorders and illness course. Brain Behav Immun Health 2022; 24:100483. [PMID: 35856063 PMCID: PMC9287150 DOI: 10.1016/j.bbih.2022.100483] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 06/28/2022] [Indexed: 12/29/2022] Open
Abstract
Background Low-grade inflammation has been implicated in the pathophysiology of severe mental disorders (SMDs) and a link between immune activation and clinical characteristics is suggested. However, few studies have investigated how patterns across immune markers are related to diagnosis and illness course. Methods A total of 948 participants with a diagnosis of schizophrenia (SCZ, N = 602) or bipolar (BD, N = 346) spectrum disorder, and 814 healthy controls (HC) were included. Twenty-five immune markers comprising cell adhesion molecules (CAMs), interleukin (IL)-18-system factors, defensins, chemokines and other markers, related to neuroinflammation, blood-brain barrier (BBB) function, inflammasome activation and immune cell orchestration were analyzed. Eight immune principal component (PC) scores were constructed by PC Analysis (PCA) and applied in general linear models with diagnosis and illness course characteristics. Results Three PC scores were significantly associated with a SCZ and/or BD diagnosis (HC reference), with largest, however small, effect sizes of scores based on CAMs, BBB markers and defensins (p < 0.001, partial η2 = 0.02-0.03). Number of psychotic episodes per year in SCZ was associated with a PC score based on IL-18 system markers and the potential neuroprotective cytokine A proliferation-inducing ligand (p = 0.006, partial η2 = 0.071). Conclusion Analyses of composite immune markers scores identified specific patterns suggesting CAMs-mediated BBB dysregulation pathways associated with SMDs and interrelated pro-inflammatory and neuronal integrity processes associated with severity of illness course. This suggests a complex pattern of immune pathways involved in SMDs and SCZ illness course.
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Affiliation(s)
| | - Thor Ueland
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- KG Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway
| | - Maren Caroline Frogner Werner
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Gabriela Hjell
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Psychiatry, Østfold Hospital, Graalum, Norway
| | - Linn Rødevand
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Linn Sofie Sæther
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Department of Psychology, University of Oslo, Oslo, Norway
| | - Synve Hoffart Lunding
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Ingrid Torp Johansen
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Torill Ueland
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Psychology, University of Oslo, Oslo, Norway
| | - Trine Vik Lagerberg
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
| | - Ingrid Melle
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Srdjan Djurovic
- Department of Medical Genetics, Oslo University Hospital and University of Oslo, Oslo, Norway
- NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Ole Andreas Andreassen
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Nils Eiel Steen
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Doney E, Cadoret A, Dion‐Albert L, Lebel M, Menard C. Inflammation-driven brain and gut barrier dysfunction in stress and mood disorders. Eur J Neurosci 2022; 55:2851-2894. [PMID: 33876886 PMCID: PMC9290537 DOI: 10.1111/ejn.15239] [Citation(s) in RCA: 55] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 03/18/2021] [Accepted: 04/12/2021] [Indexed: 02/06/2023]
Abstract
Regulation of emotions is generally associated exclusively with the brain. However, there is evidence that peripheral systems are also involved in mood, stress vulnerability vs. resilience, and emotion-related memory encoding. Prevalence of stress and mood disorders such as major depression, bipolar disorder, and post-traumatic stress disorder is increasing in our modern societies. Unfortunately, 30%-50% of individuals respond poorly to currently available treatments highlighting the need to further investigate emotion-related biology to gain mechanistic insights that could lead to innovative therapies. Here, we provide an overview of inflammation-related mechanisms involved in mood regulation and stress responses discovered using animal models. If clinical studies are available, we discuss translational value of these findings including limitations. Neuroimmune mechanisms of depression and maladaptive stress responses have been receiving increasing attention, and thus, the first part is centered on inflammation and dysregulation of brain and circulating cytokines in stress and mood disorders. Next, recent studies supporting a role for inflammation-driven leakiness of the blood-brain and gut barriers in emotion regulation and mood are highlighted. Stress-induced exacerbated inflammation fragilizes these barriers which become hyperpermeable through loss of integrity and altered biology. At the gut level, this could be associated with dysbiosis, an imbalance in microbial communities, and alteration of the gut-brain axis which is central to production of mood-related neurotransmitter serotonin. Novel therapeutic approaches such as anti-inflammatory drugs, the fast-acting antidepressant ketamine, and probiotics could directly act on the mechanisms described here improving mood disorder-associated symptomatology. Discovery of biomarkers has been a challenging quest in psychiatry, and we end by listing promising targets worth further investigation.
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Affiliation(s)
- Ellen Doney
- Department of Psychiatry and NeuroscienceFaculty of Medicine and CERVO Brain Research CenterUniversité LavalQCCanada
| | - Alice Cadoret
- Department of Psychiatry and NeuroscienceFaculty of Medicine and CERVO Brain Research CenterUniversité LavalQCCanada
| | - Laurence Dion‐Albert
- Department of Psychiatry and NeuroscienceFaculty of Medicine and CERVO Brain Research CenterUniversité LavalQCCanada
| | - Manon Lebel
- Department of Psychiatry and NeuroscienceFaculty of Medicine and CERVO Brain Research CenterUniversité LavalQCCanada
| | - Caroline Menard
- Department of Psychiatry and NeuroscienceFaculty of Medicine and CERVO Brain Research CenterUniversité LavalQCCanada
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Zhou J, Zhou J, Sun Z, Feng L, Zhu X, Yang J, Wang G. Development and Internal Validation of a Novel Model to Identify Inflammatory Biomarkers of a Response to Escitalopram in Patients With Major Depressive Disorder. Front Psychiatry 2021; 12:593710. [PMID: 34093252 PMCID: PMC8172985 DOI: 10.3389/fpsyt.2021.593710] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 04/12/2021] [Indexed: 12/28/2022] Open
Abstract
Objective: The aim of our study was to identify immune- and inflammation-related factors with clinical utility to predict the clinical efficacy of treatment for depression. Study Design: This was a follow-up study. Participants who met the entry criteria were administered with escitalopram (5-10 mg/day) as an initial treatment. Self-evaluation and observer valuations were arranged at the end of weeks 0, 4, 8, and 12, with blood samples collected at baseline and during weeks 2 and 12. Multivariable logistic regression analysis was then carried out by incorporating three cytokines selected by the Least Absolute Shrinkage and Selection Operator (LASSO) regression model. Internal validation was estimated using the bootstrap method with 1,000 repetitions. Results: A total of 85 patients with Major Depressive Disorder (MDD), including 62 responders and 23 non-responders, were analyzed. Monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and lipocalin-2 were selected by the LASSO regression model. The area under the curve (AUC) from the logistic model was 0.811 and was confirmed as 0.7887 following bootstrapping validation. Conclusions: We established and validated a good prediction model to facilitate the individualized prediction of escitalopram treatment for MDD and created a personalized approach to treatment for patients with depression.
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Affiliation(s)
- Jingjing Zhou
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Jia Zhou
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Zuoli Sun
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Lei Feng
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Xuequan Zhu
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Jian Yang
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Gang Wang
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
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Wang S, Wang F, Yang L, Li Q, Huang Y, Cheng Z, Chu H, Song Y, Shang L, Hao W, Wei X. Effects of coal-fired PM 2.5 on the expression levels of atherosclerosis-related proteins and the phosphorylation level of MAPK in ApoE -/- mice. BMC Pharmacol Toxicol 2020; 21:34. [PMID: 32384920 PMCID: PMC7206822 DOI: 10.1186/s40360-020-00411-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 04/30/2020] [Indexed: 12/19/2022] Open
Abstract
Background Air pollution increases the morbidity and mortality of cardiovascular disease (CVD). Atherosclerosis (AS) is the pathological basis of most CVD, and the progression of atherosclerosis and the increase of fragile plaque rupture are the mechanism basis of the relationship between atmospheric particulate pollution and CVD. The aim of the present study was to investigate the effects of coal-fired fine particulate matter (PM2.5) on the expression levels of atherosclerosis-related proteins (von Willebrand factor (vWF), Endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin, and to explore the role and mechanism of the progression of atherosclerosis induced by coal-fired PM2.5 via the mitogen-activated protein kinase (MAPK) signaling pathways. Methods Different concentrations of PM2.5 were given to apolipoprotein-E knockout (ApoE−/−) mice via intratracheal instillation for 8 weeks. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of vWF, ET-1 in serum of mice. Immunohistochemistry was used to observe the expression and distribution of ICAM-1 and E-selectin in the aorta of mice. Western blot was used to investigate the phosphoylation of proteins relevant to MAPK signaling pathways. Results Coal-fired PM2.5 exacerbated atherosclerosis induced by a high-fat diet. Fibrous cap formation, foam cells accumulation, and atherosclerotic lesions were observed in the aortas of PM2.5-treated mice. Coal-fired PM2.5 increased the protein levels of ET-1, ICAM-1, and E-selectin, but there was no significant difference in the vWF levels between the PM2.5-treatment mice and the HFD control mice. Coal-fired PM2.5 promoted the phosphorylation of p38, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) in aortic tissues of mice. Conclusion Coal-derived PM2.5 exacerbated the formation of atherosclerosis in mice, increased the expression levels of atherosclerosis-related proteins in mice serum, and promoted the phosphorylation of proteins relevant to MAPK signaling pathway. Thus, MAPK signaling pathway may play a role in the atherosclerosis pathogenesis induced by Coal-derived PM2.5.
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Affiliation(s)
- Siqi Wang
- Department of Toxicology, School of Public Health, Peking University Health Science Center, No.38 XueYuan Road, HaiDian District, Beijing, 100191, People's Republic of China.,Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, People's Republic of China
| | - Feifei Wang
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, People's Republic of China
| | - Lixin Yang
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, People's Republic of China
| | - Qin Li
- State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, People's Republic of China
| | - Yao Huang
- Department of Toxicology, School of Public Health, Peking University Health Science Center, No.38 XueYuan Road, HaiDian District, Beijing, 100191, People's Republic of China.,Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, People's Republic of China
| | - Zhiyuan Cheng
- Department of Toxicology, School of Public Health, Peking University Health Science Center, No.38 XueYuan Road, HaiDian District, Beijing, 100191, People's Republic of China.,Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, People's Republic of China
| | - Hongqian Chu
- Department of Toxicology, School of Public Health, Peking University Health Science Center, No.38 XueYuan Road, HaiDian District, Beijing, 100191, People's Republic of China.,Translational Medicine Center, Beijing Chest Hospital, Capital Medical University, Beijing, 101149, People's Republic of China.,Beijing Key Laboratory in Drug Resistant Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, People's Republic of China
| | - Yiming Song
- Department of Toxicology, School of Public Health, Peking University Health Science Center, No.38 XueYuan Road, HaiDian District, Beijing, 100191, People's Republic of China.,Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, People's Republic of China
| | - Lanqin Shang
- Department of Toxicology, School of Public Health, Peking University Health Science Center, No.38 XueYuan Road, HaiDian District, Beijing, 100191, People's Republic of China.,Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, People's Republic of China
| | - Weidong Hao
- Department of Toxicology, School of Public Health, Peking University Health Science Center, No.38 XueYuan Road, HaiDian District, Beijing, 100191, People's Republic of China.,Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, People's Republic of China
| | - Xuetao Wei
- Department of Toxicology, School of Public Health, Peking University Health Science Center, No.38 XueYuan Road, HaiDian District, Beijing, 100191, People's Republic of China. .,Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing, 100191, People's Republic of China.
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9
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Kesebir S, Koc MI, Yosmaoglu A. Bipolar Spectrum Disorder May Be Associated With Family History of Diseases. J Clin Med Res 2020; 12:251-254. [PMID: 32362973 PMCID: PMC7188371 DOI: 10.14740/jocmr4143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Accepted: 04/01/2020] [Indexed: 11/18/2022] Open
Abstract
Background This study aims at investigating into the presence of family history of diabetes, ischemic heart disease, thyroid disease, cancer, cerebrovascular disease, and epilepsy in bipolar patients. Methods Totally 1,148 patients admitted to our outpatient unit between January 2018 and January 2020, who were diagnosed with bipolar disorder according to Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V), from whom informed consent was obtained, were cross-sectionally and consecutively evaluated. Each patient was questioned regarding a family history of diabetes, ischemic heart disease, thyroid disease, cancer (gastrointestinal, breast and prostate cancer, leukemia, and lymphoma), cerebrovascular disease and epilepsy in first- and second-degree relatives. Results Diabetes, ischemic heart disease, cancer, cerebrovascular disease and epilepsy were more common in the family histories than in bipolar patients. A strong correlation was found between family history positive for epilepsy and bipolar disorder with psychotic symptoms. Also, a correlation was found between family history for diabetes and seasonal course and family history positive for thyroid disease and comorbid anxiety disorder. Conclusions This study is the first to investigate into the frequency of physical diseases in the family histories of bipolar patients. Current therapies target the association between common leading pathways and symptoms whereas it is the association between stress and neural circuits that underlie the pathophysiology that should be targeted.
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Affiliation(s)
- Sermin Kesebir
- Department of Psychiatry, Uskudar University, NPIstanbul Brain Hospital, Istanbul, Turkey
| | - Merve Iris Koc
- Uskudar University, NPIstanbul Brain Hospital, Istanbul, Turkey
| | - Ahmet Yosmaoglu
- Uskudar University, NPIstanbul Brain Hospital, Istanbul, Turkey
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10
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Müller N. The Role of Intercellular Adhesion Molecule-1 in the Pathogenesis of Psychiatric Disorders. Front Pharmacol 2019; 10:1251. [PMID: 31824303 PMCID: PMC6883971 DOI: 10.3389/fphar.2019.01251] [Citation(s) in RCA: 116] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Accepted: 09/27/2019] [Indexed: 01/08/2023] Open
Abstract
Intercellular adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein that is overexpressed in many pathological states. Although, like many other immune molecules, ICAM-1 plays only a limited role in the abundant concert of the immune response, it may be more important than we realize. In the central nervous system (CNS), ICAM-1 is expressed in microglial cells and astrocytes and in endothelial cells in the white and gray matter of the human forebrain. It is of particular interest in psychiatric disorders for two reasons: It has a key function for the blood-brain barrier, which plays an important role in the biology of psychiatric disorders, and it is a marker for inflammation. Although the blood level of soluble ICAM-1 (sICAM-1) might be lower in acute unmedicated schizophrenia, it has been reported to be increased in many other psychiatric conditions, such as major depression, bipolar disorder, and dementia. In bipolar disorder, high sICAM levels were found during both the depressed and the manic states and also during the euthymic phase (the free interval), possibly indicating that sICAM is a trait marker. High sICAM-1 blood levels have also been found in depression comorbid to a somatic disease state. Interestingly, sICAM-1 levels also increase during aging. Some studies investigated sICAM-1 levels in the cerebrospinal fluid of psychiatric disorders and ICAM-1 expression in postmortem CNS tissue of psychiatric patients and found that the overall duration and duration of the chronic phase of the psychiatric disorder seem to play a role in both. Moreover, confounders, such as antipsychotic and antidepressive medication, have to be considered. sICAM-1 levels seem to be associated with hypopermeability or hyperpermeability of the blood-brain barrier and thus to influence the communication between the CNS immune system, represented by glia cells, and the peripheral immune system. The balance between the influx and efflux of immune molecules into and out of the CNS may be one of the pinpoints in psychiatric disorders, in particular in the chronic phase, e.g., in schizophrenia. This aspect, however, needs further intense research, in particular to enable researchers to develop therapeutic principles based on an immune/inflammatory approach.
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Affiliation(s)
- Norbert Müller
- Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-Universität Munich, Munich, Germany
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11
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Kucukgoncu S, Kosir U, Zhou E, Sullivan E, Srihari VH, Tek C. Glucose metabolism dysregulation at the onset of mental illness is not limited to first episode psychosis: A systematic review and meta-analysis. Early Interv Psychiatry 2019; 13:1021-1031. [PMID: 30277314 PMCID: PMC6445792 DOI: 10.1111/eip.12749] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 05/16/2018] [Accepted: 09/09/2018] [Indexed: 12/15/2022]
Abstract
AIM To compare the differences of glucose metabolism outcomes between treatment-naïve, patients with first episode psychosis (FEP) and mood disorders. METHODS We conducted a systematic review and meta-analysis of glucose intolerance in treatment-naïve, first episode patients with severe mental illnesses (SMIs). RESULTS We identified 31 eligible studies. Compared to healthy controls, FEP group have higher insulin and insulin resistance levels, and both groups have higher glucose tolerance test results. No significant differences were found in glucose metabolism outcomes between FEP and mood disorder groups. CONCLUSIONS Our results highlight impaired glucose metabolism at the onset of SMIs, suggesting both patients with psychosis and mood disorders are high-risk groups for diabetes development.
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Affiliation(s)
- Suat Kucukgoncu
- Yale University Department of Psychiatry, Connecticut Mental Health Hospital, New Haven, Connecticut
| | - Urska Kosir
- Yale University Department of Psychiatry, Connecticut Mental Health Hospital, New Haven, Connecticut
| | - Elton Zhou
- Yale University Department of Psychiatry, Connecticut Mental Health Hospital, New Haven, Connecticut
| | - Erin Sullivan
- Yale University Department of Psychiatry, Connecticut Mental Health Hospital, New Haven, Connecticut
| | - Vinod H Srihari
- Yale University Department of Psychiatry, Connecticut Mental Health Hospital, New Haven, Connecticut
| | - Cenk Tek
- Yale University Department of Psychiatry, Connecticut Mental Health Hospital, New Haven, Connecticut
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12
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Pantović-Stefanović M, Petronijević N, Dunjić-Kostić B, Velimirović M, Nikolić T, Jurišić V, Lačković M, Damjanović A, Totić-Poznanović S, Jovanović AA, Ivković M. sVCAM-1, sICAM-1, TNF-α and IL-6 levels in bipolar disorder type I: Acute, longitudinal and therapeutic implications. World J Biol Psychiatry 2019; 19:S41-S51. [PMID: 27841086 DOI: 10.1080/15622975.2016.1259498] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVES To explore the serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in patients with bipolar disorder (BD), with regard to acute episode characteristics, course of the disorder and treatment. METHODS The study group consisted of 83 patients diagnosed with BD type I. The control group consisted of 73 healthy individuals, matched with the study group according to age, gender and body mass index. The serum levels of sVCAM-1, sICAM-1, TNF-α and IL-6 were measured by ELISA. RESULTS Compared with healthy controls, significantly elevated levels of IL-6 and sICAM-1 and significantly lower levels of TNF-α and sVCAM-1 were identified in acute and remission phases of BD. The acute serum levels of sVCAM-1 were associated with the type and severity of acute mood symptoms as well as with course of illness characteristics. TNF-α was associated with duration of untreated disorder and type of treatment. CONCLUSIONS BD is related to both acute and long-term alterations of immune mediators, including adhesion molecules. The potential immunomodulatory role of pharmacotherapeutic treatment is also to be considered in BD.
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Affiliation(s)
| | - Nataša Petronijević
- b School of Medicine, University of Belgrade , Belgrade , Serbia.,c Institute of Clinical and Medical Biochemistry , Belgrade , Serbia
| | | | - Milica Velimirović
- b School of Medicine, University of Belgrade , Belgrade , Serbia.,c Institute of Clinical and Medical Biochemistry , Belgrade , Serbia
| | - Tatjana Nikolić
- b School of Medicine, University of Belgrade , Belgrade , Serbia.,c Institute of Clinical and Medical Biochemistry , Belgrade , Serbia
| | - Vladimir Jurišić
- d School of Medicine, University of Kragujevac , Kragujevac , Serbia
| | - Maja Lačković
- a Clinic of Psychiatry , Clinical Centre of Serbia , Belgrade , Serbia.,b School of Medicine, University of Belgrade , Belgrade , Serbia
| | - Aleksandar Damjanović
- a Clinic of Psychiatry , Clinical Centre of Serbia , Belgrade , Serbia.,b School of Medicine, University of Belgrade , Belgrade , Serbia
| | - Sanja Totić-Poznanović
- a Clinic of Psychiatry , Clinical Centre of Serbia , Belgrade , Serbia.,b School of Medicine, University of Belgrade , Belgrade , Serbia
| | - Aleksandar A Jovanović
- a Clinic of Psychiatry , Clinical Centre of Serbia , Belgrade , Serbia.,b School of Medicine, University of Belgrade , Belgrade , Serbia
| | - Maja Ivković
- a Clinic of Psychiatry , Clinical Centre of Serbia , Belgrade , Serbia.,b School of Medicine, University of Belgrade , Belgrade , Serbia
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Kesebir S. Epigenetics of Metabolic Syndrome as a Mood Disorder. J Clin Med Res 2018; 10:453-460. [PMID: 29707086 PMCID: PMC5916533 DOI: 10.14740/jocmr3389w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2018] [Accepted: 03/26/2018] [Indexed: 12/03/2022] Open
Abstract
Mood disorders comprise major depressive disorder (MDD), bipolar disorder (BD) and the milder forms of these two disorders. Reccurring MDD is also known as unipolar disorder. The distinction between unipolar and bipolar disorders was first suggested in 1957 by Leonard and was made official after support by several studies in 1980. Indeed, in 150 AD, Aretaeus of Cappadocia wrote “It seems to me that melancholia is the beginning and a part of mania”. Additionally, Kraepelin, who proposed the first medical disease model in psychiatry a century ago, considered recurrent unipolar depression cases under the category of bipolar disorder and conceptualized spectrum disorders. Because today’s classification systems conduct cross-sectional diagnosis, they do not consider family history, long-term characteristics and multidimensional approaches on symptoms. This method prioritizes reliability over validity and it rules out psychiatric disorders in etiology. Actually, a spectrum model which covers physical diseases is conceivable. The concept of epigenetics considers mood disorders, Alzheimer’s disease, attention deficit and hyperactivity disorder, Carney syndrome, multiple endocrine neoplasia type I and II, breast and prostate cancers, carsinoid tumors, cerebrovascular and cardiovascular diseases and metabolic syndrome together. This review addressed the relationship between metabolic syndrome and mood disorders in this context along with genetic, clinical and environmental factors such as climate, geographic factors, migration and changeable lifestyles. Genetic and clinical variables are affective temperament, childhood trauma and use of antidepressants and antipsychotics.
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Affiliation(s)
- Sermin Kesebir
- Uskudar University, NPIstanbul Brain Hospital, Ahmet Tevfik Ileri C. N: 18, 34768 Umraniye, Istanbul, Turkey.
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14
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Schaefer M, Sarkar S, Schwarz M, Friebe A. Soluble Intracellular Adhesion Molecule-1 in Patients with Unipolar or Bipolar Affective Disorders: Results from a Pilot Trial. Neuropsychobiology 2017; 74:8-14. [PMID: 27442531 DOI: 10.1159/000446919] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2015] [Accepted: 05/18/2016] [Indexed: 11/19/2022]
Abstract
BACKGROUND Immunological and vascular markers may play a role in the pathophysiology of mood disorders and mood changes. AIM To test whether the cell adhesion molecule soluble intracellular adhesion molecule-1 (sICAM-1) may serve as a biomarker for patients with unipolar or bipolar affective disorders when compared to a healthy control group, and whether sICAM-1 blood levels change during different mood states. METHODS sICAM-1 serum concentrations were compared between 20 healthy controls and 48 patients with affective disorders (unipolar, bipolar II and bipolar I disorder) during different mood states (euthymic mood state, depression or mania). RESULTS When compared to healthy controls, patients with affective disorders had significantly higher sICAM-1 levels during the euthymic state (p = 0.015). Differences became more pronounced during depression (p = 0.013). When unipolar and bipolar patients were analyzed separately, unipolar patients significantly differed from controls during the euthymic and depressive mood state, while bipolar II patients showed a trend towards higher sICAM-1 levels during depression. Patients with bipolar I disorders had significantly higher sICAM-1 levels during manic states when compared to controls (p = 0.007). CONCLUSIONS sICAM-1 elevation in unipolar and bipolar patients, independent of mood changes, might support the hypothesis of chronic immune activation and endothelial dysfunction in patients with affective disorders.
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Affiliation(s)
- Martin Schaefer
- Department of Psychiatry, Psychotherapy, Psychosomatics and Addiction Medicine, Kliniken Essen-Mitte, Essen, Germany
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15
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Predictive value of sICAM-1 and sVCAM-1 as biomarkers of affective temperaments in healthy young adults. J Affect Disord 2017; 207:47-52. [PMID: 27693464 DOI: 10.1016/j.jad.2016.09.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2016] [Revised: 07/19/2016] [Accepted: 09/20/2016] [Indexed: 01/27/2023]
Abstract
BACKGROUND Affective temperaments are intermediate phenotypes for major affective disorders and are reported to have a neuroimmune etiopathogenesis. Here we investigated the role of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in affective temperaments and mood symptoms in healthy adults. METHODS Healthy adults (n=94) were screened for psychiatric disorders using the nonpatient version of the Structured Clinical Interview for DSM-IV-I and II. Subjects with medical conditions associated with changes in inflammatory response were excluded, deriving the final sample (n=68). Affective temperaments were evaluated with Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A). State mood symptoms were assessed using the Young Mania Rating Scale and Montgomery-Åsberg Depression Rating Scale. Serum sICAM-1 and sVCAM-1 levels were measured using enzyme-linked immunosorbent assay. RESULTS After adjusting for confounders (age, gender, BMI, and smoking habits), a high negative correlation between depressive and irritable temperament TEMPS-A scores and sVCAM-1 levels was detected. Although we identified no association between sICAM-1 levels and affective temperament scores, sICAM-1 was related to the state severity of manic symptoms. In a multiple linear regression model, sVCAM-1 remained a significant predictor of depressive but not irritable temperament scores. LIMITATIONS The temperaments were estimated on the basis of self-report questionnaire. CONCLUSIONS Our findings suggest that sVCAM-1 is related to affective temperaments, and it is a trait marker for liability to mood disorders. This relationship between alterations in cellular adhesion and affective temperament may be important for vulnerability to affective disorders.
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Kesebir S. Metabolic syndrome and childhood trauma: Also comorbidity and complication in mood disorder. World J Clin Cases 2014; 2:332-337. [PMID: 25133143 PMCID: PMC4133422 DOI: 10.12998/wjcc.v2.i8.332] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2014] [Revised: 05/20/2014] [Accepted: 06/18/2014] [Indexed: 02/05/2023] Open
Abstract
Studies for prevalence and causal relationship established that addressing comorbidities of mental illnesses with medical disease will be another revolution in psychiatry. Increasing number of evidence shows that there is a bidirectional connection between mood disorders and some medical diseases. Glucocorticoid/insulin signal mechanisms and immunoenflammatory effector systems are junction points that show pathophysiology between bipolar disorder and general medical situations susceptible to stress. A subgroup of mood disorder patients are under risk of developing obesity and diabetes. Their habits and life styles, genetic predisposition and treatment options are parameters that define this subgroup. Medical disease in adults had a significant relationship to adverse life experiences in childhood. This illustrates that adverse experiences in childhood are related to adult disease by two basic etiologic mechanisms: (1) conventional risk factors that actually are compensatory behaviors, attempts at self-help through the use of agents and foods; and (2) the effects of chronic stress.
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