A systematic review of evidence for the role of inflammatory biomarkers in bipolar patients

Article ID	Journal	Published Year	Pages	File Type
4931948	Journal of Psychiatric Research	2017	23 Pages	PDF

Abstract

Bipolar disorder (BD) is a neuropsychiatric disorder that is characterized by a phasic course of affective episodes interspersed with a euthymic state. Epidemiological, clinical, genetic, post-mortem and preclinical studies have shown that inflammatory reactions and immune modulation play a pivotal role in the pathophysiology of BD. It is conceptualized that biomarkers of inflammation and immune responses should be employed to monitor the disease process in bipolar patients. The objective of this systematic review is to analyse the inflammatory markers involved in human studies and to explore each individual marker for its potential clinical application and summarize evidence regarding their role in BD. A systematic review of human studies to measure inflammatory markers was conducted, and the studies were identified by searching PubMed/MEDLINE, PsycINFO, EMBASE, and Web of Science databases for peer-reviewed journals that were published until September 2015. In this review, we included peripheral markers, genetic, post-mortem and cell studies with inflammatory biomarker analysis in BD. One hundred and two (102) papers met the inclusion criteria. The pro-inflammatory cytokines were elevated and the anti-inflammatory cytokines were reduced in BD patients, particularly during manic and depressive phases when compared to the controls. These changes tend to disappear in euthymia, indicating that inflammation may be associated with acute phases of BD. Even though there are promising findings in this field, further clinical studies using more established detection techniques are needed to clearly show the benefit of using inflammatory markers in the diagnosis, follow-up and prognosis of patients with BD.

Keywords

NF-κB IFN-α TGF-β1 PBMC IgG TFR CRH PCC PHA mRNA SBP GFAP DBP HDL GPX PPI vWF ANCOVA MDD TBARS Phytohemagglutinin iNOS MCP-1 TRAP VNTR IFN-γ nNOS HAM-D GAF IL-1RA PANSS YMRS CMI GM-CSF NT-3 SCF CCL WCST IL-1R NLR TSST Th17 TIMP-1 YKL-40 Bipolar disorder type II hsCRP Bipolar Disorder Type I CXCL OPG HHV AITD C3c PCT PBLs PTX3 α1-antitrypsin TIMP-2 Th1 Th2 T helper cell type 2 sCD14 IGD sP-selectin sCD40L EDN1 IL1RN RTPCR CC16 IL-R RBANS TNF-R1 Hpx WMS-III CVLT CD40 L XCL1 TNF-R2 sTNF-R1 STNF-R2 Immunoglobulin D Premorbid Adjustment Scale IgM TGF-β cluster of differentiation 40 ligand α1-AT total reactive antioxidant potential sCD4 sCD8 Transferrin-Receptor BDNF DNA IgG1 MAPK MHC class II q-PCR SCZ sIL-6R sST2 TLRs α1 Acid glycoprotein California verbal learning test interleukin-1 receptor antagonist Major depressive disorder bipolar disorder Bipolar affective disorder attention deficit hyperactivity disorder Global Assessment of Functioning Osteoprotegerin Schizophrenia deoxyribonucleic acid ribonucleic acid Depression Unipolar depression inflammation MRI endothelin Cell-mediated immunity immunoglobulin immunoglobulin G Immunoglobulin G1 immunoglobulin M interferon-alpha Interleukin-1β tissue inhibitor of metalloproteinases-1 BAD ADHD autoimmune thyroid disease coronary artery disease cardiovascular disease transforming growth factor-beta analysis of covariance Triglycerides ELISA Enzyme-linked immunosorbent assay Trier Social Stress Test Wisconsin Card Sorting Test Magnetic resonance imaging Protein-protein interaction tumour necrosis factor-alpha variable number tandem repeat complement component 3 Suicide risk cluster of differentiation Waist circumference CVD messenger ribonucleic acid PCR-RFLP SERT serotonin transporter FAST peripheral blood mononuclear cells inducible nitric oxide synthase neuronal nitric oxide synthase Metabolic syndrome body mass index BMI MIF Mania CAD myeloid differentiation factor 88 Von Willebrand factor Fas Ligand FasL Stem Cell Factor Brain-derived neurotrophic factor TNF-α nuclear factor kappa B diastolic blood pressure systolic blood pressure glutathione peroxidase activity Fibrinogen peripheral blood lymphocytes chemokine (C-C motif) ligand high density lipoprotein low density lipoprotein LDL chemokine (C-X-C motif) ligand grey matter Cerebrospinal fluid CSF METS Protein carbonyl content Young Mania Rating Scale Hamilton Rating Scale for Depression positive and negative syndrome scale Wechsler Adult Intelligence Scale Tissue inhibitor of metalloproteinases-2 thiobarbituric acid reactive substances HPA Neutrophil-lymphocyte ratio Biomarkers PAS Neurotrophin 3 Haptoglobin Haemopexin corticotrophin releasing hormone hypothalamus-pituitary-adrenal polymerase chain reaction Real time polymerase chain reaction PCR WAIS human herpes virus Monocyte chemotactic protein-1 Glial fibrillary acidic protein clara cell protein high-sensitivity C-reactive protein C-reactive protein CRP mitogen-activated protein kinase Procalcitonin polymerase chain reaction-restriction fragment length polymorphism Pentraxin-3 Major histocompatibility complex class II total cholesterol healthy controls Interferon gamma interleukin receptor soluble interleukin-2 receptor Soluble interleukin-6 receptor interleukin-1 receptor Toll-like receptors