Biomarkers for bipolar disorder: current insights

Current Biomarker Findings Dovepress open access to scientific and medical research Review Open Access Full Text Article Current Biomarker Findings downloaded from https://www.dovepress.com/ by 88.198.20.149 on 05-May-2021 For personal use only. Biomarkers for bipolar disorder: current insights This article was published in the following Dove Press journal: Current Biomarker Findings 3 November 2015 Number of times this article has been viewed Angela Duong 1 Bushra Syed 1 Gustavo Scola 2,3 Department of Pharmacology and Toxicology, 2Department of Psychiatry, University of Toronto, 3Centre for Addiction and Mental Health, Toronto, ON, Canada 1 Introduction Correspondence: Gustavo Scola Room 4204, Medical Science Building, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8, Canada Tel/Fax +1 416 946 5722 Email Bipolar disorder (BD) is a chronic psychiatric illness with partially unknown pathophysiology and symptoms alternating between mania and depression.1 As consistently found in postmortem studies, in BD, morphological alterations are associated with disruption of cerebral functions, leading to impairment in the cellular plasticity and resilience of the brain.2 Currently, many studies have reported alterations in the morphology of brain tissues, brain cells, and in the periphery. These alterations could be directly correlated to dysregulation of the molecular pathways of inflammation and neurotrophins.3,4 The factors that regulate neurological cells are expressed in a region-specific manner in the brain and the peripheral tissues. This suggests the possibility of using peripheral markers to address alterations in the brain that occur during the development of BD and other psychiatric disorders. Biomarkers are essential tools necessary to provide insights into the molecular alterations in BD.2,3 Due to the heterogeneity of this disorder, the possibility of developing specific biomarker is still being explored; however, a set of biomarkers might be available to identify subgroups of patients and also develop new treatments. Our goal is to incorporate and critically review the published literature with regard to the morphological, genetic, and molecular alterations found in BD. The hypothetical use of these findings as potential biomarkers is also examined. Moreover, these markers could be used as tools for diagnosis, to assess illness progression, and to help with the improvement of more specific and personalized treatments for patients 79 submit your manuscript | www.dovepress.com Current Biomarker Findings 2015:5 79–92 Dovepress © 2015 Duong et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php http://dx.doi.org/10.2147/CBF.S79138 Powered by TCPDF (www.tcpdf.org) Abstract: Currently, there exists a lack of definitive diagnostic tools for neuropsychiatric disorders, particularly molecular markers that could help assess the illness and develop more personalized treatments for different disorders. Understanding of the neurobiology and potential novel treatments for bipolar disorder (BD), one of the most complex psychiatric illnesses, remains poor. This review aims to compile the most reproducible findings regarding the molecular, genetic, and structural changes that occur in BD. Neuroimaging studies have indicated alterations in neural circuits, disrupted white matter integrity, alterations in reward activation, and decreased gray matter (GM) volume. Genetic studies have identified variations in a number of genes that confer risk for BD development. Studies involving peripheral biomarkers include alterations in the levels of oxidative stress, inflammation, and neurotrophins. These potential molecular markers could be used as tools for diagnosis, to assess illness progression, and to help with the improvement of more specific and personalized treatments for patients with BD. Identification of biologically relevant markers could improve the quality of life of patients with BD and revolutionize public health. Keywords: biomarkers, neuroimaging, neural activation, gene regulation, microRNAs, oxidative stress, inflammation Duong et al Current Biomarker Findings downloaded from https://www.dovepress.com/ by 88.198.20.149 on 05-May-2021 For personal use only. with BD. This review is separated into distinct sections that comprise structural, genetic, and peripheral alterations in BD. In addition, all the potential biomarkers discussed in this report are illustrated in Table 1. Structural abnormalities and neurochemical alterations Neuroimaging in BD BD may present with early episodes of depression, often leading to its misdiagnosis as unipolar depression, which in turn can lead to misdirected treatment.5 Strategies aimed at improving diagnostic accuracy and treatment approaches for BD are therefore crucial. One such approach is using neuroimaging technologies to identify biomarkers. Neuroimaging technologies include structural neuroimaging, functional imaging, diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS). 6 Such technologies have allowed a better understanding of the pathophysiology of BD through observations of structural and functional alterations. These alterations may serve as potential biomarkers for BD and have application in diagnostic or prognostic evaluation. The ventral prefrontal cortex and the amygdala form a corticolimbic network that is involved in emotional regulation.7 Functional deficits such as impaired emotional regulation and attention have been implicated in BD.8 One of the most commonly used tools to characterize such alterations is neuroimaging, which can be divided into either functional or structural studies. Structural neuroimaging showed an increased in volume of the amygdala in patients with BD compared to those with schizophrenia;9 decreased gray matter (GM) volume in dorsal and ventral prefrontal cortices in BD;10 and little or no alteration in hippocampal volume in BD compared to healthy subjects.11 Functional neuroimaging uses functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) to determine alterations in parts of the brain in subjects during the performance of tasks that require emotion processing and executive control.8,12 Several studies have used functional neuroimaging to determine whether a significant difference in emotional processing exists in different states of BD, which can be used as a potential biomarker for (...truncated)