Biomarkers and staging of bipolar disorder: a systematic review

Abstract

Introduction: A growing body of evidence suggests that bipolar disorder (BD) is a progressive disease according to clinical, biochemical and neuroimaging findings. This study reviewed the literature on the relationship between specific biomarkers and BD stages. Methods: A comprehensive literature search of MEDLINE and PubMed was conducted to identify studies in English and Portuguese using the keywords biomarker, neurotrophic factors, inflammation, oxidative stress, neuroprogression and staging models cross-referenced with bipolar disorder. Results: Morphometric studies of patients with BD found neuroanatomic abnormalities, such as ventricular enlargement, grey matter loss in the hippocampus and cerebellum, volume decreases in the prefrontal cortex and variations in the size of the amygdala. Other studies demonstrated that serum concentrations of neurotrophic factors, inflammatory mediators and oxidative stress may be used as BD biomarkers. Conclusions: The analysis of neurobiological changes associated with BD progression and activity may confirm the existence of BD biomarkers, which may be then included in staging models that will lead to improvements in treatment algorithms and more effective, individually tailored treatment regimens. Biomarkers may also be used to define early interventions to control disease progression.

Glucose metabolism alterations in patients with bipolar disorder

“…Indeed, recent staging models include a high number of recurrences as an indicator of late stage BD (Berk et al, 2007). As suggested by a growing body of evidence, together with a clear understanding of the clinical course of the disease, the identification of biomarkers is fundamental for the development of staging models which may improve treatment guidelines and lead to the development of more efficient, individually tailored treatment regimens (Kapczinski et al, 2014;Roda et al, 2015). If confirmed by further studies, decreased levels of Glucagon and GLP-1 could represent a marker of late-stage patients with BD.…”

The Differential Levels of Inflammatory Cytokines and BDNF among Bipolar Spectrum Disorders

“…In addition, cytokines are key signaling molecules that regulate both innate and adaptive immunological responses and have widespread effects on the neuroendocrine system, neurogenesis, neurocircuitry, and neurotransmitter metabolism (Haroon et al, 2012). Therefore, peripheral cytokine fluctuations have been proposed as biomarkers for disease activity, affective state, or the disease nature for BP (Roda et al, 2015). Most studies, however, have a mixed group of BP patients (ie, BP-I patients and BP-II patients) to compare with a control group (Modabbernia et al, 2013; Munkholm et al, 2013a, 2013b).…”

Challenges and developments in research of the early stages of bipolar disorder

“…4 Moreover, correlating these symptoms with prodromal biomarkers offers an exciting juncture whereby targeted interventions could be opportunistically employed to prevent neurodegenerative changes from accruing as the disease progresses. 11,91 Nevertheless, empirical data supporting the use of biomarkers for outcome prediction in prodromal stages are limited. 92 One of the first studies, conducted by Padmos et al, 93 identified a discriminating and coherent expression of 19 pro-inflammatory genes transcription in monocytes of patients with BD and in the offspring of BD parents.…”

“…10 Biomarkers seem to play an important role in evaluating disease activity and progression associated with different mood states (mood biomarkers), as well as to identify specific characteristics of the disease (trait biomarkers). 11,12 The available evidence indicates that neurotrophins, oxidative stress, and inflammation are linked to the acute and euthymic phases of BD, 13,14 and indicate the presence of systemic toxicity. 15 The use of clinical staging models is emerging as a novel and useful paradigm to inform diagnosis and treatment of BD.…”