Biomarkers in bipolar disorder: A positional paper from the International Society for Bipolar Disorders Biomarkers Task Force

Abstract

Although the etiology of bipolar disorder remains uncertain, multiple studies examining neuroimaging, peripheral markers and genetics have provided important insights into the pathophysiologic processes underlying bipolar disorder. Neuroimaging studies have consistently demonstrated loss of gray matter, as well as altered activation of subcortical, anterior temporal and ventral prefrontal regions in response to emotional stimuli in bipolar disorder. Genetics studies have identified several potential candidate genes associated with increased risk for developing bipolar disorder that involve circadian rhythm, neuronal development and calcium metabolism. Notably, several groups have found decreased levels of neurotrophic factors and increased pro-inflammatory cytokines and oxidative stress markers. Together these findings provide the background for the identification of potential biomarkers for vulnerability, disease expression and to help understand the course of illness and treatment response. In other areas of medicine, validated biomarkers now inform clinical decision-making. Although the findings reviewed herein hold promise, further research involving large collaborative studies is needed to validate these potential biomarkers prior to employing them for clinical purposes. Therefore, in this positional paper from the ISBD-BIONET (biomarkers network from the International Society for Bipolar Disorders), we will discuss our view of biomarkers for these three areas: neuroimaging, peripheral measurements and genetics; and conclude the paper with our position for the next steps in the search for biomarkers for bipolar disorder.

The role of neuroinflammation in juvenile bipolar disorder

“…[1,3] Our review provides a summary of preliminary findings about the link between inflammatory processes, decreased neurotrophins, increased oxidative stress and juvenile or young adult age BD. Two different lines of research have been pursued in this field, one regarding early onset (pediatric) of BD and the other on the effects of course variables (duration of illness, number of episodes, hospitalizations) on changes in inflammatory markers, neurotrophins and markers of oxidative stress.…”

“…[1,11] Furthermore, adult subjects with BD are at higher risk of developing comorbid medical illnesses such as diabetes, metabolic and cardiovascular diseases that are also associated with elevated levels of proinflammatory markers. [12,13] Potentially involved cytokines include tumor necrosis factor (TNF), interleukin-2 (IL-2), IL-6, IL-8, IL-13 and apolipoprotein A1.…”

Biomarkers for bipolar disorder: current insights

“…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.…”

Bipolar bozuklukta allostaz ve allostatik yükü yeniden değerlendirmek

“…For several years, brain derived neurotrophic factor (BDNF) has been one of the most studied neurotrophins in BD (16). Recent studies reported decreased BDNF and increased glia-derived neurotrophic factor (GDNF) levels in both mania and depression (17), increased GDNF/BDNF ratio in mania (18), and increased GDNF levels during manic switch due to ECT (19) confirming the role of the disrupted supportive cellular network in BD.…”