Clinical Value of Inflammatory and Neurotrophic Biomarkers in Bipolar Disorder: A Systematic Review and Meta-Analysis

Abstract

Bipolar disorder (BD) is a multifactorial chronic psychiatric disease highly defined by genetic, clinical, environmental and social risk factors. The present systematic review and meta-analysis aimed to examine the relationship between inflammatory and neurotrophic factors and clinical, social and environmental factors involved in the development and the characterization of BD. Web of Science, PubMed, PsycINFO, Scopus and Science Direct were searched by two independent reviewers. The systematic review was registered in PROSPERO (CRD42020180626). A total of 51 studies with 4547 patients with a diagnosis of BD were selected for systematic review. Among them, 18 articles were included for meta-analysis. The study found some evidence of associations between BDNF and/or inflammatory factors and different stressors and functional and cognitive impairment, but limitations prevented firm conclusions. The main finding of the meta-analysis was a negative correlation between circulating levels of BDNF and depression severity score (standardized mean difference = −0.22, Confidence Interval 95% = −0.38, −0.05, p = 0.01). Evidence indicates that BDNF has a role in the depressive component of BD. However, the poor consistency found for other inflammatory mediators clearly indicates that highly controlled studies are needed to identity precise biomarkers of this disorder.

Advances in the pathophysiology of bipolar disorder

“…New treatments for BD are being studied, and most target disparate effector systems, mainly related to molecular targets in neuroplasticity, neurotrophic factors, inflammation, stress, mitochondrial function, and related metabolic pathways [46][47][48]. Clinical trials have demonstrated the efficacy of adjunctive inflammatory modulation with celecoxib in treatment-resistant bipolar depression, showing that add-on celecoxib reduces treatment resistance and enhances antidepressant response in patients with treatment-resistant bipolar depression [49,50].…”

Inflammation and emotional regulation: a narrative review of evidence and mechanisms in emotional dysregulation disorders

“…BDNF is a well-established antiinflammatory mediator (201), involved in neurogenesis and with neurotrophic effects (202), whose blood and brain levels decrease with peripheral inflammation. Several works indicate that BDNF may play a role in BD pathogenesis and neuroplasticity changes associated with the disorder (203,204). ELS, such as trauma, has also been shown to increase the risk for BD (205)(206)(207) and lead to unfavourable symptoms and disease progression (208).…”

“…In particular, due to its consistent alterations in BD patients, IL-6 has recently been proposed as a potential BD marker (218). However, some of these associations are not encountered or presented in the opposite direction in other works (203,218).…”

“…BDNF has also been proposed as a state marker of mood episodes in BD (232). Along these lines, a meta-analysis examined and found a negative correlation between circulating levels of the anti-inflammatory BDNF and depression severity in BD (203).…”

Transient splenial lesion syndrome in bipolar-II disorder: a case report highlighting reversible brain changes during hypomanic episodes

“…Although the underlying pathophysiology of RESLES is not yet well understood, studies have indicated that it is related to inflammation, intramyelinic cytotoxic edema ( 8 ), oxidative stress ( 9 ), and autoimmune processes ( 10 ). Vega-Nunez et al ( 11 ) mentioned in their review that there is a certain association between inflammatory biomarkers and mood episode, such as tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), cytokines, etc. Serum levels of these inflammatory biomarkers may increase or decrease with different mood episode.…”