Astrocytes in the Neuropathology of Bipolar Disorder: Review of Current Evidence

Abstract

(1) Background: Approximately one-third of patients with bipolar disorder (BD) do not experience sustained remission with current treatments. Presently, astrocytes, i.e., glial cells that act as key regulators of neuroinflammation, have been a target for therapeutic development. Research regarding their role in the neuropathology of BD is limited. We conducted a scoping review on evidence linking astrocytes to the pathology of BD. (2) Methods: The search was conducted in MEDLINE for studies published from inception to August 2022. Studies of interest were data-extracted and reported based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols. (3) Results: Overall, 650 publications were identified, of which 122 full texts were evaluated and 12 included. Four were in vitro, seven were ex vivo, and one study was both in vitro and in vivo. In vitro investigations focused on plasma levels of neuroinflammatory biomarkers S100B and glial fibrillary acidic protein (GFAP). Ex vivo investigations were post-mortem brain studies assessing astrocytes in regions of interest (i.e., anterior cingulate cortex, dorsolateral prefrontal cortex) using phosphorylated GFAP and ASCT-1. The in vivo and in vitro study evaluated morphological and chemical variations of YKL-40 between cohorts. (4) Conclusions: Reports indicate an association between astrocyte dysfunction and BD although larger studies are required to validate this association.

Platinum nanozyme-mediated temperature sensor for sensitive photothermal immunoassay of YKL-40 under near-infrared light

“…Typically, increased YKL-40 levels in the blood are associated with the progression of multiple diseases and cancers, such as gastric cancer, colon cancer, and glioma cancer. 5 Interestingly, YKL-40 secreted from macrophages can induce cell migration and invasion of colon, gastric, and breast cancers. Therefore, sensitive and specific detection of YKL-40 in biological fluids is of great interest for clinical diagnostics.…”

Collecting Contributions for a Critical Issue: Progressing from Bench to Bedside in Bipolar Disorders

“…A second biomarker examination argues for the potential importance of astrocytes in the pathophysiology of BD. Reviewing the current evidence to date, Dai et al identified several studies indicating a putative role of astrocytes in BD, with few overall studies and high heterogeneity between findings, indicating the importance of further large-scale investigations where key effect-modifying variables can be considered [ 5 ]. In terms of translation, this field could help to optimise established interventions with neuroprotective effects (including on astrocytes) such as lithium, and relevant therapies under investigation, e.g., pioglitazone, and novel targets.…”

“…Commonly, these 10 articles contained increased sample sizes compared to older studies either through primary research studies [ 3 ], secondary analyses from multiple RCTs [ 8 ], the utilisation of large, well-defined medical records cohorts [ 9 ], or undertaking scoping reviews [ 5 , 14 , 15 ], systematic reviews and/or meta-analyses [ 6 , 7 , 12 ]. Where large samples were not justified, an innovative randomised case series approach was employed [ 13 ].…”

“…This Special Issue focuses on key important questions, including how to improve diagnostic specificity for BD [ 3 , 5 , 6 ], and understand its pathophysiology using biological, [ 5 ] psychological [ 6 , 7 ] or multimodal assessments [ 3 ]. These latter questions could help to identify novel treatment targets; other articles utilised extant pathophysiological information to examine existing interventions [ 12 ], repurposing [ 14 ] and/or modifying [ 13 ] therapies from associated disorders (largely unipolar depression), or repurposing from non-psychiatric conditions [ 15 ].…”