Altered Levels of Plasma Inflammatory Cytokines and White Matter Integrity in Bipolar Disorder Patients With Suicide Attempts

Abstract

ObjectiveBipolar disorder (BD) has a higher lifetime rate of suicide attempts (SA) than other psychiatric disorders. Furthermore, BD patients with SA (BD + S) are prone to a worse quality of life. However, the pathophysiology of BD + S is poorly understood. To further reveal the potential mechanisms of BD + S, abnormalities in peripheral plasma inflammatory cytokines and brain white matter (WM) in BD + S, as well as the correlation between them are investigated.MethodsWe tested the levels of TNF-α, IL-1β, and IL-6 in peripheral plasma and collected the diffusion tensor imaging (DTI) data from 14 BD + S, 24 BD patients without SA (BD-S), and 26 healthy controls (HCs). The three groups were matched by age and gender. The levels of TNF-α, IL-1β, and IL-6 were detected by Luminex multifactor detection technology, and the fractional anisotropy (FA) values were employed to depict the alterations of WM. Partial correlation analyses were conducted to detect correlations between levels of TNF-α, IL-1β, and IL-6 and changes of WM, and the relationships between severity of clinical symptoms, including scores of HAMD-17 and YMRS, and cytokine levels or FA values in all groups.ResultsFor plasma inflammatory cytokines, there was no significant difference in their levels except for IL-6 among the three groups. Post-hoc analyses revealed that increased IL-6 level was only detected in BD + S (p < 0.05, Bonferroni correction). For DTI, BD + S showed specifically decreased FA in the bilateral middle cerebellar peduncle and the left superior corona radiata compared to BD-S and HCs (p < 0.05, Bonferroni correction). Additionally, both BD + S and BD-S groups revealed decreased FA in the bilateral body and genu of corpus callosum (CC) compared to HCs (p < 0.05, Bonferroni correction). No significant correlation between plasma inflammatory cytokines and WM integrity was found. In the BD + S group, we found negative correlation between the scores of YMRS and FA values of the left middle cerebellar peduncle (r = −0.74, p = 0.035).ConclusionThe inflammation and impaired WM integrity may provide a scientific basis to understand the potential mechanisms of BD + S.

Inflammatory markers at baseline correlate with subsequent clinical response to quetiapine in patients with bipolar disorder

“…Our working hypothesis to explain this discrepancy is that inflammatory conditions are more strictly related with negative symptoms, which are better evaluated by PBRS and MADRS scales rather than the other considered scales. Our hypothesis is supported by a recent report showing that in depressed BD subjects IL‐6 plasma levels were higher than in not depressed BD subjects (Jiang et al., 2022). Of course, this hypothesis must be confirmed by further studies aimed to clarify the role of inflammatory conditions in patients with positive/negative symptoms.…”

Immune-Related Biomarkers and Suicidal Behaviors: A Meta-Analysis

“…2 A). Five studies ( Conejero et al, 2019 ;Dolsen et al, 2021 ;Fernandez-Sevillano et al, 2022 ;Jiang et al, 2022 ;Wiebenga et al, 2022 ) investigated peripheral IL-6 in PDs with and without SB. Overall, IL-6 was higher in the PD with SB group compared with PD without SB (SMD = 0.22, 95% CI = 0.11 and 0.33, p < 0.0001, I 2 = 2%, a small effect size, Fig.…”

Plasma IGFBP-3 and IGFBP-5 levels are decreased during acute manic episodes in bipolar disorder patients

“…BD manic patients showed significantly higher TNF-α levels than controls at admission ( Kim et al, 2007 ; Junior et al, 2023 ; Polat et al, 2023 ), without receiving pharmacotherapy 2 ( Pandey et al, 2015 ) or 3 weeks before protein measurement ( Ortiz-Domínguez et al, 2007 ), when following stable treatment ( O'Brien et al, 2006 ; Kim et al, 2007 ; Kapczinski et al, 2011 ; Luo et al, 2016 ; Wang et al, 2016 ; Hoseth et al, 2017 ; Koga et al, 2019 ; Bavaresco et al, 2020 ; Zazula et al, 2022 ; Lu et al, 2023 ; Gong et al, 2022 ), and in both early ( Skibinska et al, 2022 ) and late BD stages ( Kauer-Sant Anna et al, 2009 ; Tatay-Manteiga et al, 2017 ), or significantly reduced levels in euthymic late patients but not in early BD patients ( Panizzutti et al, 2015 ). In other cases, no difference was found between controls and BD patients who were under medication ( Barbosa et al, 2011 ; Palacio et al, 2016 ; Doğanavşargil Baysal et al, 2019 ; Garés-Caballer et al, 2022 ; Jiang et al, 2022 ) with valproic acid monotherapy ( Chou et al, 2016 ) or at baseline when specified that BD patients had a manic episode ( Li et al, 2015 ; Jacoby et al, 2016 ) or were in their first episode ( Chen MH et al, 2020 ). During euthymia, TNF-α has also been unaltered compared to controls ( Kunz et al, 2011 ; Barbosa et al, 2012a ; Doganavsargil-Baysal et al, 2013 ; Wieck et al, 2014 ; Jacoby et al, 2016 ; Doğanavşargil Baysal et al, 2019 ; Millett et al, 2020 ; Vares et al, 2020 ).…”