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

Wang, Tzu Yun; Lee, Sheng Yu; Chung, Yi; Li, Chia Ling; Chang, Yun Hsuan; Wang, Liang‐Jen; Chen, Po See; Chen, Shih‐Heng; Chu, Chun Hsien; Huang, San Yuan; Tzeng, Nian Sheng; Hsieh, Tsai Hsin; Chiu, Yen Chu; Lee, I. Hui; Chen, Kao Chin; Yang, Yen Kuang; Hong, Jau–Shyong; Lu, Ru Band

doi:10.1093/ijnp/pyw012

Cited by 34 publications

(20 citation statements)

References 64 publications

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“…In this study, we found increased pro-in ammatory cytokine levels of IL-6 and IL-8 in BD group when compared to HC, which was consistent with previous studies [26,28,30,87,88]. Furthermore, we found elevated levels of IL-8 correlated with the reduction of FC in the right precentral gyrus within SMN in BD.…”

Section: Correlation Between Fc In the Right Precentral Gyrus And Il-supporting

confidence: 92%

“…Pro-in ammatory cytokines have been shown to access the brain [20] and interact with neurocircuits to in uence the risk for depression [21] and are implicated in many neurobiological processes including neuromodulator effects, neurotransmitter-like effects, regulation of neurogenesis that potentially relevant to psychiatric disorders such as BD [22]. Previous studies examined the relationship between in ammation and BD focusing on abnormal peripheral pro-in ammatory cytokines levels, and found signi cantly elevated levels of interleukin 6 (IL-6) [23][24][25][26] and interleukin 8 (IL-8) [27][28][29] in BD. Higher baseline IL-6 and IL-8 levels associated with poorer antidepressant responses have been found in BD [30].…”

Section: Introductionmentioning

confidence: 99%

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Inflammation is Correlated with Abnormal Functional Connectivity in Unmedicated Bipolar Depression: A Resting State FMRI Study

Tang¹,

Chen²,

Chen³

et al. 2020

Preprint

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Objectives Inflammation might play a role in bipolar disorder (BD), but it remains unclear the relationship between inflammation and brain structural and functional abnormalities in patients with BD. In this study, we focused on the alterations of functional connectivity (FC), peripheral pro-inflammatory cytokines and their correlations to investigate the role of inflammation in FC in BD depression.Methods In this study, 42 unmedicated patients with BD II depression and 62 healthy controls (HCs) were enrolled. Resting-state-functional magnetic resonance imaging (rs-fMRI) was performed in all participants and independent component analysis (ICA) was used. Serum levels of Interleukin-6 (IL-6) and Interleukin-8 (IL-8) were measured in all participants. Correlation between FC values and IL-6 and IL-8 levels in BD was calculated.Results Compared with the HCs, BD II patients showed decreased FC in the left orbitofrontal cortex (OFC) implicating the limbic network and the right precentral gyrus implicating the somatomotor network (SMN). BD II showed increased IL-6 (P = 0.039), IL-8 (P = 0.002) levels. Moreover, abnormal FC in the right precentral gyrus were inversely correlated with the IL-8 (r=-0.458, P = 0.004) levels in BD II. No significant correlation was found between FC in the left OFC and cytokines levels.Conclusions Our findings that serum IL-8 levels is associated with impaired FC in the right precentral gyrus in BD II patients suggest that inflammation might play a crucial role in brain functional abnormalities in BD.

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Section: Correlation Between Fc In the Right Precentral Gyrus And Il-supporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Inflammation is Correlated with Abnormal Functional Connectivity in Unmedicated Bipolar Depression: A Resting State FMRI Study

Tang¹,

Chen²,

Chen³

et al. 2020

Preprint

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“…In addition, the stratified analysis showed no correlation between BDNF levels and WCST scores in patients with BP-II. We previously66 found a trend of lower plasma levels in BP-I than in BP-II, which suggests that BDNF has a stronger effect on BP-I than on BP-II. Therefore, we hypothesized that in Val/Met genotype carriers with BP-I, peripheral BDNF levels better depict cognitive performance.…”

Section: Discussionmentioning

confidence: 87%

The correlation between plasma brain-derived neurotrophic factor and cognitive function in bipolar disorder is modulated by the BDNF Val66Met polymorphism

Lee

Wang

Chang

et al. 2016

Sci Rep

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We explored the effect of the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) on correlation between changes in plasma BDNF levels with cognitive function and quality of life (QoL) after 12 weeks of treatment in bipolar disorder (BD). Symptom severity and plasma BDNF levels were assessed upon recruitment and during weeks 1, 2, 4, 8 and 12. QoL, the Wisconsin Card Sorting Test (WCST), and the Conners’ Continuous Performance Test (CPT) were assessed at baseline and endpoint. The BDNF Val66Met polymorphism was genotyped. Changes in cognitive function and QoL over 12 weeks were reduced using factor analysis for the evaluation of their correlations with changes in plasma BDNF. Five hundred forty-one BD patients were recruited and 65.6% of them completed the 12-week follow-up. Changes in plasma BDNF levels with factor 1 (WCST) were significantly negatively correlated (r = −0.25, p = 0.00037). After stratification of BD subtypes and BDNF genotypes, this correlation was significant only in BP-I and the Val/Met genotype (r = −0.54, p = 0.008). We concluded that changes in plasma BDNF levels significantly correlated with changes in WCST scores in BD and is moderated by the BDNF Val66Met polymorphism and the subtype of BD.

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“…Another group has tried to investigate the difference in the peripheral inflammatory markers' levels between BD illness phase. BD spectrum patients have higher TNF-a, TGF-b1, and IL-8 levels than controls, even if only IL-8 levels result significantly different in the BD spectrum, with higher levels in BD type I patients compared to BD type II and other unspecified BD (114). BD type I patients also show higher levels of the sTNF-R1 compared to BD type II patients (115).…”

Section: Immune Markers As Clinical Outcome and Diagnostic Predictorsmentioning

confidence: 95%

Neuroinflammation in Bipolar Depression

et al. 2020

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Bipolar disorder (BD) is a leading cause of worldwide disability among mood disorders. Pathological mechanisms are still vastly unclear, and current treatments with conventional medications are often unsatisfactory in maintaining symptoms control and an adequate quality of life. Consequently, current research is focusing on shedding new light on disease pathogenesis, to improve therapeutic effectiveness. Recent evidence has suggested a prominent role of inflammation in mood disorders. Elevated levels of peripheral proinflammatory mediators have been reported in BD, as well as in other mood disorders, and people with systemic autoimmune diseases have an increased risk of developing BD. These immunological alterations are stable, and current medications are unable to alter peripheral concentrations even when clinical improvement is evident. These findings have also been replicated in the central nervous system (CNS) milieu, whereas genetic studies have shown that these immune alterations are not due to the disorder itself, being detectable before the illness onset. Moreover, these inflammatory modifications seem to be affected by and linked to other biomarkers of the disorder, such as alterations of white matter (WM) microstructure, metabolism, kynurenine pathway, and circadian rhythmicity. Finally, these immune variations seem to be useful as predictors of therapeutic responsiveness to medications, and in discriminating between clinically different outcomes. The objective of this review is to summarize available evidence on the connection between inflammation and BD, focusing on peripheral inflammatory markers and recent findings on their connection with other typical features of BD, to outline a general overview of the disorder. Moreover, it is meant to analyze the issues with data gathering and interpretation, given the partially contradictory and inconsistent nature of results.

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

Cited by 34 publications

References 64 publications

Inflammation is Correlated with Abnormal Functional Connectivity in Unmedicated Bipolar Depression: A Resting State FMRI Study

Inflammation is Correlated with Abnormal Functional Connectivity in Unmedicated Bipolar Depression: A Resting State FMRI Study

The correlation between plasma brain-derived neurotrophic factor and cognitive function in bipolar disorder is modulated by the BDNF Val66Met polymorphism

Neuroinflammation in Bipolar Depression

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