Circulating T lymphocyte subsets, cytokines, and immune checkpoint inhibitors in patients with bipolar II or major depression: a preliminary study

Wu, Wei; Zheng, Yali; Tian, Liang; Lai, Jianbo; Hu, Cairong; Zhang, Peng; Chen, Jingkai; Hu, Jianbo; Huang, Manli; Wei, Ning; Xu, Weijuan; Zhou, Weihua; Lu, Shengyong; Lu, Joan; Qi, Haitao; Wang, Dandan; Zhou, Xiaoyi; Duan, Jinfeng; Xu, Yi; Hu, Shaohua

doi:10.1038/srep40530

Cited by 37 publications

(36 citation statements)

References 35 publications

(40 reference statements)

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“…The expansion of conditioned pathogen (e.g., Enterobacter spp) and pathogen (e.g., Bacteroides-Prevotella group) reduced the ability of intestine to resist exogenous pathogen. Former research finds a decreased cytotoxic cell level and an increased plasma IL-6 level (54) in bipolar patients. The immune activation in bipolar disorder patients is probably part of the results of the gut dysbiosis.…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota in Bipolar Depression and Its Relationship to Brain Function: An Advanced Exploration

Lai

Lü

et al. 2019

Front. Psychiatry

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The mechanism of bipolar disorder is unclear. Growing evidence indicates that gut microbiota plays a pivotal role in mental disorders. This study aimed to find out changes in the gut microbiota in bipolar depression (BD) subjects following treatment with quetiapine and evaluate their correlations with the brain and immune function. Totally 36 subjects with BD and 27 healthy controls (HCs) were recruited. The severity of depression was evaluated with the Montgomery-Asberg depression rating scale (MADRS). At baseline, fecal samples were collected and analyzed by quantitative polymerase chain reaction (qPCR). T lymphocyte subsets were measured to examine immune function. Near-infrared spectroscopy (NIRS) was used to assess brain function. All BD subjects received quetiapine treatment (300 mg/d) for four weeks, following which the fecal microbiota and immune profiles were reexamined. Here, we first put forward the new concept of brain-gut coefficient of balance (B-GCB), which referred to the ratio of [oxygenated hemoglobin]/(Bifidobacteria to Enterobacteriaceae ratio), to analyze the linkage between the gut microbiota and brain function. At baseline, the CD3+ T cell proportion was positively correlated with log10 Enterobacter spp count, whereas the correlativity between the other bacteria and immune profiles were negative. Log10 B-GCB was positively correlated with CD3+ T cell proportion. In subjects with BD, counts of Faecalibacterium prausnitzii, Bacteroides–Prevotella group, Atopobium Cluster, Enterobacter spp, and Clostridium Cluster IV were higher, whereas the log10 (B/E) were lower than HCs (B/E refers to Bifidobacteria to Enterobacteriaceae ratio and represents microbial colonization resistance). After treatment, MADRS scores were reduced, whereas the levels of Eubacterium rectale, Bifidobacteria, and B/E increased. The composition of the gut microbiota and its relationship to brain function were altered in BD subjects. Quetiapine treatment was effective for depression and influenced the composition of gut microbiota in patients. Clinical Trial Registration: , identifier ChiCTR-COC-17011401, URL: .

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Section: Discussionmentioning

confidence: 99%

Gut Microbiota in Bipolar Depression and Its Relationship to Brain Function: An Advanced Exploration

Lai

Lü

et al. 2019

Front. Psychiatry

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“…There is now convincing data that inflammation plays a pathophysiological role in a sub-set of cases with de-pression. The evidence in this regard can be laid out as follows: (a) depressive episode-associated increases in circulating pro-inflammatory cytokines [ 37 ], (b) increased expression of inflammation-related genes in monocytes or peripheral blood mononuclear cells (PBMCs) of mood disorder patients [ 38 ], (c) the occurrence of depressive episodes in about 30% of patients receiving immune-stimulating treatments [ 39 ], (d) the development of depressive symptoms in some healthy individuals given low-dose endotoxin [ 40 ], (e) prospective studies demonstrating a positive association between the concentrations of inflam-matory mediators at baseline and the development of de novo cases of major depressive disorder (MDD) [ 41 ], (f) an epidemiological association between depression and diseases with an autoimmune or inflammatory component [ 42 ], (g) higher numbers and activation of microglial cells measured in vivo with positron emission tomography [ 43 ], and (h) increased number and activation of microglia in depressed suicide victims brains at postmortem [ 44 ]. See Table 2 for further information on the evidence presented here ( Table 2 ).…”

Section: Kynurenine Pathway and Mood Disordersmentioning

confidence: 99%

Kynurenine Pathway of Tryptophan Metabolism in Neuropsychiatric Disorders: Pathophysiologic and Therapeutic Considerations

Muneer

2020

Clin Psychopharmacol Neurosci

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Under physiological conditions 95% of the ingested essential amino acid tryptophan is metabolized by the kynurenine pathway (KP) to yield the ubiquitous co-enzyme nicotinamide adenine dinucleotide, fulfilling cellular energy require-ments. Importantly, the intermediaries of KP exert crucial effects throughout the body, including the central nervous system. Besides, KP metabolites are implicated in diverse disease processes such as inflammation/immune disorders, endocrine/metabolic conditions, cancers and neuropsychiatric diseases. A burgeoning body of research indicates that the KP plays a pathogenic role in major psychiatric diseases like mood disorders and schizophrenia. Triggered by inflammatory processes, the balance between neurotoxic and neuroprotective branches of the KP is disturbed. In preclinical models these discrepancies result in behaviors reminiscent of depression and psychosis. In clinical samples, recent studies are discovering key kynurenine pathway abnormalities which incriminate it in the pathogenesis of the main psychiatric disorders. Harnessing this knowledge has the potential to find disease biomarkers helpful in identifying and prognosticating neuropsychiatric disorders. Concurrently, earnest research efforts directed towards manipulating the KP hold the promise of discovering novel pharmacological agents that have therapeutic value. In this manuscript, an in-depth appraisal of the extant literature is done to understand the working of KP as this applies to neuropsychiatric disorders. It is concluded that this pathway plays an overarching role in the development of major psychiatric disorders, the KP metabolites have the potential to serve as disease markers and new medications based on KP modulation can bring lasting cures for patients suffering from these intractable conditions.

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“…demonstrated increased levels of soluble receptor for TNF-α type 1 20,21 . BD patients also are characterized by the reduced percentage of total T lymphocytes (CD3 + cells) 22,23 as well as population of cytotoxic T lymphocytes (CD3 + CD8 + cells) compared with healthy people 22 . Barbosa et al .…”

Section: Introductionmentioning

confidence: 99%

Peripheral blood lymphocyte subpopulations in patients with bipolar disorder type II

Pietruczuk

Lisowska

Grabowski

et al. 2019

Sci Rep

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We investigated the phenotype of peripheral blood lymphocytes of patients with bipolar disorder type II in different phases of the disease in order to check whether there are specific changes in the immune parameters. Lymphocytes subpopulations were analyzed ex vivo with flow cytometry in patients in euthymic, depression or hypomanic phase of the disease and compared with healthy controls. All BD patients were characterized by lower percentage of CD3 + CD4 + and CD3 + CD8 + cells compared with healthy people. But only patients in depression and remission had higher percentage of B cells (CD19 + cells) compared with healthy people. The percentage of CD4 + CD25 + and CD8 + CD25 + cells was decreased in patients in hypomanic phase compared with healthy control. Patients in remission were characterized by increased concentrations of IL-6 and IL-10 and decreased level of TNF in blood serum. Significant correlations between immunologic parameters and the results of Hamilton or Young scale have also been found. Our results demonstrate that there are significant differences in lymphocyte subpopulations which depend on the phase of the disease the patient is currently in.

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Circulating T lymphocyte subsets, cytokines, and immune checkpoint inhibitors in patients with bipolar II or major depression: a preliminary study

Cited by 37 publications

References 35 publications

Gut Microbiota in Bipolar Depression and Its Relationship to Brain Function: An Advanced Exploration

Gut Microbiota in Bipolar Depression and Its Relationship to Brain Function: An Advanced Exploration

Kynurenine Pathway of Tryptophan Metabolism in Neuropsychiatric Disorders: Pathophysiologic and Therapeutic Considerations

Peripheral blood lymphocyte subpopulations in patients with bipolar disorder type II

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