The relationship between circulating mitochondrial DNA and inflammatory cytokines in patients with major depression

Kageyama, Yuki; Kasahara, Takaoki; Kato, Masaki; Sakai, Shiho; Deguchi, Yasuhiko; Tani, Munehide; Kuroda, Kenji; Hattori, Kotaro; Yoshida, Sumiko; Goto, Yu‐ichi; Kinoshita, Toshihiko; Inoue, Koki; Kato, Takeshi

doi:10.1016/j.jad.2017.06.001

Cited by 88 publications

(84 citation statements)

References 20 publications

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“…Conflicting results have been demonstrated regarding correlation between circulating cell‐free mtDNA and IL‐6 in systemic circulation in various diseases . In this study, we found a weak correlation between amniotic fluid supernatant cell‐free mtDNA and IL‐6 levels in fresh uncentrifuged amniotic fluid.…”

Section: Discussioncontrasting

confidence: 78%

Amniotic fluid cell‐free DNA in preterm prelabor rupture of membranes

et al. 2018

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Introduction We evaluated the levels of cell‐free nuclear DNA (nDNA) and cell‐free mitochondrial DNA (mtDNA) in the amniotic fluid supernatant from pregnancies complicated by preterm prelabor rupture of membranes (PPROM) based on evidence of microbial invasion of the amniotic cavity (MIAC) and/or intra‐amniotic inflammation (IAI). Material and methods A total of 155 women with PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. The levels of cell‐free nDNA and mtDNA in the amniotic fluid supernatant were assessed and quantified by real‐time polymerase chain reaction. Results The levels of cell‐free nDNA and mtDNA were higher in women with MIAC and IAI than in women without these conditions (nDNA: with MIAC: median 3.9 × 104 genome equivalent [GE]/mL vs without MIAC: median 1.2 × 104 GE/mL, with IAI: median: 5.3 × 104 GE/mL vs without IAI: median 1.2 × 104 GE/mL; mtDNA: with MIAC: median 9.2 × 105 GE/mL vs without MIAC: median 2.5 × 105 GE/mL, with IAI: median 1.1 × 106 GE/mL vs without IAI: median 2.5 × 105; all P values ≤ 0.01). Women with the microbial‐associated IAI showed the highest levels of cell‐free nDNA and mtDNA. Conclusions Cell‐free nDNA and mtDNA are constituents of the amniotic fluid supernatant from PPROM pregnancies. Both cell‐free nDNA and mtDNA are involved in the intra‐amniotic inflammatory response in women with PPROM.

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Section: Discussioncontrasting

confidence: 78%

Amniotic fluid cell‐free DNA in preterm prelabor rupture of membranes

et al. 2018

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“…Immunological markers, including interleukin‐6 and tumor necrosis factor‐α, have been examined, and an elevation of cytokines is a relatively well‐replicated finding …”

Section: Biomarkersmentioning

confidence: 99%

“…194 These indicators are improved by treatment with mood stabilizers. 195 Immunological markers, including interleukin-6 and tumor necrosis factor-α, have been examined, 196 and an elevation of cytokines is a relatively well-replicated finding. 185 In metabolome analysis, elevation of isocitrate in cerebrospinal fluid was reported.…”

Section: Biomarkersmentioning

confidence: 99%

Current understanding of bipolar disorder: Toward integration of biological basis and treatment strategies

Kato

2019

Psychiatry Clin Neurosci

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Biological studies of bipolar disorder initially focused on the mechanism of action for antidepressants and antipsychotic drugs, and the roles of monoamines (e.g., serotonin, dopamine) have been extensively studied. Thereafter, based on the mechanism of action of lithium, intracellular signal transduction systems, including inositol metabolism and intracellular calcium signaling, have drawn attention. Involvement of intracellular calcium signaling has been supported by genetics and cellular studies. Elucidation of the neural circuits affected by calcium signaling abnormalities is critical, and our previous study suggested a role of the paraventricular thalamic nucleus. The genetic vulnerability of mitochondria causes calcium dysregulation and results in the hyperexcitability of serotonergic neurons, which are suggested to be susceptible to oxidative stress. Efficacy of anticonvulsants, animal studies of candidate genes, and studies using induced pluripotent stem cell‐derived neurons have suggested a relation between bipolar disorder and the hyperexcitability of neurons. Recent genetic findings suggest the roles of polyunsaturated acids. At the systems level, social rhythm therapy targets circadian rhythm abnormalities, and cognitive behavioral therapy may target emotion/cognition (E/C) imbalance. In the future, pharmacological and psychosocial treatments may be combined and optimized based on the biological basis of each patient, which will realize individualized treatment.

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“…Disease is clearly a factor 2-713, 14 , raising the possibility that comorbidities may modulate PD ccf-mtDNA levels. Serum ccf-mtDNA levels are influenced by inflammation [20], BMI [21] and psychosocial and physical stress [22]; factors previously linked to PD progression [23,24]. Elevated plasma ccf-mtDNA levels are associated with nonresponsiveness to selective serotonin reuptake inhibitor (SSRI) treatment in major depressive disorder (MDD) [4] and vitamin C infusion has been shown to reduce plasma ccf-mtDNA levels in sepsis patients [25], suggesting that treatment may be an important cofactor in any ccf-mtDNA assessment.…”

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confidence: 99%

Circulating cell-free mitochondrial DNA levels in Parkinson’s disease are influenced by treatment

Lowes

Pyle

Santibanez‐Koref

et al. 2020

Mol Neurodegeneration

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Several studies have linked circulating cell-free mitochondrial DNA (ccf-mtDNA) to human disease. In particular, reduced ccf-mtDNA levels in the cerebrospinal fluid (CSF) of both Alzheimer's and Parkinson's disease (PD) patients have raised the hypothesis that ccf-mtDNA could be used as a biomarker for neurodegenerative disease onset and progression. However, how a reduction of CSF ccf-mtDNA levels relates to neurodegeneration remains unclear. Many factors are likely to influence ccf-mtDNA levels, such as concomitant therapeutic treatment and comorbidities. In this study we aimed to investigate these factors, quantifying CSF ccf-mtDNA from the Parkinson's Progression Markers Initiative in 372 PD patients and 159 matched controls at two time points. We found that ccf-mtDNA levels appear significantly reduced in PD cases when compared to matched controls and are associated with cognitive impairment. However, our data indicate that this reduction in ccf-mtDNA is also associated with the commencement, type and duration of treatment. Additionally, we found that ccf-mtDNA levels are associated with comorbidities such as depression and insomnia, however this was only significant if measured in the absence of treatment. We conclude that in PD, similar to reports in HIV and sepsis, comorbidities and treatment can both influence ccf-mtDNA homeostasis, raising the possibility that ccf-mtDNA may be useful as a biomarker for treatment response or the development of secondary phenotypes. Given that, clinically, PD manifests often decades after neurodegeneration begins, predicting who will develop disease is important. Also, identifying patients who will respond to existing treatments or develop secondary phenotypes will have increased clinical importance as PD incidence rises.

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The relationship between circulating mitochondrial DNA and inflammatory cytokines in patients with major depression

Abstract: The present findings coincide with our hypothesis that circulating mtDNA contributes to the inflammation in MDD. Further studies are needed to conclude whether plasma mtDNA would be a biomarker of mood disorders.

Cited by 88 publications

References 20 publications

Amniotic fluid cell‐free DNA in preterm prelabor rupture of membranes

Amniotic fluid cell‐free DNA in preterm prelabor rupture of membranes

Current understanding of bipolar disorder: Toward integration of biological basis and treatment strategies

Circulating cell-free mitochondrial DNA levels in Parkinson’s disease are influenced by treatment

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