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双相情感障碍患者同胞的端粒长度、氧化应激、炎症及脑源性神经营养因子水平:对细胞加速衰老的影响

Telomere Length, Oxidative Stress, Inflammation and BDNF Levels in Siblings of Patients with Bipolar Disorder: Implications for Accelerated Cellular Aging.

作者信息

Vasconcelos-Moreno Mirela Paiva, Fries Gabriel Rodrigo, Gubert Carolina, Dos Santos Bárbara Tietböhl Martins Quadros, Fijtman Adam, Sartori Juliana, Ferrari Pamela, Grun Lucas Kich, Parisi Mariana Migliorini, Guma Fátima Theresinha Costa Rodrigues, Barbé-Tuana Florencia Maria, Kapczinski Flávio, Rosa Adriane Ribeiro, Yatham Lakshmi N, Kauer-Sant'Anna Marcia

机构信息

Laboratório de Psiquiatria Molecular, Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), Hospital deClínicas de Porto Alegre, Porto Alegre, RS, Brasil (Drs Vasconcelos-Moreno, Rodrigo Fries, Tietböhl Martins Quadros dos Santos, Fijtman, and Sartori, Ms Ferrari, and Drs Kapczinski, Ribeiro Rosa, Kauer-Sant'Anna); Programa de Pós Graduação em Ciências Médicas - Psiquiatria, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil (Drs Paiva Vasconcelos-Moreno and Sartori, Ms Ferrari, Drs Kapczinski, Ribeiro Rosa, and Kauer-Sant'Anna); Programa de Pós-Graduação Ciências Biológicas - Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil (Dr Rodrigo Fries and Ms Gubert); Laboratório de Biologia Molecular e Bioinformática, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil (Mr Kich Grun, Ms Migliorini Parisi, and Drs Theresinha Costa Rodrigues Guma and Barbé-Tuana); Mood Disorders Center, University of British Columbia, Vancouver, BC, Canada (Dr Yatham).

出版信息

Int J Neuropsychopharmacol. 2017 Jun 1;20(6):445-454. doi: 10.1093/ijnp/pyx001.

Abstract

BACKGROUND

Growing evidence supports the existence of neurobiological trait abnormalities in individuals at genetic risk for bipolar disorder. The aim of this study was to examine potential differences in brain-derived neurotrophic factor, cytokines, oxidative stress, and telomere length markers between patients with bipolar disorder, their siblings, and healthy controls.

METHODS

Thirty-six patients with bipolar disorder type I, 39 siblings, and 44 healthy controls were assessed. Serum levels of brain-derived neurotrophic factor, interleukin-6, interleukin-10, tumor necrosis factor-α, C-C motif chemokine 11, C-C motif chemokine 24, and 3-nitrotyrosine were measured, as were the activities of glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Telomere length (T/S ratio) was measured using quantitative polymerase chain reaction.

RESULTS

Telomere length was different between the 3 groups (P = .041) with both patients and siblings showing a shorter T/S ratio compared with healthy controls. Patients showed increased levels of interleukin-6 (P = .005) and interleukin-10 (P = .002) compared with controls as well as increased levels of interleukin-6 (p = 0.014) and CCL24 (P = .016) compared with their siblings. C-C motif chemokine 11 levels were increased in siblings compared with controls (P = .015), and a similar tendency was found in patients compared with controls (P = .045). Glutathione peroxidase activity was decreased in patients compared with controls (P = .006) and siblings (P = .025). No differences were found for the other markers.

CONCLUSIONS

The present results suggest that unaffected siblings may present accelerated aging features. These neurobiological findings may be considered as endophenotypic traits. Further prospective studies are warranted.

摘要

背景

越来越多的证据支持双相情感障碍遗传风险个体存在神经生物学特质异常。本研究旨在探讨双相情感障碍患者、其同胞以及健康对照者之间脑源性神经营养因子、细胞因子、氧化应激和端粒长度标志物的潜在差异。

方法

对36例I型双相情感障碍患者、39名同胞和44名健康对照者进行评估。检测血清脑源性神经营养因子、白细胞介素-6、白细胞介素-10、肿瘤坏死因子-α、C-C基序趋化因子11、C-C基序趋化因子24和3-硝基酪氨酸水平,以及谷胱甘肽过氧化物酶、谷胱甘肽还原酶和谷胱甘肽S-转移酶的活性。采用定量聚合酶链反应测量端粒长度(T/S比值)。

结果

三组之间端粒长度存在差异(P = 0.041),患者和同胞的T/S比值均低于健康对照者。与对照组相比,患者的白细胞介素-6(P = 0.005)和白细胞介素-10(P = 0.002)水平升高,与同胞相比,白细胞介素-6(p = 0.014)和CCL24(P = 0.016)水平升高。与对照组相比,同胞的C-C基序趋化因子11水平升高(P = 0.015),患者与对照组相比也有类似趋势(P = 0.045)。与对照组(P = 0.006)和同胞(P = 0.025)相比,患者的谷胱甘肽过氧化物酶活性降低。其他标志物未发现差异。

结论

目前的结果表明,未受影响的同胞可能呈现加速衰老特征。这些神经生物学发现可被视为内表型特征。有必要进行进一步的前瞻性研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/570b/5458375/270da244b76c/pyx00101.jpg

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