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双相情感障碍和惊恐障碍可能与先天性免疫系统的遗传缺陷有关。

Bipolar and panic disorders may be associated with hereditary defects in the innate immune system.

作者信息

Foldager Leslie, Köhler Ole, Steffensen Rudi, Thiel Steffen, Kristensen Ann Suhl, Jensenius Jens Christian, Mors Ole

机构信息

Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark; iPSYCH: The Lundbeck Foundation Initiative for Integrated Psychiatric Research, Aarhus and Copenhagen, Denmark.

iPSYCH: The Lundbeck Foundation Initiative for Integrated Psychiatric Research, Aarhus and Copenhagen, Denmark; Research Department P, Aarhus University Hospital, Risskov, Denmark.

出版信息

J Affect Disord. 2014 Aug;164:148-54. doi: 10.1016/j.jad.2014.04.017. Epub 2014 Apr 19.

Abstract

BACKGROUND

Mannan-binding lectin (MBL) and mannan-binding lectin-associated serine protease-2 (MASP-2) represent important arms of the innate immune system, and different deficiencies may result in infections or autoimmune diseases. Both bipolar and panic disorders are associated with increased inflammatory response, infections and mutual comorbidity. However, associations with MBL, MASP-2 or the gene, MBL2, coding for MBL, have not been investigated thoroughly.

METHODS

One hundred patients with bipolar disorder, 100 with panic disorder and 349 controls were included. Serum concentrations of MBL and MASP-2 were measured and seven single nucleotide polymorphisms (SNPs) influencing these concentrations were genotyped. Disease association with genetic markers and serum levels were investigated.

RESULTS

In panic disorder, we observed a large proportion (30%) of MBL deficient (<100ng/ml) individuals and significantly lower levels of MBL and MASP-2 plus association with the MBL2 YA two-marker haplotype. Bipolar disorder was associated with the MBL2 LXPA haplotype and lower MASP-2 levels.

LIMITATIONS

No information on course or severity of disorders was included, and only MBL and MASP-2 were measured, excluding other components from the complement pathway. Restrictions defined by ethnical committees preclude information of control׳s ethnic origin.

CONCLUSIONS

Significant differences in MBL and MASP-2 concentrations were observed between cohorts, especially an intriguing finding associating panic disorder with MBL deficiency. These differences could not be fully explained by allele or haplotype frequency variations. Since MBL deficiency is highly heterogeneous and associated with both infectious and autoimmune states, more research is needed to identify which complement pathway components could be associated with bipolar respectively panic disorder.

摘要

背景

甘露聚糖结合凝集素(MBL)和甘露聚糖结合凝集素相关丝氨酸蛋白酶-2(MASP-2)是先天性免疫系统的重要组成部分,不同的缺陷可能导致感染或自身免疫性疾病。双相情感障碍和惊恐障碍都与炎症反应增加、感染以及共同的合并症有关。然而,MBL、MASP-2或编码MBL的基因MBL2之间的关联尚未得到充分研究。

方法

纳入100例双相情感障碍患者、100例惊恐障碍患者和349名对照。测量血清中MBL和MASP-2的浓度,并对影响这些浓度的7个单核苷酸多态性(SNP)进行基因分型。研究疾病与遗传标记和血清水平的关联。

结果

在惊恐障碍中,我们观察到很大一部分(30%)MBL缺乏(<100ng/ml)的个体,且MBL和MASP-2水平显著降低,同时与MBL2 YA双标记单倍型相关。双相情感障碍与MBL2 LXPA单倍型和较低的MASP-2水平相关。

局限性

未纳入有关疾病病程或严重程度的信息,仅测量了MBL和MASP-2,排除了补体途径中的其他成分。伦理委员会规定的限制排除了对照种族来源的信息。

结论

在不同队列中观察到MBL和MASP-2浓度存在显著差异,特别是惊恐障碍与MBL缺乏相关这一有趣发现。这些差异不能完全由等位基因或单倍型频率变化来解释。由于MBL缺乏具有高度异质性,且与感染和自身免疫状态均相关,因此需要更多研究来确定哪些补体途径成分可能分别与双相情感障碍和惊恐障碍相关。

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