Host-parasite interaction associated with major mental illness.
Host-parasite interaction associated with major mental illness.
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DOI：
10.1038/s41380-018-0217-z
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发表时间：
2020-01
影响因子：
11
通讯作者：
Sawa A
中科院分区：
文献类型：
--
作者：
Kano SI;Hodgkinson CA;Jones-Brando L;Eastwood S;Ishizuka K;Niwa M;Choi EY;Chang DJ;Chen Y;Velivela SD;Leister F;Wood J;Chowdari K;Ducci F;Caycedo DA;Heinz E;Newman ER;Cascella N;Mortensen PB;Zandi PP;Dickerson F;Nimgaonkar V;Goldman D;Harrison PJ;Yolken RH;Sawa A
临床研究经常报告，患有严重精神疾病(如精神分裂症和双相情感障碍)的患者有共病的身体状况，这表明影响大脑和周围组织的系统性变化可能是这些疾病的基础。许多研究报告称，抗T抗体水平升高。在患有严重精神疾病的患者中发现了弓形虫抗体，但其潜在机制尚不清楚。利用多学科的流行病学、细胞生物学和基因表达谱方法，我们报告了多条证据表明，一种主要的精神疾病相关的易感因子，在精神分裂症中被破坏(DISC1)，参与了对弓形虫感染的宿主免疫反应的改变。具体地说，我们的细胞生物学和基因表达研究表明，DISC1 Leu607Phe变异改变了DISC1与激活转录因子4(ATF4)的相互作用，改变了弓形虫感染后的基因表达模式。我们的流行病学数据还表明，DISC1607Phe/Phe基因型与血清中较高的弓形虫抗体水平相关。虽然还需要进一步的研究，但我们的研究提供了对少数几个在重大精神疾病中良好复制的血清学观察之一的机械性见解。
Clinical studies frequently report that patients with major mental illness such as schizophrenia and bipolar disorder have co-morbid physical conditions, suggesting that systemic alterations affecting both brain and peripheral tissues might underlie the disorders. Numerous studies have reported elevated levels of anti-T. gondii antibodies in patients with major mental illnesses, but the underlying mechanism was unclear. Using multidisciplinary epidemiological, cell biological, and gene expression profiling approaches, we report here multiple lines of evidence suggesting that a major mental illness-related susceptibility factor, Disrupted in schizophrenia (DISC1), is involved in altered host immune responses against Toxoplasma gondii (T. gondii) infection. Specifically, our cell biology and gene expression studies have revealed that DISC1 Leu607Phe variation, which changes DISC1 interaction with activating transcription factor 4 (ATF4), modifies gene expression patterns upon T. gondii infection. Our epidemiological data have also shown that DISC1 607 Phe/Phe genotype was associated with higher T. gondii antibody levels in sera. Although further studies are required, our study provides mechanistic insight into one of the few well-replicated serological observations in major mental illness.
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影响因子：
3.5
作者：
Eastwood, Sharon L.;Walker, Mary;Harrison, Paul J.
通讯作者：
Harrison, Paul J.
DOI：
10.1126/science.1224026
发表时间：
2012-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bogunovic D;Byun M;Durfee LA;Abhyankar A;Sanal O;Mansouri D;Salem S;Radovanovic I;Grant AV;Adimi P;Mansouri N;Okada S;Bryant VL;Kong XF;Kreins A;Velez MM;Boisson B;Khalilzadeh S;Ozcelik U;Darazam IA;Schoggins JW;Rice CM;Al-Muhsen S;Behr M;Vogt G;Puel A;Bustamante J;Gros P;Huibregtse JM;Abel L;Boisson-Dupuis S;Casanova JL
通讯作者：
Casanova JL
影响因子：
6.6
作者：
Carruthers, Vern B.;Suzuki, Yasuhiro
通讯作者：
Suzuki, Yasuhiro
影响因子：
11
作者：
Farrell, M. S.;Werge, T.;Sklar, P.;Owen, M. J.;Ophoff, R. A.;O'Donovan, M. C.;Corvin, A.;Cichon, S.;Sullivan, P. F.
通讯作者：
Sullivan, P. F.
影响因子：
64.8
作者：
Birey F;Andersen J;Makinson CD;Islam S;Wei W;Huber N;Fan HC;Metzler KRC;Panagiotakos G;Thom N;O'Rourke NA;Steinmetz LM;Bernstein JA;Hallmayer J;Huguenard JR;Paşca SP
通讯作者：
Paşca SP