Exploring the mediation of DNA methylation across the epigenome between childhood adversity and First Episode of Psychosis-findings from the EU-GEI study

被引：8

作者：

Alameda, Luis ^{[1
,2
,3
]}

Liu, Zhonghua ^{[4
]}

Sham, Pak C. ^{[5
,6
]}

Aas, Monica ^{[7
]}

Trotta, Giulia ^{[7
]}

Rodriguez, Victoria ^{[2
]}

Di Forti, Marta ^{[7
]}

Stilo, Simona A. ^{[8
]}

Kandaswamy, Radhika ^{[7
]}

Arango, Celso ^{[9
]}

Arrojo, Manuel ^{[10
]}

Bernardo, Miguel ^{[11
]}

Bobes, Julio ^{[12
,13
]}

de Haan, Lieuwe ^{[14
]}

Del-Ben, Cristina Marta ^{[15
]}

Gayer-Anderson, Charlotte ^{[16
]}

Sideli, Lucia ^{[17
,18
]}

Jones, Peter B. ^{[19
,20
]}

Jongsma, Hannah E. ^{[21
]}

Kirkbride, James B. ^{[21
]}

La Cascia, Caterina ^{[22
]}

Lasalvia, Antonio ^{[23
]}

Tosato, Sarah ^{[23
]}

Llorca, Pierre-Michel ^{[24
]}

Menezes, Paulo Rossi ^{[25
]}

van Os, Jim ^{[2
,26
,27
]}

Quattrone, Diego ^{[7
]}

Rutten, Bart P. ^{[26
]}

Santos, Jose Luis ^{[28
]}

Sanjuan, Julio ^{[29
]}

Selten, Jean-Paul ^{[26
,30
]}

Szoke, Andrei

Tarricone, Ilaria ^{[32
]}

Tortelli, Andrea ^{[31
,33
]}

Velthorst, Eva ^{[34
]}

Morgan, Craig ^{[16
]}

Dempster, Emma ^{[35
]}

Hannon, Eilis ^{[35
]}

Burrage, Joe ^{[35
]}

Dwir, Daniella ^{[36
]}

Arumuham, Atheeshaan ^{[2
,37
,38
,39
]}

Mill, Jonathan ^{[35
]}

Murray, Robin M. ^{[2
]}

Wong, Chloe C. Y. ^{[7
]}

机构：

[1] Lausanne Univ Hosp CHUV, Treatment & Early Intervent Psychosis Program, Serv Gen Psychiat, Lausanne, Switzerland

[2] Kings Coll London, Inst Psychiat Psychol & Neurosci, Psychosis Studies, London, England

[3] Univ Seville, Hosp Univ Virgen Rocio, Dept Psychiat, Inst Invest Sanitaria Sevilla,IbiS, Seville, Spain

[4] Columbia Univ, Dept Biostat, New York, NY USA

[5] Univ Hong Kong, Li Ka Shing Fac Med, Dept Psychiat, State Key Lab Brain & Cognit Sci,Pok Fu Lam, Hong Kong, Peoples R China

[6] Univ Hong Kong, Li Ka Shing Fac Med, Ctr Panor Sci, Pok Fu Lam, Hong Kong, Peoples R China

[7] Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, London, England

[8] ASP Crotone, Dept Mental Hlth & Addict Serv, Crotone, Italy

[9] Univ Complutense, Hosp Gen Univ Gregorio Maranon, Inst Psychiat & Mental Hlth, Sch Med,Dept Child & Adolescent Psychiat,IiSGM,CI, Madrid, Spain

[10] Complejo Hosp Univ Santiago De Compostela, Dept Psychiat, Inst Invest Sanitaria Santiago De Compostela, Psychiat Genet Grp, Santiago, Spain

[11] Univ Barcelona, Hosp Clin Barcelona, Biomed Res Networking Ctr Mental Hlth CIBERSAM, Inst Invest Biomed August Pi & Sunyer,Neurosci In, Barcelona, Spain

[12] Inst Invest Sanitaria Principado Asturias ISPA, Oviedo, Spain

[13] Univ Oviedo, Ctr Invest Biomed Red Salud Mental CIBERSAM, Sch Med, Dept Med,Psychiat Area, Oviedo, Spain

[14] Univ Amsterdam, Dept Psychiat, Early Psychosis Sect, Amsterdam UMC, Amsterdam, Netherlands

[15] Univ Sao Paulo, Ribeirao Preto Med Sch, Neurosci & Behav Dept, Sao Paulo, Brazil

[16] Kings Coll London, ESRC Ctr Soc & Mental Hlth, London, England

[17] LUMSA Univ, Dept Human Sci, Rome, Italy

[18] KCL, Dept Psychosis Studies, Rome, Italy

[19] Univ Cambridge, Dept Psychiat, Cambridge, England

[20] Cambridgeshire & Peterborough NHS Fdn Trust, CAMEO Early Intervent Serv, Cambridge, England

[21] UCL, Div Psychiat, Psylife Grp, London, England

[22] Univ Palermo, Dept Biomed Neurosci & Adv Diagnost BiND, Sect Psychiat, Palermo, Italy

[23] Univ Verona, Dept Neurosci Biomed & Movement, Sect Psychiat, Verona, Italy

[24] Univ Clermont Auvergne, Clermont Ferrand, France

[25] Univ Sao Paulo, Fac Med, Dept Prevent Med, Sao Paulo, Brazil

[26] Maastricht Univ, Sch Mental Hlth & Neurosci, South Limburg Mental Hlth Res & Teaching Network, Dept Psychiat & Neuropsychol,Med Ctr, Maastricht, Netherlands

[27] Univ Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, Med Ctr, Utrecht, Netherlands

[28] Hosital Virgen Luz, Dept Psychiat, Serv Psiquiatria, C Hermandad Donantes Sangre, Cuenca 16002, Spain

[29] Univ Valencia, Ctr Invest Biomed Red Salud Mental CIBERSAM, Sch Med, Dept Psychiat, C Avda Blasco Ibanez 15, Valencia 46010, Spain

[30] Rivierduinen Inst Mental Hlth Care, Leiden, Netherlands

[31] Univ Paris Est Creteil, Hop Univ H Mondor, AP HP, IMRB,DHU IMPACT,INSERM, Creteil, France

[32] Alma Mater Studiorum Univ Bologna, Dept Med & Surg Sci, Bologna Transcultural Psychosomat Team BoTPT, Bologna, Italy

[33] Inst Mondor Rech Biomed, Creteil, France

[34] GGZ Mental Hlth Serv Noord Holland Noord, Heerhugowaard, Netherlands

[35] Lausanne Univ Hosp CHUV, Ctr Psychiat Neurosci, Dept Psychiat, Lausanne, Switzerland

[36] Univ Exeter, Univ Exeter Med Sch, Fac Hlth & Life Sci, Dept Clin & Biomed Sci, Exeter, England

[37] MRC London Inst Med Sci, Psychiat Imaging Grp, London, England

[38] South London & Maudsley NHS Fdn Trust, London, England

[39] Imperial Coll London, Inst Clin Sci ICS, Fac Med, London, England

来源：

MOLECULAR PSYCHIATRY | 2023年 / 28卷 / 05期

关键词：

HISTAMINE H-2-RECEPTOR; GENE-EXPRESSION; WEIGHT-GAIN; SCHIZOPHRENIA; ASSOCIATION; OLANZAPINE; BLOOD; RELIABILITY; FAMOTIDINE; NIZATIDINE;

D O I：

10.1038/s41380-023-02044-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

AbtractStudies conducted in psychotic disorders have shown that DNA-methylation (DNAm) is sensitive to the impact of Childhood Adversity (CA). However, whether it mediates the association between CA and psychosis is yet to be explored. Epigenome wide association studies (EWAS) using the Illumina Infinium-Methylation EPIC array in peripheral blood tissue from 366 First-episode of psychosis and 517 healthy controls was performed. Adversity scores were created for abuse, neglect and composite adversity with the Childhood Trauma Questionnaire (CTQ). Regressions examining (I) CTQ scores with psychosis; (II) with DNAm EWAS level and (III) between DNAm and caseness, adjusted for a variety of confounders were conducted. Divide-Aggregate Composite-null Test for the composite null-hypothesis of no mediation effect was conducted. Enrichment analyses were conducted with missMethyl package and the KEGG database. Our results show that CA was associated with psychosis (Composite: OR = 1.68; p = p < 0.001; neglect: OR = 2.27; p = <0.001). None of the CpG sites significantly mediated the adversity-psychosis association after Bonferroni correction (p < 8.1 x 10(-8)). However, 28, 34 and 29 differentially methylated probes associated with 21, 27, 20 genes passed a less stringent discovery threshold (p < 5 x 10(-5)) for composite, abuse and neglect respectively, with a lack of overlap between abuse and neglect. These included genes previously associated to psychosis in EWAS studies, such as PANK1, SPEG TBKBP1, TSNARE1 or H2R. Downstream gene ontology analyses did not reveal any biological pathways that survived false discovery rate correction. Although at a non-significant level, DNAm changes in genes previously associated with schizophrenia in EWAS studies may mediate the CA-psychosis association. These results and associated involved processes such as mitochondrial or histaminergic disfunction, immunity or neural signalling requires replication in well powered samples. The lack of overlap between mediating genes associated with abuse and neglect suggests differential biological trajectories linking CA subtypes and psychosis.

引用

页码：2095 / 2106

页数：12

共 22 条

[21] A history of childhood trauma is associated with slower improvement rates: Findings from a one-year follow-up study of patients with a first-episode psychosis
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BMC PSYCHIATRY, 2016, 16
[22] Cannabis Use Cessation and the Risk of Psychotic Disorders: A Case-Control Analysis from the First Episode Case-Control EU-GEI WP2 Study: L'arrêt de l'utilisation du cannabis et le risque de troubles psychotiques: Une analyse cas-témoins tirée de l'étude cas-témoins EU-GEI WP2 centrée sur les premiers épisodes psychotiques
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Duric, Bea
Spinazzola, Edoardo
Trotta, Giulia
Chesney, Edward
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Quattrone, Diego
Tripoli, Giada
Gayer-Anderson, Charlotte
Rodriguez, Victoria
Ferraro, Laura
La Cascia, Caterina
Tarricone, Ilaria
Szoke, Andrei
Arango, Celso
Bobes, Julio
Bernardo, Miquel
Del-Ben, Cristina Marta
Menezes, Paulo Rossi
Selten, Jean-Paul
Rutten, Bart P. F.
de Haan, Lieuwe
Stilo, Simona
Schurhoff, Franck
Pignon, Baptiste
Freeman, Tom P.
Vassos, Evangelos
Murray, Robin M.
Austin-Zimmerman, Isabelle
Di Forti, Marta
CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE, 2025, : 182 - 193

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