Gene expression in blood of children and adolescents: MOediation between childhood maltreatment and major depressive disorder

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dc.contributor.author Spindola, Leticia Maria [UNIFESP]
dc.contributor.author Pan, Pedro Mario [UNIFESP]
dc.contributor.author Moretti, Patricia Natalia [UNIFESP]
dc.contributor.author Ota, Vanessa Kiyomi [UNIFESP]
dc.contributor.author Santoro, Marcos Leite [UNIFESP]
dc.contributor.author Cogo-Moreira, Hugo [UNIFESP]
dc.contributor.author Gadelha, Ary [UNIFESP]
dc.contributor.author Salum, Giovanni
dc.contributor.author Manfro, Gisele Gus
dc.contributor.author Mari, Jair Jesus [UNIFESP]
dc.contributor.author Brentani, Helena
dc.contributor.author Grassi-Oliveira, Rodrigo
dc.contributor.author Brietzke, Elisa [UNIFESP]
dc.contributor.author Miguel, Euripedes Constantino
dc.contributor.author Rohde, Luis Augusto
dc.contributor.author Sato, Joao Ricardo
dc.contributor.author Bressan, Rodrigo Affonseca [UNIFESP]
dc.contributor.author Belangero, Sintia Iole [UNIFESP]
dc.date.accessioned 2019-08-19T11:49:40Z
dc.date.available 2019-08-19T11:49:40Z
dc.date.issued 2017
dc.identifier http://dx.doi.org/10.1016/j.jpsychires.2017.03.015
dc.identifier.citation Journal Of Psychiatric Research. Oxford, v. 92, p. 24-30, 2017.
dc.identifier.issn 0022-3956
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/51369
dc.description.abstract Investigating major depressive disorder (MDD) in childhood and adolescence can help reveal the relative contributions of genetic and environmental factors to MDD, since early stages of disease have less influence of illness exposure. Thus, we investigated the mRNA expression of 12 genes related to the hypothalamic pituitary adrenal (HPA) axis, inflammation, neurodevelopment and neurotransmission in the blood of children and adolescents with MDD and tested whether a history of childhood maltreatment (CM) affects MDD through gene expression. Whole-blood mRNA levels of 12 genes were compared among 20 children and adolescents with MDD diagnosis (MDD group), 49 participants without MDD diagnosis but with high levels of depressive symptoms (DS group), and 61 healthy controls (HC group). The differentially expressed genes were inserted in a mediation model in which CM, MDD, and gene expression were, respectively, the independent variable, outcome, and intermediary variable. NR3C1, TNF, TNFR1 and IL1B were expressed at significantly lower levels in the MDD group than in the other groups. CM history did not exert a significant direct effect on MDD. However, an indirect effect of the aggregate expression of the 4 genes mediated the relationship between CM and MDD. In the largest study investigating gene expression in children with MDD, we demonstrated that NR3C1, TNF, TNFR1 and IL1B expression levels are related to MDD and conjunctly mediate the effect of CM history on the risk of developing MDD. This supports a role of glucocorticoids and inflammation as potential effectors of environmental stress in MDD. (C) 2017 Elsevier Ltd. All rights reserved. en
dc.format.extent 24-30
dc.language.iso eng
dc.publisher Pergamon-Elsevier Science Ltd
dc.rights Acesso restrito
dc.subject Major depressive disorder en
dc.subject Gene expression en
dc.subject Inflammation en
dc.subject Glucocorticoids en
dc.subject Childhood maltreatment en
dc.subject Child en
dc.title Gene expression in blood of children and adolescents: MOediation between childhood maltreatment and major depressive disorder en
dc.type Artigo
dc.description.affiliation Univ Fed São Paulo UNIFESP, Div Genet, Dept Morphol & Genet, São Paulo, Brazil
dc.description.affiliation Univ Fed São Paulo, LiNC Interdisciplinary Lab Clin Neurosci, São Paulo, Brazil
dc.description.affiliation Natl Inst Dev Psychiat Children & Adolescents INP, Porto Alegre, RS, Brazil
dc.description.affiliation Univ Fed São Paulo, Dept Psychiat, São Paulo, Brazil
dc.description.affiliation Pontificia Univ Catolica Rio Grande do Sul, Postgrad Program Psychol, Porto Alegre, RS, Brazil
dc.description.affiliation Pontificia Univ Catolica Rio Grande do Sul, Dev Cognit Neurosci Lab, Porto Alegre, RS, Brazil
dc.description.affiliation Univ Fed Rio Grande do Sul, Dept Psychiat, Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil
dc.description.affiliation Univ Fed ABC, Ctr Math Computat & Cognit, Santo Andre, Brazil
dc.description.affiliationUnifesp Univ Fed São Paulo UNIFESP, Div Genet, Dept Morphol & Genet, São Paulo, Brazil
dc.description.affiliationUnifesp Univ Fed São Paulo, LiNC Interdisciplinary Lab Clin Neurosci, São Paulo, Brazil
dc.description.affiliationUnifesp Univ Fed São Paulo, Dept Psychiat, São Paulo, Brazil
dc.identifier.doi 10.1016/j.jpsychires.2017.03.015
dc.description.source Web of Science
dc.identifier.wos WOS:000404701100004



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