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

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

Author Spindola, Leticia Maria Autor UNIFESP Google Scholar
Pan, Pedro Mario Autor UNIFESP Google Scholar
Moretti, Patricia Natalia Autor UNIFESP Google Scholar
Ota, Vanessa Kiyomi Autor UNIFESP Google Scholar
Santoro, Marcos Leite Autor UNIFESP Google Scholar
Cogo-Moreira, Hugo Autor UNIFESP Google Scholar
Gadelha, Ary Autor UNIFESP Google Scholar
Salum, Giovanni Google Scholar
Manfro, Gisele Gus Google Scholar
Mari, Jair Jesus Autor UNIFESP Google Scholar
Brentani, Helena Google Scholar
Grassi-Oliveira, Rodrigo Google Scholar
Brietzke, Elisa Autor UNIFESP Google Scholar
Miguel, Euripedes Constantino Google Scholar
Rohde, Luis Augusto Google Scholar
Sato, Joao Ricardo Google Scholar
Bressan, Rodrigo Affonseca Autor UNIFESP Google Scholar
Belangero, Sintia Iole Autor UNIFESP Google Scholar
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.
Keywords Major depressive disorder
Gene expression
Childhood maltreatment
Language English
Date 2017
Published in Journal Of Psychiatric Research. Oxford, v. 92, p. 24-30, 2017.
ISSN 0022-3956 (Sherpa/Romeo, impact factor)
Publisher Pergamon-Elsevier Science Ltd
Extent 24-30
Access rights Closed access
Type Article
Web of Science ID WOS:000404701100004

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