title: Mineralocorticoid receptor genotype moderates the association between physical neglect and serum BDNF.
abstract: The objective of this study is to investigate if a polymorphism in the NR3C2 gene moderates the association between childhood trauma on serum levels of brain derived neurothrophic factor (sBDNF). sBDNF was used here as a general marker of alteration in brain function. This is a community cross sectional study comprising 90 adolescents (54 with anxiety disorders). DNA was extracted from saliva in order to genotype the MR-2G/C (rs2070951) polymorphism using real time PCR. Blood was collected for sBDNF Elisa immunoassay. The Childhood Trauma Questionnaire (CTQ) was used to evaluate childhood abuse and neglect. Main effects and gene environment interactions were tested using linear regression models. Anxiety disorders were not associated with the MR-2G/C polymorphism or with sBDNF levels, but the number of C alleles of the MR-2G/C polymorphism was significantly associated with higher sBDNF levels (b = 8.008; p-value = 0.001). Subjects with intermediate and high exposure to physical neglect showed higher sBDNF levels if compared to subjects non-exposed (b = 11.955; p = 0.004 and b = 16.186; p = 0.009, respectively). In addition, we detected a significant physical neglect by MR-2G/C C allele interaction on sBDNF levels (p = 0.005), meaning that intermediate and high exposure to childhood neglect were only associated with increased sBDNF levels in subjects with the CC genotype, but not in subjects with other genotypes. Our findings suggest that genetic variants in NR3C2 gene may partially explain plastic brain vulnerability to traumatic events. Further studies are needed to investigate the moderating effects of NR3C2 gene in more specific markers of alteration in brain function.
authors.affiliation: Anxiety Disorders Outpatient Program for Children and Adolescents, PROTAIA, Federal University of Rio Grande do Sul, UFRGS/Hospital de Clínicas de Porto Alegre, HCPA, Porto Alegre, Brazil; Post Graduate Program in Neuroscience, Institute of Basic Sciences/Health, Federal University of Rio Grande do Sul, UFRGS, Porto Alegre, Brazil; Basic Research and Advanced Investigations in Neurosciences, BRAIN Laboratory, Hospital de Clínicas de Porto Alegre, HCPA, Porto Alegre, Brazil. Electronic address: andresbt10@yahoo.com.br.
authors.forename: Andressa
authors.initials: A
authors.lastname: Bortoluzzi
authors.affiliation: Anxiety Disorders Outpatient Program for Children and Adolescents, PROTAIA, Federal University of Rio Grande do Sul, UFRGS/Hospital de Clínicas de Porto Alegre, HCPA, Porto Alegre, Brazil; Post Graduate Program in Medical Sciences: Psychiatry, Federal University of Rio Grande do Sul, UFRGS, Porto Alegre, Brazil; National Institute of Developmental Psychiatry for Children and Adolescents (INPD/ CNPq), Brazil.
authors.forename: Giovanni Abrahão
authors.initials: GA
authors.lastname: Salum
authors.affiliation: Anxiety Disorders Outpatient Program for Children and Adolescents, PROTAIA, Federal University of Rio Grande do Sul, UFRGS/Hospital de Clínicas de Porto Alegre, HCPA, Porto Alegre, Brazil; Health Sciences Federal University of Porto Alegre, UFCSPA, Porto Alegre, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: Blaya
authors.affiliation: Post Graduate Program in Neuroscience, Institute of Basic Sciences/Health, Federal University of Rio Grande do Sul, UFRGS, Porto Alegre, Brazil; Department of Pediatrics, Faculty of Medicine, UFRGS, Porto Alegre, Brazil.
authors.forename: Patrícia Pelufo
authors.initials: PP
authors.lastname: Silveira
authors.affiliation: Developmental Cognitive Neuroscience Research Group, Post-Graduate Program in Psychology - Human Cognition, Pontifical Catholic University of Rio Grande do Sul, PUCR-RS, Porto Alegre, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Grassi-Oliveira
authors.affiliation: Anxiety Disorders Outpatient Program for Children and Adolescents, PROTAIA, Federal University of Rio Grande do Sul, UFRGS/Hospital de Clínicas de Porto Alegre, HCPA, Porto Alegre, Brazil; Basic Research and Advanced Investigations in Neurosciences, BRAIN Laboratory, Hospital de Clínicas de Porto Alegre, HCPA, Porto Alegre, Brazil.
authors.forename: Eduarda Dias
authors.initials: ED
authors.lastname: da Rosa
authors.affiliation: National Institute of Science and Technology Translational Medicine (INCT/CNPq), Porto Alegre, Brazil.
authors.forename: Bianca Wollenhaupt
authors.initials: BW
authors.lastname: de Aguiar
authors.affiliation: National Institute of Science and Technology Translational Medicine (INCT/CNPq), Porto Alegre, Brazil.
authors.forename: Laura
authors.initials: L
authors.lastname: Stertz
authors.affiliation: Center for Child and Adolescent Health Studies (NESCA), Hospital de Clínicas de Porto Alegre (HCPA), Brazil.
authors.forename: Vera Lúcia
authors.initials: VL
authors.lastname: Bosa
authors.affiliation: Center for Child and Adolescent Health Studies (NESCA), Hospital de Clínicas de Porto Alegre (HCPA), Brazil.
authors.forename: Ilaine
authors.initials: I
authors.lastname: Schuch
authors.affiliation: Center for Child and Adolescent Health Studies (NESCA), Hospital de Clínicas de Porto Alegre (HCPA), Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Goldani
authors.affiliation: Post Graduate Program in Medical Sciences: Psychiatry, Federal University of Rio Grande do Sul, UFRGS, Porto Alegre, Brazil; National Institute of Science and Technology Translational Medicine (INCT/CNPq), Porto Alegre, Brazil.
authors.forename: Flavio
authors.initials: F
authors.lastname: Kapczinski
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre, HCPA, Porto Alegre, Brazil.
authors.forename: Sandra
authors.initials: S
authors.lastname: Leistner-Segal
authors.affiliation: Anxiety Disorders Outpatient Program for Children and Adolescents, PROTAIA, Federal University of Rio Grande do Sul, UFRGS/Hospital de Clínicas de Porto Alegre, HCPA, Porto Alegre, Brazil; Post Graduate Program in Neuroscience, Institute of Basic Sciences/Health, Federal University of Rio Grande do Sul, UFRGS, Porto Alegre, Brazil; Post Graduate Program in Medical Sciences: Psychiatry, Federal University of Rio Grande do Sul, UFRGS, Porto Alegre, Brazil; Basic Research and Advanced Investigations in Neurosciences, BRAIN Laboratory, Hospital de Clínicas de Porto Alegre, HCPA, Porto Alegre, Brazil; National Institute of Developmental Psychiatry for Children and Adolescents (INPD/ CNPq), Brazil. Electronic address: gmanfro@gmail.com.
authors.forename: Gisele Gus
authors.initials: GG
authors.lastname: Manfro
mesh_terms: D000293:Adolescent; D001008:Anxiety Disorders / Q000097:blood / Q000209:etiology / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D002648:Child; D002649:Child Abuse / Q000523:psychology*; D003430:Cross-Sectional Studies; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018161:Receptors, Mineralocorticoid / Q000235:genetics*; D011795:Surveys and Questionnaires
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C561839:NR3C2 protein, human; D018161:Receptors, Mineralocorticoid
keywords: Adolescent; MR-2G/C; NR3C2; Physical neglect; sBDNF