title: Corticosteroid receptor genes and childhood neglect influence susceptibility to crack/cocaine addiction and response to detoxification treatment.
abstract: The aim of this study was to analyze hypotheses-driven gene-environment and gene-gene interactions in smoked (crack) cocaine addiction by evaluating childhood neglect and polymorphisms in mineralocorticoid and glucocorticoid receptor genes (NR3C2 and NR3C1, respectively). One hundred thirty-nine crack/cocaine-addicted women who completed 3 weeks of follow-up during early abstinence composed our sample. Childhood adversities were assessed using the Childhood Trauma Questionnaire (CTQ), and withdrawal symptoms were assessed using the Cocaine Selective Severity Assessment (CSSA) scale. Conditional logistic regression with counterfactuals and generalized estimating equation modeling were used to test gene-environment and gene-gene interactions. We found an interaction between the rs5522-Val allele and childhood physical neglect, which altered the risk of crack/cocaine addiction (Odds ratio = 4.0, P = 0.001). Moreover, a NR3C2-NR3C1 interaction (P = 0.002) was found modulating the severity of crack/cocaine withdrawal symptoms. In the post hoc analysis, concomitant carriers of the NR3C2 rs5522-Val and NR3C1 rs6198-G alleles showed lower overall severity scores when compared to other genotype groups (P-values ≤ 0.035). This gene-environment interaction is consistent with epidemiological and human experimental findings demonstrating a strong relationship between early life stress and the hypothalamic-pituitary-adrenal (HPA) axis dysregulation in cocaine addiction. Additionally, this study extended in crack/cocaine addiction the findings previously reported for tobacco smoking involving an interaction between NR3C2 and NR3C1 genes.
authors.affiliation: Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Diego L
authors.initials: DL
authors.lastname: Rovaris
authors.affiliation: Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Nina R
authors.initials: NR
authors.lastname: Mota
authors.affiliation: Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Guilherme P
authors.initials: GP
authors.lastname: Bertuzzi
authors.affiliation: Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Angelita P
authors.initials: AP
authors.lastname: Aroche
authors.affiliation: Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Department of Statistics, Instituto de Matemática, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Sidia M
authors.initials: SM
authors.lastname: Callegari-Jacques
authors.affiliation: Biostatistics Unit, Grupo de Pesquisa e Pós-graduação, Hospital de Clínicas de Porto Alegre, Brazil.
authors.forename: Luciano S P
authors.initials: LS
authors.lastname: Guimarães
authors.affiliation: Postgraduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Brazil.
authors.forename: Júlio C
authors.initials: JC
authors.lastname: Pezzi
authors.affiliation: Developmental Cognitive Neuroscience Research Group (GNCD), Biomedical Research Institute (IPB), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Brazil.
authors.forename: Thiago W
authors.initials: TW
authors.lastname: Viola
authors.affiliation: Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. Electronic address: claiton.bau@ufrgs.br.
authors.forename: Claiton H D
authors.initials: CH
authors.lastname: Bau
authors.affiliation: Developmental Cognitive Neuroscience Research Group (GNCD), Biomedical Research Institute (IPB), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Grassi-Oliveira
mesh_terms: D000328:Adult; D002648:Child; D002649:Child Abuse / Q000523:psychology*; D019970:Cocaine-Related Disorders / Q000235:genetics / Q000523:psychology / Q000628:therapy; D016578:Crack Cocaine; D003430:Cross-Sectional Studies; D004843:Epistasis, Genetic; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D008297:Male; D008609:Mental Status Schedule; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011987:Receptors, Steroid / Q000235:genetics*; D055815:Young Adult
chemical_list: D016578:Crack Cocaine; D011987:Receptors, Steroid
keywords: Childhood trauma; Cocaine; Gene-environment correlation; Gene-environment interaction; Gene-gene interaction; Glucocorticoid receptor; Mineralocorticoid receptor; NR3C1; NR3C2; Stress