title: Effects of crack cocaine addiction and stress-related genes on peripheral BDNF levels.
abstract: This study examined the effects of glucocorticoid receptor (NR3C1), corticotropin-releasing hormone receptor 1 (CRHR1), and brain-derived neurotrophic factor (BDNF) genes on susceptibility to crack cocaine addiction and BDNF levels. Crack addicted patients who sought treatment (n = 280) and non-addicted individuals (n = 241) were assessed. Three SNPs in NR3C1 (rs6198, rs41423247, and rs10052957), three in CRHR1 (rs12944712, rs110402, and rs878886), and one in BDNF (rs6265) were genotyped. No significant effect was seen in the case-control analyses. Crack cocaine addicted patients showed significantly lower serum BDNF levels. Significant effects were observed for NR3C1 rs41423247 and rs10052957. These effects were restricted to non-addicted individuals and they were supported by significant gene-by-disease status interactions. For CRHR1, all SNPs were associated with BDNF levels. Although there were significant effects only in the analysis restricted to non-addicted individuals, the lack of significant results in the gene-by-disease status interaction analyses suggest a general effect on BDNF levels. The haplotype analyses presented the same effect seen in the single marker analyses. This study suggests that SNPs in the NR3C1 and CRHR1 genes may influence BDNF levels, but this effect is blunted in the context of crack cocaine addiction. Therefore, our data may be interpreted in light of several studies showing pronounced effects of crack cocaine on BDNF levels. Since peripheral BDNF is a biomarker for several psychiatric phenotypes, our results may be useful in interpreting previous associations between stress-related SNPs, drug addiction, and depression.
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: Jaqueline B
authors.initials: JB
authors.lastname: Schuch
authors.affiliation: Developmental Cognitive Neuroscience Lab, Biomedical Research Institute, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Grassi-Oliveira
authors.affiliation: Developmental Cognitive Neuroscience Lab, Biomedical Research Institute, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Breno
authors.initials: B
authors.lastname: Sanvicente-Vieira
authors.affiliation: Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Bruna S
authors.initials: BS
authors.lastname: da Silva
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center, Houston, USA.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Walss-Bass
authors.affiliation: Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Diana
authors.initials: D
authors.lastname: Müller
authors.affiliation: Center for Drug and Alcohol Research, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Anderson R
authors.initials: AR
authors.lastname: Stolf
authors.affiliation: Center for Drug and Alcohol Research, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Lisia
authors.initials: L
authors.lastname: von Diemen
authors.affiliation: Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Keila M M
authors.initials: KMM
authors.lastname: Ceresér
authors.affiliation: Child and Adolescent Psychiatric Service, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Thiago G
authors.initials: TG
authors.lastname: Pianca
authors.affiliation: Child and Adolescent Psychiatric Service, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Szobot
authors.affiliation: Center for Drug and Alcohol Research, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Felix H P
authors.initials: FHP
authors.lastname: Kessler
authors.affiliation: Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Roman
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: CHD
authors.lastname: Bau
mesh_terms: D000293:Adolescent; D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood* / Q000235:genetics; D002648:Child; D019970:Cocaine-Related Disorders / Q000235:genetics / Q000378:metabolism*; D016578:Crack Cocaine / Q000008:administration & dosage; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult; D000099052:CRF Receptor, Type 1
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016578:Crack Cocaine; C497713:NR3C1 protein, human; D018019:Receptors, Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid; D000099052:CRF Receptor, Type 1
keywords: BDNF; Brain-derived neurotrophic factor; Cocaine addiction; Corticotropin-releasing hormone receptor 1; Glucocorticoid receptor; NR3C1