PMID- 28237884 OWN - NLM STAT- MEDLINE DCOM- 20180319 LR - 20181202 IS - 1879-1379 (Electronic) IS - 0022-3956 (Linking) VI - 90 DP - 2017 Jul TI - Effects of crack cocaine addiction and stress-related genes on peripheral BDNF levels. PG - 78-85 LID - S0022-3956(16)30218-7 [pii] LID - 10.1016/j.jpsychires.2017.02.011 [doi] AB - 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. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Rovaris, Diego L AU - Rovaris DL AD - Department of Genetics, Instituto de Biociencias, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. FAU - Schuch, Jaqueline B AU - Schuch JB AD - Department of Genetics, Instituto de Biociencias, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. FAU - Grassi-Oliveira, Rodrigo AU - Grassi-Oliveira R AD - Developmental Cognitive Neuroscience Lab, Biomedical Research Institute, Pontificia Universidade Catolica do Rio Grande do Sul, Porto Alegre, Brazil. FAU - Sanvicente-Vieira, Breno AU - Sanvicente-Vieira B AD - Developmental Cognitive Neuroscience Lab, Biomedical Research Institute, Pontificia Universidade Catolica do Rio Grande do Sul, Porto Alegre, Brazil. FAU - da Silva, Bruna S AU - da Silva BS AD - Department of Genetics, Instituto de Biociencias, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. FAU - Walss-Bass, Consuelo AU - Walss-Bass C AD - Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center, Houston, USA. FAU - Muller, Diana AU - Muller D AD - Department of Genetics, Instituto de Biociencias, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. FAU - Stolf, Anderson R AU - Stolf AR AD - Center for Drug and Alcohol Research, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. FAU - von Diemen, Lisia AU - von Diemen L AD - Center for Drug and Alcohol Research, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. FAU - Cereser, Keila M M AU - Cereser KMM AD - Laboratory of Molecular Psychiatry, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. FAU - Pianca, Thiago G AU - Pianca TG AD - Child and Adolescent Psychiatric Service, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. FAU - Szobot, Claudia M AU - Szobot CM AD - Child and Adolescent Psychiatric Service, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. FAU - Kessler, Felix H P AU - Kessler FHP AD - Center for Drug and Alcohol Research, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. FAU - Roman, Tatiana AU - Roman T AD - Department of Genetics, Instituto de Biociencias, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. FAU - Bau, Claiton H D AU - Bau CHD AD - Department of Genetics, Instituto de Biociencias, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. Electronic address: claiton.bau@ufrgs.br. LA - eng PT - Journal Article DEP - 20170211 PL - England TA - J Psychiatr Res JT - Journal of psychiatric research JID - 0376331 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Crack Cocaine) RN - 0 (NR3C1 protein, human) RN - 0 (Receptors, Corticotropin-Releasing Hormone) RN - 0 (Receptors, Glucocorticoid) RN - 5CLY6W2H1M (CRF receptor type 1) SB - IM MH - Adolescent MH - Adult MH - Brain-Derived Neurotrophic Factor/*blood/genetics MH - Child MH - Cocaine-Related Disorders/genetics/*metabolism MH - Crack Cocaine/administration & dosage MH - Female MH - Genotype MH - Humans MH - Logistic Models MH - Male MH - Middle Aged MH - Polymorphism, Single Nucleotide/*genetics MH - Receptors, Corticotropin-Releasing Hormone/*genetics MH - Receptors, Glucocorticoid/*genetics/metabolism MH - Young Adult OTO - NOTNLM OT - BDNF OT - Brain-derived neurotrophic factor OT - Cocaine addiction OT - Corticotropin-releasing hormone receptor 1 OT - Glucocorticoid receptor OT - NR3C1 EDAT- 2017/02/27 06:00 MHDA- 2018/03/20 06:00 CRDT- 2017/02/27 06:00 PHST- 2016/08/14 00:00 [received] PHST- 2016/12/21 00:00 [revised] PHST- 2017/02/09 00:00 [accepted] PHST- 2017/02/27 06:00 [pubmed] PHST- 2018/03/20 06:00 [medline] PHST- 2017/02/27 06:00 [entrez] AID - S0022-3956(16)30218-7 [pii] AID - 10.1016/j.jpsychires.2017.02.011 [doi] PST - ppublish SO - J Psychiatr Res. 2017 Jul;90:78-85. doi: 10.1016/j.jpsychires.2017.02.011. Epub 2017 Feb 11.