TY - JOUR
T1 - Effects of crack cocaine addiction and stress-related genes on peripheral BDNF levels
AU - Rovaris, Diego L.
AU - Schuch, Jaqueline B.
AU - Grassi-Oliveira, Rodrigo
AU - Sanvicente-Vieira, Breno
AU - da Silva, Bruna S.
AU - Walss-Bass, Consuelo
AU - Müller, Diana
AU - Stolf, Anderson R.
AU - von Diemen, Lisia
AU - Ceresér, Keila M M
AU - Pianca, Thiago G.
AU - Szobot, Claudia M.
AU - Kessler, Felix H P
AU - Roman, Tatiana
AU - Bau, Claiton H D
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
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.
KW - BDNF
KW - Brain-derived neurotrophic factor
KW - Cocaine addiction
KW - Corticotropin-releasing hormone receptor 1
KW - Glucocorticoid receptor
KW - NR3C1
UR - http://www.scopus.com/inward/record.url?scp=85013793558&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85013793558&partnerID=8YFLogxK
U2 - 10.1016/j.jpsychires.2017.02.011
DO - 10.1016/j.jpsychires.2017.02.011
M3 - Article
C2 - 28237884
AN - SCOPUS:85013793558
VL - 90
SP - 78
EP - 85
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
SN - 0022-3956
ER -