BDNF Val(66)Met genotype is associated with drug-seeking phenotypes in heroin-dependent individuals: a pilot study

Abstract

Brain-derived neurotrophic factor (BDNF) Val(66)Met genotype has been associated with neurobehavioral deficits. To examine its relevance for addiction, we examined BDNF genotype differences in drug-seeking behavior. Heroin-dependent volunteers (n = 128) completed an interview that assessed past-month naturalistic drug-seeking/use behaviors. In African Americans (n = 74), the Met allele was uncommon (carrier frequency 6.8%); thus, analyses focused on European Americans (n = 54), in whom the Met allele was common (carrier frequency 37.0%). In their natural setting, Met carriers (n = 20) reported more time- and cost-intensive heroin-seeking and more cigarette use than Val homozygotes (n = 34). BDNF Val(66)Met genotype predicted 18.4% of variance in 'weekly heroin investment' (purchasing time × amount × frequency). These data suggest that the BDNF Met allele may confer a 'preferred drug-invested' phenotype, resistant to moderating effects of higher drug prices and non-drug reinforcement. These preliminary hypothesis-generating findings require replication, but are consistent with pre-clinical data that demonstrate neurotrophic influence in drug reinforcement. Whether this genotype is relevant to other abused substances besides opioids or nicotine, or treatment response, remains to be determined.

Trial registration: ClinicalTrials.gov NCT00218309 NCT00218361 NCT00608504.

Keywords: BDNF; cigarette; drug-seeking; genotype; heroin; opioid..

Conflict of interest statement

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest with respect to the conduct or content of this work.

© 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

Figures

Figure 1

Response distributions for European American participants (N=54) with means (horizontal bars) by BDNF rs6265 genotype (Met carriers [n=20] vs. Val homozygotes [n=34]) for heroin-seeking phenotypes: Purchase Time (upper left panel), Purchase Amount (upper right panel), Weekly Purchases (lower left panel), and the empirically derived index “Weekly Heroin Investment” (lower right panel), which is the product score of purchase time × purchase amount × weekly purchases (measured in dollar-minutes weekly). For each measure, the log10-transformed scores are shown on the left ordinate, and the corresponding untransformed scores are illustrated on the right ordinate. For all measures except weekly heroin purchases, Met carriers significantly differed from Val homozygotes.

Figure 2

Relationships between drug-seeking phenotypes in European-American participants (total N=54). Each panel illustrates a significant (p< .05) overall correlation between two heroin-seeking phenotypes (upper left: purchase time × purchase amount; upper right: purchase time × weekly purchases; lower left: purchase amount × weekly purchases), as well as differences in the response distributions between BDNF Met allele carriers (n=20; closed circles) and Val/Val genotype (n=34; open circles). Lower right panel: Combined prediction of ‘weekly heroin investment’ by BDNF genotype and past-month income (see Table 3, regression analysis).