Injectable extended-release naltrexone (XRNTX) presents an effective therapeutic strategy for opioid addiction, however its utility could be hampered by poor adherence. To gain a better insight into this phenomenon, we utilized blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) in conjunction with a validated cue-induced craving procedure to examine neural correlates of XRNTX adherence. We operationalized treatment adherence as the number of monthly XRNTX injections (range: 0–3) administered to a group of fully detoxified heroin-dependent subjects (n=32). Additional outcomes included urine toxicology screening and self-reported tobacco use. The presented heroin-related visual cues reliably elicited heroin craving in all tested subjects. Nine, five, three and 15 of the participants, respectively, received zero, one, two and three XRNTX injections, predicted by the individual baseline fMRI signal change in response to the cues in the medial prefrontal cortex, a brain region involved in inhibitory self-control and emotional appraisal. The incidence of opioid-positive urines during the XRNTX therapy was low and remained about half the pre-treatment rate after the XRNTX ended. During the treatment, cigarette smoking behaviors followed patterns of opioid use, while cocaine consumption was increased with reductions in opioid use. The present data support the hypothesis that medial prefrontal cortex functions are involved in adherence to opioid antagonist therapy. A potential role of concurrent non-opioid addictive substances consumption during the XRNTX pharmacotherapy warrants further investigation. Our findings set the stage for further bio-behavioral investigations of the mechanisms of relapse prevention in opioid dependence.

ABSTRACT. Brain-derived neurotrophic factor (BDNF) promotes synaptic remodeling and modulates the function of other neurotransmitters. Allergic inflammation triggers neuronal dysfunction and structural changes in the airways. Genetic polymorphisms in functional regions of the BDNF gene have a plausible role in modulating the risk of child asthma (CA). This study examined the potential association between CA and three single nucleotide polymorphisms (SNPs) in BDNF (rs2030323, rs6265, and rs16917204 in the promoter, exon 4, and 3'-untranslated regions, respectively). The study was conducted in 350 children with asthma and 356 healthy controls. The genotype and allele frequencies and difference between groups were analyzed using HaploView 4.0 and SPSS 20.0 software platforms. The analysis revealed a strong association between the rs6265 genotype distribution and CA. The frequency of the G allele was significantly higher 16233-16240 (2015) in CA patients than in healthy controls (P = 0.0007, odds ratio = 1.323, 95% confidence interval = 1.073-1.632). Strong linkage disequilibrium was observed between rs16917204 and rs6265. A significantly higher number of G-G haplotypes were observed in CA patients than in controls (P = 0.024 after Bonferroni correction), while the G-A haplotypes were more significant in controls (P = 0.013 after Bonferroni correction). This suggested that BDNF gene polymorphisms confer susceptibility to CA, and also support the notion that BDNF dysfunction is involved in the pathophysiological process of CA.