Novel associations between FAAH genetic variants and postoperative central opioid-related adverse effects.

Opioid effects are potentiated by cannabinoid agonists including anandamide, an endocannabinoid. Inter-individual variability in responses to opioids is a major clinical problem. Multiple deaths and anoxic brain injuries occur every year because of opioid-induced respiratory depression (RD) in surgical patients and drug abusers of opioids and cannabinoids. This study aimed to determine specific associations between genetic variants of fatty acid amide hydrolase (FAAH) and postoperative central opioid adverse effects in children undergoing tonsillectomy. This is a prospective genotype-blinded observational study in which 259 healthy children between 6 and 15 years of age who received standard perioperative care with a standard anesthetic and an intraoperative dose of morphine were enrolled. Associations between frequent polymorphisms of FAAH and central postoperative opioid adverse effects including, RD, postoperative nausea and vomiting (PONV) and prolonged stay in Post Anesthesia Recovery Room (postoperative anesthesia care unit, PACU) due to RD and PONV were analyzed. Five specific FAAH single nucleotide polymorphisms (SNPs) had significant associations with more than twofold increased risk for refractory PONV (adjusted P<0.0018), and nominal associations (P<0.05) with RD and prolonged PACU stay in white children undergoing tonsillectomy. The FAAH SNP, rs324420, is a missense mutation with altered FAAH function and it is linked with other FAAH SNPs associated with PONV and RD in our cohort; association between PONV and rs324420 was confirmed in our extended cohort with additional 66 white children. Specific FAAH polymorphisms are associated with refractory PONV, opioid-related RD, and prolonged PACU stay due to opioid adverse effects in white children undergoing tonsillectomy.

Association of OPRM1 A118G variant with risk of morphine-induced respiratory depression following spine fusion in adolescents.

The µ1 opioid receptor (OPRM1) genetic variant A118G results in decreased µ-receptor binding potential in the brain and increases morphine requirement. We hypothesized that OPRM1 A118G polymorphism will affect morphine-induced respiratory depression (MIRD) risk in children receiving morphine. A prospective genotype-blinded study was conducted in 88 healthy adolescents (11-18 years; 67% female, 85% Caucasian) who underwent spine fusion for scoliosis. They were followed for 48 h postoperatively for MIRD, pain scores, morphine consumption and use of analgesic adjuvants. Patients were genotyped for OPRM1 A118G variant-76% were wild type (AA) and 24% heterozygous/homozygous for variant (AG/GG). Multivariable logistic regression showed that the risk of MIRD in patients with AA genotype was significantly higher (odds ratio 5.6, 95% CI: 1.4-37.2, P=0.030). Presence of G allele was associated with higher pain scores (effect size 0.73, P=0.045). This novel association is an important step toward predicting MIRD susceptibility and personalizing morphine use.

Self-esteem and performance on word tasks.

The authors investigated word-task performance of 192 postgraduate Indian women, grouped according to high or low self-esteem, after different causal attributions for failure. The subsequent performance of the low-self-esteem (LSE) participants improved after reattribution training. When the LSE participants were induced to attribute their prior failure to external causes, the external attribution not only reduced their natural tendency toward self-blame but also broke the self-defeating cycle, thereby enabling them to improve their subsequent performance.