Anti-NR3C2 (aa 1-110) polyclonal antibody

Objective: Adolescence is a time of increased susceptibility to environmental stress and mood disorders, and girls are particularly at risk. Genes interacting with the environment (G x E) are implicated in hypothalamic-pituitary-adrenal axis dysregulation, hippocampal volume changes and risk or resilience to mood disorders. In this study, we assessed the effects of stress system G x E interactions on hippocampal volumes and cortisol secretion in adolescent girls. Methods: We recruited 229 girls aged 12-18 years, and scans were obtained from 202 girls. Of these, 76 had been exposed to higher emotional trauma (abuse or neglect). Hippocampal volumes were measured using Freesurfer and high-resolution structural magnetic resonance imaging scans. Saliva samples were collected for measurement of cortisol levels and genotyping of stress system genes: FKBP5, NR3C1 (both N = 194) and NR3C2 (N = 193). Results: Among girls with the 'G' allelic variant of the NR3C1 gene, those who had been exposed to higher emotional trauma had significantly smaller left hippocampal volumes (N = 44; mean = 4069.58 mm(3), standard deviation = 376.99) than girls who had been exposed to minimal emotional trauma with the same allelic variant (N = 69; mean = 4222.34 mm(3), standard deviation = 366.74). Conclusion: In healthy adolescents, interactions between emotional trauma and the 'protective' NR3C1 'GG' variant seem to induce reductions in left hippocampal volumes. These G x E interactions suggest that vulnerability to mood disorders is perhaps driven by reduced 'protection' that may be specific to emotional trauma. This novel but preliminary evidence has implications for targeted prevention of mood disorders and prospective multimodal neuroimaging and longitudinal studies are now needed to investigate this possibility.

Study Objective. To identify patient-specific factors associated with spironolactone-induced potassium level elevation in patients with heart failure. Design. Prospective cohort study. Setting. Two adult heart failure clinics. Patients. Sixty-two adult (mean +/- SD age 54 +/- 16 yrs) aldosterone antagonist-naive patients with heart failure. Intervention. Patients received spironolactone 12.5 mg/day, titrated to 25 mg/day if tolerated. Measurements and Main Results. Blood samples were obtained at baseline, 1 week after spironolactone initiation, and 1 week after spironolactone dose titration for assessment of baseline aldosterone level, serum chemistry, and angiotensinogen (AGT) c.-6G>A and p.M268T and mineralocorticoid receptor (NR3C2) c.21.5C>G and p.1180V genotypes. Patient characteristics, laboratory values, and genotypes were compared between those whose potassium levels increased by more than 0.5 mEq/L (15 patients) and those with lower potassium level elevations (47 patients) after spironolactone initiation and dose titration. Patients with a greater potassium level elevation had a higher mean +/- SD aldosterone concentration (178 +/- 92 vs 1.02 +/- 57 pg/ml, p=0.007) and NR3C2 215G allele frequency (50% vs 22%, p<0.01). Aldosterone concentrations positively correlated with diuretic dose (r=0.31.3, p=0.014) and negatively correlated with serum potassium level (r=-0.319, p=0.012). On regression analysis, factors predictive of potassium level increases greater than 0.5 mEq/L with spironolactone were aldosterone level greater than 150 pg/ml (odds ratio [OR] 30, 95% confidence interval [CI] 3.2-2871 and NR3C2 215G carrier status (OR 17, 95% CI 1.6-467). Conclusion. Our data suggest that potassium should be monitored with particular caution when spironolactone is started in patients with heart failure who have evidence of elevated aldosterone levels, such as high diuretic requirements, or the NR3C2 215G allele.