Faculty Bibliography

OBJECTIVE:In October 2004, the Food and Drug Administration directed pharmaceutical companies to issue a black box warning about the potential link between the use of antidepressants and suicidal ideation among children. This study analyzed long-run trends in antidepressant use among children before and after the black box warning for those with and without severe psychological impairment. METHODS:The analysis used data from the Medical Expenditure Panel Survey for children ages five to 17, covering years 2000-2011 (N=75,819). The study used multivariate probit models to compare the changes in the rate of any antidepressant use in the early (2004-2007) and late (2008-2011) postwarning years with the rate in the prewarning years (2002-2003). Recycled predictions methods were used to estimate yearly predicted probabilities of use. RESULTS:After adjustment for all covariates, there was a .5% statistically significant decline in the probability of using any antidepressants during the early postwarning years (2004-2007) compared with prewarning years. In the long run (2008-2011), however, there was no statistically significant difference. Five years after the black box warning, the adjusted rates of use increased to their prewarning levels (2.29% in 2003 and 2.26% in 2009). The initial impact of the warning differed between the severe and nonsevere populations, with a significant effect on those with nonsevere psychological impairment. CONCLUSIONS:The return to the rates before the black box warning raises concern that the impact of the warning may have dissipated over time. More frequent updates of the warning might be necessary.

Context:Vitamin D inadequacy is common in the adult population of the United States. Although the genetic determinants underlying vitamin D inadequacy have been studied in people of European ancestry, less is known about populations with Hispanic or African ancestry. Objective:The Trans-Ethnic Evaluation of Vitamin D (TRANSCEN-D) genomewide association study (GWAS) consortium was assembled to replicate genetic associations with 25-hydroxyvitamin D [25(OH)D] concentrations from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits (SUNLIGHT) meta-analyses of European ancestry and to identify genetic variants related to vitamin D concentrations in African and Hispanic ancestries. Design:Ancestry-specific (Hispanic and African) and transethnic (Hispanic, African, and European) meta-analyses were performed with Meta-Analysis Helper software (METAL). Patients or Other Participants:In total, 8541 African American and 3485 Hispanic American (from North America) participants from 12 cohorts and 16,124 European participants from SUNLIGHT were included in the study. Main Outcome Measures:Blood concentrations of 25(OH)D were measured for all participants. Results:Ancestry-specific analyses in African and Hispanic Americans replicated single nucleotide polymorphisms (SNPs) in GC (2 and 4 SNPs, respectively). An SNP (rs79666294) near the KIF4B gene was identified in the African American cohort. Transethnic evaluation replicated GC and DHCR7 region SNPs. Additionally, the transethnic analyses revealed SNPs rs719700 and rs1410656 near the ANO6/ARID2 and HTR2A genes, respectively. Conclusions:Ancestry-specific and transethnic GWASs of 25(OH)D confirmed findings in GC and DHCR7 for African and Hispanic American samples and revealed findings near KIF4B, ANO6/ARID2, and HTR2A. The biological mechanisms that link these regions with 25(OH)D metabolism warrant further investigation.