Shuai Wang

IMPORTANCE: Despite evidence of the increasing use of psychotropic medications, little is known about the broader changes in the delivery of outpatient mental health treatment to children, adolescents, and adults. OBJECTIVE: To assess national trends and patterns in the mental health care of children, adolescents, and adults in office-based medical practice. DESIGN, SETTING, AND PARTICIPANTS: Outpatient visits to physicians in office-based practice from the 1995-2010 National Ambulatory Medical Care Surveys (N = 446 542). Trends (1995-2010) in visits with mental health care indicators are first compared between youths (<21 years) and adults (≥21 years) and then between children (0-13 years) and adolescents (14-20 years). Background and clinical characteristics of recent visits (2007-2010) resulting in a mental disorder diagnosis are also compared among children, adolescents, and adults. MAIN OUTCOMES AND MEASURES: Visits resulting in mental disorder diagnoses, prescription of psychotropic medications, provision of psychotherapy, or psychiatrist care. RESULTS: Between 1995-1998 and 2007-2010, visits resulting in mental disorder diagnoses per 100 population increased significantly faster for youths (from 7.78 to 15.30 visits) than for adults (from 23.23 to 28.48 visits) (interaction: P < .001). Psychiatrist visits also increased significantly faster for youths (from 2.86 to 5.71 visits) than for adults (from 10.22 to 10.87 visits) (interaction: P < .001). Psychotropic medication visits increased at comparable rates for youths (from 8.35 to 17.12 visits) and adults (from 30.76 to 65.90 visits) (interaction: P = .13). While psychotherapy visits increased from 2.25 to 3.17 per 100 population for youths, they decreased from 8.37 to 6.36 for adults (interaction: P < .001). In 2007-2010, 27.4% of child visits, 47.9% of adolescent visits, and 36.6% of adult visits resulting in a mental disorder diagnosis were to a psychiatrist. CONCLUSIONS AND RELEVANCE: Compared with adult mental health care, the mental health care of young people has increased more rapidly and has coincided with increased psychotropic medication use. A great majority of mental health care in office-based medical practice to children, adolescents, and adults is provided by nonpsychiatrist physicians calling for increased consultation and communication between specialties.

CONTEXT Although antipsychotic treatment has recently increased, little is known about how this development has differentially affected the office-based care of adults and young people in the United States. OBJECTIVE To compare national trends and patterns in antipsychotic treatment of adults and youths in office-based medical practice. DESIGN Trends between 1993 and 2009 in visits with antipsychotics for children (0-13 years), adolescents (14-20 years), and adults (≥21 years) are described on a per population basis and as a proportion of total medical office visits. Background and clinical characteristics of recent (2005-2009) antipsychotic visits are also compared by patient age. SETTING Outpatient visits to physicians in office-based practice. PARTICIPANTS Visits from the 1993-2009 National Ambulatory Medical Care Surveys (N = 484 889). MAIN OUTCOME MEASURES Visits with a prescription of antipsychotic medications. RESULTS Between 1993-1998 and 2005-2009, visits with a prescription of antipsychotic medications per 100 persons increased from 0.24 to 1.83 for children, 0.78 to 3.76 for adolescents, and 3.25 to 6.18 for adults. The proportion of total visits that included a prescription of antipsychotics increased during this period from 0.16% to 1.07% for youths and from 0.88% to 1.73% for adults. From 2005 to 2009, disruptive behavior disorders were the most common diagnoses in child and adolescent antipsychotic visits, accounting for 63.0% and 33.7%, respectively, while depression (21.2%) and bipolar disorder (20.2%) were the 2 most common diagnoses in adult antipsychotic visits. Psychiatrists provided a larger proportion of the antipsychotic visits for children (67.7%) and adolescents (71.6%) than to adults (50.3%) (P &lt; .001). From 2005 to 2009, antipsychotics were included in 28.8% of adult visits and 31.1% of youth visits to psychiatrists. CONCLUSIONS On a population basis, adults make considerably more medical visits with a prescription of antipsychotics than do adolescents or children. Yet antipsychotic treatment has increased especially rapidly among young people, and recently antipsychotics have been prescribed in approximately the same proportion of youth and adult visits to psychiatrists.

Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 10 -3 ) and candidate genes from knockout mice (P = 5.2 10 -3 ). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000-185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts.

A modification and inducing endothelial cell inflammatory response as well as atherosclerotic plaque formation. Decreased expression of METTL14 can inhibit endothelial inflammation and atherosclerosis development. Therefore, METTL14 may serve as a potential target for the clinical treatment of atherosclerosis.

N 6 -methyladenosine (m 6 A) is the most abundant messenger RNA (mRNA) modification and plays crucial roles in diverse physiological processes. Using a massively parallel assay for m 6 A (MPm 6 A), we discover that m 6 A specificity is globally regulated by suppressors that prevent m 6 A deposition in unmethylated transcriptome regions. We identify exon junction complexes (EJCs) as m 6 A suppressors that protect exon junction–proximal RNA within coding sequences from methylation and regulate mRNA stability through m 6 A suppression. EJC suppression of m 6 A underlies multiple global characteristics of mRNA m 6 A specificity, with the local range of EJC protection sufficient to suppress m 6 A deposition in average-length internal exons but not in long internal and terminal exons. EJC-suppressed methylation sites colocalize with EJC-suppressed splice sites, which suggests that exon architecture broadly determines local mRNA accessibility to regulatory complexes.