The Utah psychotropic oversight program: collaboratively addressing antipsychotic use within youth in foster care without prior authorization.

Objectives: Fostered youth have increased risk of exposure to trauma. Antipsychotic medications are often utilized within the foster care system, potentially to address problematic behaviors that may be associated with trauma. The Utah Psychotropic Oversight Program (UPOP) was formed to support prescribers and encourage evidence-based treatment approaches for fostered youth. However, it is unclear what impact an oversight program can have on a high turnover population and without tools such as prior authorization. This study evaluates 4 years of collected data from the UPOP program for efficacy and to identify future intervention targets. Methods: Deidentified data were collected as a routine function of the oversight program over 4 years (01/2019-12/2022), from individuals aged 0-18 years old (total N = 8,523, 48.3% female). UPOP oversight criteria: ≤6yo + any psychotropic medication, ≥7yo + 2 or more psychotropic medications. For this analysis, youth were divided by UPOP individuals ever receiving an antipsychotic (AP) prescription (UPOP_AP; N = 755, 42.3% female) or not (UPOP_NAP, N = 1,006, 48.3% female) and non-UPOP fostered (N = 6,762, 48.9% female). Comparisons were made across demographic and clinical variables via ANOVA, Chi-square, unpaired t-test, and logistic regression. Results: UPOP_AP more likely to be older males with behavioral diagnoses, increased polypharmacy, longer duration of fostering, and higher care level. AP prescription rates dropped from 52.8 to 39.1% for males and 43.3 to 38.2% in females with unchanged number of psychotropic prescriptions and care level across 2019-2022. UPOP_AP that discontinued AP treatment had fewer average psychotropic medications, but increased antidepressant and sleep prescriptions, as compared with individuals that remained on AP. Conclusion: Youth within the foster care system receive antipsychotics at high rates and in an uneven distribution. Prescribing practices can change in the context of supportive oversight programs without components such as prior authorization, and without increasing the need for higher levels of care. Specific emphasis on the treatment of mood, anxiety, and sleep issues may also lead to greater success in discontinuing AP treatment. Oversight may support treatment providers while reducing exposure to medications with considerable side effect burden that could cause future comorbidity.

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. CONCLUSIONS: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.

Differentiating nicotine- versus schizophrenia-associated decreases of the alpha7 nicotinic acetylcholine receptor transcript, CHRFAM7A, in peripheral blood lymphocytes.

Nicotine addiction is prevalent in individuals with schizophrenia. Nicotine activation of nicotinic receptors (nAChRs) is time- and dose-dependent, but gene expression analyses often rely on qualitative self- or family-reported measures of smoking. We sought lymphocyte surrogates for cerebral alpha7-nAChR activity and tested if receptor transcription correlated with concurrently measured serum biomarkers for smoking [cotinine, C-reactive protein (CRP)]. PCR surveys to detect lymphocytic alpha7-related isoforms identified CHRFAM7A as the only consistently amplifiable transcript. In 20 smoking-matched people (n = 10 schizophrenia, n = 10 controls), we found significantly lower CHRFAM7A in cotinine and self-reported smokers versus nonsmokers (p