Mental health care utilization in individuals with high levels of psychosis-like experiences: Associations with race and potentially traumatic events.

Objective: Racial inequities in mental health care utilization (MHCU) are well documented. Marginalized racial groups are more likely to report psychosis-like experiences (PLEs) and are at elevated risk for racial discrimination and trauma, impacting PLE severity. Little is known about how factors associated with race impact treatment seeking among individuals reporting PLEs. The present study examined associations between race, trauma, discrimination, PLEs, and MHCU among people endorsing high levels of PLEs. Method: Participants were Asian/Asian American, Black/African American, or White/European American college students ages 18-25 years meeting PLE self-report measure cutoff scores (N = 177). Binary logistic and multiple linear regressions were used to examine associations between past, current, and prospective MHCU and race, potentially traumatic events, discrimination, and PLEs. Results: Participants endorsing more PLEs were more likely to report past and current treatment and to be considering future services. Asian/Asian American and Black/African American participants were less likely to endorse past, current, and prospective future mental health care. Potentially traumatic events predicted increased utilization of past treatment. Conclusions: Results suggest service differences among participants, such that Black/African American and Asian/Asian American young adults reporting PLEs were less likely than White/European American counterparts to seek treatment even when accounting for traumatic events and discrimination. These findings highlight the need to further elucidate MHCU among marginalized racial groups experiencing psychosis-like symptoms. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Advancing drug discovery using the power of the human genome.

Human genetics plays an increasingly important role in drug development and population health. Here we review the history of human genetics in the context of accelerating the discovery of therapies, present examples of how human genetics evidence supports successful drug targets, and discuss how polygenic risk scores could be beneficial in various clinical settings. We highlight the value of direct-to-consumer platforms in the era of fast-paced big data biotechnology, and how diverse genetic and health data can benefit society. © 2021 23andMe, Inc. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Telepsychotherapy with Youth at Clinical High Risk for Psychosis: Clinical Issues and Best Practices during the COVID-19 Pandemic.

Early detection and prevention of psychosis has become an international priority. Much of this work has focused on youth presenting with attenuated symptoms of psychosis-those at Clinical High Risk for psychosis (CHR)-given their elevated probability of developing the full disorder in subsequent years. Individuals at CHR may be prone to exacerbated psychological distress during the COVID-19 pandemic and its subsequent physical isolation measures, due to heightened stress sensitivity and comorbid mental health problems. Telepsychotherapy holds promise for reaching this population, especially during the current COVID-19 outbreak. However, there are limited evidence-based guidelines or interventions for use of telepsychotherapy with this population. In this paper, we review common clinical issues for individuals at CHR and how they might be exacerbated by the COVID-19 pandemic; best practices for treatment and adaptations for telepsychotherapy for individuals at CHR; and highlight real clinical issues that we are currently experiencing in a United States-based specialized CHR clinic as we conduct telepsychotherapy via videoconferencing. We conclude with questions for those in the field to contemplate, as well as potential challenges and benefits in using telepsychotherapy with individuals at CHR and their families.

Weight gain trajectories in hospital-based treatment of anorexia nervosa.

Weight gain is a primary treatment goal for anorexia nervosa (AN); however little is known about heterogeneity in weight gain pattern during treatment. Preliminary evidence suggests weight gain trajectory is associated with treatment outcome. This study grouped patients using mixture modeling into weight gain trajectories, and compared predictors and treatment outcomes between trajectory groups. Women diagnosed with AN or subthreshold AN (N = 211) completed self-report measures at admission and six-months after discharge from an integrated inpatient (IP)-partial hospitalization (PH) behavioral specialty eating disorders program. Gowned weights were measured daily. Three distinct trajectories emerged: negative quadratic (Optimal), negative quadratic with fast weight gain (Fast), and positive linear with slower weight gain (Slow). The majority of patients were assigned to the Optimal group. Trajectory groups differed on admission, discharge, and follow-up variables. The Fast group emerged as most distinct. Women in this group were more than twice as likely to binge and or vomit regularly compared with the other two groups and were most likely to achieve weight restoration by discharge and to have more positive weight outcomes at short-term follow-up. There were no group differences in eating disorder behavioral frequencies at follow-up when adjusting for behavioral severity at admission. Weight gain trajectory may serve as a personalized in-treatment marker of outcome and could inform research on moderators and mediators of treatment response. Randomized controlled treatment studies, utilizing weight gain trajectories to determine group membership, may help identify subgroups of patients with differential responses to treatment interventions.

Synthesis and evaluation of ether-linked demethylepipodophyllotoxin dimers.

A series of novel ether-linked dimers of demethylepipodophyllotoxin are topoisomerase II poisons that exhibit higher levels of double-stranded versus single-stranded DNA cleavage than their corresponding monomers. The dimers also have higher levels of tumor cell cytotoxicity than the monomers, lending support to the two-drug model for interaction of demethylepipodophyllotoxins with human topoisomerase IIα.

Discovery of RXFP2 genetic association in resistant hypertensive men and RXFP2 antagonists for the treatment of resistant hypertension.

Hypertension remains a leading cause of cardiovascular and kidney diseases. Failure to control blood pressure with ≥ 3 medications or control requiring ≥ 4 medications is classified as resistant hypertension (rHTN) and new therapies are needed to reduce the resulting increased risk of morbidity and mortality. Here, we report genetic evidence that relaxin family peptide receptor 2 (RXFP2) is associated with rHTN in men, but not in women. This study shows that adrenal gland gene expression of RXFP2 is increased in men with hypertension and the RXFP2 natural ligand, INSL3, increases adrenal steroidogenesis and corticosteroid secretion in human adrenal cells. To address the hypothesis that RXFP2 activation is an important mechanism in rHTN, we discovered and characterized small molecule and monoclonal antibody (mAb) blockers of RXFP2. The novel chemical entities and mAbs show potent, selective inhibition of RXFP2 and reduce aldosterone and cortisol synthesis and release. The RXFP2 mAbs have suitable rat pharmacokinetic profiles to evaluate the role of RXFP2 in the development and maintenance of rHTN. Overall, we identified RXFP2 activity as a potential new mechanism in rHTN and discovered RXFP2 antagonists for the future interrogation of RXFP2 in cardiovascular and renal diseases.

Aging as accelerated accumulation of somatic variants: whole-genome sequencing of centenarian and middle-aged monozygotic twin pairs.

It has been postulated that aging is the consequence of an accelerated accumulation of somatic DNA mutations and that subsequent errors in the primary structure of proteins ultimately reach levels sufficient to affect organismal functions. The technical limitations of detecting somatic changes and the lack of insight about the minimum level of erroneous proteins to cause an error catastrophe hampered any firm conclusions on these theories. In this study, we sequenced the whole genome of DNA in whole blood of two pairs of monozygotic (MZ) twins, 40 and 100 years old, by two independent next-generation sequencing (NGS) platforms (Illumina and Complete Genomics). Potentially discordant single-base substitutions supported by both platforms were validated extensively by Sanger, Roche 454, and Ion Torrent sequencing. We demonstrate that the genomes of the two twin pairs are germ-line identical between co-twins, and that the genomes of the 100-year-old MZ twins are discerned by eight confirmed somatic single-base substitutions, five of which are within introns. Putative somatic variation between the 40-year-old twins was not confirmed in the validation phase. We conclude from this systematic effort that by using two independent NGS platforms, somatic single nucleotide substitutions can be detected, and that a century of life did not result in a large number of detectable somatic mutations in blood. The low number of somatic variants observed by using two NGS platforms might provide a framework for detecting disease-related somatic variants in phenotypically discordant MZ twins.

Use of divalent metal ions in the DNA cleavage reaction of topoisomerase IV.

It has long been known that type II topoisomerases require divalent metal ions in order to cleave DNA. Kinetic, mutagenesis and structural studies indicate that the eukaryotic enzymes utilize a novel variant of the canonical two-metal-ion mechanism to promote DNA scission. However, the role of metal ions in the cleavage reaction mediated by bacterial type II enzymes has been controversial. Therefore, to resolve this critical issue, this study characterized the DNA cleavage reaction of Escherichia coli topoisomerase IV. We utilized a series of divalent metal ions with varying thiophilicities in conjunction with oligonucleotides that replaced bridging and non-bridging oxygen atoms at (and near) the scissile bond with sulfur atoms. DNA scission was enhanced when thiophilic metal ions were used with substrates that contained bridging sulfur atoms. In addition, the metal-ion dependence of DNA cleavage was sigmoidal in nature, and rates and levels of DNA cleavage increased when metal ion mixtures were used in reactions. Based on these findings, we propose that topoisomerase IV cleaves DNA using a two-metal-ion mechanism in which one of the metal ions makes a critical interaction with the 3'-bridging atom of the scissile phosphate and facilitates DNA scission by the bacterial type II enzyme.

Exploring the relation between psychosis-like experiences and suicidal ideation, plans, and attempts among college students in the United States.

AIM: The suicide rate among college students is particularly high, with evidence that psychosis-like experiences (PLEs) put these individuals at greater risk. The current study explored whether there are differential relations between four subtypes of PLEs and three suicide outcomes. METHODS: We analysed a large sample of college students from the Fall semester cohort of the 2020 Healthy Minds Study (HMS) (weighted N = 36727). PLEs and suicide outcomes were assessed using binary variables from the World Health Organization Composite International Diagnostic Interview. RESULTS: Findings revealed that reporting any of the subtypes of PLEs was associated with greater odds of suicidal ideation (SI), a suicide plan (SP) and a suicide attempt (SA) (signficant a ORs ranging from 1.30 to 3.30). For college students who endorsed SI or a SP in the past year, experiencing delusional mood (aOR [95% CI] = 1.30 [1.02-1.65]), suspiciousness (aOR [95% CI] = 1.31 [1.00-1.71]) and hallucinatory experiences (aOR [95% CI] = 2.76 [2.05-3.71]) in their lifetime increased their odds of reporting a SA in the past year. There was also evidence of a dose-dependent relation between the number of PLEs endorsed and all three suicide outcomes. CONCLUSIONS: Certain subtypes of PLEs including delusional mood, suspiciousness and hallucinatory experiences may contribute to an elevated risk of suicide outcomes in college students. Moreover, the odds of reporting suicide outcomes were greater for individuals who endorsed a greater number of PLEs. It may be helpful to assess for indicated subtypes when determining suicide risk among college students and to be particularly mindful of those who report three or more PLEs.