The influence of psychotic-like experiences on intent to seek treatment: Findings from a multi-site community survey of mental health experiences.

Psychotic-like experiences (PLEs) may reflect elevated risk for serious mental illness, including psychosis. Although some studies report an association between PLEs and increased service utilization, there is evidence of unmet need among individuals with PLEs, with few studies exploring the relation between PLEs and intent to seek treatment. Characterizing factors that underlie intent to seek treatment in individuals not otherwise engaged in treatment may assist in determining the role of PLEs and future intentions, and help prioritize symptoms of greatest significance. Non-help-seeking participants ages 16-30 years (nanalysis = 2529) in a multi-site study completed online questionnaires of PLEs (PRIME with distress), depression (CESD), anxiety (STAI), and intention to seek mental health treatment. Associations between PLEs and intent to seek treatment were analyzed through multiple linear regressions. PRIME scores predicted intent to seek treatment, and item-level analyses suggested that this association was driven by items 12 ("going crazy"), 7 (wondering if people may hurt me), 5 (confused if things are real or imagination/dreams), and 1 (odd/unusual things going on). When accounting for the effects of anxiety and depression, PLE sum scores as well as individual experiences remained statistically significant, although effect sizes were negligible. Findings suggest that PLEs can play a role in identifying individuals who intend to seek mental health services and warrant further research in independent samples.

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).

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.

Internalized stigma mediates the relation between psychosis-risk symptoms and subjective quality of life in a help-seeking sample.

Subjective quality of life can be compromised in individuals with psychosis-risk symptoms, with poorer quality of life being associated with worse functioning and later transition to psychosis. Individuals who experience psychosis-related symptoms also tend to endorse more internalized (or self-) mental health stigma when compared to controls, potentially contributing to delays in seeking treatment and increased duration of untreated psychosis, as well as interfering with treatment engagement and retention in those already receiving care. Despite these findings, and the growing recognition for prevention in earlier phases of psychotic illness, few studies have examined the relation between psychosis-risk symptoms, internalized stigma, and subjective quality of life in a younger, help-seeking sample. The present study examined whether internalized stigma mediates the relation between psychosis-risk symptoms and subjective quality of life in a transdiagnostic sample of youth (M age = 17.93, SD = 2.90) at clinical high-risk for psychosis (CHR), with early psychosis, or with non-psychotic disorders (N = 72). Psychosis-risk symptom severity was assessed using the Structured Interview for Psychosis-Risk Syndromes (SIPS). Internalized stigma was assessed using the Internalized Stigma of Mental Illness Inventory (ISMI), and subjective quality of life was assessed using the Youth Quality of Life Instrument - Short Form (YQOL-SF). Internalized stigma fully mediated the relation between psychosis-risk symptoms and subjective quality of life across the full sample (p < .05, f2 = 0.06). Findings suggest that internalized stigma may be an important target in efforts to improve quality of life for individuals in early stages of psychosis.

Psychometric Properties and Factor Analysis of a Short Form of the Multidimensional Measure of Emotional Abuse.

The 28-item Multidimensional Measure of Emotional Abuse (MMEA) assesses four common forms of emotional abuse in intimate relationships and has been used extensively to study the development of intimate partner violence (IPV), the consequences of emotional abuse, and the outcomes of IPV interventions. The current study provides psychometric analyses of a shortened version of the MMEA using self-report data from a sample of men receiving treatment at a community-based relationship violence intervention program (RVIP; N = 467) and reports from their relationship partners (N = 252), and data from a sample of undergraduate students (N = 194) who reported on their own and their partners' abusive behavior. Theoretical and statistical considerations, including internal consistency after item deletion, were used to select items for the shortened version. In the clinic sample (for self- and partner reports) and in the undergraduate sample (for self-report only), the 16-item MMEA-Short Form (MMEA-SF) retains the 4-factor structure of the 28-item MMEA. In both samples and across reporting methods (self and partner), the 16-item MMEA-SF has good internal consistency, good concurrent validity with the Revised Conflict Tactics Scales (CTS2) psychological aggression subscale, and similar correlations with CTS2 physical assault subscale as the original 28-item MMEA version. The MMEA-SF can reduce assessment burden while maintaining good domain coverage and strong psychometric properties and will be an asset to researchers and practitioners who need a brief, multifaceted measure of emotional relationship abuse in both clinic and undergraduate samples.

Efficacy of contact intervention videos on college students' intentions toward mental health help-seeking.

ObjectiveUntreated mental health (MH) concerns have significant implications for college students. This study examined the efficacy of a video contact intervention targeting students' intentions to seek counseling. Participants: One-hundred and sixty-three college students (Mage = 21.05, SD = 2.20) from a Mid-Atlantic university participated. The sample was predominantly female (74%). Method: Students were randomly assigned to view a student-targeted contact video (ie, clips from college students who share their mental health experiences), a MH comparison contact video, or a non-MH comparison video. Intentions to seek counseling and psychological distress were measured pretest and post-test. Results: Intentions to seek counseling significantly increased from pretest to post-test in the student-targeted contact video condition (F[1, 156] = 22.75, p < .001, partial η2 = .13), but not in the comparison conditions. Further, this effect was only observed among participants who reported preexisting psychological distress (F[1, 153] = 28.00, p < .001, partial η2 = .16). Conclusions: This study provides initial support for the utility of a student-targeted contact intervention video for increasing help-seeking intentions among those reporting current psychological distress.

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.

Disease risk scores for skin cancers.

We trained and validated risk prediction models for the three major types of skin cancer- basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma-on a cross-sectional and longitudinal dataset of 210,000 consented research participants who responded to an online survey covering personal and family history of skin cancer, skin susceptibility, and UV exposure. We developed a primary disease risk score (DRS) that combined all 32 identified genetic and non-genetic risk factors. Top percentile DRS was associated with an up to 13-fold increase (odds ratio per standard deviation increase >2.5) in the risk of developing skin cancer relative to the middle DRS percentile. To derive lifetime risk trajectories for the three skin cancers, we developed a second and age independent disease score, called DRSA. Using incident cases, we demonstrated that DRSA could be used in early detection programs for identifying high risk asymptotic individuals, and predicting when they are likely to develop skin cancer. High DRSA scores were not only associated with earlier disease diagnosis (by up to 14 years), but also with more severe and recurrent forms of skin cancer.

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.

Associations between Race, Discrimination, Community Violence, Traumatic Life Events, and Psychosis-Like Experiences in a Sample of College Students.

Self-report tools of psychosis-like experiences contribute to the understanding of psychosis and may aid in identification and prevention efforts across the severity spectrum. Current tools are likely limited by biases, leading to potential systematic health disparities. Principal component analyses in diverse samples of community participants reporting psychosis-like experiences may aid in the detection of measurement biases. The current study evaluated the fit of a two-component model for the Prime Screen, a self-report psychosis-like experiences measure, in a sample of Black (n = 82) and White (n = 162) community participants, and subsequently evaluated the relation of these components with measures of mental well-being, traumatic life experiences, community violence, and experiences of discrimination. Analyses indicated limited support for a two-component model of the Prime Screen, with four of the items showing high cross-loading across both components ("poor fit" items). Although many Prime Screen items correlated with mental well-being as expected, correlations between item scores and mental well-being were non-significant for poor fit items. Community violence emerged as a significant predictor of some individual item scores for both good and poor fit items, while discrimination predicted only some poor fit item scores. Results highlight the potential limitations of current self-report tools of psychosis-like experiences, as well as possible considerations for improvement for use in diverse populations.

The impact of age on the validity of psychosis-risk screening in a sample of help-seeking youth.

Self-report screening instruments offer promise in furthering early identification of at-risk youth, yet current efforts are limited by false positive rates. Identifying moderators of accuracy is a potential step towards improving identification and prevention efforts. We investigated the moderating effect of age on self-reported attenuated positive symptoms from the Prime Screen and clinician diagnosed clinical high-risk/early psychosis (CHR/EP) status. Participants (N = 134) were racially diverse, lower-income, help-seeking adolescents and young adults from a primarily urban community. The overall model predicting CHR/EP status was significant, with results suggesting the presence of a trending interaction between age and Prime Screen symptoms. Analyses indicated that number of items endorsed to predict CHR/EP decreased with age (youngest group [M = 12.99] cut off = 6 items; middle age group [M = 14.97] cut off = 3; oldest age group [M = 18.40] cut off = 1). Although younger participants endorsed more risk items on average, follow up analyses suggested that the Prime Screen was a more accurate predictor of clinician-diagnosed-risk among older participants relative to their younger peers. The current study builds on the literature identifying moderators of psychosis-risk screening measure accuracy, highlighting potential limitations of CHR/EP screening tools in younger populations.

Family functioning moderates the impact of psychosis-risk symptoms on social and role functioning.

BACKGROUND: Youth at clinical high-risk (CHR) for psychosis often experience difficulties in social and role functioning. Given evidence that family stress and support can impact psychosis-risk symptoms, as well as an individual's ability to fulfill social and role functions, family dynamics are hypothesized to moderate the effect of psychosis-risk symptoms on functioning. METHODS: Participants at CHR (N = 52) completed the clinician-administered Structured Interview for Psychosis-risk Syndromes (SIPS) and the Family Assessment Device (FAD) General Functioning Scale, a self-report measure of family functioning including cohesion and support. Interviewers rated participants' current social and role functioning using the Global Functioning: Social and Role Scales. RESULTS: Regression results indicated that positive symptoms, but not ratings of family functioning, statistically predicted social and role functioning. Perceived family functioning, however, moderated the effect of symptoms on social/role functioning. For individuals who perceived lower levels of family functioning, symptoms were moderately associated with social and role functioning (f2 = 0.17 and f2 = 0.23, respectively). In contrast, psychosis-risk symptoms were not significantly associated with social/role functioning for individuals with higher levels of perceived family functioning. Notably, positive symptoms and perceived family functioning were not associated with one another, suggesting that perceived family functioning did not directly impact symptom severity, or vice versa. CONCLUSIONS: Findings support the notion that family functioning may be a clinically meaningful factor for individuals at CHR. Although this cross-sectional data limits our discussion of potential mechanisms underlying the pattern of findings, results suggest that familial support may be beneficial for individuals at risk for psychosis.

A randomized clinical trial of motivational enhancement therapy for alcohol problems in partner violent men.

This study examined the efficacy of brief alcohol intervention in the context of community-based treatment for partner violence. In a randomized clinical trial, 228 partner-violent men with hazardous or problem drinking were recruited at three Intimate Partner Violence (IPV) treatment agencies and randomly assigned to receive one of two 4-session alcohol interventions: Motivational Enhancement Therapy (MET: N = 110) or Alcohol Education (AE: N = 118). After completing alcohol intervention, participants received standard agency counseling services for IPV. Participants completed assessments of alcohol use, drug use, and IPV at pre-treatment, post-alcohol intervention, and quarterly follow-ups for 12 months. At the end of the 4-session alcohol intervention, MET participants displayed greater acknowledgment of problems with alcohol than AE participants (Partial ή2 = 0.039, p = 0.006). Significant changes from baseline across treatment conditions (at p < 0.001) were observed for percent days of alcohol abstinence [95% empirical CI for Partial ή2 =0.226, 0.296], heavy drinking [0.292, 0.349], illicit drug use [0.096, 0.156] and partner violence [0.282, 0.334]. No significant condition differences (treatment by time interactions) were found for alcohol abstinence [95% empirical CI for Partial ή2 = 0.007, 0.036], heavy drinking [0.016, 0.055], illicit drug use [0.005, 0.035] or partner violence [0.001, 0.004]. Results encourage continued use of brief alcohol interventions in community IPV services, but do not provide evidence of a unique benefit of MET in reducing alcohol use in this population.

Epitope Mapping Using Yeast Display and Next Generation Sequencing.

Monoclonal antibodies are the largest class of therapeutic proteins due in part to their ability to bind an antigen with a high degree of affinity and specificity. A precise determination of their epitope is important for gaining insights into their therapeutic mechanism of action and to help differentiate antibodies that bind the same antigen. Here, we describe a method to precisely and efficiently map the epitopes of multiple antibodies in parallel over the course of just several weeks. This approach is based on a combination of rational library design, yeast surface display, and next generation DNA sequencing and provides quantitative insights into the epitope residues most critical for the antibody-antigen interaction. As an example, we will use this method to map the epitopes of several antibodies that neutralize alpha toxin from Staphylococcus aureus.

Productive common light chain libraries yield diverse panels of high affinity bispecific antibodies.

The commercial success of bispecific antibodies generally has been hindered by the complexities associated with generating appropriate molecules for both research scale and large scale manufacturing purposes. Bispecific IgG (BsIgG) based on two antibodies that use an identical common light chain can be combined with a minimal set of Fc mutations to drive heavy chain heterodimerization in order to address these challenges. However, the facile generation of common light chain antibodies with properties similar to traditional monoclonal antibodies has not been demonstrated and they have only been used sparingly. Here, we describe the design of a synthetic human antibody library based on common light chains to generate antibodies with biochemical and biophysical properties that are indistinguishable to traditional therapeutic monoclonal antibodies. We used this library to generate diverse panels of well-behaved, high affinity antibodies toward a variety of epitopes across multiple antigens, including mouse 4-1BB, a therapeutically important T cell costimulatory receptor. Over 200 BsIgG toward 4-1BB were generated using an automated purification method we developed that enables milligram-scale production of BsIgG. This approach allowed us to identify antibodies with a wide range of agonistic activity that are being used to further investigate the therapeutic potential of antibodies targeting one or more epitopes of 4-1BB.

Perceived social stress and symptom severity among help-seeking adolescents with versus without clinical high-risk for psychosis.

Research suggests that social stress exposure influences illness presentation and course among youth at clinical high-risk (CHR) for psychosis, though less is known about the extent to which self-reported perceptions of social stress relate to the severity of positive symptoms. Importantly, despite the notion that youth at CHR are especially susceptible to elevations in positive symptoms under conditions of stress, no study has examined this presumption relative to other psychiatric groups. Extending previous work demonstrating that perceived social stress was higher in a CHR group than in a clinical group of non-CHR, help-seeking controls, the current study aimed to: (1) examine whether perceived social stress is related to the severity of attenuated positive symptoms in the full sample (N=110); and (2) determine whether CHR status moderates the stress-symptom relation. Exploratory analyses examined relations of perceived social stress to negative, disorganized, and general symptoms. Greater perceptions of social stress were associated with more severe positive symptoms in the entire sample; however, although positive symptoms and perceived social stress were higher in the CHR group, the strength of this relation was statistically indistinguishable across groups. No differential effect of perceived social stress was observed for any symptom domain. Results provide some support for the diathesis-stress model of psychosis, while also suggesting that social stress and symptomatology are related independent of clinical vulnerability to psychosis. Future research would benefit from longitudinal studies of stress-symptom relations across CHR and help-seeking control groups.

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.

Differential relations of locus of control to perceived social stress among help-seeking adolescents at low vs. high clinical risk of psychosis.

Research suggests that perceived social stress influences illness presentation and course among youth in the clinical high-risk (CHR) phase of psychosis. Little is known, however, about the social cognitive factors associated with social stress perception in this population, particularly relative to youth with non-CHR psychopathology. Individuals with psychosis tend to endorse an external locus of control (LOC), which is associated with the stress response in healthy individuals. LOC may therefore be related to perceived social stress in youth at CHR. We examined the differential relations of self-reported LOC and perceived social stress, as measured by the Behavior Assessment System for Children, Second Edition, across 45 CHR and 65 help-seeking control (HSC) participants. Youth at CHR reported more social stress (F[1, 107]=6.28, p=0.01) and a more external LOC (F[1, 107]=4.98, p=0.03) than HSCs. Further, external LOC was more strongly associated with feelings of social stress in the CHR group relative to the HSC group (interaction: b=0.35, t[105]=2.32, p<0.05, f2=0.05). Group differences in social stress, however, were nonsignificant at internal levels of LOC (b=-2.0, t[105]=-0.72, p=0.48; f2=0.00). Results suggest that perceptions of uncontrollability over one's social environment may more often induce or exacerbate feelings of stress and tension in CHR youth relative to HSCs. A better understanding of the social cognition-stress relation may improve understanding of CHR phenomenology, etiology, and treatment.

Germline-encoded neutralization of a Staphylococcus aureus virulence factor by the human antibody repertoire.

Staphylococcus aureus is both an important pathogen and a human commensal. To explore this ambivalent relationship between host and microbe, we analysed the memory humoral response against IsdB, a protein involved in iron acquisition, in four healthy donors. Here we show that in all donors a heavily biased use of two immunoglobulin heavy chain germlines generated high affinity (pM) antibodies that neutralize the two IsdB NEAT domains, IGHV4-39 for NEAT1 and IGHV1-69 for NEAT2. In contrast to the typical antibody/antigen interactions, the binding is primarily driven by the germline-encoded hydrophobic CDRH-2 motifs of IGHV1-69 and IGHV4-39, with a binding mechanism nearly identical for each antibody derived from different donors. Our results suggest that IGHV1-69 and IGHV4-39, while part of the adaptive immune system, may have evolved under selection pressure to encode a binding motif innately capable of recognizing and neutralizing a structurally conserved protein domain involved in pathogen iron acquisition.

Childhood pegboard task predicts adult-onset psychosis-spectrum disorder among a genetic high-risk sample.

Motor abnormalities have been established as a core aspect of psychosis-spectrum disorders, with numerous studies identifying deficits prior to clinical symptom presentation. Additional research is needed to pinpoint standardized motor assessments associated with psychosis-spectrum disorders prior to illness onset to enhance prediction and understanding of etiology. With a long history of findings among people with diagnosable psychosis-spectrum disorders, but little research conducted during the premorbid phase, pegboard tasks are a viable and understudied measure of premorbid for psychosis motor functioning. In the current study, examining data from the Copenhagen Perinatal Cohort, the Simultaneous Pegs Test was performed with children (n=244, aged 10-13) at genetic high risk for psychosis (n=94) and controls (n=150). Findings suggest that children who eventually developed a psychosis-spectrum disorder (n=33) were less likely to successfully complete the task within time limit relative to controls (χ2(2, N=244)=6.94, p=0.03, ϕ=0.17). Additionally, children who eventually developed a psychosis-spectrum disorder took significantly longer to complete the task relative to controls (χ2(2, N=244)=7.06, p=0.03, ϕ=0.17). As pegboard performance is thought to tap both diffuse and specific brain networks, findings suggest that pegboard tests may be useful premorbid measures of motor functioning among those on a trajectory towards a psychosis-spectrum disorder.