Exploring service provider perspectives on service user engagement across service components in coordinated specialty care programs for psychosis.

Engagement in services is a core element to successful outcomes for service users and programs. In coordinated specialty care (CSC) programs, designed for individuals experiencing first-episode psychosis, engagement has only been measured programmatically and not by service component. This qualitative study sought to explore provider perspectives on service user engagement in service components of CSC. Semistructured interviews were conducted with 20 service providers from five community-based early intervention programs for psychosis in the United States. Interviews were recorded and transcribed verbatim, and thematic analysis was used to analyze the data collected. Provider participants described barriers and facilitators that contribute to disengagement or engagement in four service components within early intervention programs: individual psychotherapy, family education and support, medication management, and vocational services. Barriers identified included substance use, stigma, trauma, and external pressures. Identified barriers to engagement in CSC were both unique to individual components and cut across them. By better understanding the complexity of barriers and their intersections within and across CSC components, there can be more effective policy and program development to reduce disengagement and hopefully increase positive outcomes for service users. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Recent substance use among clients with early psychosis and the potential to graduate from New Journeys.

AIM: This study examined the relationship between recent substance use prior to intake and program graduation among young adults with early psychosis enrolled in coordinated specialty care. METHODS: Participants (N = 248) were from New Journeys, a network of coordinated specialty care programs in Washington State. Recent (i.e., past 30 days) alcohol, cannabis, and other substance use was collected at intake and process data (e.g., contact) was collected by clinicians across a 2-year period. RESULTS: At intake, 32% of participants reported alcohol use only, 26% cannabis use only, and 15% both alcohol and cannabis use. Participants who reported alcohol use only (p = .02), cannabis use only (p = .03), and any substance use (p = .02) had significantly lower chances of graduating from coordinated specialty care than individuals who do not use substances. CONCLUSIONS: Unlike prior work, recent substance use influences clients' potential to graduate from New Journeys. Additional focus on the implementation of substance use treatment, with an emphasis on alcohol use, in coordinated specialty care programs is needed improve program completion rates.

A Multifaceted Technical Assistance Strategy to Facilitate Measurement Delivery in Coordinated Specialty Care.

In recent years, coordinated specialty care (CSC) providers have worked to harmonize and deliver data collection measures across programs so that they can provide data that enable measurement-informed care. However, the strategies that can effectively support the integration of a core assessment battery in clinical care remain unclear. This column presents an evaluation of a multifaceted technical assistance strategy for the delivery and completion of an assessment battery in nine CSC programs (N=247 clients). The findings suggest that a multifaceted technical assistance strategy can effectively support the integration of a comprehensive assessment battery in the care delivered by providers. Similar technical assistance strategies may assist CSC providers as they move toward providing data-driven care in an effort to improve quality of care.

Taking a Look at How Family Member Engagement Influences Service User Engagement in New Journeys: a Coordinated Specialty Care Program.

Family members are integral to the care and support of individuals experiencing early psychosis, and while studies have brought to light the impact of family engagement, there is a dearth in the literature on the ways family engagement in services affects service user engagement. The present study examined the relationship between initial family engagement and service user engagement among 349 service users enrolled in New Journeys, a network of coordinated specialty care (CSC) programs. Service users whose family members were initially engaged in treatment in the first month were more likely to remain engaged and attend appointments during the first 7 months relative to service users whose family members were not initially engaged (χ-2=88.4; p < 0.001). Overall, for a one unit increase in total number of appointments attended by family members in the first 24 months, the odds of service users' engagement increased by 14% (OR: 1.14, CI: 1.12-1.16). Findings demonstrate the association between family engagement and the engagement of service users in CSC.

Exploring Provider Perspectives on Implementing Coordinated Specialty Care: A Qualitative Study.

This study aimed to explore clinician roles and experiences related to the implementation and sustainability of coordinated specialty care (CSC) programs for first episode psychosis. Qualitative interviews were conducted with 20 CSC providers and team members, recruited from five CSC programs. Using a semi-structured guide, interviews explored experiences with the delivery of CSC in the context of community-based outpatient mental health agencies and the challenges with implementation. Interviews were audio recorded, transcribed, and analyzed using thematic analysis. Themes were parsed into two overarching categories, provider, and organizational-level factors, and further distilled into subthemes which interacted with one another to form an interacting web of barriers to successful programmatic implementation for CSC programs. Study findings have important implications for development of future policy for financing mental health agencies, the creation of additional materials, supports for the model, and hiring and retention of staff for future implemented CSC programs.

Geographic Disparities in Access to Specialty Care Programs for Early Psychosis in Washington State.

Supported by the 10% set-aside funds in the Community Mental Health Block grant, distributed at the state level, coordinated specialty care (CSC) have been widely disseminated throughout the U.S. This study explores variations in the geographical accessibility of CSC programs by neighborhood level characteristics in Washington State. CSC locations were geocoded. Socioeconomic neighborhood deprivation (i.e., Area deprivation index) and rurality (i.e., Rural-Urban Commuting Area codes) were neighborhood level characteristics extracted from the 2018 American Community Survey. Geographic accessibility of CSC was assessed using a two-step floating catchment area technique and multilevel linear models were used to examine the association between specific neighborhood characteristics and geographic accessibility. The association between access and socioeconomically deprived neighborhoods varied differentially by neighborhood rurality (an interaction effect). Model estimates indicated that the least deprived, metropolitan neighborhoods had the best access (M = 0.38; CI: 0.34, 0.42) and rural neighborhoods in the second most deprived quartile had the worst access (M = 0.16; CI: 0.11, 0.21) to CSC. There was a clear decrease in accessibility for more rural neighborhoods, regardless of other neighborhood characteristics. In conclusions, findings provide important insight into how resource distribution contributes to geographic disparities in access to CSC. The use of spatial analytic techniques has the potential to identify specific neighborhoods and populations where there is a need to expand and increase availability of CSC to ensure access to rural and socioeconomically deprived neighborhoods.

Cortisol Levels in Childhood Associated With Emergence of Attenuated Psychotic Symptoms in Early Adulthood.

BACKGROUND: In individuals at clinical high-risk for psychosis, elevated cortisol levels predict subsequent onset of psychotic disorder. However, it is unclear whether cortisol alterations are evident at an earlier clinical stage and promote progression of psychosis expression. This study aimed to address this issue by investigating whether cortisol levels in childhood were associated with the emergence of attenuated psychotic symptoms in early adulthood. In exploratory analyses, we examined whether cortisol and psychosocial stress measures interacted in predicting attenuated psychotic symptoms. METHODS: A sample of children (N = 109) enriched for psychosis risk factors were recruited at age 9-12 years and assessed at age 11-14 years (T1) and 17-21 years (T2). Measures of psychopathology, psychosocial stressors, and salivary cortisol were obtained at T1. Attenuated psychotic symptoms were assessed at T2 using the Prodromal Questionnaire. RESULTS: Diurnal cortisol (ß = 0.915, 95% CI: 0.062-1.769) and daily stressors (ß = 0.379, 95% CI: 0.034-0.723) at T1 were independently associated with total Prodromal Questionnaire scores at T2 after accounting for demographic factors and T1 psychopathology. Exploratory analyses indicated a significant interaction between T1 diurnal cortisol and daily stressors (ß = 0.743, 95% CI: 0.081-1.405), with the highest predicted T2 total Prodromal Questionnaire scores occurring when both diurnal cortisol and daily stressors were increased. CONCLUSIONS: Our findings suggest that daily stressors and elevations in diurnal cortisol in late childhood/early adolescence increases risk for developing attenuated psychotic symptoms. These findings emphasize the importance of assessing environmental and biological risk factors for psychosis during neurodevelopmentally vulnerable time periods.

Mixed-methods trial of a phosphatidylethanol-based contingency management intervention to initiate and maintain alcohol abstinence in formerly homeless adults with alcohol use disorders.

BACKGROUND: Contingency management (CM) is an intervention where incentives are provided in exchange for biochemically confirmed alcohol abstinence. CM is effective at initiating alcohol abstinence, but it is less effective at maintaining long-term abstinence. Phosphatidylethanol (PEth), collected via a finger-stick, can detect alcohol use for 14-28 days. PEth allows for the development of a CM model that includes increasingly less frequent monitoring of abstinence to assist high risk groups, such as formerly homeless individuals, maintain long-term abstinence. AIMS: Investigate whether PEth-based CM intervention targeting alcohol abstinence in formerly homeless, currently housed individuals with alcohol use disorders is: (1) acceptable and feasible for housing program tenants and personnel; and is associated with increased (2) alcohol abstinence and (3) housing tenure. METHODS: Acceptability and feasibility will be assessed using a QUAL+quant mixed-methods design using qualitative interviews and quantitative measures of satisfaction and attrition. Effectiveness will be evaluated through a randomized pilot trial of 50 study participants who will receive 6 months of either treatment as usual (TAU) including incentives (e.g., gift cards) for providing blood samples (Control Condition) or TAU and incentives for negative PEth results (PEth-CM Condition). Outcomes will be assessed during the intervention and at a three-month follow-up visit. The trial will be conducted via telehealth as a result of COVID-19. DISCUSSION: This protocol seeks to utilize a novel alcohol biomarker to evaluate the acceptability, feasibility, and initial effectiveness of a CM model that encourages long-term abstinence in a high-risk group.

Barriers and Facilitators That Influence Providers' Ability to Educate, Monitor, and Treat Substance Use in First-Episode Psychosis Programs Using the Theoretical Domains Framework.

In this qualitative study, we explore providers' experiences with addressing substance use among individuals with first-episode psychosis (FEP) enrolled in coordinated specialty care (CSC) programs. Three focus groups were conducted with 24 providers from CSC programs for FEP in Washington. Questions were focused on barriers and facilitators to addressing substance use using the Theoretical Domains Framework (TDF) as a guide. Thematic analysis was used to code all transcripts. Identified TDF domains were then mapped onto the COM-B (Capability, Opportunity, Motivation, Behavior) intervention functions and behavior change techniques. Seven theoretical domains were identified as the most relevant to addressing substance use: "Knowledge," "Skills," "Environmental Context and Resources," "Social Influences," "Social and Professional Role and Identity," "Beliefs about Capabilities," and "Reinforcement." The use of the TDF provides a framework to explore barriers and facilitators for targeting substance use and suggestions for behavior change techniques when considering implementation of evidence-based strategies to enhance CSC models.

Family Experiences Prior to the Initiation of Care for First-Episode Psychosis: A Meta-Synthesis of Qualitative Studies.

OBJECTIVES: This study systematically reviewed existing qualitative evidence of family members' experiences prior to the initiation of mental health services for a loved one experiencing their first episode of psychosis (FEP). METHODS: A meta-synthesis review of published peer-reviewed qualitative studies conducted between 2010 and 2019 were included. Keyword searches were performed in four electronic databases and the reference lists of primary manuscripts. Two independent reviewers used the Critical Appraisal Skills Programme (CASP) qualitative checklist to assess methodological quality of each study. RESULTS: A total of 365 articles were initially identified and 9 were articles identified in a secondary review and literature search. A total of 21 met inclusion criteria. Of those included in this review 169, mothers were the primary family to recall experiences. The meta-synthesis identified four major themes related to family member experiences prior to the initiation of mental health services for FEP: the misinterpretation of signs, the emotional impact of FEP on family members, the effect of stigma on family members, and engaging with resources prior to mental health services for FEP. CONCLUSIONS: Additional research is needed to develop healthy communication strategies that effectively deliver educational information about psychosis. This meta-synthesis also identified the need to understand help-seeking behaviors among families of those with FEP in effort to reduce the duration of untreated psychosis and improve pathways to care often initiated by a family member.

A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease.

There is unmet need for chemical tools to explore the role of the Mediator complex in human pathologies ranging from cancer to cardiovascular disease. Here we determine that CCT251545, a small-molecule inhibitor of the WNT pathway discovered through cell-based screening, is a potent and selective chemical probe for the human Mediator complex-associated protein kinases CDK8 and CDK19 with >100-fold selectivity over 291 other kinases. X-ray crystallography demonstrates a type 1 binding mode involving insertion of the CDK8 C terminus into the ligand binding site. In contrast to type II inhibitors of CDK8 and CDK19, CCT251545 displays potent cell-based activity. We show that CCT251545 and close analogs alter WNT pathway-regulated gene expression and other on-target effects of modulating CDK8 and CDK19, including expression of genes regulated by STAT1. Consistent with this, we find that phosphorylation of STAT1(SER727) is a biomarker of CDK8 kinase activity in vitro and in vivo. Finally, we demonstrate in vivo activity of CCT251545 in WNT-dependent tumors.

Amyloid-associated nucleic acid hybridisation.

Nucleic acids promote amyloid formation in diseases including Alzheimer's and Creutzfeldt-Jakob disease. However, it remains unclear whether the close interactions between amyloid and nucleic acid allow nucleic acid secondary structure to play a role in modulating amyloid structure and function. Here we have used a simplified system of short basic peptides with alternating hydrophobic and hydrophilic amino acid residues to study nucleic acid - amyloid interactions. Employing biophysical techniques including X-ray fibre diffraction, circular dichroism spectroscopy and electron microscopy we show that the polymerized charges of nucleic acids concentrate and enhance the formation of amyloid from short basic peptides, many of which would not otherwise form fibres. In turn, the amyloid component binds nucleic acids and promotes their hybridisation at concentrations below their solution K(d), as shown by time-resolved FRET studies. The self-reinforcing interactions between peptides and nucleic acids lead to the formation of amyloid nucleic acid (ANA) fibres whose properties are distinct from their component polymers. In addition to their importance in disease and potential in engineering, ANA fibres formed from prebiotically-produced peptides and nucleic acids may have played a role in early evolution, constituting the first entities subject to Darwinian evolution.

Young people's satisfaction with residential care: identifying strengths and weaknesses in service delivery.

This paper presents findings from a landmark Australian study investigating the experiences and perspectives of young people in residential care. Data from a representative sample are analyzed to identify young people's satisfaction with various aspects of their residential care experience: their sense of safety, normality, support, comfort in general living environment, participation in decision-making, and improvements in well-being. Findings point to strengths and weaknesses in current service delivery. The vast majority of respondents felt safe and well-treated and satisfied with the care and support provided by staff. Respondents were less commonly satisfied with the care and support provided by caseworkers, their participation in higher order decision-making, their sense of normality, and the amount of contact with their families. Compared with older respondents, younger respondents less commonly expressed satisfaction with various aspects of their care. Similarly, those reporting more placements were less satisfied with their care and support than those reporting fewer placements.

Two functionally distinct Axin-like proteins regulate canonical Wnt signaling in C. elegans.

Axin is a central component of the canonical Wnt signaling pathway that interacts with the adenomatous polyposis coli protein APC and the kinase GSK3beta to downregulate the effector beta-catenin. In the nematode Caenorhabditis elegans, canonical Wnt signaling is negatively regulated by the highly divergent Axin ortholog PRY-1. Mutation of pry-1 leads to constitutive activation of BAR-1/beta-catenin-dependent Wnt signaling and results in a range of developmental defects. The pry-1 null phenotype is however not fully penetrant, indicating that additional factors may partially compensate for PRY-1 function. Here, we report the cloning and functional analysis of a second Axin-like protein, which we named AXL-1. We show that despite considerable sequence divergence with PRY-1 and other Axin family members, AXL-1 is a functional Axin ortholog. AXL-1 functions redundantly with PRY-1 in negatively regulating BAR-1/beta-catenin signaling in the developing vulva and the Q neuroblast lineage. In addition, AXL-1 functions independently of PRY-1 in negatively regulating canonical Wnt signaling during excretory cell development. In contrast to vertebrate Axin and the related protein Conductin, AXL-1 and PRY-1 are not functionally equivalent. We conclude that Axin function in C. elegans is divided over two different Axin orthologs that have specific functions in negatively regulating canonical Wnt signaling.

Structural basis for recruitment of glycogen synthase kinase 3beta to the axin-APC scaffold complex.

Glycogen synthase kinase 3beta (GSK3beta) is a serine/threonine kinase involved in insulin, growth factor and Wnt signalling. In Wnt signalling, GSK3beta is recruited to a multiprotein complex via interaction with axin, where it hyperphosphorylates beta-catenin, marking it for ubiquitylation and destruction. We have now determined the crystal structure of GSK3beta in complex with a minimal GSK3beta-binding segment of axin, at 2.4 A resolution. The structure confirms the co-localization of the binding sites for axin and FRAT in the C-terminal domain of GSK3beta, but reveals significant differences in the interactions made by axin and FRAT, mediated by conformational plasticity of the 285-299 loop in GSK3beta. Detailed comparison of the axin and FRAT GSK3beta complexes allows the generation of highly specific mutations, which abrogate binding of one or the other. Quantitative analysis suggests that the interaction of GSK3beta with the axin scaffold enhances phosphorylation of beta-catenin by >20 000-fold.

The regulation of glycogen synthase kinase-3 nuclear export by Frat/GBP.

Previous studies have shown that nuclear levels of glycogen synthase kinase-3 (GSK-3) are dynamically regulated and may affect access of GSK-3 to its substrates. In this study we show that the GSK-3-binding protein Frat/GBP regulates the nuclear export of GSK-3. We show that Frat/GBP contains a nuclear export sequence that promotes its own nuclear export and that of associated GSK-3. Treating cells with leptomycin B increased nuclear levels of endogenous GSK-3 suggesting that an endogenous process targets GSK-3 for nuclear export. To investigate this further, we used two approaches to disrupt the interaction between GSK-3 and endogenous Frat. First we isolated mutants of GSK-3 that selectively interfered with Frat binding and found that these mutants were poorly exported. Second we expressed a peptide that competes with Frat for GSK-3 binding and found that it caused endogenous GSK-3 to accumulate in the nucleus. Together these data suggest that Frat may be the endogenous factor that targets GSK-3 for nuclear export. The dynamic expression patterns of Frat mRNAs together with the role of Frat in mediating GSK-3 nuclear export have important implications for the control of the substrate access of GSK-3 in several signaling pathways.

Identification of the Axin and Frat binding region of glycogen synthase kinase-3.

Glycogen synthase kinase-3 (GSK-3) is a key component of several signaling pathways including those regulated by Wnt and insulin ligands. Specificity in GSK-3 signaling is thought to involve interactions with scaffold proteins that localize GSK-3 regulators and substrates. This report shows that GSK-3 forms a low affinity homodimer that is disrupted by binding to Axin and Frat. Based on the crystal structure of GSK-3, we have used surface-scanning mutagenesis to identify residues that differentially affect GSK-3 interactions. Mutations that disrupt Frat and Axin cluster at the dimer interface explaining their effect on homodimer formation. Loss of the Axin binding site blocks the ability of dominant negative GSK-3 to cause axis duplication in Xenopus embryos. The Axin binding site is conserved within all GSK-3 proteins, and its loss affects both cell motility and gene expression in the nonmetazoan, Dictyostelium. Surprisingly, we find no genetic interaction between a non-Axin-binding GSK-3 mutant and T-cell factor activity, arguing that Axin interactions alone cannot explain the regulation of T-cell factor-mediated gene expression.