Harmonizing the structured interview for psychosis-risk syndromes (SIPS) and the comprehensive assessment of at-risk mental states (CAARMS): An initial approach.

The two most used semi-structured psychometric instruments that define criteria for being at clinical high risk (CHR) for psychosis are the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Structured Interview for Psychosis-Risk Syndromes (SIPS). Although very similar there are important differences between these two measures. Developing harmonized psychometric criteria for defining CHR and associated outcomes would be beneficial for future research. This article describes the first step in this process by reporting on a NIMH workshop held in Washington DC, in February 2019 that was attended by experts in the field. The aim of this workshop was to examine the similarities and differences between the two measures and consider how the harmonization process could proceed.

Associations between childhood ethnoracial minority density, cortical thickness, and social engagement among minority youth at clinical high-risk for psychosis.

An ethnoracial minority density (EMD) effect in studies of psychotic spectrum disorders has been observed, whereby the risk of psychosis in ethnoracial minority group individuals is inversely related to the proportion of minorities in their area of residence. The authors investigated the relationships among area-level EMD during childhood, cortical thickness (CT), and social engagement (SE) in clinical high risk for psychosis (CHR-P) youth. Data were collected as part of the North American Prodrome Longitudinal Study. Participants included 244 ethnoracial minoritized (predominantly Hispanic, Asian and Black) CHR-P youth and ethnoracial minoritized healthy controls. Among youth at CHR-P (n = 164), lower levels of EMD during childhood were associated with reduced CT in the right fusiform gyrus (adjusted ß = 0.54; 95% CI 0.17 to 0.91) and right insula (adjusted ß = 0.40; 95% CI 0.05 to 0.74). The associations between EMD and CT were significantly moderated by SE: among youth with lower SE (SE at or below the median, n = 122), lower levels of EMD were significantly associated with reduced right fusiform gyrus CT (adjusted ß = 0.72; 95% CI 0.29 to 1.14) and reduced right insula CT (adjusted ß = 0.57; 95% CI 0.18 to 0.97). However, among those with greater SE (n = 42), the associations between EMD and right insula and fusiform gyrus CT were not significant. We found evidence that lower levels of ethnic density during childhood were associated with reduced cortical thickness in regional brain regions, but this association may be buffered by greater levels of social engagement.

The Association Between Neighborhood Poverty and Hippocampal Volume Among Individuals at Clinical High-Risk for Psychosis: The Moderating Role of Social Engagement.

Reductions in hippocampal volume (HV) have been associated with both prolonged exposure to stress and psychotic illness. This study sought to determine whether higher levels of neighborhood poverty would be associated with reduced HV among individuals at clinical high-risk for psychosis (CHR-P), and whether social engagement would moderate this association. This cross-sectional study included a sample of participants (N  =  174, age-range = 12-33 years, 35.1% female) recruited for the second phase of the North American Prodrome Longitudinal Study. Generalized linear mixed models tested the association between neighborhood poverty and bilateral HV, as well as the moderating role of social engagement on this association. Higher levels of neighborhood poverty were associated with reduced left (ß â€…=  -0.180, P  =  .016) and right HV (ß â€…=  -0.185, P  =  .016). Social engagement significantly moderated the relation between neighborhood poverty and bilateral HV. In participants with lower levels of social engagement (n  =  77), neighborhood poverty was associated with reduced left (ß â€…=  -0.266, P  =  .006) and right HV (ß = -0.316, P  = .002). Among participants with higher levels of social engagement (n = 97), neighborhood poverty was not significantly associated with left (ß â€…=  -0.010, P  =  .932) or right HV (ß â€…=  0.087, P  =  .473). In this study, social engagement moderated the inverse relation between neighborhood poverty and HV. These findings demonstrate the importance of including broader environmental influences and indices of social engagement when conceptualizing adversity and potential interventions for individuals at CHR-P.

Computerized Assessment of Psychosis Risk.

Early detection and intervention with young people at clinical high risk (CHR) for psychosis is critical for prevention efforts focused on altering the trajectory of psychosis. Early CHR research largely focused on validating clinical interviews for detecting at-risk individuals; however, this approach has limitations related to: (1) specificity (i.e., only 20% of CHR individuals convert to psychosis) and (2) the expertise and training needed to administer these interviews is limited. The purpose of our study is to develop the computerized assessment of psychosis risk (CAPR) battery, consisting of behavioral tasks that require minimal training to administer, can be administered online, and are tied to the neurobiological systems and computational mechanisms implicated in psychosis. The aims of our study are as follows: (1A) to develop a psychosis-risk calculator through the application of machine learning (ML) methods to the measures from the CAPR battery, (1B) evaluate group differences on the risk calculator score and test the hypothesis that the risk calculator score of the CHR group will differ from help-seeking and healthy controls, (1C) evaluate how baseline CAPR battery performance relates to symptomatic outcome two years later (i.e., conversion and symptomatic worsening). These aims will be explored in 500 CHR participants, 500 help-seeking individuals, and 500 healthy controls across the study sites. This project will provide a next-generation CHR battery, tied to illness mechanisms and powered by cutting-edge computational methods that can be used to facilitate the earliest possible detection of psychosis risk.

An Economic Evaluation of Coordinated Specialty Care (CSC) Services for First-Episode Psychosis in the U.S. Public Sector.

BACKGROUND: Schizophrenia spectrum disorders exert a large and disproportionate economic impact. Early intervention services may be able to alleviate the burden of schizophrenia spectrum disorders on diagnosed individuals, caregivers, and society at large. Economic analyses of observational studies have supported investments in specialized team-based care for early psychosis; however, questions remain regarding the economic viability of first-episode services in the fragmented U.S. healthcare system. The clinic for Specialized Treatment Early in Psychosis (STEP) was established in 2006, to explicitly model a nationally-relevant U.S. public-sector early intervention service. The purpose of this study was to conduct an economic evaluation of STEP, a Coordinated Specialty Care service (CSC) based in a U.S. State-funded community mental health center, relative to usual treatment (UT). METHODS: Eligible patients were within 5 years of psychosis onset and had no more than 12 weeks of lifetime antipsychotic exposure. Participants were randomized to STEP or UT. The annual per-patient cost of the STEP intervention per se was estimated assuming a steady-state caseload of 30 patients. A cost-offset analysis was conducted to estimate the net value of STEP from a third-party payer perspective. Participant healthcare service utilization was evaluated at 6 months and over the entire 12 months post randomization. Generalized linear model multivariable regressions were used to estimate the effect of STEP on healthcare costs over time, and generate predicted mean costs, which were combined with the per-patient cost of STEP. RESULTS: The annual per-patient cost of STEP was $1,984. STEP participants were significantly less likely to have any inpatient or ED visits; among individuals who did use such services in a given period, the associated costs were significantly lower for STEP participants at month 12. We did not observe a similar effect with regard to other healthcare services. The predicted average total costs were lower for STEP than UT, indicating a net benefit for STEP of $1,029 at month 6 and $2,991 at month 12; however, the differences were not statistically significant. CONCLUSIONS: Our findings are promising with regard to the value of STEP to third-party payers.

Reducing the duration of untreated psychosis and its impact in the U.S.: the STEP-ED study.

BACKGROUND: Early intervention services for psychotic disorders optimally interlock strategies to deliver: (i) Early Detection (ED) to shorten the time between onset of psychotic symptoms and effective treatment (i.e. Duration of Untreated Psychosis, DUP); and (ii) comprehensive intervention during the subsequent 2 to 5 years. In the latter category, are teams ('First-episode Services' or FES) that integrate several empirically supported treatments and adapt their delivery to younger patients and caregivers. There is an urgent need to hasten access to established FES in the U.S. Despite improved outcomes for those in treatment, these FES routinely engage patients a year or more after psychosis onset. The Scandinavian TIPS study was able to effectively reduce DUP in a defined geographic catchment. The guiding questions for this study are: can a U.S. adaptation of the TIPS approach to ED substantially reduce DUP and improve outcomes beyond existing FES? METHODS/DESIGN: The primary aim is to determine whether ED can reduce DUP in the US, as compared to usual detection. ED will be implemented by one FES (STEP) based in southern Connecticut, and usual detection efforts will continue at a comparable FES (PREP(R)) serving the greater Boston metropolitan area. The secondary aim is to determine whether DUP reduction can improve presentation, engagement and early outcomes in FES care. A quasi-experimental design will compare the impact of ED on DUP at STEP compared to PREP(R) over 3 successive campaign years. The campaign will deploy 3 components that seek to transform pathways to care in 8 towns surrounding STEP. Social marketing approaches will inform a public education campaign to enable rapid and effective help-seeking behavior. Professional outreach and detailing to a wide variety of care providers, including those in the healthcare, educational and judicial sectors, will facilitate rapid redirection of appropriate patients to STEP. Finally, performance improvement measures within STEP will hasten engagement upon referral. DISCUSSION: STEP-ED will test an ED campaign adapted to heterogeneous U.S. pathways to care while also improving our understanding of these pathways and their impact on early outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02069925 . Registered 20 February 2014.

Who is paying the price? Loss of health insurance coverage early in psychosis.

OBJECTIVE: Discontinuities in health insurance coverage may make it difficult for individuals early in psychosis to receive the services that are critical in determining long-term outcome. This study reports on the rates and continuity of insurance coverage among a cohort of early-psychosis patients enrolled in Specialized Treatment Early in Psychosis (STEP) at the Connecticut Mental Health Center. METHODS: Insurance status at baseline, six months, and 12 months was collected from 82 participants from a combination of self-reports, clinical chart review, clinician reports, and a database maintained by the state Department of Social Services. RESULTS: A total of 34 participants did not know whether they had health insurance or did not appear for follow-up assessments at six and 12 months. Among the remaining 48 participants, at baseline 18 had private insurance, 13 had public insurance, and 16 had no insurance. By the 12-month assessment, 13 (72%) privately insured and five (38%) publicly insured participants had lost coverage; less than one-third of the 48 participants (N=14) maintained continuous coverage. CONCLUSIONS: Specialty services for individuals experiencing early psychosis should address the difficulty of maintaining health insurance coverage during a period of illness in which continuity of care is critical to recovery.

Multifamily psychoeducation for first-episode psychosis: a cost-effectiveness analysis.

OBJECTIVE: Family psychoeducation is considered part of optimal treatment for first-episode psychosis, but concerns about the cost of this intervention have limited its availability. Although evidence suggests that family psychoeducation is cost-effective, many cost-effectiveness analyses have suffered from limitations that reduce their utility in guiding decisions to incorporate this intervention within existing clinical services. These include not presenting results in present-day dollars and not examining whether the intervention would remain cost-effective in situations where the clinical benefits achieved were smaller than those reported in past studies. Thus the goal of this study was to investigate the cost of providing a specific psychoeducation program-multifamily group psychoeducation-to individuals with first-episode psychosis and their families. METHODS: Statistical simulation was used to estimate the cost and burden of illness associated with usual treatment versus usual treatment plus multifamily group psychoeducation. In addition, the simulation model was rerun to test whether multifamily psychoeducation would remain cost-effective in situations where the clinical benefits achieved were smaller than those reported in past studies. RESULTS: When provided for two years, multifamily group psychoeducation ranged from a cost-effective to a cost-saving intervention, depending on the clinical benefits achieved by staff delivering the intervention. When provided for longer durations (five, ten, or 20 years), multifamily psychoeducation was a cost-saving intervention even in scenarios where the clinical benefits of the intervention were reduced by 90%. CONCLUSIONS: The results suggest that multifamily group psychoeducation may not only be a cost-effective intervention for first-episode psychosis but may often be a cost-saving intervention.

Assessment of social judgments and complex mental states in the early phases of psychosis.

OBJECTIVES: Social cognition plays an important role in the functioning of individuals with psychosis. In this study, we explored two areas of social cognition not previously investigated early in the course of psychosis. METHOD: Eighty-eight clinical high risk participants, 26 participants diagnosed with schizophrenia for less than 5 years, and 41 non-clinical control participants completed two measures of social cognition. RESULTS: Clinical high risk participants demonstrated biased responses to untrustworthy faces compared to both of the other groups. Early schizophrenia participants performed more poorly on an advanced theory of mind task compared to the clinical high risk and control groups. CONCLUSIONS: There are different patterns of performance on social cognitive tasks in these groups, which require further examination in longitudinal studies.

Cost-efficacy of individual and combined treatments for panic disorder.

OBJECTIVE: The objective of this study was to examine the relative cost-efficacy of empirically supported treatments for panic disorder. As psychosocial, pharmacologic, and combined treatments have all demonstrated efficacy in the treatment of panic disorder, cost-efficacy analysis provides an additional source of information to guide clinical decision making. METHOD: Cost-efficacy was examined based on results from the Multicenter Comparative Treatment Study of Panic Disorder, a randomized controlled trial of treatment for panic disorder (DSM-III-R). The trial was conducted from May 1991 to April 1998. Cost-efficacy ratios representing the cost per 1-unit improvement in Panic Disorder Severity Scale mean item score were calculated for 3 monotherapies (cognitive-behavioral therapy [CBT], imipramine, and paroxetine) and 2 combination treatments (CBT-imipramine and CBT-paroxetine) at the end of acute, maintenance, and follow-up phases. RESULTS: Results demonstrated consistently greater cost-efficacy for individual over combined treatments, with imipramine representing the most cost-efficacious treatment option at the completion of the acute phase (cost-efficacy ratio = $972) and CBT representing the most cost-efficacious option at the end of maintenance treatment (cost efficacy ratio = $1449) and 6 months after treatment termination (cost-efficacy ratio = $1227). CONCLUSION: In the context of similar efficacy for combined treatments, but poorer cost-efficacy, current monotherapies should be considered the first-line treatment of choice for panic disorder. Additionally, CBT emerged as the most durable and cost-effective monotherapy and, hence, should be considered as a particularly valuable treatment from the perspective of cost accountability.

Recruitment and treatment practices for help-seeking "prodromal" patients.

The prodrome of psychosis has become a target for early identification and for treatments that address both symptoms and risk for future psychosis. Interest and activity in this realm is now worldwide. Clinical trials with rigorous methodology have only just begun, making treatment guidelines premature. Despite the sparse evidence base, treatments are currently applied to patients in the new prodromal clinics, usually treatments developed for established psychosis and modified for the prodromal phase. This communication will describe representative samplings of how treatment-seeking prodromal patients are currently recruited and treated in prodromal clinics worldwide. Recruitment includes how prodromal patients are sought, initially evaluated, apprised of their high-risk status, and informed of the risks and benefits of prodromal treatments and how their mental state is monitored over time. The treatment modalities offered (and described) include engagement, supportive therapy, case management, stress management, cognitive behavioral treatment, family-based treatment, antipsychotic pharmacotherapy, and non-antipsychotic pharmacotherapy. References for details are noted.

Prevention of schizophrenia: can it be achieved?

Schizophrenia is a serious mental disorder with a profound impact on patients, their caregivers and society. It is also an expensive disorder to treat, despite being relatively rare. In this paper, prevention of schizophrenia is described in terms of primary, secondary and tertiary prevention. Schizophrenia is regarded as a neurodevelopmental disorder with different phases. Primary prevention essentially involves education programmes about the association of obstetric complications and the increased risk of schizophrenia. Secondary prevention involves intervention at the prodromal phase. We review the literature and discuss the evidence relating to intervention in this phase of the illness. Early intervention could result in reduction in morbidity and better quality of life for the patients and their families. The prodromal phase can now be identified, based on current symptoms, with reliability and predictive validity for the risk of development of schizophrenia in the following year. We also discuss possible risks faced by prodromal patients, such as unnecessary stigmatisation, and the role of drug treatment during intervention at this stage. Any recommendation that anti-psychotic medications be routinely prescribed in this phase should be supported by more research work. Drug and psychosocial intervention is indicated as part of tertiary prevention to prevent further disability in the illness.

Quantitative analysis of sponsorship bias in economic studies of antidepressants.

BACKGROUND: Concern is widespread about potential sponsorship influence on research, especially in pharmacoeconomic studies. Quantitative analysis of possible bias in such studies is limited. AIMS: To determine whether there is an association between sponsorship and quantitative outcomes in pharmacoeconomic studies of antidepressants. METHOD: Using all identifiable articles with original comparative quantitative cost or cost-effectiveness outcomes for antidepressants, we performed contingency table analyses of study sponsorship and design v. study outcome. RESULTS: Studies sponsored by selective serotonin reuptake inhibitor (SSRI) manufacturers favoured SSRIs over tricyclic antidepressants more than non-industry-sponsored studies. Studies sponsored by manufacturers of newer antidepressants favoured these drugs more than did non-industry-sponsored studies. Among industry-sponsored studies, modelling studies favoured the sponsor's drug more than did administrative studies. Industry-sponsored modelling studies were more favourable to industry than were non-industry-sponsored ones. CONCLUSIONS: Pharmacoeconomic studies of antidepressants reveal clear associations of study sponsorship with quantitative outcome.

Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability.

As the number of studies related to the early identification of and intervention in the schizophrenia prodrome continues to grow, it becomes increasingly critical to develop methods to diagnose this new clinical entity with validity. Furthermore, given the low incidence of patients and the need for multisite collaboration, diagnostic and symptom severity reliability is also crucial. This article provides further data on these psychometric parameters for the prodromal assessment instruments developed by the Prevention through Risk Identification, Management, and Education (PRIME) prodromal research team at Yale University: the Structured Interview for Prodromal Syndromes and the Scale of Prodromal Symptoms. It also presents data suggesting that excellent interrater reliability can be established for diagnosis in a day-and-a-half-long training workshop.