Exploring the acceptability, barriers, and facilitators to psychosis screening in the integrated behavioral health primary care setting: a qualitative study.

BACKGROUND: A longer duration of untreated psychosis (DUP) is associated with poorer treatment outcomes. Screening for psychosis spectrum disorders in the primary care setting could help support the earlier detection and treatment of individuals in need. However, the acceptability of screening for psychosis in this setting as part of routine care is currently unknown. METHODS: We conducted a qualitative interview study with providers and service users who participated in an early psychosis screening program conducted in an integrated behavioral health primary care (IBH-PC) setting. Interviews were recruited from one of eight WellSpace Federally Qualified Health Center IBH-PC clinics in the Sacramento, CA area. Transcripts of the recorded interviews were analyzed using thematic analysis. RESULTS: In total, 12 providers and eight service users participated in the interviews. Most service user and provider participants were supportive of psychosis screening in an IBH-PC setting, but not as part of the general practitioner consultation due to the brief, non-behavioral health nature of many of the appointments, and the expected low prevalence of psychosis in this population. The support of leadership, adequate training and support, staff turnover, and organizational changes were all seen to impact the successful implementation of the program. Different barriers and facilitators were considered important at each stage of the process from introducing the screening procedures to service users; to determining when, where, and how to screen; and how to effectively manage the referral and post-referral stages. CONCLUSIONS: Despite the additional challenges of screening in an IBH-PC setting relative to secondary mental health services, the process was considered acceptable and feasible to providers and service users. Services that plan to conduct psychosis screening in their clinics need to consider the challenges and their potential solutions to implementation at each stage of the screening process.

Evidence for functional improvement in reward anticipation in recent onset schizophrenia after one year of coordinated specialty care.

BACKGROUND: Motivational impairment associated with deficits in processing the anticipation of future reward is hypothesized to be a cardinal feature of schizophrenia spectrum disorders (SZ). Evidence from short-term follow-up (6-week post-treatment) studies suggests that these deficits may improve or be reversed with treatment, although longer-term outcomes are unknown. Here we examined the one-year trajectory of functional activation in brain circuitry associated with reward anticipation in people with recent onset SZ who participated in coordinated specialty care (CSC) treatment, hypothesizing normalization of brain response mirroring previous short-term findings in first-episode individuals. METHOD: Blood oxygen level-dependent (BOLD) response in the dorsal anterior cingulate cortex, anterior insula, and ventral striatum (VS) associated with reward anticipation during the Incentivized Control Engagement Task (ICE-T) was analyzed in a baseline sample of 49 healthy controls (HCs) and 52 demographically matched people with SZ, with follow-up data available for 35 HCs and 17 people with SZ. RESULTS: In agreement with our hypothesis, significant time × diagnosis interactions were observed across all regions, in which reward anticipation-associated BOLD response increased in SZ to above baseline HC levels at follow-up. Increased VS activation was associated with decreased reality distortion symptoms over the follow-up period. Baseline reward anticipation-associated BOLD response in the right anterior insula was associated with improvement in reality distortion symptoms. CONCLUSIONS: These findings suggest that functional deficits in reward anticipation may be reversed after one year of CSC in recent onset participants with SZ, and that this improvement is associated with reduced positive symptoms in the illness.

Extracellular free water and glutathione in first-episode psychosis-a multimodal investigation of an inflammatory model for psychosis.

Evidence has been accumulating for an immune-based component to the etiology of psychotic disorders. Advancements in diffusion magnetic resonance imaging (MRI) have enabled estimation of extracellular free water (FW), a putative biomarker of neuroinflammation. Furthermore, inflammatory processes may be associated with altered brain levels of metabolites, such as glutathione (GSH). Consequently, we sought to test the hypotheses that FW is increased and associated with decreased GSH in patients with first-episode schizophrenia (SZ) compared with healthy controls (HC). SZ (n = 36) and HC (n = 40) subjects underwent a multi-shell diffusion MRI scan on a Siemens 3T scanner. 1H-MR spectroscopy data were acquired using a GSH-optimized MEGA-PRESS editing sequence and GSH/creatine ratios were calculated for DLPFC (SZ: n = 33, HC: n = 37) and visual cortex (SZ: n = 29, HC: n = 35) voxels. Symptoms and functioning were measured using the SANS, SAPS, BPRS, and GSF/GRF. SZ demonstrated significantly elevated FW in whole-brain gray (p = .001) but not white matter (p = .060). There was no significant difference between groups in GSH in either voxel. However, there was a significant negative correlation between DLPFC GSH and both whole-brain and DLPFC-specific gray matter FW in SZ (r = -.48 and -.47, respectively; both p < .05), while this relationship was nonsignificant in HC and in both groups in the visual cortex. These data illustrate an important relationship between a metabolite known to be important for immune function-GSH-and the diffusion extracellular FW measure, which provides additional support for these measures as neuroinflammatory biomarkers that could potentially provide tractable treatment targets to guide pharmacological intervention.

Task-specific Disruptions in Theta Oscillations during Working Memory for Temporal Order in People with Schizophrenia.

Prior studies demonstrated that neural oscillations are enhanced during working memory (WM) maintenance and that this activity can predict behavioral performance in healthy individuals. However, it is unclear whether the relationship holds for people with WM deficits. People with schizophrenia have marked WM deficits, and such deficits are most prominent when patients are required to process relationships between items, such as temporal order. Here, we used EEG to compare the relationship between oscillatory activity and WM performance in patients and controls. EEG was recorded as participants performed tasks requiring maintenance of complex objects ("Item") or the temporal order of objects ("Order"). In addition to testing for group differences, we examined individual differences in EEG power and WM performance across groups. Behavioral results demonstrated that patients showed impaired performance on both Item and Order trials. EEG analyses revealed that patients showed an overall reduction in alpha power, but the relationship between alpha activity and performance was preserved. In contrast, patients showed a reduction in theta power specific to Order trials, and theta power could predict performance on Order trials in controls, but not in patients. These findings demonstrate that WM impairments in patients may reflect two different processes: a general deficit in alpha oscillations and a specific deficit in theta oscillations when temporal order information must be maintained. At a broader level, the results highlight the value of characterizing brain-behavior relationships, by demonstrating that the relationship between neural oscillations and WM performance can be fundamentally disrupted in those with WM deficits.

Predicting psychosis risk using a specific measure of cognitive control: a 12-month longitudinal study.

BACKGROUND: Identifying risk factors of individuals in a clinical-high-risk state for psychosis are vital to prevention and early intervention efforts. Among prodromal abnormalities, cognitive functioning has shown intermediate levels of impairment in CHR relative to first-episode psychosis and healthy controls, highlighting a potential role as a risk factor for transition to psychosis and other negative clinical outcomes. The current study used the AX-CPT, a brief 15-min computerized task, to determine whether cognitive control impairments in CHR at baseline could predict clinical status at 12-month follow-up. METHODS: Baseline AX-CPT data were obtained from 117 CHR individuals participating in two studies, the Early Detection, Intervention, and Prevention of Psychosis Program (EDIPPP) and the Understanding Early Psychosis Programs (EP) and used to predict clinical status at 12-month follow-up. At 12 months, 19 individuals converted to a first episode of psychosis (CHR-C), 52 remitted (CHR-R), and 46 had persistent sub-threshold symptoms (CHR-P). Binary logistic regression and multinomial logistic regression were used to test prediction models. RESULTS: Baseline AX-CPT performance (d-prime context) was less impaired in CHR-R compared to CHR-P and CHR-C patient groups. AX-CPT predictive validity was robust (0.723) for discriminating converters v. non-converters, and even greater (0.771) when predicting CHR three subgroups. CONCLUSIONS: These longitudinal outcome data indicate that cognitive control deficits as measured by AX-CPT d-prime context are a strong predictor of clinical outcome in CHR individuals. The AX-CPT is brief, easily implemented and cost-effective measure that may be valuable for large-scale prediction efforts.

Neural and behavioral measures suggest that cognitive and affective functioning interactions mediate risk for psychosis-proneness symptoms in youth with chromosome 22q11.2 deletion syndrome.

Behavioral components of chromosome 22q11.2 deletion syndrome (22q), caused by the most common human microdeletion, include cognitive and adaptive functioning impairments, heightened anxiety, and an elevated risk of schizophrenia. We investigated how interactions between executive function and the largely overlooked factor of emotion regulation might relate to the incidence of symptoms of psychotic thinking in youth with 22q. We measured neural activity with event-related potentials (ERPs) in variants of an inhibitory function (Go/No-Go) experimental paradigm that presented affective or non-affective stimuli. The study replicated inhibition impairments in the 22q group that were amplified in the presence of stimuli with negative, more than positive affective salience. Importantly, the anterior N2 conflict monitoring ERP significantly increased when youth with 22q viewed angry and happy facial expressions, unlike the typically developing participants. This suggests that youth with 22q may require greater conflict monitoring resources when controlling their behavior in response to highly salient social signals. This evidence of both behavioral and neurophysiological differences in affectively influenced inhibitory function suggests that frequently anxious youth with 22q may struggle more with cognitive control in emotionally charged social settings, which could influence their risk of developing symptoms of psychosis.

Conflict-Related Anterior Cingulate Functional Connectivity Is Associated With Past Suicidal Ideation and Behavior in Recent-Onset Psychotic Major Mood Disorders.

Suicidal ideation and behavior are highly prevalent in psychotic major mood disorders, yet their relationship to brain function remains unclear. Thirty patients with recent-onset of bipolar disorder type I (N=21) or major depressive disorder (N=9) with past psychosis were evaluated for past suicidal ideation/behavior and functional MRI during conflict-monitoring. Suicidal ideation was related to relatively higher dorsal anterior cingulate cortex (dACC)-seeded functional connectivity with dorsal fronto-parietal and inferior temporal-occipital cortex, as well as lower dACC connectivity with bilateral ventrolateral prefrontal cortex (PFC) and adjacent fronto-striatal regions. Past suicidal behavior was associated with lower dACC functional connectivity with dorsolateral PFC and premotor cortex, as well as temporal-parietal cortex.

Examining the Most Important Risk Factors for Predicting Youth Persistent and Distressing Psychotic-Like Experiences.

BACKGROUND: Persistence and distress distinguish more clinically significant psychotic-like experiences (PLEs) from those that are less likely to be associated with impairment and/or need for care. Identifying risk factors that identify clinically relevant PLEs early in development is important for improving our understanding of the etiopathogenesis of these experiences. Machine learning analyses were used to examine the most important baseline factors distinguishing persistent distressing PLEs. METHODS: Using Adolescent Brain Cognitive Development (ABCD) Study data on PLEs from 3 time points (ages 9-13 years), we created the following groups: individuals with persistent distressing PLEs (n = 305), individuals with transient distressing PLEs (n = 374), and individuals with low-level PLEs demographically matched to either the persistent distressing PLEs group (n = 305) or the transient distressing PLEs group (n = 374). Random forest classification models were trained to distinguish persistent distressing PLEs from low-level PLEs, transient distressing PLEs from low-level PLEs, and persistent distressing PLEs from transient distressing PLEs. Models were trained using identified baseline predictors as input features (i.e., cognitive, neural [cortical thickness, resting-state functional connectivity], developmental milestone delays, internalizing symptoms, adverse childhood experiences). RESULTS: The model distinguishing persistent distressing PLEs from low-level PLEs showed the highest accuracy (test sample accuracy = 69.33%; 95% CI, 61.29%-76.59%). The most important predictors included internalizing symptoms, adverse childhood experiences, and cognitive functioning. Models for distinguishing persistent PLEs from transient distressing PLEs generally performed poorly. CONCLUSIONS: Model performance metrics indicated that while most important factors overlapped across models (e.g., internalizing symptoms), adverse childhood experiences were especially important for predicting persistent distressing PLEs. Machine learning analyses proved useful for distinguishing the most clinically relevant group from the least clinically relevant group but showed limited ability to distinguish among clinically relevant groups that differed in PLE persistence.

Using Task-fMRI to Explore the Relationship Between Lifetime Cannabis Use and Cognitive Control in Individuals With First-Episode Schizophrenia.

While continued cannabis use and misuse in individuals with schizophrenia is associated with a variety of negative outcomes, individuals with a history of use tend to show higher cognitive performance compared to non-users. While this is replicated in the literature, few studies have used task-based functional magnetic resonance imaging (fMRI) to evaluate whether the brain networks underpinning these cognitive features are similarly impacted. Forty-eight first-episode individuals with schizophrenia (FES) with a history of cannabis use (FES + CAN), 28 FES individuals with no history of cannabis use (FES-CAN), and 59 controls (CON) performed the AX-Continuous Performance Task during fMRI. FES+CAN showed higher cognitive control performance (d'-context) compared to FES-CAN (P < .05, ηp 2 = 0.053), and both FES+CAN (P < .05, ηp 2 = 0.049) and FES-CAN (P < .001, ηp 2 = 0.216) showed lower performance compared to CON. FES+CAN (P < .05, ηp 2 = 0.055) and CON (P < 0.05, ηp 2 = 0.058) showed higher dorsolateral prefrontal cortex (DLPFC) activation during the task compared to FES-CAN, while FES+CAN and CON were not significantly different. Within the FES+CAN group, the younger age of initiation of cannabis use was associated with lower IQ and lower global functioning. More frequent use was also associated with higher reality distortion symptoms at the time of the scan. These data are consistent with previous literature suggesting that individuals with schizophrenia and a history of cannabis use have higher cognitive control performance. For the first time, we also reveal that FES+CAN have higher DLPFC brain activity during cognitive control compared to FES-CAN. Several possible explanations for these findings are discussed.

Reimbursement for a Broader Array of Services in Coordinated Specialty Care for Early Psychosis.

Despite the growing evidence supporting the benefits of coordinated specialty care (CSC) for early psychosis, access to this multimodal, evidence-based program in the United States has been hindered by a lack of funding for core CSC services and activities. The recent approval of team-based reimbursement codes by the Centers for Medicare and Medicaid Services has the potential to fund substantially more CSC services for clients with insurance coverage that accepts the new team-based billing codes. This streamlined and more inclusive billing strategy may reduce administrative burden and support the financial viability of CSC programs.

Exploring Data Collection Priorities of Community Partners in Early Psychosis Care.

OBJECTIVE: Learning health care networks can significantly improve the effectiveness, consistency, and cost-effectiveness of care delivery. As part of a data harmonization process, incorporation of the perspectives of community partners to maximize the relevance and utility of the data is critical. METHODS: A mixed-methods focus group study was conducted with early psychosis program providers, leadership, service users, and family members to explore their priorities regarding data collection in early psychosis care. Focus group transcripts were analyzed through thematic analysis. RESULTS: Twenty-two focus groups comprising 178 participants were conducted across 10 early psychosis programs. Participants considered functioning, quality of life, recovery, and symptoms of psychosis as key outcomes to assess, although variation by participants' roles was also evident. Participants emphasized the clinical utility of assessing a broad range of predictors of care outcomes, favored a broad conceptualization of the constructs assessed, and indicated a preference for client-reported measures. Participants also emphasized the importance of surveys adopting a recovery-oriented, strengths-based approach. CONCLUSIONS: Large-scale aggregation of health care data collected as part of routine care offers opportunities for research and may have a positive impact on care delivery and quality improvement activities. However, these benefits are contingent on the data being both relevant and accessible to those who deliver and receive such care. This study highlights an approach that may inform the development of core assessment batteries used, optimizing the utility of such data for all community partners.

The diagnostic accuracy of screening for psychosis spectrum disorders in behavioral health clinics integrated into primary care.

Screening for psychosis spectrum disorders in primary care could improve early identification and reduce the duration of untreated psychosis. However, the accuracy of psychosis screening in this setting is unknown. To address this, we conducted a diagnostic accuracy study of screening for psychosis spectrum disorders in eight behavioral health services integrated into primary care clinics. Patients attending an integrated behavioral health appointment at their primary care clinic completed the Prodromal Questionnaire - Brief (PQ-B) immediately prior to their intake assessment. This was compared to a diagnostic phone interview based on the Structured Interview for Psychosis Risk Syndromes (SIPS). In total, 145 participants completed all study procedures, of which 100 screened positive and 45 negative at a provisional PQ-B threshold of ≥20. The PQ-B was moderately accurate at differentiating psychosis spectrum from no psychosis spectrum disorders; a PQ-B distress score of ≥27 had a sensitivity and specificity of 71.2 % and 57.0 % respectively. In total, 66 individuals (45.5 %) met criteria for a psychosis spectrum disorder and 24 (16.7 %) were diagnosed with full psychosis, indicating a high prevalence of psychosis in the sample. Overall, screening for psychosis spectrum disorders in an IBH primary care setting identified a relatively high number of individuals and may identify people that would otherwise be missed. The PQ-B performed slightly less well than in population-based screening in community mental health settings. However, the findings suggest this may represent an effective way to streamline the pathway between specialty early psychosis programs and primary care clinics for those in need.

Ethnoracial Risk Variation Across the Psychosis Continuum in the US: A Systematic Review and Meta-Analysis.

Importance: Studies suggest a higher risk of schizophrenia diagnoses in Black vs White Americans, yet a systematic investigation of disparities that include other ethnoracial groups and multiple outcomes on the psychosis continuum is lacking. Objective: To identify ethnoracial risk variation in the US across 3 psychosis continuum outcomes (ie, schizophrenia and other psychotic disorders, clinical high risk for psychosis [CHR-P], and psychotic symptoms [PSs] and psychotic experiences [PEs]). Data Sources: PubMed, PsycINFO and Embase were searched up to December 2022. Study Selection: Observational studies on ethnoracial differences in risk of 3 psychosis outcomes. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Using a random-effects model, estimates for ethnoracial differences in schizophrenia and PSs/PEs were pooled and moderation by sampling and setting was determined, along with the assessment of heterogeneity and risk of bias. Main Outcomes and Measures: Risk of schizophrenia and other psychotic disorder, CHR-P, and conversion to psychosis among CHR-P and PSs/PEs. Results: Of 64 studies in the systematic review, 47 were included in the meta-analysis comprising 54 929 people with schizophrenia and 223 097 with data on PSs/PEs. Compared with White individuals, Black individuals had increased risk of schizophrenia (pooled odds ratio [OR], 2.07; 95% CI, 1.64-2.61) and PSs/PEs (pooled standardized mean difference [SMD], 0.10; 95% CI, 0.03-0.16), Latinx individuals had higher risk of PSs/PEs (pooled SMD, 0.15; 95% CI, 0.08-0.22), and individuals classified as other ethnoracial group were at significantly higher risk of schizophrenia than White individuals (pooled OR, 1.81; 95% CI, 1.31-2.50). The results regarding CHR-P studies were mixed and inconsistent. Sensitivity analyses showed elevated odds of schizophrenia in Asian individuals in inpatient settings (pooled OR, 1.84; 95% CI, 1.19-2.84) and increased risk of PEs among Asian compared with White individuals, specifically in college samples (pooled SMD, 0.16; 95% CI, 0.02-0.29). Heterogeneity across studies was high, and there was substantial risk of bias in most studies. Conclusions and Relevance: Findings of this systematic review and meta-analysis revealed widespread ethnoracial risk variation across multiple psychosis outcomes. In addition to diagnostic, measurement, and hospital bias, systemic influences such as structural racism should be considered as drivers of ethnoracial disparities in outcomes across the psychosis continuum in the US.

Psychosis Risk: Time to Look Empirically at a First-step Economical-pragmatic Way to Examine Anomalous Self-experience. Exploring the SQuEASE-11.

BACKGROUND: Since the late 1990s, there has been a worldwide surge of scientific interest in the pre-psychotic phase, resulting in the introduction of several clinical tools for early detection. The predictive accuracy of these tools has been limited, motivating the need for methodological and perspectival improvements. The EASE manual supports systematic assessment of anomalous self-experience, and proposes an overall model of understanding how most psychotic experiences may be initially generated on the basis of a unifying, fundamental, pre-reflective distortion of subjectivity. STUDY DESIGN: The EASE is time-consuming, so in order to spread the use of this essential perspective of psychosis risk we selected prototypical and frequent phenomena from the EASE, combining them into SQuEASE-11. To investigate this instrument for clinical relevance, basic psychometric properties, factor structure, and relationships with gold standard instruments and the full EASE, it was administered as an interview in the STEP intervention trial (Melbourne, Australia), with 328 clinical high-risk for psychosis (CHR-P) patients. STUDY RESULTS: The SQuEASE-11 had moderate internal consistency and revealed two correlated factors. Significant relationships were observed between the SQuEASE-11 and the widely used and validated instruments CAARMS, BPRS, SANS, MADRS, DACOBS, and SOFAS. The correlation with the full EASE was very strong. CONCLUSIONS: These 11 items do not necessarily relate specifically to ipseity disturbance, but the SQuEASE-11 seems to be a clinically relevant and brief supplementary first-line interview in CHR-P subjects. It may give a qualified indication of the need for a complete EASE interview, and it may also, importantly, inform treatment planning.

Incorporating Community Partner Perspectives on eHealth Technology Data Sharing Practices for the California Early Psychosis Intervention Network: Qualitative Focus Group Study With a User-Centered Design Approach.

BACKGROUND: Increased use of eHealth technology and user data to drive early identification and intervention algorithms in early psychosis (EP) necessitates the implementation of ethical data use practices to increase user acceptability and trust. OBJECTIVE: First, the study explored EP community partner perspectives on data sharing best practices, including beliefs, attitudes, and preferences for ethical data sharing and how best to present end-user license agreements (EULAs). Second, we present a test case of adopting a user-centered design approach to develop a EULA protocol consistent with community partner perspectives and priorities. METHODS: We conducted an exploratory, qualitative, and focus group-based study exploring mental health data sharing and privacy preferences among individuals involved in delivering or receiving EP care within the California Early Psychosis Intervention Network. Key themes were identified through a content analysis of focus group transcripts. Additionally, we conducted workshops using a user-centered design approach to develop a EULA that addresses participant priorities. RESULTS: In total, 24 participants took part in the study (14 EP providers, 6 clients, and 4 family members). Participants reported being receptive to data sharing despite being acutely aware of widespread third-party sharing across digital domains, the risk of breaches, and motives hidden in the legal language of EULAs. Consequently, they reported feeling a loss of control and a lack of protection over their data. Participants indicated these concerns could be mitigated through user-level control for data sharing with third parties and an understandable, transparent EULA, including multiple presentation modalities, text at no more than an eighth-grade reading level, and a clear definition of key terms. These findings were successfully integrated into the development of a EULA and data opt-in process that resulted in 88.1% (421/478) of clients who reviewed the video agreeing to share data. CONCLUSIONS: Many of the factors considered pertinent to informing data sharing practices in a mental health setting are consistent among clients, family members, and providers delivering or receiving EP care. These community partners' priorities can be successfully incorporated into developing EULA practices that can lead to high voluntary data sharing rates.

Cortical and subcortical brain morphometry abnormalities in youth at clinical high-risk for psychosis and individuals with early illness schizophrenia.

Neuroimaging studies have documented morphometric brain abnormalities in schizophrenia, but less is known about them in individuals at clinical high-risk for psychosis (CHR-P), including how they compare with those observed in early schizophrenia (ESZ). Accordingly, we implemented multivariate profile analysis of regional morphometric profiles in CHR-P (n = 89), ESZ (n = 93) and healthy controls (HC; n = 122). ESZ profiles differed from HC and CHR-P profiles, including 1) cortical thickness: significant level reduction and regional non-parallelism reflecting widespread thinning, except for entorhinal and pericalcarine cortex, 2) basal ganglia volume: significant level increase and regional non-parallelism reflecting larger caudate and pallidum, and 3) ventricular volume: significant level increase with parallel regional profiles. CHR-P and ESZ cerebellar profiles showed significant non-parallelism with HC profiles. Regional profiles did not significantly differ between groups for cortical surface area or subcortical volume. Compared to CHR-P followed for ≥18 months without psychosis conversion (n = 31), CHR-P converters (n = 17) showed significant non-parallel ventricular volume expansion reflecting specific enlargement of lateral and inferolateral regions. Antipsychotic dosage in ESZ was significantly correlated with frontal cortical thinning. Results suggest that morphometric abnormalities in ESZ are not present in CHR-P, except for ventricular enlargement, which was evident in CHR-P who developed psychosis.

Youth Mental Health Screening and Linkage to Care.

One Mind, in partnership with Meadows Mental Health Policy Institute, convened several virtual meetings of mental health researchers, clinicians, and other stakeholders in 2020 to identify first steps toward creating an initiative for early screening and linkage to care for youths (individuals in early adolescence through early adulthood, ages 10-24 years) with mental health difficulties, including serious mental illness, in the United States. This article synthesizes and builds on discussions from those meetings by outlining and recommending potential steps and considerations for the development and integration of a novel measurement-based screening process in youth-facing school and medical settings to increase early identification of mental health needs and linkage to evidence-based care. Meeting attendees agreed on an initiative incorporating a staged assessment process that includes a first-stage brief screener for several domains of psychopathology. Individuals who meet threshold criteria on the first-stage screener would then complete an interview, a second-stage in-depth screening, or both. Screening must be followed by recommendations and linkage to an appropriate level of evidence-based care based on acuity of symptoms endorsed during the staged assessment. Meeting attendees proposed steps and discussed additional considerations for creating the first nationwide initiative for screening and linkage to care, an initiative that could transform access of youths to mental health screening and care.

Effect of Technology-Enhanced Screening in Addition to Standard Targeted Clinician Education on the Duration of Untreated Psychosis: A Cluster Randomized Clinical Trial.

Importance: Reducing the duration of untreated psychosis (DUP) is essential to improving outcomes for people with first-episode psychosis (FEP). Current US approaches are insufficient to reduce DUP to international standards of less than 90 days. Objective: To determine whether population-based electronic screening in addition to standard targeted clinician education increases early detection of psychosis and decreases DUP, compared with clinician education alone. Design, Setting, and Participants: This cluster randomized clinical trial included individuals aged 12 to 30 years presenting for services between March 2015 and September 2017 at participating sites that included community mental health clinics and school support and special education services. Eligible participants were referred to the Early Diagnosis and Preventative Treatment (EDAPT) Clinic. Data analyses were performed in September and October 2019 for the primary and secondary analyses, with the exploratory subgroup analyses completed in May 2021. Interventions: All sites in both groups received targeted education about early psychosis for health care professionals. In the active screening group, clients also completed the Prodromal Questionnaire-Brief using tablets at intake; referrals were based on those scores and clinical judgment. In the group receiving treatment as usual (TAU), referrals were based on clinical judgment alone. Main Outcomes and Measures: Primary outcomes included DUP, defined as the period from full psychosis onset to the date of the EDAPT diagnostic telephone interview, and the number of individuals identified with FEP or a psychosis spectrum disorder. Exploratory analyses examined differences by site type, completion rates between conditions, and days from service entry to telephone interview. Results: Twenty-four sites agreed to participate, and 12 sites were randomized to either the active screening or TAU group. However, only 10 community clinics and 4 school sites were able to fully implement population screening and were included in the final analysis. The total potentially eligible population size within each study group was similar, with 2432 individuals entering at active screening group sites and 2455 at TAU group sites. A total of 303 diagnostic telephone interviews were completed (178 [58.7%] female individuals; mean [SD] age, 17.09 years [4.57]). Active screening sites reported a significantly higher detection rate of psychosis spectrum disorders (136 cases [5.6%], relative to 65 [2.6%]; P < .001) and referred a higher proportion of individuals with FEP and DUP less than 90 days (13 cases, relative to 4; odds ratio, 0.30; 95% CI, 0.10-0.93; P = .03). There was no difference in mean (SD) DUP between groups (active screening group, 239.0 days [207.4]; TAU group 262.3 days [170.2]). Conclusions and Relevance: In this cluster trial, population-based technology-enhanced screening across community settings detected more than twice as many individuals with psychosis spectrum disorders compared with clinical judgment alone but did not reduce DUP. Screening could identify people undetected in US mental health services. Significant DUP reduction may require interventions to reduce time to the first mental health contact. Trial Registration: ClinicalTrials.gov Identifier: NCT02841956.

A Sequential Adaptive Intervention Strategy Targeting Remission and Functional Recovery in Young People at Ultrahigh Risk of Psychosis: The Staged Treatment in Early Psychosis (STEP) Sequential Multiple Assignment Randomized Trial.

Importance: Clinical trials have not established the optimal type, sequence, and duration of interventions for people at ultrahigh risk of psychosis. Objective: To determine the effectiveness of a sequential and adaptive intervention strategy for individuals at ultrahigh risk of psychosis. Design, Setting, and Participants: The Staged Treatment in Early Psychosis (STEP) sequential multiple assignment randomized trial took place within the clinical program at Orygen, Melbourne, Australia. Individuals aged 12 to 25 years who were seeking treatment and met criteria for ultrahigh risk of psychosis according to the Comprehensive Assessment of At-Risk Mental States were recruited between April 2016 and January 2019. Of 1343 individuals considered, 342 were recruited. Interventions: Step 1: 6 weeks of support and problem solving (SPS); step 2: 20 weeks of cognitive-behavioral case management (CBCM) vs SPS; and step 3: 26 weeks of CBCM with fluoxetine vs CBCM with placebo with an embedded fast-fail option of ω-3 fatty acids or low-dose antipsychotic medication. Individuals who did not remit progressed through these steps; those who remitted received SPS or monitoring for up to 12 months. Main Outcomes and Measures: Global Functioning: Social and Role scales (primary outcome), Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Montgomery-Åsberg Depression Rating Scale, quality of life, transition to psychosis, and remission and relapse rates. Results: The sample comprised 342 participants (198 female; mean [SD] age, 17.7 [3.1] years). Remission rates, reflecting sustained symptomatic and functional improvement, were 8.5%, 10.3%, and 11.4% at steps 1, 2, and 3, respectively. A total of 27.2% met remission criteria at any step. Relapse rates among those who remitted did not significantly differ between SPS and monitoring (step 1: 65.1% vs 58.3%; step 2: 37.7% vs 47.5%). There was no significant difference in functioning, symptoms, and transition rates between SPS and CBCM and between CBCM with fluoxetine and CBCM with placebo. Twelve-month transition rates to psychosis were 13.5% (entire sample), 3.3% (those who ever remitted), and 17.4% (those with no remission). Conclusions and Relevance: In this sequential multiple assignment randomized trial, transition rates to psychosis were moderate, and remission rates were lower than expected, partly reflecting the ambitious criteria set and challenges with real-world treatment fidelity and adherence. While all groups showed mild to moderate functional and symptomatic improvement, this was typically short of remission. While further adaptive trials that address these challenges are needed, findings confirm substantial and sustained morbidity and reveal relatively poor responsiveness to existing treatments. Trial Registration: ClinicalTrials.gov Identifier: NCT02751632.

Meta-analytic evidence for a superordinate cognitive control network subserving diverse executive functions.

Classic cognitive theory conceptualizes executive functions as involving multiple specific domains, including initiation, inhibition, working memory, flexibility, planning, and vigilance. Lesion and neuroimaging experiments over the past two decades have suggested that both common and unique processes contribute to executive functions during higher cognition. It has been suggested that a superordinate fronto-cingulo-parietal network supporting cognitive control may also underlie a range of distinct executive functions. To test this hypothesis in the largest sample to date, we used quantitative meta-analytic methods to analyze 193 functional neuroimaging studies of 2,832 healthy individuals, ages 18-60, in which performance on executive function measures was contrasted with an active control condition. A common pattern of activation was observed in the prefrontal, dorsal anterior cingulate, and parietal cortices across executive function domains, supporting the idea that executive functions are supported by a superordinate cognitive control network. However, domain-specific analyses showed some variation in the recruitment of anterior prefrontal cortex, anterior and midcingulate regions, and unique subcortical regions such as the basal ganglia and cerebellum. These results are consistent with the existence of a superordinate cognitive control network in the brain, involving dorsolateral prefrontal, anterior cingulate, and parietal cortices, that supports a broad range of executive functions.