Using brain structural neuroimaging measures to predict psychosis onset for individuals at clinical high-risk.

Machine learning approaches using structural magnetic resonance imaging (sMRI) can be informative for disease classification, although their ability to predict psychosis is largely unknown. We created a model with individuals at CHR who developed psychosis later (CHR-PS+) from healthy controls (HCs) that can differentiate each other. We also evaluated whether we could distinguish CHR-PS+ individuals from those who did not develop psychosis later (CHR-PS-) and those with uncertain follow-up status (CHR-UNK). T1-weighted structural brain MRI scans from 1165 individuals at CHR (CHR-PS+, n = 144; CHR-PS-, n = 793; and CHR-UNK, n = 228), and 1029 HCs, were obtained from 21 sites. We used ComBat to harmonize measures of subcortical volume, cortical thickness and surface area data and corrected for non-linear effects of age and sex using a general additive model. CHR-PS+ (n = 120) and HC (n = 799) data from 20 sites served as a training dataset, which we used to build a classifier. The remaining samples were used external validation datasets to evaluate classifier performance (test, independent confirmatory, and independent group [CHR-PS- and CHR-UNK] datasets). The accuracy of the classifier on the training and independent confirmatory datasets was 85% and 73% respectively. Regional cortical surface area measures-including those from the right superior frontal, right superior temporal, and bilateral insular cortices strongly contributed to classifying CHR-PS+ from HC. CHR-PS- and CHR-UNK individuals were more likely to be classified as HC compared to CHR-PS+ (classification rate to HC: CHR-PS+, 30%; CHR-PS-, 73%; CHR-UNK, 80%). We used multisite sMRI to train a classifier to predict psychosis onset in CHR individuals, and it showed promise predicting CHR-PS+ in an independent sample. The results suggest that when considering adolescent brain development, baseline MRI scans for CHR individuals may be helpful to identify their prognosis. Future prospective studies are required about whether the classifier could be actually helpful in the clinical settings.

Persistent and distressing psychotic-like experiences using adolescent brain cognitive development℠study data.

Childhood psychotic-like experiences (PLEs) are associated with a range of impairments; a subset of children experiencing PLEs will develop psychiatric disorders, including psychotic disorders. A potential distinguishing factor between benign PLEs versus PLEs that are clinically relevant is whether PLEs are distressing and/or persistent. The current study used three waves of Adolescent Brain Cognitive Development℠ (ABCD) study PLEs assessments to examine the extent to which persistent and/or distressing PLEs were associated with relevant baseline risk factors (e.g., cognition) and functioning/mental health service utilization domains. Four groups varying in PLE persistence and distress endorsement were created based on all available data in ABCD Release 3.0, with group membership not contingent on complete data: persistent distressing PLEs (n = 272), transient distressing PLEs (n = 298), persistent non-distressing PLEs (n = 221), and transient non-distressing PLEs (n = 536) groups. Using hierarchical linear models, results indicated youth with distressing PLEs, whether transient or persistent, showed delayed developmental milestones (ß = 0.074, 95%CI:0.013,0.134) and altered structural MRI metrics (ß = -0.0525, 95%CI:-0.100,-0.005). Importantly, distress interacted with PLEs persistence for the domains of functioning/mental health service utilization (ß = 0.079, 95%CI:0.016,0.141), other reported psychopathology (ß = 0.101, 95%CI:0.030,0.170), cognition (ß = -0.052, 95%CI:0.-0.099,-0.002), and environmental adversity (ß = 0.045, 95%CI:0.003,0.0.86; although no family history effects), with the interaction characterized by greatest impairment in the persistent distressing PLEs group. These results have implications for disentangling the importance of distress and persistence for PLEs with regards to impairments, including functional, pathophysiological, and environmental outcomes. These novel longitudinal data underscore that it is often only in the context of distress that persistent PLEs were related to impairments.

Validation of ketamine as a pharmacological model of thalamic dysconnectivity across the illness course of schizophrenia.

N-methyl-D-aspartate receptor (NMDAR) hypofunction is a leading pathophysiological model of schizophrenia. Resting-state functional magnetic resonance imaging (rsfMRI) studies demonstrate a thalamic dysconnectivity pattern in schizophrenia involving excessive connectivity with sensory regions and deficient connectivity with frontal, cerebellar, and thalamic regions. The NMDAR antagonist ketamine, when administered at sub-anesthetic doses to healthy volunteers, induces transient schizophrenia-like symptoms and alters rsfMRI thalamic connectivity. However, the extent to which ketamine-induced thalamic dysconnectivity resembles schizophrenia thalamic dysconnectivity has not been directly tested. The current double-blind, placebo-controlled study derived an NMDAR hypofunction model of thalamic dysconnectivity from healthy volunteers undergoing ketamine infusions during rsfMRI. To assess whether ketamine-induced thalamic dysconnectivity was mediated by excess glutamate release, we tested whether pre-treatment with lamotrigine, a glutamate release inhibitor, attenuated ketamine's effects. Ketamine produced robust thalamo-cortical hyper-connectivity with sensory and motor regions that was not reduced by lamotrigine pre-treatment. To test whether the ketamine thalamic dysconnectivity pattern resembled the schizophrenia pattern, a whole-brain template representing ketamine's thalamic dysconnectivity effect was correlated with individual participant rsfMRI thalamic dysconnectivity maps, generating "ketamine similarity coefficients" for people with chronic (SZ) and early illness (ESZ) schizophrenia, individuals at clinical high-risk for psychosis (CHR-P), and healthy controls (HC). Similarity coefficients were higher in SZ and ESZ than in HC, with CHR-P showing an intermediate trend. Higher ketamine similarity coefficients correlated with greater hallucination severity in SZ. Thus, NMDAR hypofunction, modeled with ketamine, reproduces the thalamic hyper-connectivity observed in schizophrenia across its illness course, including the CHR-P period preceding psychosis onset, and may contribute to hallucination severity.

Thalamic dysconnectivity in the psychosis risk syndrome and early illness schizophrenia.

BACKGROUND: Schizophrenia (SZ) is associated with thalamic dysconnectivity. Compared to healthy controls (HCs), individuals with SZ have hyperconnectivity with sensory regions, and hypoconnectivity with cerebellar, thalamic, and prefrontal regions. Despite replication of this pattern in chronically ill individuals, less is known about when these abnormalities emerge in the illness course and if they are present prior to illness onset. METHODS: Resting-state functional magnetic resonance imaging data were collected from psychosis risk syndrome (PRS) youth (n = 45), early illness SZ (ESZ) (n = 74) patients, and HCs (n = 85). Age-adjusted functional connectivity, seeded from the thalamus, was compared among the groups. RESULTS: Significant effects of group were observed in left and right middle temporal regions, left and right superior temporal regions, left cerebellum, and bilateral thalamus. Compared to HCs, ESZ demonstrated hyperconnectivity to all temporal lobe regions and reduced connectivity with cerebellar, anterior cingulate, and thalamic regions. Compared to HCs, PRS demonstrated hyperconnectivity with the left and right middle temporal regions, and hypoconnectivity with the cerebellar and other thalamic regions. Compared to PRS participants, ESZ participants were hyperconnected to temporal regions, but did not differ from PRS in hypoconnectivity with cerebellar and thalamic regions. Thalamic dysconnectivity was unrelated to positive symptom severity in ESZ or PRS groups. CONCLUSIONS: PRS individuals demonstrated an intermediate level of thalamic dysconnectivity, whereas ESZ showed a pattern consistent with prior observations in chronic samples. These cross-sectional findings suggest that thalamic dysconnectivity may occur prior to illness onset and become more pronounced in early illness stages.

Deficient auditory predictive coding during vocalization in the psychosis risk syndrome and in early illness schizophrenia: the final expanded sample.

BACKGROUND: During vocalization, efference copy/corollary discharge mechanisms suppress the auditory cortical response to self-generated sounds. Previously, we found attenuated vocalization-related auditory cortical suppression in psychosis and a similar trend in the psychosis risk syndrome. Here, we report data from the final sample of early illness schizophrenia patients (ESZ), individuals at clinical high risk for psychosis (CHR), and healthy controls (HC). METHODS: Event-related potentials (ERP) were recorded from ESZ (n = 84), CHR (n = 71), and HC (n = 103) participants during a vocalization paradigm. The N1 ERP component was elicited during production (Talk) and playback (Listen) of vocalization. Age effects on N1 suppression (Talk-Listen), Talk N1, and Listen N1 were compared across groups. N1 measures were adjusted for normal aging before testing for group differences. RESULTS: Both ESZ and CHR groups showed reduced Talk-Listen N1 suppression relative to HC, but did not differ from each other. Listen N1 was reduced in ESZ, but not in CHR, relative to HC. Deficient Talk-Listen N1 suppression was associated with greater unusual thought content in CHR individuals. N1 suppression increased with age in HC (12-36 years), and while CHR individuals showed a similar age-related increase, no such relationship was evident in ESZ. CONCLUSIONS: Putative efference copy/corollary discharge-mediated auditory cortical suppression during vocalization is deficient in ESZ and precedes psychosis onset, particularly in CHR individuals with greater unusual thought content. Furthermore, this suppression increases from adolescence through early adulthood, likely reflecting the effects of normal brain maturation. This maturation effect is disrupted in ESZ, presumably due to countervailing illness effects.

Dynamic functional connectivity impairments in early schizophrenia and clinical high-risk for psychosis.

Individuals at clinical high-risk (CHR) for psychosis are characterized by attenuated psychotic symptoms. Only a minority of CHR individuals convert to full-blown psychosis. Therefore, there is a strong interest in identifying neurobiological abnormalities underlying the psychosis risk syndrome. Dynamic functional connectivity (DFC) captures time-varying connectivity over short time scales, and has the potential to reveal complex brain functional organization. Based on resting-state functional magnetic resonance imaging (fMRI) data from 70 healthy controls (HCs), 53 CHR individuals, and 58 early illness schizophrenia (ESZ) patients, we applied a novel group information guided ICA (GIG-ICA) to estimate inherent connectivity states from DFC, and then investigated group differences. We found that ESZ patients showed more aberrant connectivities and greater alterations than CHR individuals. Results also suggested that disease-related connectivity states occurred in CHR and ESZ groups. Regarding the dominant state with the highest contribution to dynamic connectivity, ESZ patients exhibited greater impairments than CHR individuals primarily in the cerebellum, frontal cortex, thalamus and temporal cortex, while CHR and ESZ populations shared common aberrances mainly in the supplementary motor area, parahippocampal gyrus and postcentral cortex. CHR-specific changes were also found in the connections between the superior frontal gyrus and calcarine cortex in the dominant state. Our findings suggest that CHR individuals generally show an intermediate functional connectivity pattern between HCs and SZ patients but also have unique connectivity alterations.

Adjustment of Regional Cortical Thickness Measures for Global Cortical Thickness Obscures Deficits Across the Schizophrenia Spectrum: A Cautionary Note about Normative Modeling of Brain Imaging Data.

Recent neuroimaging studies and publicly-disseminated analytic tools advocate that regional morphometric analyses covary for global thickness. We empirically demonstrate that this statistical approach severely underestimates regional thickness dysmorphology in psychiatric disorders. Study 1 included 90 healthy controls, 51 clinical high-risk for psychosis, and 78 early illness schizophrenia participants. Study 2 included 56 healthy controls, 83 non-affective psychosis, and 30 affective psychosis participants. We examined global and regional thickness correlations, global thickness group differences, and regional thickness group differences with/without global thickness covariation. Global and regional thickness were strongly correlated across groups. Global thickness was lower in schizophrenia-spectrum groups versus other groups. Regional thickness deficits in schizophrenia-spectrum groups were attenuated/eliminated with global thickness covariation. Depriving regional thickness of its shared variance with global thickness removes disease-related effects. This statistical method results in erroneous conclusions that regional thickness is normal in disorders like schizophrenia or clinical high-risk syndrome.

Brain Age Gap in Early Illness Schizophrenia and the Clinical High-Risk Syndrome: Associations With Experiential Negative Symptoms and Conversion to Psychosis.

BACKGROUND AND HYPOTHESIS: Brain development/aging is not uniform across individuals,spawning efforts to characterize brain age from a biological perspective to model the effects of disease and maladaptive life processes on the brain. The brain age gap represents the discrepancy between estimated brain biological age and chronological age (in this case, based on structural magnetic resonance imaging, MRI). Structural MRI studies report an increased brain age gap (biological age > chronological age) in schizophrenia, with a greater brain age gap related to greater negative symptom severity. Less is known regarding the nature of this gap early in schizophrenia (ESZ), if this gap represents a psychosis conversion biomarker in clinical high-risk (CHR-P) individuals, and how altered brain development and/or agingmap onto specific symptom facets. STUDY DESIGN: Using structural MRI, we compared the brain age gap among CHR-P (n = 51), ESZ (n = 78), and unaffected comparison participants (UCP; n = 90), and examined associations with CHR-P psychosis conversion (CHR-P converters n = 10; CHR-P non-converters; n = 23) and positive and negative symptoms. STUDY RESULTS: ESZ showed a greater brain age gap relative to UCP and CHR-P (Ps < .010). CHR-P individuals who converted to psychosis showed a greater brain age gap (P = .043) relative to CHR-P non-converters. A larger brain age gap in ESZ was associated with increased experiential (P = .008), but not expressive negative symptom severity. CONCLUSIONS: Consistent with schizophrenia pathophysiological models positing abnormal brain maturation, results suggest abnormal brain development is present early in psychosis. An increased brain age gap may be especially relevant to motivational and functional deficits in schizophrenia.

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.

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.

Rich-club connectivity and structural connectome organization in youth at clinical high-risk for psychosis and individuals with early illness schizophrenia.

Brain dysconnectivity has been posited as a biological marker of schizophrenia. Emerging schizophrenia connectome research has focused on rich-club organization, a tendency for brain hubs to be highly-interconnected but disproportionately vulnerable to dysconnectivity. However, less is known about rich-club organization in individuals at clinical high-risk for psychosis (CHR-P) and how it compares with abnormalities early in schizophrenia (ESZ). Combining diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI), we examined rich-club and global network organization in CHR-P (n = 41) and ESZ (n = 70) relative to healthy controls (HC; n = 74) after accounting for normal aging. To characterize rich-club regions, we examined rich-club MRI morphometry (thickness, surface area). We also examined connectome metric associations with symptom severity, antipsychotic dosage, and in CHR-P specifically, transition to a full-blown psychotic disorder. ESZ had fewer connections among rich-club regions (ps < .024) relative to HC and CHR-P, with this reduction specific to the rich-club even after accounting for other connections in ESZ relative to HC (ps < .048). There was also cortical thinning of rich-club regions in ESZ (ps < .013). In contrast, there was no strong evidence of global network organization differences among the three groups. Although connectome abnormalities were not present in CHR-P overall, CHR-P converters to psychosis (n = 9) had fewer connections among rich-club regions (ps < .037) and greater modularity (ps < .037) compared to CHR-P non-converters (n = 19). Lastly, symptom severity and antipsychotic dosage were not significantly associated with connectome metrics (ps < .012). Findings suggest that rich-club and connectome organization abnormalities are present early in schizophrenia and in CHR-P individuals who subsequently transition to 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.

Online Psychosis Screening: Characterizing an Underexamined Population to Improve Access and Equity.

OBJECTIVE: Online resources represent an important avenue to identify and support individuals who may be experiencing symptoms of psychosis but have yet to engage in care. Understanding the experiences and needs of this group is critical to inform outreach for early psychosis and improve outcomes by addressing barriers to early treatment. METHODS: The authors conducted a retrospective, explorative, cross-sectional analysis by using data collected by Mental Health America as part of their online psychosis screening and support program. Data included scores from the Prodromal Questionnaire-Brief, basic demographic information, and respondents' plans for next steps. RESULTS: Of 120,937 respondents, most (82.1%) reported distressing psychosis-like experiences at levels sufficient to merit a referral to specialty care for additional evaluation. However, only 17.1% planned to seek treatment as a next step, with most (53.6%) wanting instead more information. Higher distress was only weakly associated with the plan to seek treatment. In the multivariable analysis, respondents who were younger; lesbian, gay, bisexual, transgender, or queer; or Native American or who had lower income reported the greatest symptom-related distress. Younger and higher-income respondents were less likely to plan to seek treatment next. Across race-ethnicity, African Americans were most likely to plan to seek treatment. CONCLUSIONS: Most respondents reported that psychosis-like experiences caused significant distress, but they did not plan to seek treatment next. Addressing this treatment gap requires careful consideration regarding what services individuals want, how services should be presented, and what barriers may limit help seeking. These steps are critical to improve access to early intervention for individuals with psychosis spectrum disorders.

Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis.

Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.

Links Between Human and Animal Models of Trauma and Psychosis: A Narrative Review.

Traumatic experiences during development are associated with an increased risk of developing psychosis. Individuals with psychosis also report a higher rate of past trauma than healthy control subjects and worse outcomes than those who do not have these experiences. It is thought that traumatic experiences negatively impact specific neurobiological processes to confer this increased risk, and that systems affected by trauma are similarly changed in individuals with psychosis. Examining animal models of psychosis and the shared neurobiological changes in response to stressors can offer valuable insight into biological mechanisms that mediate symptoms and targets for intervention. This targeted review highlights a subset of models of psychosis across humans and animals, examines the similarities with the brain's response to stress and traumatic events, and discusses how these models may interact. Suggestions for future research are described.

Theta Phase Synchrony Is Sensitive to Corollary Discharge Abnormalities in Early Illness Schizophrenia but Not in the Psychosis Risk Syndrome.

BACKGROUND: Prior studies have shown that the auditory N1 event-related potential component elicited by self-generated vocalizations is reduced relative to played back vocalizations, putatively reflecting a corollary discharge mechanism. Schizophrenia patients and psychosis risk syndrome (PRS) youth show deficient N1 suppression during vocalization, consistent with corollary discharge dysfunction. Because N1 is an admixture of theta (4-7 Hz) power and phase synchrony, we examined their contributions to N1 suppression during vocalization, as well as their sensitivity, relative to N1, to corollary discharge dysfunction in schizophrenia and PRS individuals. METHODS: Theta phase and power values were extracted from electroencephalography data acquired from PRS youth (n = 71), early illness schizophrenia patients (ESZ; n = 84), and healthy controls (HCs; n = 103) as they said "ah" (Talk) and then listened to the playback of their vocalizations (Listen). A principal component analysis extracted theta intertrial coherence (ITC; phase consistency) and event-related spectral power, peaking in the N1 latency range. Talk-Listen suppression scores were analyzed. RESULTS: Talk-Listen suppression was greater for theta ITC (Cohen's d = 1.46) than for N1 in HC (d = 0.63). Both were deficient in ESZ, but only N1 suppression was deficient in PRS. When deprived of variance shared with theta ITC suppression, N1 suppression no longer differentiated ESZ and PRS individuals from HC. Deficits in theta ITC suppression were correlated with delusions (P = .007) in ESZ. Theta power suppression did not differentiate groups. CONCLUSIONS: Theta ITC-suppression during vocalization is a more sensitive index of corollary discharge-mediated auditory cortical suppression than N1 suppression and is more sensitive to corollary discharge dysfunction in ESZ than in PRS individuals.

Training early psychosis community clinicians in CBT for psychosis: Implementation and feasibility.

OBJECTIVE: Cognitive behavioural therapy (CBT) has demonstrated efficacy for treating of psychotic symptoms and is recommended as an evidence-based practice (EBP) in early psychosis services. Despite this recommendation, there is limited information about the feasibility of training community clinicians, working in an early psychosis service, to competence in the delivery of this intervention. METHOD: Fifty clinicians working in an early psychosis service across five programs in Northern California were trained in CBT for psychosis (CBTp) between 2010 and 2014. Following the training, clinicians attended weekly group consultation and submitted taped sessions for review. Tapes were rated for competency using the Cognitive Therapy Scale-Revised (CTS-R). Clinicians who achieved competence were engaged in a train-the-trainer model to support ongoing sustainability of the training program. RESULTS: Data from 40 clinicians were reviewed for achievement of competence. Over the training period 18 clinicians achieved competence while 20 clinicians left the service before achieving competence and 12 were still in the process of achieving competence at the point of data analysis. It took on average 54 weeks (range 17-130 weeks) and an average of six tape reviews (range 3-18) to train clinicians to competency. CONCLUSIONS: Community clinicians working in an early psychosis program can be trained to competence in CBTp following an initial didactic period and ongoing weekly group consultation, although staff turnover hindered implementation. Challenges and opportunities for future implementation in community sites are presented in the context of further expansion of early psychosis services in the United States.

Replication of Associations With Psychotic-Like Experiences in Middle Childhood From the Adolescent Brain Cognitive Development (ABCD) Study.

The fields of psychology and psychiatry are increasingly recognizing the importance of replication efforts. The current study aimed to replicate previous findings examining the construct validity and psychometric properties of a psychotic-like experiences (PLEs) measure in middle childhood using an independent subset of the baseline Adolescent Brain Cognitive Development (ABCD) sample. Using a remainder baseline sample of 7013 nine- to eleven-year-old children with complete data, we examined measurement invariance across race/ethnicity and sex, and examined the associations between the Prodromal Questionnaire Brief-Child Version (PQ-BC) and other measures of PLEs, internalizing symptoms, neuropsychological test performance, and developmental milestones, to determine whether previously obtained results replicated in this nonoverlapping baseline sample subset. The results replicated measurement invariance across ethnicity and sex, and analyses again found higher PQ-BC scores for African American (ß = .364, 95% CI = 0.292, 0.435) and Hispanic (ß = .255, 95% CI = 0.185, 0.324) groups. We also replicated that higher PQ-BC scores were associated with psychosis risk measures, higher rates of child-reported internalizing symptoms (Distress: ß = .378, 95% CI = 0.357,0.398), neuropsychological test performance deficits (eg, working memory; Distress: ß = -.069, 95% CI = -0.096, -0.042), and motor (Distress: ß = .026, 95% CI = 0.003, 0.049) and speech (Distress: ß = .042, 95% CI = 0.018, 0.065) developmental milestone delays. The current results replicated many findings from the original study examining the PQ-BC. We replicated evidence for mean differences in race/ethnicity, and associations with other PLE measures, greater internalizing symptoms, cognitive impairments, and developmental milestone delays. These findings indicate robust and reliable associations between PLEs and hypothesized correlates can be found in middle childhood nonclinical samples.

Psychosis screening in schools: Considerations and implementation strategies.

AIM: Duration of untreated psychosis, or the time between onset of psychosis symptoms and accurate diagnosis and treatment, is a significant predictor of both initial treatment response and long-term outcomes. As such, efforts to improve rapid identification are key. Because early signs of psychosis commonly emerge in adolescence, schools have the potential to play an important role in the identification of psychosis-spectrum disorders. METHODS: To illustrate the potential role of schools in this effort, the current paper describes implementation of a psychosis screening tool as part of a larger study focused on reducing the duration of untreated psychosis in Sacramento, CA. RESULTS: Clinical considerations related to screening for psychosis in schools, including ethical concerns, logistics, screening population and stigma are addressed. Implementation strategies to address these concerns are suggested. CONCLUSIONS: Early psychosis screening in the school system could improve early identification, reduce stigma and may represent an important further step towards an integrative system of mental health.