BACKGROUND AND HYPOTHESIS:Adolescents and young adults at clinical high risk for developing psychosis (CHR) show persistent impairments in social and role functioning. Poor social functioning has been linked to greater risk of psychosis, but it remains unclear how functional trajectories differ across clinical outcomes. STUDY DESIGN:Ninety-six healthy controls (HC), 70 CHR-Converters and 415 CHR individuals who did not develop psychosis classified into Remission, Symptomatic, and Progression subgroups were included as part of the third phase of the North American Prodrome Longitudinal Study. Social and role functioning were assessed at baseline, 2, 4, 6, and 8 months using the Global Functioning: Social and Role scales, alongside clinical symptoms and intellectual functioning. STUDY RESULTS:Compared to HCs, all CHR subgroups showed significant social and role functioning impairments across time (Ps < .001). However, the pattern of impairment among the CHR subgroups differed by domain. For social functioning, converters had the lowest functioning compared to both HCs and the 3 non-converter subgroups. In contrast, for role functioning, converters were only significantly different from the progression subgroup. This pattern remained after adjusting for positive and depressive symptoms and intellectual functioning. In follow-up Cox regression analyses adjusting for positive symptoms, depressive symptoms, and intellectual functioning, lower baseline social functioning predicted shorter time to psychosis onset (HR = -0.168, 95%CI, 0.722-0.989; P = .036), but baseline role functioning did not emerge as a significant predictor (P = .057). CONCLUSIONS:CHR individuals who transition to psychosis show enduring impairments in social and role functioning that are evident at baseline and stable across the short-term follow-up period. Poor baseline social, but not role functioning independently predicted time to psychosis onset, underscoring its importance as a prognostic marker in the early identification of psychosis risk.

BACKGROUND AND HYPOTHESIS:Negative symptoms are important and common concerns in individuals at clinical high risk for psychosis (CHR-P) but are not systematically utilized to predict or improve outcomes. We explored the ability of various negative symptom models to predict the onset of psychosis while controlling for potential secondary sources of these symptoms. STUDY DESIGN:A total of 581 participants from the North American Prodrome Longitudinal Study (NAPLS3) were assessed at baseline, 2-, 4-, and 6-month follow-up. This included 70 high-risk individuals who transitioned to psychosis (CHR-T) and 415 who did not transition to psychosis (CHR-NT), as well as 96 healthy controls (HCs). Attenuated positive and negative symptoms were rated on the Scale of Prodromal Symptoms. Three negative symptom models were evaluated: (1) total negative symptoms; (2) experiential and expressive negative symptoms; and (3) separate analyses for each negative symptom. Depressive symptoms were determined via the Calgary Depression Scale for Schizophrenia. STUDY RESULTS:Total negative symptoms differed significantly between all 3 groups across time, such that CHR-T > CHR-NT > HC (P < .001). This pattern remained after adjusting for positive and depressive symptoms (P < .001). Baseline negative symptom severity predicted psychosis (P = .007), even with positive and depressive symptoms included in the model. Similar results were observed for experiential (P = .016) and expressive (P = .027) negative symptoms as well as social anhedonia (P = .011) and ideational richness (P = .002). CONCLUSIONS:Our findings reinforce the importance of negative symptoms in predicting psychosis in CHR-P youth. The data support consideration of negative symptoms in predictive algorithms for enhancing early recognition and treatment strategies.

Background Social functioning difficulties in adolescents and young adults at clinical high risk for psychosis (CHR-P) are among the strongest risk factors for psychosis onset. Recent research in patients with schizophrenia has demonstrated complex relationships between early auditory processing deficits as measured by the mismatch negativity (MMN) response of the auditory event-related potential, neurocognition, social cognition, negative symptoms, and social functioning. However, the interrelationships of these variables and associations with social functioning impairments prior to the onset of the illness are unclear. The present study used a structural equation modeling (SEM) approach to integrate these factors to determine the specific determinants that lead to poor social functioning in CHR-P youth. Methods A total of 518 CHR-P individuals from the NAPLS2 (North American Prodrome Longitudinal Study) were used to evaluate SEMs with pathways starting from MMN to social functioning. The intervening variables included processing speed, social cognition, and negative symptoms. Results A final trimmed model revealed that early auditory processing (MMN) had a direct effect on processing speed, and both processing speed and negative symptoms had direct effects on social functioning. The direct effect from social cognition to social functioning was not significant. Conclusions Our findings suggest that neurophysiological deficits are associated with social functioning by way of processing speed impairments, which fully accounted for the relationship in CHR-P youths prior to psychosis onset. These results may have implications for early intervention strategies that target early information-processing deficits with the aim of improving social trajectories and limiting psychosis onset in young CHR-P individuals.

Cognitive impairment occurs at higher rates in individuals at clinical high risk (CHR) for psychosis relative to healthy peers, and it contributes unique variance to multivariate prediction models of transition to psychosis. Such impairment is considered a core biomarker of schizophrenia. Thus, cognition is a key domain measured in the Accelerating Medicines Partnership® program for Schizophrenia (AMP SCZ initiative). The aim of this paper is to describe the rationale, processes, considerations, and final harmonization of the cognitive battery used in AMP SCZ across the two data collection networks. This battery comprises tests of general intellect and specific cognitive domains. We estimate premorbid intelligence at baseline and measure current intelligence at baseline and 2 years. Eight tests from the Penn Computerized Neurocognitive Battery (PennCNB), which measure verbal learning and memory, sensorimotor ability, attention, emotion recognition, working memory, processing speed, verbal memory, visual memory, and motor speed are administered repeatedly at baseline, and four follow-up timepoints over 2 years.

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.

AIM:Recent preventative approaches with young people at clinical high risk for psychosis (CHR-P) have focused on the remediation of the cognitive deficits that are readily apparent and predictive of future illness. However, the small number of trials using cognitive remediation with CHR-P individuals have reported mixed results. The proposed 2-phased study will test an innovative internet-based and remotely-delivered Specific COgnitive REmediation plus Surround (or SCORES) intervention that targets early processing speed deficits in CHR-P adolescents aged 14-20 years old. METHODS:In the first R61 phase, a single-arm 2-year proof of concept study, 30 CHR-P individuals will receive SCORES for 10 weeks (4 h per week/40 h total) with a midpoint assessment at 20 h (5 weeks) to demonstrate target engagement and identify the optimal dose needed to engage the target. The Go/No-Go criteria to move to the R33 phase will be processing speed scores improving by a medium effect size (Cohen's d ≥ .6). The proposed package includes a set of complimentary support surround procedures to increase enjoyment and ensure that participants will complete the home-based training. In the second R33 phase, a 3-year pilot study, we will replicate target engagement in a new and larger sample of 54 CHR-P individuals randomized to SCORES (optimized dose) or to a video game playing control condition. In addition, the R33 phase will determine if changes in processing speed are associated with improved social functioning and decreasing attenuated positive symptoms. The support surround components of the intervention will remain constant across phases and conditions in the R33 phase to firmly establish the centrality of processing speed training for successful remediation. CONCLUSIONS:The SCORES study is a completely virtual intervention that targets a core cognitive mechanism, processing speed, which is a rate-limiting factor to higher order behaviours and clinical outcomes in CHR-P adolescents. The virtual nature of this study should increase feasibility as well improve the future scalability of the intervention with considerable potential for future dissemination as a complete treatment package.

The prodromal phase of schizophrenia provides an optimal opportunity to mitigate the profound functional disability that is often associated with fully expressed psychosis. Considerable evidence supports the importance of neurocognition in the development of interpersonal (social) and academic (role) skills. Further findings from adolescents and young adults at clinical high risk for developing psychosis (CHRP) suggest that treatment for functioning might be most effective when targeting early and specific neurocognitive deficits. The current study addresses this critical intervention issue by examining the potential of neurocognitive deficits at intake for predicting social and role functioning over time in CHR-P youth. The study included 345 CHR-P participants from the second phase of the North American Prodrome Longitudinal Study (NAPLS2) with baseline neurocognition and 2-year follow-up data on social and role functioning. Slower baseline processing speed consistently predicted poor social functioning over time, while attention deficits predicted poor role functioning at baseline and follow-up. In addition, the impact of processing speed and attention impairments on social and role functioning, respectively, persisted even when adjusting the regression models for attenuated positive, negative, and disorganized symptoms, and transition status. The current study demonstrates for, arguably the first time, that processing speed and attention are strongly predictive of social and role functioning over time, respectively, above and beyond the impact of symptoms and those CHR-P individuals that develop psychosis over the course of the study. These findings imply that early neurocognition is a critical treatment target linked to the developmental trajectory of social and role functioning.

BACKGROUND:While an established clinical outcome of high importance, social functioning has been emerging as possibly having a broader significance to the evolution of psychosis and long term disability. In the current study we explored the association between social decline, conversion to psychosis, and functional outcome in individuals at clinical high risk (CHR) for psychosis.METHODS:585 subjects collected in the North American Prodrome Longitudinal Study (NAPLS2) were divided into 236 Healthy Controls (HCs), and CHR subjects that developed psychosis (CHR + C, N = 79), or those that did not (Non-Converters, CHR-NC, N = 270). CHR + C subjects were further divided into those that experienced an atypical decline in social functioning prior to baseline (beyond typical impairment levels) when in min-to-late adolescence (CHR + C-SD, N = 39) or those that did not undergoing a decline (CHR + C-NSD, N = 40).RESULTS:Patterns of poor functional outcomes varied across the CHR subgroups: CHR-NC (Poor Social 36.3%, Role 42.2%) through CHR + C-NSD (Poor Social 50%, Poor Role 67.5%) to CHR + C-SD (Poor Social 76.9%, Poor Role 89.7%) functioning. The two Converter subgroups had comparable positive symptoms at baseline. At 12 months, the CHR + C-SD group stabilized, but social functioning levels remained significantly lower than the other two subgroups.CONCLUSIONS:The current study demonstrates that pre-baseline social decline in mid-to-late adolescence predicts psychosis. In addition, we found that this social decline in converters is strongly associated with especially poor functional outcome and overall poorer prognosis. Role functioning, in contrast, has not shown similar predictor potential, and rather appears to be an illness indicator that worsens over time.

Digital communication can mitigate some of the challenges inherent in face-to-face communication; however, it is unclear whether this communication format is preferred among youth with emerging psychosis. Therefore, we examined characteristics of face-to-face and digital communication in youth at clinical high risk for psychosis (CHR; n = 19) or in the first episode of psychosis (FEP; n = 57), as well as age-matched community comparisons (n = 51). Participants completed a 25-item self-report questionnaire to assess between- and within-group differences in the frequency of, satisfaction with, and barriers to face-to-face and digital communication. Compared to controls, both clinical groups endorsed a lower frequency of face-to-face and digital interactions across a range of communication partners. Controls reported higher satisfaction and fewer challenges with both communication formats than CHR and FEP groups. No between-group differences were identified among clinical participants in characteristics of face-to-face and digital interactions. Youth at clinical high risk for, or in the first episode of, psychosis exhibited similar communication patterns and perceptions that significantly diverged from community controls. These findings highlight that reductions in the quality and quantity of social interactions extend to digital contexts, and that both communication formats are relevant clinical targets in the high risk and early stages of psychosis.

OBJECTIVE Traditional measures for assessing functioning with adult patients with schizophrenia have been shown to be insufficient for assessing the issues that occur in adolescents and young adults at clinical high risk (CHR) for psychosis. The current study provides an expanded validation of the Global Functioning: Social (GF:Social) and Role (GF:Role) scales developed specifically for use with CHR individuals and explores the reliability and accuracy of the ratings, the validity of the scores in comparison to other established clinical measures, stability of functioning over a 2-year period, and psychosis predictive ability. METHODS Seven hundred fifty-five CHR individuals and 277 healthy control (HC) participants completed the GF:Social and Role scales at baseline as part of the North American Prodrome Longitudinal Study (NAPLS2). RESULTS Inter-rater reliability and accuracy were high for both scales. Correlations between the GF scores and other established clinical measures demonstrated acceptable convergent and discriminant validity. In addition, GF:Social and Role scores were unrelated to positive symptoms. CHR participants showed large impairments in social and role functioning over 2-years, relative to the HCs, even after adjusting for age, IQ, and attenuated positive symptoms. Finally, social decline prior to baseline was more pronounced in CHR converters, relative to non-converters. CONCLUSIONS The GF scales can be administered in a large-scale multi-site study with excellent inter-rater reliability and accuracy. CHR individuals showed social and role functioning impairments over time that were not confounded by positive symptom severity levels. The results of this study demonstrate that social decline is a particularly effective predictor of conversion outcome.

Cognitive deficits have an important role in the neurodevelopment of schizophrenia and other psychotic disorders. However, there is a continuing debate as to whether cognitive impairments in the psychosis prodrome are stable predictors of eventual psychosis or undergo a decline due to the onset of psychosis. In the present study, to determine how cognition changes as illness emerges, we examined baseline neurocognitive performance in a large sample of helping-seeking youth ranging in clinical state from low-risk for psychosis through individuals at clinical high-risk (CHR) for illness to early first-episode patients (EFEP). At baseline, the MATRICS Cognitive Consensus battery was administered to 322 individuals (205 CHRs, 28 EFEPs, and 89 help-seeking controls, HSC) that were part of the larger Early Detection, Intervention and Prevention of Psychosis Program study. CHR individuals were further divided into those who did (CHR-T; n = 12, 6.8%) and did not (CHR-NT, n = 163) convert to psychosis over follow-up (Mean = 99.20 weeks, SD = 21.54). ANCOVAs revealed that there were significant overall group differences (CHR, EFEP, HSC) in processing speed, verbal learning, and overall neurocognition, relative to healthy controls (CNTL). In addition, the CHR-NTs performed similarly to the HSC group, with mild to moderate cognitive deficits relative to the CTRL group. The CHR-Ts mirrored the EFEP group, with large deficits in processing speed, working memory, attention/vigilance, and verbal learning (> 1 SD below CNTLs). Interestingly, only verbal learning impairments predicted transition to psychosis, when adjusting for age, education, symptoms, antipsychotic medication, and neurocognitive performance in the other domains. Our findings suggest that large neurocognitive deficits are present prior to illness onset and represent vulnerability markers for psychosis. The results of this study further reinforce that verbal learning should be specifically targeted for preventive intervention for psychosis.

Background: Recent studies have recognized that signs of functional disability in schizophrenia are evident in early phases of the disorder, and, as a result, can potentially serve as vulnerability markers of future illness. However, functional measures in the psychosis prodrome have focused exclusively on real-world accomplishment (ie, achievement), rather than on the skills required to carry-out a particular real-world function (ie, capacity). From this perspective capacity provides the foundation for what can actually be achieved. This is comparable to the comparison between IQ (capacity) vs grades at school (achievement). In one of the first reports of its kind, we introduced the Map task, a laboratory-based measure specifically designed to assess a young person’s basic capacity to carry-out age-appropriate skills that lead to independent community living (McLaughlin et al., 2016). Poor performance on the Map task was found to be predictive of conversion to psychosis, suggesting that functional capacity in the prodrome may represent a basic biologically-based vulnerability factor. Given that diminished functional capacity is often a key barrier to good functional outcomes in patients with schizophrenia, the current study sought to next evaluate whether deficits in capacity can also predict social and role (ie, academic) functioning in the prodrome. Methods: The Map task was administered to 609 subjects at Clinical High-Risk (CHR) for psychosis and 242 Healthy Controls (HCs) participating in the North American Prodrome Longitudinal Study (NAPLS2). Subjects were required to efficiently complete a set of specified errands in a fictional town. Results: Individuals with poor role functioning at study outcome had a lower Map efficiency score than those with good role outcome. In addition, the Map efficiency score predicted role functioning at outcome (OR = −0.971, 95% CI = 0.946 to 0.997; P = .027), even after accounting for conversion status, baseline IQ, and baseline role functioning). In contrast, the Map Efficiency score did not predict social outcome (OR = 0.989, 95% CI = 0.964–1.015; P = .416), supporting previous findings that social and role functioning are 2 distinct functional domains, with different developmental courses, with each having potential to provide predictors of long-term prognosis. Conclusion: Our findings support the notion that functional capacity may well represent a distinct vulnerability factor related to the multi-faceted long-term disability typically associated with schizophrenia. Poor performance on the Map task was significantly associated with impaired role functioning at study outcome, even after controlling for the contribution of conversion and intellectual performance. Thus, deficits in both role “capacity” and role “achievement” are present before the onset of the illness, and are not an artifact of psychosis onset or intellectual impairments.

Background: Social functioning deficits are present prior to the onset of psychosis and predict psychosis conversion in high-risk youth (Cornblatt et al, 2015; Cannon et al, 2008). In addition, past research from the Recognition and Prevention (RAP) Program found that social skill deficits are lifelong traits related to poor functional outcome in general (Cornblatt et al, 2015; Carrion et al, 2013). This poster reassesses the implications of social skill deficits as a developmental trait by examining change in social functioning. Methods: Subjects include 88 clinical high risk (CHR) participants enrolled in Phase 1 of the RAP Program and 347 CHR participants enrolled in the North American Prodrome Longitudinal Study 2 (NAPLS2). Social functioning deficits were assessed with the Global Functioning: Social (GF:S) scale, an interview measure of social interactions rated from 1–10 with higher scores indicating better functioning (Cornblatt et al, 2007). Associations between GF:S scores and baseline demographics, SIPS attenuated positive and negative symptoms, and Axis I diagnoses were examined. Conversion to psychosis and functional outcome were assessed at follow up (RAP = 3 years, NAPLS2 = 2 years). CHR participants were divided according to whether their GF:S score improved, did not change, or declined over follow up. GF:S scores were also dichotomized into Good (GF:S ≥ 7) vs Poor (GF:S ≤ 6) functioning at baseline and follow up. Results: For the RAP sample, there were no significant differences between groups on demographic variables or SIPS symptoms. The Improver and No Change groups were significantly more likely to be diagnosed with Social Phobia compared to Decliners (Ps < .01). Similar results were found in the larger NAPLS2 sample for demographic variables, SIPS symptoms, and Axis I diagnoses (all ns). Significantly more Decliners in both samples converted to psychosis (RAP 32%, NAPLS2 36%) compared to the Improvers (RAP 10.5%, NAPLS2 10%; Ps ≤ .03). Decliners were also more likely to convert than the No Change (8%) group (RAP, P = .03; NAPLS, trend). In addition, No Change subjects were more likely to have poor functioning at baseline and outcome (RAP 72%, NAPLS2 51%). Conclusion: As expected, CHRs with decline in social functioning are at greatest risk for psychosis. In contrast, CHRs who improve over time are likely not at risk for either psychosis or functional disability. The remaining subjects display stable poor functioning, but are less likely to develop psychosis, suggesting their risk is for long term functional disability. Only one clinical variable, Social Phobia, differentiated groups, indicating that social anxiety is more likely found in false positives. These findings have two major implications: (1) stable social skill deficits appear to relate to long-term disability and (2) change in adolescence is predictive of psychosis.

OBJECTIVESRecent studies have recognized that signs of functional disability in schizophrenia are evident in early phases of the disorder, and, as a result, can potentially serve as vulnerability markers of future illness. However, functional measures in the psychosis prodrome have focused exclusively on real-world achievements, rather than on the skills required to carry-out a particular real-world function (ie, capacity). Despite growing evidence that diminished capacity is critical to the etiology of the established disorder, virtually no attention has been directed towards assessing functional capacity in the pre-illness stages. In the present study, we introduce the Map task, a measure to assess functional capacity in adolescent and young-adult high-risk populations.METHODSThe Map task was administered to 609 subjects at Clinical High-Risk (CHR) for psychosis and 242 Healthy Controls (HCs) participating in the North American Prodrome Longitudinal Study (NAPLS2). Subjects were required to efficiently complete a set of specified errands in a fictional town.RESULTSCHR participants showed large impairments across major indices of the Map task, relative to the HCs. Most importantly, poor performance on the Map task significantly predicted conversion to psychosis, even after adjusting for age, IQ, clinical state, and other potential confounders.CONCLUSIONSTo the best of our knowledge, the Map task is one of the first laboratory-based measures to assess functional capacity in high-risk populations. Functional capacity deficits prior to the onset of psychosis may reflect a basic mechanism that underlies risk for psychosis. Early intervention targeting this domain may help to offset risk and independently improve long-term outcome.

Research in individuals at clinical high-risk (CHR) for psychosis has focused on subjects with no more than 12 months of present or worsened attenuated positive symptoms. However, the impact of long duration attenuated positive and/or negative prodromal symptoms on outcomes is unclear. Seventy-six CHR subjects with attenuated positive symptoms and at least moderate severity level negative symptoms rated on the Scale of Prodromal Symptoms (SOPS) were prospectively followed for a mean of 3.0 ± 1.6 years. Social and Role functioning was assessed with the Global Functioning: Social and Role scales. Correlations between attenuated positive and negative symptom duration and severity and conversion to psychosis and functional outcomes were analyzed. The average onset of SOPS rated negative symptoms (M = 53.24 months, SD = 48.90, median = 37.27) was approximately twelve months prior to the emergence of attenuated positive symptom (M = 40.15 months, SD = 40.33, median = 24.77, P < 0.05). More severe positive symptoms (P = 0.004), but not longer duration of positive (P = 0.412) or negative (P = 0.754) symptoms, predicted conversion to psychosis. Neither positive symptom duration (P = 0.181) nor severity (P = 0.469) predicted role or social functioning at study endpoint. Conversely, longer negative symptom duration predicted poor social functioning (P = 0.004). Overall, our findings suggest that the severity of attenuated positive symptoms at baseline may be more important than symptom duration for determining individuals at increased risk of developing psychosis. In contrast, long-standing negative symptoms may be associated with persistent social difficulties and therefore have an important position in the treatment of disability.

Background: There is a growing recognition that individuals at clinical high risk need intervention for functional impairments, along with emerging psychosis, as the majority of clinical high risk (CHR) individuals show persistent deficits in social and role functioning regardless of transition to psychosis. Recent studies have demonstrated reduced reading ability as a potential cause of functional disability in schizophrenia, related to underlying deficits in generation of mismatch negativity (MMN). The present study extends these findings to subjects at CHR.Methods: The sample consisted of 34 CHR individuals and 33 healthy comparison subjects (CNTLs) from the Recognition and Prevention (RAP) Program at the Zucker Hillside Hospital in New York. At baseline, reading measures were collected, along with MMN to pitch, duration, and intensity deviants, and measures of neurocognition, and social and role (academic/work) functioning.Results: CHR subjects showed impairments in reading ability, neurocognition, and MMN generation, relative to CNTLs. Lower-amplitude MMN responses were correlated with worse reading ability, slower processing speed, and poorer social and role functioning. However, when entered into a simultaneous regression, only reduced responses to deviance in sound duration and volume predicted poor social and role functioning, respectively.Conclusions: Deficits in reading ability exist even prior to illness onset in schizophrenia and may represent a decline in performance from prior abilities. As in schizophrenia, deficits are related to impaired MMN generation, suggesting specific contributions of sensory-level impairment to neurocognitive processes related to social and role function. (C) 2015 Elsevier B.V. All rights reserved.