We present a novel comprehensive literature review of studies of the psychosocial functioning (PF) and quality of life (QoL) of patients with childhood glaucoma and their caregivers. Our findings demonstrate variable study quality and approach, as well as inconsistent results relating to the association of glaucoma-specific factors and sociodemographic variables with measured PF and QoL. Future studies should focus on the development of culturally cognizant and standardized assessment tools, execution of multi-center longitudinal studies with global representation, evaluation of PF and QoL among siblings and childhood glaucoma providers, and implementation of interventions to improve patient and caregiver PF and QoL.

Abstract 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.

Abstract 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.

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.

Objectives

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 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.

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

CHR 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.

Conclusions

To 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.

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.