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.

From the psychosis prodrome to the first-episode of psychosis: No evidence of a cognitive decline.

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.

Factor analysis of the Scale of Prodromal Symptoms: data from the Early Detection and Intervention for the Prevention of Psychosis Program.

AIM: The Scale of Prodromal Symptoms (SOPS) was developed to identify individuals experiencing early signs of psychosis, a critical first step towards early intervention. Preliminary dimension reduction analyses suggested that psychosis-risk symptoms may deviate from the traditional symptom structure of schizophrenia, but findings have been inconsistent. This study investigated the phenomenology of psychosis risk symptoms in a large sample from a multi-site, national study using rigorous factor analysis procedure. METHODS: Participants were 334 help-seeking youth (age: 17.0 ± 3.3) from the Early Detection and Intervention for the Prevention of Psychosis Program, consisting of 203 participants at clinically higher risk (sum of P scores ≥ 7), 87 with clinically lower risk (sum of P scores < 7) and 44 in very early first-episode psychosis (<30 days of positive symptoms). Baseline SOPS data were subjected to principal axis factoring (PAF), estimating factors based on shared variance, with Oblimin rotation. RESULTS: PAF yielded four latent factors explaining 36.1% of total variance: positive symptoms; distress; negative symptoms; and deteriorated thought process. They showed reasonable internal consistency and good convergence validity, and were not orthogonal. CONCLUSIONS: The empirical factors of the SOPS showed similarities and notable differences compared with the existing SOPS structure. Regrouping the symptoms based on the empirical symptom dimensions may improve the diagnostic validity of the SOPS. Relative prominence of the factors and symptom frequency support early identification strategies focusing on positive symptoms and distress. Future investigation of long-term functional implications of these symptom factors may further inform intervention strategies.

Personalized Prediction of Psychosis: External Validation of the NAPLS-2 Psychosis Risk Calculator With the EDIPPP Project.

OBJECTIVE: As part of the second phase of the North American Prodrome Longitudinal Study (NAPLS-2), Cannon and colleagues report, concurrently with the present article, on a risk calculator for the individualized prediction of a psychotic disorder in a 2-year period. The present study represents an external validation of the NAPLS-2 psychosis risk calculator using an independent sample of patients at clinical high risk for psychosis collected as part of the Early Detection, Intervention, and Prevention of Psychosis Program (EDIPPP). METHOD: Of the total EDIPPP sample of 210 subjects rated as being at clinical high risk based on the Structured Interview for Prodromal Syndromes, 176 had at least one follow-up assessment and were included in the construction of a new prediction model with six predictor variables in the NAPLS-2 psychosis risk calculator (unusual thoughts and suspiciousness, symbol coding test performance, verbal learning test performance, decline in social functioning, baseline age, and family history). Discrimination performance was assessed with the area under the receiver operating characteristic curve (AUC). The NAPLS-2 risk calculator was then used to generate a psychosis risk estimate for each case in the external validation sample. RESULTS: The external validation model showed good discrimination, with an AUC of 0.790 (95% CI=0.644-0.937). In addition, the personalized risk generated by the risk calculator provided a solid estimation of the actual conversion outcome in the validation sample. CONCLUSIONS: Two independent samples of clinical high-risk patients converge to validate the NAPLS-2 psychosis risk calculator. This prediction calculator represents a meaningful step toward early intervention and the personalized treatment of psychotic disorders.

Early Detection, Intervention and Prevention of Psychosis Program: Community Outreach and Early Identification at Six U.S. Sites.

OBJECTIVE: This study assessed the effects of a community outreach and education model implemented as part of the Early Detection, Intervention and Prevention of Psychosis Program (EDIPPP), a national multisite study in six U.S. regions. METHODS: EDIPPP's model was designed to generate rapid referrals of youths at clinical high risk of psychosis by creating a network of professionals and community members trained to identify signs of early psychosis. Qualitative and quantitative data were gathered through an evaluation of outreach efforts at five sites over a two-year period and through interviews with staff at all six sites. All outreach activities to groups (educational, medical, and mental health professionals; community groups; media; youth and parent groups; and multicultural communities) were counted for the six sites to determine correlations with total referrals and enrollments. RESULTS: During the study period (May 2007-May 2010), 848 formal presentations were made to 22,840 attendees and 145 informal presentations were made to 11,528 attendees at all six sites. These presentations led to 1,652 phone referrals. A total of 520 (31%) of these individuals were offered in-person orientation, and 392 (75%) of those were assessed for eligibility. A total of 337 individuals (86% of those assessed) met criteria for assignment to the EDIPPP study. CONCLUSIONS: EDIPPP's outreach and education model demonstrated the effectiveness of following a protocol-defined outreach strategy combined with flexibility to reach culturally diverse audiences or initially inaccessible systems. All EDIPPP sites yielded appropriate referrals of youths at risk of psychosis.

Clinical and functional outcomes after 2 years in the early detection and intervention for the prevention of psychosis multisite effectiveness trial.

OBJECTIVE: To test effectiveness of the Early Detection, Intervention, and Prevention of Psychosis Program in preventing the onset of severe psychosis and improving functioning in a national sample of at-risk youth. METHODS: In a risk-based allocation study design, 337 youth (age 12-25) at risk of psychosis were assigned to treatment groups based on severity of positive symptoms. Those at clinically higher risk (CHR) or having an early first episode of psychosis (EFEP) were assigned to receive Family-aided Assertive Community Treatment (FACT); those at clinically lower risk (CLR) were assigned to receive community care. Between-groups differences on outcome variables were adjusted statistically according to regression-discontinuity procedures and evaluated using the Global Test Procedure that combined all symptom and functional measures. RESULTS: A total of 337 young people (mean age: 16.6) were assigned to the treatment group (CHR + EFEP, n = 250) or comparison group (CLR, n = 87). On the primary variable, positive symptoms, after 2 years FACT, were superior to community care (2 df, p < .0001) for both CHR (p = .0034) and EFEP (p < .0001) subgroups. Rates of conversion (6.3% CHR vs 2.3% CLR) and first negative event (25% CHR vs 22% CLR) were low but did not differ. FACT was superior in the Global Test (p = .0007; p = .024 for CHR and p = .0002 for EFEP, vs CLR) and in improvement in participation in work and school (p = .025). CONCLUSION: FACT is effective in improving positive, negative, disorganized and general symptoms, Global Assessment of Functioning, work and school participation and global outcome in youth at risk for, or experiencing very early, psychosis.