Compensatory Cognitive Training for Latino Youth at Clinical High Risk for Psychosis: Study Protocol for a Randomized Controlled Trial.

Background: Early psychosocial interventions targeting cognitive and functional outcomes in individuals at clinical high risk for psychosis are a research priority. An even greater need is the identification of effective interventions in underserved populations. Compensatory Cognitive Training (CCT) is a psychosocial intervention with demonstrated efficacy in chronic schizophrenia and first episode psychosis, but remains to be evaluated in pre-illness phases. The aim of this study was to describe the development and implementation of an ongoing pilot randomized controlled trial investigating the efficacy of group-based, manualized CCT, as compared to recreational therapy (RT), for Latino participants at clinical high risk for psychosis (CHR) in both the United States and Mexico. It is hypothesized that, in comparison to those receiving RT, participants receiving CCT will show significant improvements in neurocognitive performance and functional capacity (co-primary outcomes) and self-rated functioning and clinical symptoms (secondary outcomes). Methods: Latino CHR participants aged 12-30 years will be included in the study. Both CCT and RT will be delivered in either Spanish or English, depending on group preference. Additionally, all assessments will be administered in participants' preferred language. A comprehensive assessment of neurocognitive and functional performance and clinical symptomatology will be performed at baseline, mid-intervention (4 weeks, 8 weeks), post-intervention (12 weeks) and 3-month follow-up. The primary outcome measures are neurocognition and functional capacity, as assessed by the MATRICS (Measurement and Treatment Research in Cognition in Schizophrenia) Consensus Cognitive Battery and the University of California, San Diego Performance-Based Skills Assessment-Brief, respectively. Furthermore, secondary outcomes measures will be used to examine change in clinical symptoms and self-reported functioning in response to CCT versus RT. Discussion: The evaluation of a novel treatment such as CCT in CHR youth will provide empirical support for a low risk, comprehensive cognitive intervention that could have important implications for public health if it improves neurocognition and functioning

Intact implicit processing of facial threat cues in schizophrenia

An emerging body of research suggests that people with schizophrenia retain the ability to implicitly perceive facial affect, despite well-documented difficulty explicitly identifying emotional expressions. It remains unclear, however, whether such functional implicit processing extends beyond emotion to other socially relevant facial cues. Here, we constructed two novel versions of the Affect Misattribution Procedure, a paradigm in which affective responses to primes are projected onto neutral targets. The first version included three face primes previously validated to elicit varying inferences of threat from healthy individuals via emotion-independent structural modification (e.g., nose and eye size). The second version included the threat-relevant emotional primes of angry, neutral, and happy faces. Data from 126 participants with schizophrenia and 84 healthy controls revealed that although performing more poorly on an assessment of explicit emotion recognition, patients showed normative implicit threat processing for both non-emotional and emotional facial cues. Collectively, these results support recent hypotheses postulating that the initial perception of salient facial information remains intact in schizophrenia, but that deficits arise at subsequent stages of contextual integration and appraisal. Such a breakdown in the stream of face processing has important implications for mechanistic models of social cognitive impairment in schizophrenia and treatment strategies aiming to improve functional outcome

Social cognition in schizophrenia : Factor structure of emotion processing and theory of mind

Factor analytic studies examining social cognition in schizophrenia have yielded inconsistent results most likely due to the varying number and quality of measures. With the recent conclusion of Phase 3 of the Social Cognition Psychometric Evaluation (SCOPE) Study, the most psychometrically sound measures of social cognition have been identified. Therefore, the aims of the present study were to: 1) examine the factor structure of social cognition in schizophrenia through the utilization of psychometrically sound measures, 2) examine the stability of the factor structure across two study visits, 3) compare the factor structure of social cognition in schizophrenia to that in healthy controls, and 4) examine the relationship between the factors and relevant outcome measures including social functioning and symptoms. Results supported a one-factor model for the patient and healthy control samples at both visits. This single factor was significantly associated with negative symptoms in the schizophrenia sample and with social functioning in both groups at both study visits

Does the Experience of Childhood Trauma Lead to a Pro-Inflammatory Phenotype in Youth at Clinical High Risk for Psychosis?

Rationale: Childhood adversity is strongly associated with increased risk for psychosis. Despite clear evidence for an association between childhood trauma (CT) and psychosis, the biological mechanisms that mediate the relationship between CT and clinical outcomes in psychosis remain largely unknown. The aim of this study is to better understand associations between inflammation, CT, and clinical outcomes in subjects identified to be at clinical high risk for developing psychosis (CHR) and evaluate whether inflammation mediates the relationship between CT and clinical outcomes.Design and Methods: Participants included 67 CHR subjects and 34 unaffected comparison subjects (UC; N = 101) ages 12-35 who participated in the North American Prodrome Longitudinal Study 2 (NAPLS2). Experience of CT was assessed using the Childhood Trauma and Abuse Scale. Severity of psychosis-risk symptoms was measured using the Structured Interview for Prodromal Syndromes (SIPS). Functioning was assessed using Global Assessment of Functioning (GAF) scale. Blood samples were analyzed using validated multiplex immunoassay. Group differences between UC and CHR in CT, functioning, psychosis risk symptom severity, and inflammation were evaluated using independent samples t-tests and Chi-squared tests. Two mediation models were tested to explore whether inflammation mediated the association between 1. total CT and GAF and 2. total CT and psychosis risk positive symptom severity. Results: Compared to UC, CHR subjects demonstrated significantly higher incidence of total CT, greater severity of psychosis risk symptoms, and significantly lower global, role, and social functioning. Regression analyses revealed that total CT and a 15-Analyte Inflammatory Index uniquely predicted psychosis risk positive symptom severity (β = 0.24, t(65) = 1.9, p = 0.05) and GAF scores (β = -0.26, t(65) =-2.25, p = 0.03). Combined, these variables explained a significant proportion of variance in psychosis risk positive symptom severity (R2 = 0.122) and GAF (R2 = 0.151) scores. Conclusions and Clinical Implications: The relationship between CT, increased psychosis-risk symptom severity, and decreased functioning was replicated in this study and results demonstrated novel associations between total CT, psychosis risk positive symptom severity, and GAF. This is the first study to demonstrate that CT and inflammation may have unique and additive effects on increased psychosis risk positive symptom severity and reduced global functioning in individuals at CHR for psychosis

Does the Experience of Childhood Trauma Lead to a Pro-Inflammatory Phenotype in Youth at Clinical High Risk for Psychosis?

Rationale: Childhood adversity is strongly associated with increased risk for psychosis. Despite clear evidence for an association between childhood trauma (CT) and psychosis, the biological mechanisms that mediate the relationship between CT and clinical outcomes in psychosis remain largely unknown. The aim of this study is to better understand associations between inflammation, CT, and clinical outcomes in subjects identified to be at clinical high risk for developing psychosis (CHR) and evaluate whether inflammation mediates the relationship between CT and clinical outcomes.Design and Methods: Participants included 67 CHR subjects and 34 unaffected comparison subjects (UC; N = 101) ages 12-35 who participated in the North American Prodrome Longitudinal Study 2 (NAPLS2). Experience of CT was assessed using the Childhood Trauma and Abuse Scale. Severity of psychosis-risk symptoms was measured using the Structured Interview for Prodromal Syndromes (SIPS). Functioning was assessed using Global Assessment of Functioning (GAF) scale. Blood samples were analyzed using validated multiplex immunoassay. Group differences between UC and CHR in CT, functioning, psychosis risk symptom severity, and inflammation were evaluated using independent samples t-tests and Chi-squared tests. Two mediation models were tested to explore whether inflammation mediated the association between 1. total CT and GAF and 2. total CT and psychosis risk positive symptom severity. Results: Compared to UC, CHR subjects demonstrated significantly higher incidence of total CT, greater severity of psychosis risk symptoms, and significantly lower global, role, and social functioning. Regression analyses revealed that total CT and a 15-Analyte Inflammatory Index uniquely predicted psychosis risk positive symptom severity (β = 0.24, t(65) = 1.9, p = 0.05) and GAF scores (β = -0.26, t(65) =-2.25, p = 0.03). Combined, these variables explained a significant proportion of variance in psychosis risk positive symptom severity (R2 = 0.122) and GAF (R2 = 0.151) scores. Conclusions and Clinical Implications: The relationship between CT, increased psychosis-risk symptom severity, and decreased functioning was replicated in this study and results demonstrated novel associations between total CT, psychosis risk positive symptom severity, and GAF. This is the first study to demonstrate that CT and inflammation may have unique and additive effects on increased psychosis risk positive symptom severity and reduced global functioning in individuals at CHR for psychosis

The effect of age, race, and sex on social cognitive performance in individuals with schizophrenia

Age, race, and sex are linked to social cognitive performance among healthy individuals, but whether similar effects are evident in schizophrenia is unknown. Data from 170 individuals with schizophrenia or schizoaffective disorder and 98 healthy controls were used to examine relations between these demographic factors and performance across multiple domains and measures of social cognition. Sex was not related to performance on any domain, but older age was related to poorer emotion recognition from dynamic stimuli in both patients and controls. In patients, older age was also associated with better abilities to decipher hints. Both Caucasian patients and controls performed better than African American individuals on emotion recognition and mental state attribution tasks that use only Caucasian individuals as visual stimuli. Findings suggest rather limited influences of demographic factors but do demonstrate normative age and race effects among patients. Findings also highlight important methodological considerations for measurement of social cognition

The effect of age, race, and sex on social cognitive performance in individuals with schizophrenia

Age, race, and sex are linked to social cognitive performance among healthy individuals, but whether similar effects are evident in schizophrenia is unknown. Data from 170 individuals with schizophrenia or schizoaffective disorder and 98 healthy controls were used to examine relations between these demographic factors and performance across multiple domains and measures of social cognition. Sex was not related to performance on any domain, but older age was related to poorer emotion recognition from dynamic stimuli in both patients and controls. In patients, older age was also associated with better abilities to decipher hints. Both Caucasian patients and controls performed better than African American individuals on emotion recognition and mental state attribution tasks that use only Caucasian individuals as visual stimuli. Findings suggest rather limited influences of demographic factors but do demonstrate normative age and race effects among patients. Findings also highlight important methodological considerations for measurement of social cognition

Social cognition psychometric evaluation (SCOPE) in people with early psychosis : A preliminary study

Social cognition is an important outcome in schizophrenia research. Unfortunately, there has been a lack of consensus regarding which measures of social cognition best capture this domain of functioning. The Social Cognition Psychometric Evaluation (SCOPE) study was developed to address the need for a battery of measures that have sound psychometric properties and can be implemented in clinical trials for individuals with chronic schizophrenia. The current study expands upon the SCOPE study by examining the psychometric properties of the eight candidate measures administered to individuals early in the course of psychosis. Thirty-eight stable outpatients with first episode psychosis and thirty-nine healthy controls completed the battery at baseline and one-month follow-up assessments. The SCOPE battery was evaluated on a collection of psychometric properties, including: (1) Reliability – including test-retest and internal consistency, (2) Between group differences, (3) Utility as a repeated measure, (4) Relationship to social and occupational functioning, (5) Incremental validity – variance in functioning beyond neurocognition, and (6) Feasibility – including practicality of administration and tolerability. Social cognition accounted for substantially more variance in functional outcome than neurocognition. Only one measure, the Hinting task, displayed adequate psychometric properties to be recommended for use in clinical research with first episode psychosis. The remaining candidate measures would require modifications before implementation or cannot be recommended for use in clinical research with first episode psychosi