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

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

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

Metabolic abnormalities and low dietary Omega 3 are associated with symptom severity and worse functioning prior to the onset of psychosis: Findings from the North American Prodrome Longitudinal Studies Consortium

Objective: Patients with schizophrenia have a high prevalence of metabolic disorders and cardiovascular mortality. It is possible that a vulnerability to metabolic abnormalities is associated with risk for psychosis, symptoms and functionality. In this study, we evaluate demographic information, cardiometabolic indices, symptoms and functioning in an antipsychotic free cohort at Clinical High Risk (CHR) for psychosis from the NAPLS Omega 3 fatty acid clinical trial. Method: Subjects received physical exams and metabolic monitoring prior to randomization into the Omega 3 versus Placebo trial. Anthropometrical measures, vital signs, glucose, and lipids were assessed along with symptoms, functioning, dietary Omega 3 fatty acids, erythrocyte polyunsaturated fatty acid content and a measure of lipid peroxidation (TBARS, Thiobarbituric acid-reactive substances). Results: The sample included 113 CHR subjects (42.1% female; 17.5% Latino) ages 12–29. The mean BMI was 24.3 with a trend toward higher BMI and a higher incidence of metabolic syndrome in Latino subjects; 36% of the sample was obese/overweight; 37.6% met criteria for prehypertension/hypertension; 4.2% met criteria for prediabetes/diabetes; 9.6% showed evidence of insulin resistance and 44.7% had dyslipidemia. The TBARS was elevated at 9.8 μM ± 6.1 (normal 1.86–3.94 μM). Metabolic parameters and a diet low in Omega 3 rich foods were significantly associated with prodromal symptoms and poor functioning. Conclusions: CHR subjects show a high percentage of metabolic abnormalities prior to exposure to antipsychotic medication. These findings reinforce that early detection of metabolic disturbances and food insecurity is crucial since these factors are modifiable with the potential for significant gains in terms of quality of life, physical and mental health

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