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Schizophrenia is associated with an elevated risk for impulsive aggression for which there are few psychosocial treatment options. Neurocognitive and social cognitive deficits have been associated with aggression with social cognitive deficits seemingly a more proximal contributor. The current study examined the effects of combining cognitive and social cognition treatment on impulsive aggression among inpatients with chronic schizophrenia and schizoaffective disorder and a history of aggression compared to cognitive remediation treatment alone.The two-center study randomized 130 participants to receive 36 sessions of either a combination of cognitive remediation and social cognition treatment or cognitive remediation plus a computer-based control. Participants had at least one aggressive incident within the past year or a Life History of Aggression (LHA) score of 5 or more. Participants completed measures of neurocognition, social cognition, symptom severity, and aggression at baseline and endpoint.Study participants were mostly male (84.5 %), had a mean age 34.9 years, and 11.5 years of education. Both Cognitive Remediation Training (CRT) plus Social Cognition Training (SCT) and CRT plus control groups were associated with significant reductions in aggression measures with no group differences except on a block of the Taylor Aggression Paradigm (TAP), a behavioral task of aggression which favored the CRT plus SCT group. Both groups showed significant improvements in neurocognition and social cognition measures with CRT plus SCT being associated with greater improvements.CRT proved to be an effective non-pharmacological treatment in reducing impulsive aggression in schizophrenia inpatient participants with a history of aggressive episodes. The addition of social cognitive training did not enhance this anti-aggression treatment effect but did augment the CRT effect on cognitive functions, on emotion recognition and on mentalizing capacity of our participants.

Background Clinician-administered measures of negative symptoms may not capture patients' subjective experiences. The Self-Evaluation of Negative Symptoms (SNS) has shown good psychometric properties when used in outpatients with higher-level functioning schizophrenia. We aimed to evaluate the psychometric properties of the SNS in low functioning participants with treatment-resistant schizophrenia (TRS). Methods Participants were assessed using the following measures at two time-points; time-point 1: SNS, Wide Range Achievement Test, 4th Edition Reading Subtest (WRAT-4), and Brief Assessment of Cognition in Schizophrenia (BACS). Time-point 2 (within a week of time-point 1): SNS, Negative Symptom Assessment 16 items (NSA-16), Scale to Assess Unawareness in Mental Disorder-Abbreviated (SUMD-A), Clinical Global Impression Severity Scale (CGI-S), Simpson Angus Scale (SAS), Calgary Depression Scale for Schizophrenia (CDSS), and the Patient Feasibility Questionnaire. Results Fifty participants with TRS were enrolled, a mean age of 43.8 years (SD = 11.19, min = 25, max = 64), a mean IQ of 80.62 (SD = 17.12, min = 65, max = 110), and a mean BACS Composite T-Score of 14.08 (SD = 17.16, min = −27, max = 49). Participants responded to SNS prompts with moderate consistency across two time-points. There were no significant correlations between the SNS and the NSA-16 Global Symptom score (Pearson r = 0.207, p = .150, Spearman r = 0.101, p = .483), NSA-16 Global Functioning score (Pearson r = 0.209, p = .145, Spearman r = 0.126, p = .384), nor the NSA-16 total score (Pearson r = 0.149, p = .302, Spearman r = 0.116, p = .421). However, when participants were stratified by BACS Composite T-score, there was a significant positive correlation between the SNS total and the NSA-16 Global Functioning score (Pearson r = 0.500, p = .048, Spearman r = 0.546, p = .029) among participants who demonstrated higher cognitive functioning. Conclusion Participants with TRS and low functioning were able to respond to questions on the SNS regarding their subjective assessment of negative symptoms. However, self-reported and clinician-rated negative symptoms were not equivalent, except in a subgroup with higher cognitive functioning. This discrepant self-reporting appeared to relate to their low levels of insight and cognitive impairments.

Background Patient-centered outcomes research (PCOR) emphasizes the patient perspective and input to inform the research process with the aim to improve the quality of care. Given PCOR's emphasis on the patient perspective, methods to incorporate patient-reported outcomes (PROs) are important. Electronic PROs (ePROs) have been implemented successfully in many populations; however, many of these measurements do not incorporate patient perspective in the development of ePROs. For epilepsy and seizure disorders, user perspectives are key to developing measurements that capture real-time data, as seizures are not timed events; therefore, patients can wait days or even weeks and then try to recall their experience which can lead to variations in recall. ePRO can provide the necessary assurance that data were entered by the patient at the time the episode occurs. The aim of the present study was to assess patient perceptions of completing ePROs, expectations of ePRO devices for PCOR and on-site clinical visit in order to guide the development of successful ePRO deployment in seizure-related disorders. Methods This study used a naturalistic cohort design. A sample of 713 persons completed an online survey which consisted of 11 situational questions. Of the 713 individuals, results from 640 participants were included. Results were compared using a Wilcoxon signed-rank test. Results Most participants (71.9%) were able to accurately identify a seizure and 86.3% of participants felt it would be beneficial to have a short training on seizure symptoms prior to completing a daily seizure diary, and seizures should be reasonably reported within 10 mins (n = 426, 66.6%). Participants endorsed that repetitive movements and loss of consciousness as the most predominant symptoms they would look for in an ePRO. A majority of participants, 67.0% indicated that they regularly use accessibility features on using smartphones and tablets, and 38.6% indicated they would like to see more than one item per screen but only if they are related and to see all text in a larger size with scrolling features using fingers (n = 246; 38.4%). Conclusion This study has demonstrated the importance of developing ePROs that satisfy the needs of the participants and caregivers without compromising the scientific and clinical aspects of the disease construct. Developing tools using participant needs, observations, characteristics and input is essential to putting the participant perspective in patient-centered outcomes research.

OBJECTIVE: While clozapine is recognized as the most effective antipsychotic for individuals with treatment-resistant schizophrenia, its effects on neurocognition remain unclear. This study aimed to compare the neurocognitive effects of clozapine treatment to those of non-clozapine antipsychotics in patients with schizophrenia and to examine the role of anticholinergic burden on cognitive impairments. DESIGN: This was a naturalistic study. Cross-sectional data were drawn from participants with chronic schizophrenia in two clinical trials assessing cognition. Cognition was evaluated using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). Anticholinergic burden was calculated for each medication using the Anticholinergic Cognitive Burden (ACB) scoring system. We stratified the participants treated with non-clozapine antipsychotics into high ACB score versus low ACB score groups. RESULTS: One hundred and seventy participants were enrolled and treated with clozapine (n=58) or non-clozapine antipsychotics (n=112). We observed no significant differences in the MCCB T-scores between the clozapine and the total non-clozapine groups for the cognitive composite score and the seven domain scores. However, the non-clozapine high ACB group showed significant impairments in processing speed and attention/vigilance, in contrast to the non-clozapine low ACB group (p

This review of research utilizing the Schizophrenia Cognition Rating Scale (SCoRS) outlines the development, evaluation, validation, and implementation of the SCoRS to assess whether the scale meets the criteria as a functional co-primary as defined by the MATRICS-CT initiative. Interview-based co-primary assessments should be: 1) practical and easy to administer for a clinician or researcher; 2) validated in individuals with schizophrenia; 3) contain the relevant areas of cognition and functioning applicable to schizophrenia; 4) able to assess all phases and severity levels of schizophrenia; 5) capable of monitoring disease progression; 6) minimal burden to patients; and 7) sensitive to assess treatment effects. A review of the literature was conducted to present information on the development, psychometric properties and usage of the SCoRS. Review of the development of the SCoRS followed the parameters outlined for scale development on content expert validation and feedback. The SCoRS shows good psychometric properties in various studies, and demonstrates low burden on clinicians and patients. The items measure global concepts that do not require notable cultural modification, making international use feasible. While multiple performance-based tests in cognition and functional outcomes are available, there is a need for a multi-domain, interview-based assessment of cognitive progression and treatment response in clinical trials. The SCoRS appears to meet many of the criteria for an optimal co-primary measure for schizophrenia cognition clinical trials as defined in the MATRICS-CT initiative.

Individuals from academia, the pharmaceutical industry, and regulators reevaluated earlier recommendations for the design of clinical trials for negative symptoms based on data from recent large trials. A session in February, 2018 at the International Society of CNS Clinical Trails and Methodology (ISCTM) annual meeting reviewed results from selected trials that reported findings between 2013 and 2018. The group reached a consensus on prior recommendations that should be reconsidered in future trials which included: (1) How can placebo effects be minimized? (2) Should global measures of negative symptoms be included? (3) Should a new drug targeting negative symptoms be tested in a monotherapy design or in an add-on design? (4) Can new information from negative symptom trials inform the selection of clinical outcome assessments (COA’s) for future trials? For each of these issues new data was evaluated, discussed by the group, and in some cases the earlier recommendations were revised.

This study demonstrates the quantitative characteristics of the first patient‐reported outcome (PRO) tool developed for patients with nontransfusion‐dependent β‐thalassemia (NTDT), the NTDT‐PRO©. A multicenter validation study was performed over 24 weeks, involving 48 patients from Italy, Lebanon, Greece, and Thailand. Most patients were female (68.8%), with a median age of 34.5 years (range, 18‐52); 66.7% were diagnosed with β‐thalassemia intermedia, and median time since diagnosis was 22 years (range, 0‐43). The NTDT‐PRO comprises 6 items across 2 domains (Tiredness/Weakness and Shortness of Breath [SoB]), and was valid and reliable, with good consistency. At baseline, most patients reported symptoms as present via the NTDT‐PRO, and were highly compliant, ≥90% completing the NTDT‐PRO tool. In a pairwise correlation analysis, all items were positively correlated. Correlations between NTDT‐PRO and existing tools—36‐Item Short Form Health Survey version 2 (SF‐36v2) and Functional Assessment of Cancer Therapy‐Anemia (FACT‐An)—were assessed at weeks 1, 3, and 12; robust correlations were seen between SoB and SF‐36v2‐Vitality (r s = −0.53), and between SoB and Fact‐An‐Fatigue Experience (r s = −0.66) at week 1. Internal consistency was high for both Tiredness/Weakness (Cronbach alpha, 0.91) and SoB (Spearman‐Brown coefficient, 0.78); intraclass correlation coefficients were high (Tiredness/Weakness, 0.88 and 0.97; SoB, 0.92 and 0.98), demonstrating stability. Further studies are required to fully support the validity of this tool, this study demonstrated the usefulness of the NTDT‐PRO in the clinical setting and for longitudinal clinical research, particularly in trials where patient health‐related quality of life is expected to change.

The MATRICS Consensus Cognitive Battery (MCCB) was developed to assess cognitive treatment effects in schizophrenia clinical trials, and is considered the FDA gold standard outcome measure for that purpose. The aim of the present study was to establish pre-treatment psychometric characteristics of the MCCB in a large pooled sample. The dataset included 2616 stable schizophrenia patients enrolled in 15 different clinical trials between 2007 and 2016 within the United States (94%) and Canada (6%). The MCCB was administered twice prior to the initiation of treatment in 1908 patients. Test-retest reliability and practice effects of the cognitive composite score, the neurocognitive composite score, which excludes the domain Social Cognition, and the subtests/domains were examined using Intra-Class Correlations (ICC) and Cohen's d. Simulated regression models explored which domains explained the greatest portion of variance in composite scores. Test-retest reliability was high (ICC=0.88) for both composite scores. Practice effects were small for the cognitive (d=0.15) and neurocognitive (d=0.17) composites. Simulated bootstrap regression analyses revealed that 3 of the 7 domains explained 86% of the variance for both composite scores. The domains that entered most frequently in the top 3 positions of the regression models were Speed of Processing, Working Memory, and Visual Learning. Findings provide definitive psychometric characteristics and a benchmark comparison for clinical trials using the MCCB. The test-retest reliability of the MCCB composite scores is considered excellent and the learning effects are small, fulfilling two of the key criteria for outcome measures in cognition clinical trials.

Background Studies have shown a convergence of neural systems implicated in cognitive control and social emotional functions with mechanisms involved in emotion regulation, awareness, and impulsive aggression. In a sample of patients with a history of aggression, we examined the association of cognitive and social cognitive functions with emotion regulation capacity, emotional awareness, impulse control, and aggression. Methods Participants were 78 individuals with schizophrenia or schizoaffective disorder that participated in a cognitive training study. Emotion regulation capacity was indexed by obtaining participants’ heart rate variability (HRV), respiration, and skin conductance while participants viewed pictures selected from the International Affective Picture System (IAPS). Three blocks of pictures were presented—a neutral block depicting pictures of everyday objects preceded by audio recordings of their description; an emotionally-evocative block preceded by their description, and a reappraisal block of emotionally-evocative pictures preceded by reappraisal statements. A subset of participants (N=37) completed the emotion regulation task. The MATRICS Consensus Cognitive Battery (MCCB), the Reading the Mind in the Eyes Task (Eyes Task), and the Emotion Recognition-40 (ER-40) were administered to assess cognitive functioning, mentalizing, and facial affect recognition respectively. Negative affectivity was captured using the Positive and Negative Affect Schedule (PANAS) whereas aggression was measured with the Taylor Aggression Paradigm (TAP) and the Overt Aggression Scale Modified (OAS-M). In a smaller subsample of 12 individuals, we performed analyses of activation patterns during the performance of the emotion regulation task. Regions of interest (ROI) included the dACC, DLPFC, VLPFC, vmPFC, left and right amygdala, and the subcallosal cingulate. We created a regional mask of the cognitive control and emotional appraisal regions for event-related fMRI. Results There were inverse associations between performance on the MCCB and the Eyes Task and indices of emotion regulation capacity—in particular, significant associations were obtained with Low Frequency/High Frequency HRV ratio (r=-0.324, p There were inverse associations between activation within the event-related regional mask and low frequency/high frequency heart rate variability ratio at rest (r=-0.504, p=0.095) and during the viewing of emotionally-evocative pictures (r = -0.264, p=0.36). Associations with HRV were especially remarkable for the dorsomedial, ventrolateral, and right amygdala regions. Remarkably, increased activation in the regional mask when reappraisal statements were provided with emotionally-evocative pictures was inversely correlated with the life history of aggression LHA (r=-0.32, p=0.28, n=14) and OAS (r=-0.284, p=0.34, n=14) aggression scores. This pattern was present when the dACC, right and left amygdala, DLPFC, VLPFC, and the subcallosal cingulate were set as the seed region. Discussion The results show an association between cognitive functions and emotion regulation capacity indexed by measuring physiological arousal during the performance of the picture viewing task. Emotion regulation capacity also showed significant association with aggression. Deficits in cognitive and social cognitive abilities may contribute to and be viable targets for improving emotion regulation capacity and decreasing aggression risk.

Background Many individuals with chronic or treatment resistant schizophrenia experience multiple relapses or treatment failures during the course of the illness. Some of these relapses are due to poor treatment compliance that is inherent to schizophrenia. Poor insight may be a leading cause for partial- or non-adherence to treatment as a high proportion of individuals with schizophrenia are partially or completely unaware of their mental disorder. The first two years after stabilization are thought to be key for long-term functional and clinical prognosis. In the present study, we first estimated the rate of treatment failure or relapse following clinical stability at one and two years, investigate the time to occurrence of relapse among individuals with chronic schizophrenia and the association between baseline clinical features recorded during the inpatient hospitalization and relapse at one- and two-year time points. We hypothesized that lack of insight, as measured by the PANSS item G12, would be a greater predictor of relapse than other characteristics previously suggested as possible predictors, including other symptoms from the PANSS, age, duration of illness, age at onset of illness, substance use, number of prior hospitalizations, and length of stay of the pre-discharge hospitalization. Methods A total of 138 participants diagnosed with schizophrenia or schizo-affective disorder were assessed with a comprehensive assessment at one year and two-year following discharge from a long-term psychiatric facility. Regression models were used to determine factors predicting time to relapse and other elements of functioning. Baseline factors examined included PANSS, MCCB, PSP, demographics and treatment variables. Results Relapse rates were 56.52% (n=78 of 138) by Year 1, and 69.56% (n=96 of 138) by end of Year 2. The estimated relapse-free period for all individuals at the end of the study was 8.78 months. The backward elimination (–2 log likelihood=189.59, χ2=9.01, df=2, p=.021) showed that the best predictive variables for relapse were lack of insight/judgment as assessed by PANSS item G12 at baseline (B=.20, SE=.09, df=1, p=.011, Exp[B]=1.36), lifetime years of substance use (B=.16, SE=.11, df=1, p=.029, Exp[B]=1.33), PANSS Factor baseline score on Disorganization (B=.15, SE=.12, df=1, p=.031, Exp[B]=1.56), and number of previous hospitalizations (B=.13, SE=.11, df=1, p=.048, Exp[B]=1.23). No other baseline variables were found to be significant. Discussion Poor insight is a fundamental symptom of schizophrenia that, while not entirely and uniformly expressed in all individuals, is among the most common symptoms across subjects. Our study shows that the numerous negative consequences of lack of insight should lead clinicians and researchers to make insight a high priority for allocation of clinical resources. Effective approaches to managing these predictive characteristics will allow affected individuals and their families and care providers to take part in collaborative treatment and relapse risk-management paradigms.

Background The Virtual Reality Functional Capacity Assessment Tool (VRFCAT) is an “applied” game-based assessment that uses a multi-level functional task to assess instrumental activities of daily living (iADL). This study examines the feasibility, convergent validity, and predictive ability of the VRFCAT in a sample of inpatients with chronic schizophrenia. Methods Inpatients with a DSM-5 diagnosis of schizophrenia or schizoaffective disorder, completed the VRFCAT prior to discharge. The UPSA-B, SLOF, and PSP were administered, both at baseline and after four-weeks in the community. VRFCAT performance scores were compared to published data from the VRFCAT validation study. Results All 62 participants completed the VRFCAT. Compared to the performance of stable outpatients, participants performed 1.50 SDs below the VRFCAT mean adjusted total time (ATT) (Validation study: Mean T Score = 32.5, SD = 16.59) with more errors. The VRFCAT ATT T-score was significantly correlated with baseline UPSA-B total score (p = 0.005) and PSP Global score (p = 0.010). 34 participants completed the follow-up period (55%), and 28 were lost to follow-up. There were no statistically significant differences in VRFCAT scores between these two groups (all p > 0.29). The VRFCAT composite score at baseline was significantly associated with the UPSA-B total score (p = 0.010) and the PSP total score (p = 0.008) at four-weeks, as was the PSP Socially Useful Activities subscale score (p = 0.006). Conclusion The VRFCAT is a valid measure of iADLs in inpatients with chronic schizophrenia. The VRFCAT predicted instrumental functioning four-weeks post-discharge. Future studies should examine other moderators of measures of functional capacity pre-discharge, predicting function later in the community.

As part of a project to translate and validate scales used in the diagnosis and treatment of Arab patients with schizophrenia, this study aimed to explore the experience of clinical research coordinators (CRCs) while administering the Arabic version of the Positive and Negative Syndrome Scale (PANSS) on Arab schizophrenia patients. We previously reported that the Arabic version of PANSS is a valid and reliable tool to assess Arab patients with schizophrenia. Five CRCs and the principal investigator attended focus group discussions on cultural issues in administering the PANSS. A thematic analysis approach was utilized for data coding and analysis. The results identified issues related to the translation of the instrument, the structure of the interview, the cultural sensitivity of some questions, and the procedures for rating items of the PANSS. Qualitative analysis also identified four main themes relevant to clinical assessment of patients from Middle Eastern cultures: religion, beliefs and values, gender, and semantic expressions. In conclusion, researchers or clinicians administering the PANSS scale interview in Arabic should be trained to consider the roles of local dialects, familiarity with abstract thinking, religion, and social constructs when assessing psychosis.

Background An individual’s mental health is best captured by considering the overall associations of biological, behavioral, and social functions that comprise the framework of individual experience. As such, accessing data on various health indicators concurrently can influence prediction of disease progression or change in response to treatment. Data generated passively by smartphones to measure human behavior has generated significant research interest and has increasingly been utilized in psychiatric disorders. In schizophrenia, passive and continuous assessment of how an individual uses their mobile device may give rise to clinically useful markers that can be used to improve treatment processes, adapt treatment choices, identify early risk for relapse to initiate clinical intervention, and develop new clinical models. A promising approach is to leverage current advances in mobile technology, data analytics and machine learning to enable automated and fast phenotyping of digital data. . In this context, the workflow for phenotyping (passive data collection → data storage and curation → trait extraction → machine learning/classification → models/apps for decision support) has to be carefully designed and efficiently executed to minimize resource usage and maximize utility. Digital phenotyping can be used in conjunction with standard care to reduce time to recognition and acknowledgement that worsening of a symptom needs to be addressed, to reduce time to receiving appropriate level of care, to increase ability to analyze and collect data from a variety of sources to improve mental health needs assessment and delivery of services, and to advance outcome measurement through comparison of passive and active data sets. Aim The aim of this pilot study is to test whether a smartphone digital phenotyping application can help detect early signs of treatment failure or response in individuals with chronic schizophrenia after discharge from hospital. Methods 17 individuals with DSM-5 schizophrenia were provided with a smartphone and digital phenotyping app, MindStrong Health app, following discharge from an inpatient psychiatric facility. The participants were followed for 6 months with monthly rater administered evaluations assessing neurocognition (Brief Assessment of Cognition in Schizophrenia (BACS)), symptomatology (PANSS; CGI-S/I), quality of life (SF-36), healthcare utilization, alcohol/drug use, level of clinical insight and depression (Calgary Depression Rating Scale, CDSS). Digital phenotyping data included gestures (swipes, taps, other), orientation (the way the phone is pointing), acceleration (sudden movements of the phone), keystroke patterns with characters encoded, number of calls made, number of emails sent, number of text messages sent, and location information from the GPS. Predictive models were built using multiple machine learning techniques - random forest plots, linear regression and gradient boosting, to predict the target scores based on phone usage patterns. Results Of the 17 enrolled participants, 10 provided analyzable data (i.e., had at least 22 target days with data). There was a gradual reduction of passive data generation due to either non-use of the smart phone or due to non-recharging of the device. The mean PANSS score was 80.12 (14.56). BACS scores corresponding to motor speed (token motor task), verbal fluency (category instances, letter fluency), and attention and processing speed (symbol coding) were found to be highly correlated with a composite digital phenotyping marker while scores on the PANSS or CDSS were not. Discussion The study provides a basis for using smartphone-base mobile apps to use as an augmentation within clinical practice to gather further information on patients outside the clinic setting, focusing on their behavior in the ‘real world.’ In particular, the cognitive data derived from the digital device correlated well with rater administered traditional cognitive ratings. Collecting digital data can provide a much needed window into the lives of patients in between normally scheduled visits, while minimizing costs and inconvenience to the patient. Studies with larger sample sizes are required to assess relationships with relapse, rehospitalizations and treatment failure.

Background: Negative symptoms and cognitive deficits have a substantial predictive value for functional deficits and recovery in schizophrenia. However, the relationship between negative symptoms and cognitive abnormalities is unclear possibly due to the heterogeneity of negative symptoms. This study used the model of expressive and experiential negative symptoms subfactors to decrease this heterogeneity. It examined these subfactors and cognition before and after treatment with computerized cognitive remediation training (CRT) in chronically-hospitalized individuals with psychosis and predominant negative symptoms. Methods: Seventy-eight adult participants with a DSM-IV-TR diagnosis of schizophrenia or schizoaffective disorder were enrolled in a 12-week CRT program. Assessments of demographic and illness variables, baseline and endpoint assessments of psychopathology (Positive and Negative Syndrome Scale) and cognition (MATRICS Consensus Cognitive Battery - MCCB) were conducted. Results: The baseline expressive negative subfactor was associated with Processing Speed (r = −0.352, p ≤ 0.001) and Reasoning/Problem Solving (r = −0.338, p ≤ 0.001). Following CRT, there was a significant decrease in the experiential negative subfactor (p

BACKGROUND: Continuing advances in the understanding of Alzheimer’s disease progression have inspired development of disease-modifying therapeutics intended for use in preclinical populations. However, identification of clinically meaningful cognitive and functional outcomes for individuals who are, by definition, asymptomatic remains a significant challenge. Clinical trials for prevention and early intervention require measures with increased sensitivity to subtle deficits in instrumental activities of daily living (IADL) that comprise the first functional declines in prodromal disease. Validation of potential endpoints is required to ensure measure sensitivity and reliability in the populations of interest. OBJECTIVES: The present research validates use of the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) for performance-based assessment of IADL functioning in older adults (age 55+) with subjective cognitive decline. DESIGN: Cross-sectional validation study. SETTING: All participants were evaluated on-site at NeuroCog Trials, Durham, NC, USA. PARTICIPANTS: Participants included 245 healthy younger adults ages 20-54 (131 female), 247 healthy older adults ages 55-91 (151 female) and 61 older adults with subjective cognitive decline (SCD) ages 56-97 (45 female). MEASURES: Virtual Reality Functional Capacity Assessment Tool; Brief Assessment of Cognition App; Alzheimer’s Disease Cooperative Study Prevention Instrument Project – Mail-In Cognitive Function Screening Instrument; Alzheimer’s Disease Cooperative Study Instrumental Activities of Daily Living – Prevention Instrument, University of California, San Diego Performance-Based Skills Assessment – Validation of Intermediate Measures; Montreal Cognitive Assessment; Trail Making Test- Part B. RESULTS: Participants with SCD performed significantly worse than age-matched normative controls on all VRFCAT endpoints, including total completion time, errors and forced progressions (p≤0001 for all, after Bonferonni correction). Consistent with prior findings, both groups performed significantly worse than healthy younger adults (age 20-54). Participants with SCD also performed significantly worse than controls on objective cognitive measures. VRFCAT performance was strongly correlated with cognitive performance. In the SCD group, VRFCAT performance was strongly correlated with cognitive performance across nearly all tests with significant correlation coefficients ranging from 0.3 to 0.7; VRFCAT summary measures all had correlations greater than r=0.5 with MoCA performance and BAC App Verbal Memory (p

This study demonstrates the quantitative characteristics of the first patient-reported outcome (PRO) tool developed for patients with nontransfusion-dependent β-thalassemia (NTDT), the NTDT-PRO© . A multicenter validation study was performed over 24 weeks, involving 48 patients from Italy, Lebanon, Greece, and Thailand. Most patients were female (68.8%), with a median age of 34.5 years (range, 18-52); 66.7% were diagnosed with β-thalassemia intermedia, and median time since diagnosis was 22 years (range, 0-43). The NTDT-PRO comprises 6 items across 2 domains (Tiredness/Weakness and Shortness of Breath [SoB]), and was valid and reliable, with good consistency. At baseline, most patients reported symptoms as present via the NTDT-PRO, and were highly compliant, ≥90% completing the NTDT-PRO tool. In a pairwise correlation analysis, all items were positively correlated. Correlations between NTDT-PRO and existing tools-36-Item Short Form Health Survey version 2 (SF-36v2) and Functional Assessment of Cancer Therapy-Anemia (FACT-An)-were assessed at weeks 1, 3, and 12; robust correlations were seen between SoB and SF-36v2-Vitality (rs = -0.53), and between SoB and Fact-An-Fatigue Experience (rs = -0.66) at week 1. Internal consistency was high for both Tiredness/Weakness (Cronbach alpha, 0.91) and SoB (Spearman-Brown coefficient, 0.78); intraclass correlation coefficients were high (Tiredness/Weakness, 0.88 and 0.97; SoB, 0.92 and 0.98), demonstrating stability. Further studies are required to fully support the validity of this tool, this study demonstrated the usefulness of the NTDT-PRO in the clinical setting and for longitudinal clinical research, particularly in trials where patient health-related quality of life is expected to change.

Background Transcranial direct-current stimulation (tDCS), a non-invasive neurostimulation treatment, has been reported in a number of sham-controlled studies to show significant improvements in treatment-resistant auditory hallucinations in schizophrenia patients, primarily in ambulatory and higher-functioning patients, but little is known of the effects of tDCS on hospitalized, low-functioning inpatients. Objective/Hypothesis The purpose of this study was to examine the efficacy and safety of tDCS for auditory hallucinations in hospitalized ultra-treatment-resistant schizophrenia (TRS) and to evaluate the effects of tDCS on cognitive functions. We hypothesized that treatment non-response reported in previous tDCS studies may have been due to the insufficient duration of direct-current stimulation. Methods Inpatient participants with DSM-V schizophrenia, long-standing treatment-resistance, and auditory verbal hallucinations (AVH) participated in this 4-week sham-controlled, randomized trial. Assessments included the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) at baseline and endpoint (at the end of Week 4), and the Auditory Hallucinations Rating Scale (AHRS) administered at baseline, endpoint, and weekly throughout the study. Participants were randomized to receive active vs. sham tDCS treatments twice daily for 4 weeks. Results Twenty-eight participants were enrolled (tDCS, n = 15; control, n = 13) and 21 participants completed all 4 weeks of the trial. Results showed a significant reduction for the auditory hallucination total score (p ≤ 0.05). We found a 21.9% decrease in AHRS Total Score for the tDCS group and a 12.6% decrease in AHRS Total Score for the control group. Significant reductions in frequency, number of voices over time, length of auditory hallucinations, and overall psychopathology were also observed for the tDCS group. When assessing cognitive functioning, only Working Memory showed improvement for the tDCS group. Conclusion Although there was only a small improvement noted in auditory hallucination scores for the tDCS group, this improvement was meaningful when compared to no standard treatment of the control group. While this makes the interpretation of clinical significance debatable, it does confirm that tDCS combined with pharmacological intervention can provide clinical gains over pharmacological intervention alone. Therefore, tDCS treatment appears to be effective not only for ambulatory, higher-functioning patients, but also for patients with ultra-treatment-resistant schizophrenia.

Objectives Cognitive remediation therapy (CRT) has shown significant improvement in cognition in schizophrenia. However, effect sizes of CRT have been reported to be modest raising the issue how to augment the effects of CRT on neurocognition and social cognition. Our aim was to examine whether the addition of computerized social cognition training would enhance the effects on neurocognition and social cognition as compared to CRT alone. Methods This is a 12-week, parallel group trial of 131 in- and out-patients with schizophrenia randomized to CRT (COGPACK or Brain Fitness) with computerized social cognition training (MRIGE), or CRT alone for 36 sessions. Participants were assessed at baseline and after 12 weeks of treatment. Assessments included neurocognition, social cognition, psychopathology, and functioning. Results The combined intervention, CRT + MRIGE, showed greater improvements in the MCCB indices of Visual Learning, Working Memory, Reasoning and Problem-Solving, and the neurocognitive composite score compared to CRT alone (Bonferroni adjusted p = 0.004, p = 0.005, p = 0.01, respectively), as did social cognition measures (Bonferroni adjusted p = 0.006, p = 0.005, respectively). Conclusions Supplementing CRT with computerized social cognition training produced greater benefits in neurocognition, including visual learning, memory, executive functions, and social cognition relative to cognitive training alone. These findings favoring the combined training may be contributed to both the greater overall amount of cognitive practice, as well as the specific cognitive functions engaged by the social cognition training.

Objective: Recognizing the discrete dimensions that underlie negative symptoms in schizophrenia and how these dimensions are understood across localities might result in better understanding and treatment of these symptoms. To this end, the objectives of this study were to 1) identify the Positive and Negative Syndrome Scale negative symptom dimensions of expressive deficits and experiential deficits and 2) analyze performance on these dimensions over 15 geographical regions to determine whether the items defining them manifest similar reliability across these regions. Design: Data were obtained for the baseline Positive and Negative Syndrome Scale visits of 6,889 subjects across 15 geographical regions. Using confirmatory factor analysis, we examined whether a two-factor negative symptom structure that is found in schizophrenia (experiential deficits and expressive deficits) would be replicated in our sample, and using differential item functioning, we tested the degree to which specific items from each negative symptom subfactor performed across geographical regions in comparison with the United States. Results: The two-factor negative symptom solution was replicated in this sample. Most geographical regions showed moderate-to-large differential item functioning for Positive and Negative Syndrome Scale expressive deficit items, especially N3 Poor Rapport, as compared with Positive and Negative Syndrome Scale experiential deficit items, showing that these items might be interpreted or scored differently in different regions. Across countries, except for India, the differential item functioning values did not favor raters in the United States. Conclusion: These results suggest that the Positive and Negative Syndrome Scale negative symptom factor can be better represented by a two-factor model than by a single-factor model. Additionally, the results show significant differences in responses to items representing the Positive and Negative Syndrome Scale expressive factors, but not the experiential factors, across regions. This could be due to a lack of equivalence between the original and translated versions, cultural differences with the interpretation of items, dissimilarities in rater training, or diversity in the understanding of scoring anchors. Knowing which items are challenging for raters across regions can help to guide Positive and Negative Syndrome Scale training and improve the results of international clinical trials aimed at negative symptoms.

BACKGROUND: The risk of impulsive aggression is elevated in schizophrenia and reducing the risk of violent acts in patients is a critical to their overall functional recovery. Cognitive training interventions have been shown in previous studies to decrease the risk of aggression. The current study examined whether cognitive training leads to improvements in emotion regulation and impulse control, two contributors to aggression. METHODS: The study recruited participants (N=90) with schizophrenia or schizoaffective disorder with a past year history of one or more violent acts or a significant lifetime history of aggression as indicated by a score of 5 or more on the Life History of Aggression (LHA) interview. Participants were randomized into one of two cognitive training groups—a cognitive remediation training plus social cognition training (CRT+SCT) group versus CRT alone. The study primary outcome—aggression—was measured using the Overt Aggression Scale (OAS), Point Subtraction Aggression Paradigm (PSAP), and the Taylor Aggression Paradigm (TAP). Emotion Regulation Capacity was indexed by obtaining participants’ heart rate, respiration, and skin conductance while participants viewed pictures selected from the International Affective Picture System (IAPS). Negative emotionality was captured using the Positive and Negative Affect Schedule (PANAS). The Go/NoGo task was used to measure impulse control. RESULTS: Participants were 35.23 years old (SD=9.99) and had completed 11.82 (SD=1.94) years of education. Most were men (83.5%) and African-American (44.4%). All participants had a past year history of violence and an LHA score of 19.57 (SD=5.70). The study data included 49 completers and 5 intent-to-treat samples. Both cognitive training groups showed reductions in negative affectivity scores from baseline but differences were minimal between both groups. Both groups demonstrated pre-to-post reductions in their Low Frequency/High Frequency heart rate variability ratio (Cohen’s d=-0.83) and skin conductance (Cohen’s d = -0.48). Pre-to-post differences between the two training groups were minimal. Both groups demonstrated large pre-to-post reductions in misses on the No-Go trials of the Go No-Go Task (d =-1.74). Reductions were greater in the CRT+SCT than the CRT only group (d=0.27) suggesting that the CRT+SCT group show greater improvements in impulse control after cognitive training. Both groups also showed pre-to-post reductions on the TAP, the PSAP, and the OAS. Differences favored the CRT+SCT group on TAP (F(1,37)=3.99, p

BACKGROUND: Few studies have compared clinical evaluations of negative symptoms to those done by patients. Self-report tools may better reflect the patients’ subjective experience. The Self-Evaluation of Negative Symptoms (SNS; Dollfus et al., 2015), a 20-item scale, was developed to assess the subjective experience of negative symptoms by schizophrenia patients. Dollfus et al (2015) found that the SNS had good psychometric properties and demonstrated that the patients’ ratings were highly correlated with observer ratings. Patients included in the Dollfus et al (2015) study were stable outpatients with a high level of functioning. It remains to be explored whether patients with a lower level of functioning can identify their negative symptoms in a reliable fashion. Our goals were (1) to examine if chronic, low functioning patients can complete the instrument without assistance, potentially providing more immediate insight into their internal perception of negative symptoms and (2) to examine the correlation of their subjective reports with the research assessment of negative symptoms. METHODS: Stable in- and outpatients who met DSM-5 criteria for schizophrenia spectrum disorder were included in the study. After consenting, patients self-administered the SNS assessment at two time points, separated by one week, with other rater-administered concurrent evaluations: the 16-Item Negative Symptom Assessment (NSA-16), a validated clinical assessment for negative symptoms, the CGI-S, WRAT, BACS, and CDSS. RESULTS: A total of 50 subjects with a mean age of 43.71 years (SD = 11.03), 86% male, 64.81% African American, with a mean chlorpromazine equivalency dose of 869.22 (SD = 59.69). Mean premorbid IQ was 79.71 (SD = 17.51) determined by WRAT Standard Total, and BACS Composite T Score mean was 33.56 (SD = 12.11). Cronbach’s coefficient of the SNS (α = 0.903) showed good internal consistency. The intraclass correlation coefficients (ICCs) between SNS time point 1 and SNS time point 2 showed good inter-rater reliability (ICC = .849, 95% CI [.739, .928]. Of the 20 SNS items, significant correlations with the NSA-16 Global Level are reported for only 2 items: “I don’t take any great pleasure in talking with people” (r = 0.65, p < 0.001), and item “I am not interested in having sex, with “Sexual interest” (r = 0.58, p = 0.003). There was a significant difference in the SNS total score between Visit 1 (t(53) = 9.11, p < 0.001) and Visit 2 (t(53) = 8.23, p < 0.001). Significant correlations were also identified for SNS Item “I don’t take any great pleasure in talking with people” and the SUM-D Awareness of Asociality item (r = 0.564, p = .005) and SNS Item “I am not interested in going out with friends or with a family member” and the SUM-D “Awareness of mental disorder” (r = 0.578, p = .004). DISCUSSION: This study shows that patients with negative symptoms can self-administer a patient reported outcome measure. However, the relatively low correlation between the self-reported SNS items and the research rated NSA-16, suggests that the agreement between self-rating and observer-rating of negative symptoms in patients with chronic schizophrenia is rather low, except for two items. Patients also evaluated the severity of their negative symptoms rather differently one week apart suggesting different subjective assessment levels by patients at different times. It appears that patients with chronic schizophrenia and low levels of functioning are not able to self-evaluate their negative symptoms and give variable answers on repeat self-evaluations.

Objective: Autism Behavior Inventory (ABI) is a new measure for assessing changes in core and associated symptoms of autism spectrum disorder (ASD) in participants (ages: 3 years-adulthood) diagnosed with ASD. It is a web-based tool with five domains (two ASD core domains: social communication, restrictive and repetitive behaviors; three associated domains: mental health, self-regulation, and challenging behavior). This study describes design, development, and initial psychometric properties of the ABI. Methods: ABI items were generated following review of existing measures and inputs from expert clinicians. Initial ABI scale contained 161 items that were reduced to fit a factor analytic model, retaining items of adequate reliability. Two versions of the scale, ABI-full (ABI-F; 93 items) and ABI-short version (ABI-S; 36 items), were developed and evaluated for psychometric properties, including validity comparisons with commonly used measures. Both scales were administered to parents and healthcare professionals (HCPs) involved with study participants. Results: Test–retest reliability (intraclass correlation coefficient [ICC] = 0.79) for parent ratings on ABI was robust and compared favorably to existing scales. Test–retest correlations for HCP ratings were generally lower versus parent ratings. ABI core domains and comparison measures strongly correlated (r ≥ 0.70), demonstrating good concurrent validity. Conclusions: Overall, ABI demonstrates promise as a tool for measuring change in core symptoms of autism in ASD clinical studies, with further validation required.

Objective Current dopamine-blocking antipsychotic drugs have little impact on the cognitive deficits associated with schizophrenia. We evaluated whether MIN-101, a molecule that combines sigma-2 antagonism and 5-HT2A antagonism, might improve cognitive deficits in individuals with moderate to severe negative symptoms in schizophrenia. Methods Individuals (N = 244) aged 18 to 60 years with stable symptoms of DSM-5-defined schizophrenia and moderate to severe negative symptoms were randomized to placebo (n = 83), MIN-101 32 mg (n = 78), or MIN-101 64 mg (n = 83) in a 12-week, phase 2b, prospective, double-blind, placebo-controlled, parallel-group trial between May 2015 and December 2015. In a post hoc analysis, mean z and T score changes from baseline at 12 weeks of treatment in the cognitive composite score and individual tests on the Brief Assessment of Cognition in Schizophrenia (BACS) Battery were compared between MIN-101 and placebo. Results A total of 79 patients (95.2%) from the placebo group, 76 (97.4%) from the MIN-101 32 mg group, and 79 (95.2%) from the MIN-101 64 mg group completed the BACS at baseline. The BACS token motor (P = .04), verbal fluency (P = .01), and composite z scores (P = .05) showed significant improvements in the MIN-101 32 mg group compared to the placebo group. At week 4, the clinical improvements from baseline in the Positive and Negative Syndrome Scale (PANSS) negative factor showed a significant correlation with improvements from baseline on the BACS composite in the 64 mg group (r = -0.292, P = .020). At week 12, improvement in the PANSS negative factor showed significant correlations with improvements in the BACS composite (r = -0.408, P = .002), Trail Making Test (r = -0.394, P = .003), and verbal memory (r = -0.322, P = .017) for the 64 mg group. Conclusions Results suggest a possible benefit of MIN-101 on cognitive performance in individuals with schizophrenia with stable positive symptoms and concurrent clinically significant negative symptoms. Trial registration EU Clinical Trials Register identifier: 2014-004878-42​.

International Society for CNS Clinical Trials and Methodology convened an expert working-group that assembled consistency/inconsistency flags for the Positive and Negative Syndrome Scale (PANSS). Twenty-four flags were identified and divided based on extent to which they represent error (Possibly, Probably, Very probably or definitely). The flags were applied to assessments derived from the NEWMEDS data repository and the CATIE clinical trial data. Almost 40% of ratings had at least one inconsistency flag raised and 10% had two. Application of flags to clinical rating can improve reliability and validity of trials.

Background The Positive and Negative Syndrome Scale (PANSS) assesses multiple domains of schizophrenia. Evaluation of each of these domains was conducted to assess differences in the characteristics of psychopathology and their relative predominance in sub-populations. Method Subjects (N = 1,832) with DSM-IV schizophrenia were represented in three sub-populations: First Episodes, n = 305, Chronic Inpatients, n = 694, and Ambulatory Outpatients, n = 833. Nonparametric Item Response Analysis (IRT) was performed with Option Characteristic Curves (OCC), Item Characteristic Curves (ICC), slopes and item biserial correlation. Items were characterized as Very Good, Good, or Weak based on specified operational criteria for item selection. Results First episode patients were represented by negative, disorganized hostility and anxiety. Some negative domain items (Poor Rapport, Passive/Apathetic Social Withdrawal) and most positive domain items were scored as Weak. For chronic inpatients, all items of the anxiety domain and some items of the positive domain (Suspiciousness/Persecution, Stereotyped Thinking, Somatic Concerns) were Weak; for all other domains, items were Very Good or Good. For ambulatory outpatients, most items in the anxiety and hostility domain were scored as Weak. The majority of PANSS items were either Very Good or Good at assessing the overall illness severity: chronic inpatients (73.33%, 22 items), first episodes (60.00%, 18 items), and only 46.67% (14 items) in the ambulatory group. Conclusion Findings confirm differences in symptom presentation and predominance of particular domains in subpopulations of schizophrenia. Identifying symptom domains characteristic of subpopulations may be more useful in assessing efficacy endpoints than total or subscale scores.

Background Transcranial direct-current stimulation (tDCS), a noninvasive neurostimulation treatment, has been reported to show improvements in treatment-resistant auditory hallucinations in patients with schizophrenia. tDCS administered over a limited number of sessions effectively produced lasting attenuation of auditory hallucinations in otherwise stable outpatients. It has also been shown that tDCS may be a useful intervention for ameliorating cognitive deficits in patients with chronic schizophrenia. The purpose of this study was to test tDCS for auditory hallucinations in ultra-treatment resistant schizophrenia to assess if this form of neurostimulation can alleviate treatment-refractory auditory hallucination symptoms up to 4 weeks after the final treatment. In addition, we also wanted to examine the effects of tDCS on cognitive functions. Methods 28 inpatients with DSM-V schizophrenia and long-standing treatment resistance and persistent auditory verbal hallucinations were recruited. Each individual participated in behavioral assessments at baseline, endpoint and follow-up [PANSS and Auditory Hallucinations Rating Scale (AHRS) and MCCB cognitive battery] and were randomized to receive active vs. sham tDCS treatments. For active treatment, patients had the inhibitory (cathodal) tDCS electrode placed over left auditory cortex relative to an excitatory (anodal) electrode placed over frontal cortex on the right side. tDCS treatments took place for 20 min twice daily for 5 consecutive days. Assessment batteries were repeated following the 4 weeks of treatment. The Chattanooga, dual channel CHA-1335 stimulator with two 7 × 5 cm (35 cm2) sponge electrodes soaked in a saline solution (0.9% NaCl) was used for the delivery of 2 mA current. Results A total of 28 subjects were enrolled (tDCS, n = 13; Control, n = 15). 20 subjects completed the trial. 3 subjects dropped out of the active tDCS treatment group, while 4 subjects did not complete the control treatment due to early discharge from the hospital. Most subjects were male (tDCS n = 10, 76.9%; Control n = 6, 40.0%). Length of present psychiatric admission ranged from 1–25 months, with a mode of 2 months (n = 12) and average of 2.9 months. Participating inpatients were on clozapine, haloperidol, paliperidone depot, fluphenazine decanoate, paliperidone, olanzapine, and risperidone as primary medications. Repeated Measures ANOVA showed a significant difference for the auditory hallucination total score, frequency and number of voices over time (p < 0.05) with greater reduction in scores observed for the tDCS group. Improvements were maintained after 4 weeks. There was no significant change over time observed for the PANSS positive symptoms or total score, or for the PANSS Hallucinatory Behavior item score. When assessing cognitive functioning, only Working Memory change was significant (p = 0.048) between the tDCS and the Control group with the tDCS group showing significant improvement in T-Score as compared to the Control group. Discussion Subjects who received tDCS treatment showed a significant reduction in the frequency, number of voices, and total scores of their auditory hallucination. Additionally, subjects in the tDCS group showed significant improvement in the Working Memory. Our results indicate that patients who have been ultra-resistant to antipsychotic treatments and who received tDCS treatment presented with robust diminution of their auditory hallucinations. We conclude that tDCS seems to be effective not only for ambulatory, higher functioning patients, but also for much lower functioning patients with medication-refractory auditory verbal hallucinations.

Background Debate persists with regard to how best to categorize the syndromal dimension of negative symptoms in schizophrenia. The aim was to first review published Principle Components Analysis (PCA) of the PANSS, and extract items most frequently included in the negative domain, and secondly, to examine the quality of items using Item Response Theory (IRT) to select items that best represent a measurable dimension (or dimensions) of negative symptoms. Methods First, 22 factor analyses and PCA met were included. Second, using a large dataset (n = 7187) of participants in clinical trials with chronic schizophrenia, we extracted items loading on one or more PCA. Third, items not loading with a value of ≥ 0.5, or loading on more than one component with values of ≥ 0.5 were discarded. Fourth, resulting items were included in a non-parametric IRT and retained based on Option Characteristic Curves (OCCs) and Item Characteristic Curves (ICCs). Results 15 items loaded on a negative domain in at least one study, with Emotional Withdrawal loading on all studies. Non-parametric IRT retained nine items as an Integrated Negative Factor: Emotional Withdrawal, Blunted Affect, Passive/Apathetic Social Withdrawal, Poor Rapport, Lack of Spontaneity/Conversation Flow, Active Social Avoidance, Disturbance of Volition, Stereotyped Thinking and Difficulty in Abstract Thinking. Conclusions This is the first study to use a psychometric IRT process to arrive at a set of negative symptom items. Future steps will include further examination of these nine items in terms of their stability, sensitivity to change, and correlations with functional and cognitive outcomes.

Background: The Positive and Negative Syndrome Scale (PANSS) is a widely used assessment for patients with schizophrenia across clinical and research settings. This scale allows the classification of the psychotic symptoms to better understand the psychopathology in patients with schizophrenia. There are no available data on the different components of psychopathology in Arab patients with schizophrenia. Objectives: This study examined the factor structure of the validated Arabic version of the PANSS in a sample of Arab patients with schizophrenia. Methods: The Arabic version of the PANSS was administered to 101 patients with schizophrenia, and principal component analysis (PCA) was carried out after the cross-cultural adaptation and validation of this version. Results: This sample had more males (66.3%) than females (33.7%) with a mean age of 35.03 years (SD = 9.99). PCA showed that 28 items loaded on 5 components: cognitive, negative, excited, depressed and positive. These factors explained 63.19% of variance. The 2 remaining items, grandiosity and somatic concerns, did not load well on any of these components. Conclusion: Our results support the common 5-dimension PANSS model shown in other cultures with different languages. Nevertheless, there were minor differences, which could reflect cultural or semantic differences.

This study aims to examine the effects of change in neurocognition on functional outcomes and to examine predictors of change in social functions following a 12-week course of cognitive remediation in patients with schizophrenia and schizoaffective disorder with severe cognitive impairments.Level of social functioning was assessed using a performance based measure of functional capacity (PSP) in patients prior to and after the completion of 12-week cognitive remediation treatment (CRT). Participants completed a neuropsychological battery (MCCB-MATRICS) and clinical measures at both time points.63 subjects with a mean age of 41.4 (SD=12.2) and with 12.2years of education (SD=2.4) were enrolled. There were significant improvements in overall PSP score from baseline to endpoint (p=0.021) as well as in PSP domain A (socially useful activities) (p≤0.001), domain B (personal and social relationships) (p=0.009), and domain D (disturbing and aggressive behaviors) (p=0.003). There was a significant improvement in the composite MCCB score (p=0.020) and the Working Memory (p0.046). Stepwise logistic regression yielded a significant association for baseline Visual Learning (Wald=6.537, p=0.011, OR=1.195), Speed of Processing (Wald=4.112, p=0.043, OR=0.850) and level of PANSS positive symptoms (Wald=4.087, p=0.043, OR=0.739) with PSP overall improvement.Faster speed of processing, better visual and verbal learning and less prominent positive symptoms were associated with greater functional improvement after a systematic cognitive intervention within a rehabilitative setting.

Background: The Positive and Negative Syndrome Scale (PANSS) is widely used for patients with schizophrenia. This scale is reliable and valid. The PANSS was translated and validated in several languages. Objective: The aim of this study was to translate and validate the PANSS in the Arab population. Subjects and Methods: The PANSS was translated into formal Arabic language using the back-translation method. 101 Arab patients with schizophrenia and 98 Arabs with no diagnosis of any mental disorder were recruited. The Arabic version of the Mini International Neuropsychiatric Interview (MINI-6) was used as a diagnostic tool to confirm the diagnosis of schizophrenia or rule out any diagnosis for the healthy control group. Reliability of the scale was assessed by calculating internal consistency, interrater reliability and test-retest reliability. Construct validity was assessed using the Arabic version of the MINI-6. PANSS total scores were correlated with the Clinical Global Impression-Severity scale. Results: Our findings showed that the internal consistency was good (0.92). Scores on the PANSS of the patients were much higher than those of the healthy controls. The PANSS showed good interrater reliability and test-retest reliability (0.92 and 0.75, respectively). In comparison with the MINI-6, the PANSS showed good sensitivity and specificity, which implies good construct validity of this version. Conclusion: In conclusion, the Arabic version of the PANSS is a reliable and valid instrument for the assessment of patients with schizophrenia in the Arab population.

Background The metabolic syndrome (MetS) and cognitive impairments are common in schizophrenia. Both are associated with poor outcomes, which have received increasing medical and mental health attention. Whether MetS is associated with impaired cognitive functions in schizophrenia has not been thoroughly addressed. The aim of this study was to compare the association between patients with and without MetS and its contributing components with neurocognitive performance. We hypothesized that patients with MetS would be associated with more impaired cognitive performance. Methods 159 patients with schizophrenia or schizoaffective disorder, with available metabolic data were included in the study. Patients were classified as either having or not having MetS as defined by the NCEP Adult Panel-III criteria. All patients completed neurocognitive and metabolic tests. Results Of the 159 patients, 43.34% had MetS. Patients without the MetS performed significantly better on tests measuring processing speed (p = 0.050), attention/vigilance (p = 0.040), working memory (p = 0.041) and problem solving/reasoning (p = 0.050) compared with those with MetS. Patients with MetS showed significantly lower cognitive domain scores. After Bonferroni correction greater waist circumference was associated with lower scores on attention/vigilance (β = − 0.551; p ≤ .0083), HDL was positively associated with scores on attention/vigilance (β = 0.900, p ≤ .0083) and higher triglycerides were associated with lower scores on attention/vigilance (β = − 1.004, p ≤ .0083). Conclusions Schizophrenia patients with MetS showed significant cognitive impairments in three key cognitive domains. Aggressive medical treatment of the constituent components of MetS may provide the potential for important beneficial effects on patients' cognitive functioning.

Background: Social cognition is significantly impaired in schizophrenia and contributes to poor community functioning. This study examined whether cognitive remediation (CR; COGPACK), shown to improve neurocognition, improves an integral component of social cognition, emotion perception, compared with CR combined with a computerized Emotion Perception intervention (Mind Reading: Interactive Guide to Emotions [MRIGE]).

Despite numerous studies of diabetes mellitus type II (DM-II) in schizophrenia and schizoaffective disorder, there have been no studies on the glycemic effects of switching patients with long-standing symptomatic DM-II from their current antipsychotic regimen to ziprasidone.An open-label, prospective inpatient study was conducted with 26 suboptimally responding inpatients with DSM-IV diagnoses of schizophrenia or schizoaffective disorder and comorbid DM-II who were switched to ziprasidone monotherapy and followed for 8 weeks. Outcome measures were fasting glucose, triglycerides, cholesterol, insulin levels, capillary blood glucose levels and weight. After a 3-week cross-titration period, patients were treated with ziprasidone up to a dose of 320 mg daily.Of the 26 study participants, 16 completed the entire study period of 63 days and 10 (38.46%) discontinued participation, primarily due to psychotic relapse. There was a statistically significant reduction in fasting glucose (F=4.43, p=0.05; 14.68 mg/dL mean reduction), capillary blood glucose levels (F=8.90, p=0.01; 25.36 mg/dL mean reduction), weight (F=4.46, p=0.05; 4.68 lb mean weight loss) and Body Mass Index (F=4.40, p=0.05; 3.62 kg/m(2) mean reduction). There was also a reduction in the use of antidiabetic medications after the switch to ziprasidone. Nine (34.62%) patients met criteria for metabolic syndrome (MetS) at baseline, as compared to 4 (15.38%) at endpoint. No change was observed in positive symptoms (F=0.62, p=0.44), negative symptoms (F=1.47, p=0.24) and in total PANSS score (F=0.12, p=0.74).This study suggests significant improvement in metabolic side effects and MetS in the subset of the patients who were able to tolerate switching from a polypharmacy regimen to ziprasidone. There was a large discontinuation rate, which limited the sustained beneficial effects of ziprasidone. The decision to switch to ziprasidone in patients with prior suboptimal response has to balance the potential metabolic benefits and the potential relapse risks of the individual patient first and foremost.

Quetiapine is often prescribed at doses higher than those approved by regulatory authorities, with limited evidence from controlled trials. The objective of this study was to assess the safety, tolerability, and efficacy of high-dose quetiapine (1200 mg/d) compared with a standard dose of 600 mg/d among patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, schizophrenia or schizoaffective disorder hospitalized at 2 state-operated psychiatric facilities. In order to be eligible for randomization, subjects were required to prospectively fail to demonstrate an initial therapeutic response during a 4-week run-in phase with quetiapine at 600 mg/d (immediate release and dosed twice a day). Lack of an adequate initial response was defined a 15% or lower decrease in the Positive and Negative Syndrome Scale total score. Patients were then randomized to either continue quetiapine at 600 mg/d for an additional 8 weeks or to receive 1200 mg/d quetiapine instead. No significant differences were observed between the high dose (n = 29) and standard dose (n = 31) groups in change from baseline to endpoint on extrapyramidal symptoms, electrocardiographic changes, or most laboratory measures between groups. There was a significant difference between groups for triglycerides (P = 0.035), and post hoc tests revealed a decrease in triglycerides from baseline (mean [SD], 162.7 [59.3] mg/dL) to endpoint (mean [SD], 134.8 [ 62.7] mg/dL) for the 600 mg/d group (P = 0.019). The mean change in the Positive and Negative Syndrome Scale total score did not differ between groups. In conclusion, quetiapine at 1200 mg/d, although reasonably tolerated, did not confer any advantages over quetiapine at 600 mg/d among patients who had failed to demonstrate an adequate response to a prospective 4-week trial of 600 mg/d.

To assess the impact of adjunctive aripiprazole versus adjunctive placebo treatment on suicidality in patients with major depressive disorder.Data were pooled from 2 identical aripiprazole augmentation studies. Patients with DSM-IV-TR-diagnosed major depressive disorder with an inadequate response to 8 weeks of prospective antidepressant treatment were randomly assigned to adjunctive placebo or adjunctive aripiprazole (2-20 mg/d) treatment for 6 weeks. Adverse events related to suicidality were identified in the adverse event database using the Medical Dictionary for Regulatory Activities-preferred term. Treatment-emergent suicidal ideation was defined using item 10 (suicidality) of the Montgomery-Åsberg Depression Rating Scale (MADRS) and item 18 (suicidality) of the Inventory of Depressive Symptomatology (IDS).In total, 737 patients were included in the safety database (aripiprazole n = 371; placebo n = 366). No suicides were reported. There were no treatment-emergent, suicide-related adverse events in the aripiprazole group; 2 patients in the placebo group had ≥ 1 adverse event related to suicide (both suicidal ideation). More placebo than aripiprazole patients25 years old experienced a 2-point (P.01) or 1-point (P.05) worsening of MADRS item 10 scores. For this age group, 2-point improvement in MADRS item 10 scores and 1-point improvement of IDS item 18 scores were significantly more common in aripiprazole patients than placebo patients (both P.05).This post hoc analysis demonstrated that adjunctive aripiprazole treatment in patients with depression with a history of an inadequate response to antidepressant medication is associated with a decreased rate of suicidality in a group of subjects not at significant risk. Prospective trials directly assessing suicidality are needed to further understand the benefits of an adjunctive antipsychotic in an at-risk population.clinicaltrials.gov Identifiers: NCT00095823 and NCT00095758.

Background Schizophrenia is a severe and chronic mental illness characterized by continual relapses that may require hospitalization, changes in medications, arrests, emergency room hospitalizations, self-harm or suicidal behavior. Research has shown that costs associated with treatment received following relapse may constitute the largest share of treatment costs psychiatric illnesses. Although, demographic and clinical characteristics associated with relapse have been examined in previous research, information about potential predictors of relapse are limited. The aim of this study was to evaluate the effect of patient and disease characteristics, cognitive, functioning, and COMT gene polymorphism (rs4680) on relapse during 2-year following completion of an inpatient rehabilitation and cognitive treatment. Methods Data were taken from a COMT genotype and response to cognitive remediation study of schizophrenia in the United States conducted between 07/2005 and 10/2015 for inpatients with schizophrenia who were also participating in psychiatric rehabilitation. Patients with and without relapse 2 years following completion of the study were compared on clinical, demographic, cognitive, functional and COMT genotype characteristics. The COMT gene rs4680 polymorphism was genotyped using a DNA sequence detection system. Relapse or events identified as treatment failures include: arrest, psychiatric re-hospitalization, suicide, discontinuation of antipsychotic treatment due to inadequate efficacy, treatment supplementation with another antipsychotic due to inadequate efficacy, discontinuation of antipsychotic treatment due to safety or tolerability, or increase in the level of psychiatric services. Baseline (end of study, start of 2-year follow-up) predictors of subsequent relapse were also assessed. Univariate Analsyis and Cox’s regression was used to examine the effect of potential predictors on outcome. Results Of 140 subjects with eligible data, 91 (65.00%) relapsed during the 2-year follow-up period. Patients who relapsed were younger (< 45 years), higher number of previous hospitalizations, shorter chronicity of illness (< 10 years), PANSS baseline score of >4 on the core PANSS items (conceptual disorganization, hallucinatory behavior, suspiciousness, unusual thought content), higher negative symptom factor, substance use, PSP score of < 60 and lower MCCB composite T score (> 2 SD below the mean). Univariate analysis shows that COMT rs4680 gene variants were different between relapse and stable groups. The COMT rs4680 gene had an interaction with PANSS baseline core item scores and MCCB composite score. Number of previous antipsychotic trials did not predict relapse. Discussion There is a high relapse rate within 2 years in chronic schizophrenia. Behavioral symptoms, aided by genetic and environmental factors common to this population (homelessness, unemployment, and social isolation) frequently lead to treatment failure. Knowing potential triggers of relapse can help in developing resources for this population to reduce treatment failures and associated costs.

Background Recognizing the discrete dimensions that underlie negative symptoms in schizophrenia and how these dimensions are conceptualized across geographical regions may result in better understanding and treatment. The expressive-experiential distinction has been shown to have vast importance in relation to functional outcomes in schizophrenia. Previous studies have shown that the PANSS may not be equivalently rated across counties and cultures, suggesting regional differences in both symptom expression and rater judgment of symptom severity. Items that perform in markedly different ways across demographic, regional, cultural, or clinical severity characteristics may not offer valid representations of the target construct. 1) Will the expressive and experiential dimensions of the PANSS vary over 15 geographical regions and will the item ratings defining each dimension manifest similar reliability across these regions? 2) In large multi-center, international trials where data are combined, which of the two dimensions are disposed to social, linguistic and cultural inconsistency? Methods Data was obtained for the baseline PANSS visits of 6,889 subjects. Using Confirmatory Factor Analysis (CFA), we examined whether the expressive-experiential distinction would be replicated in our sample. We investigated the validity of the expressive-experiential distinction using Differential Item Functioning (DIF; Mantel-Haenszel) across 15 geographical regions – South America-Mexico, Austria-Germany, Belgium-Netherlands, Brazil, Canada, Nordic regions (Denmark, Finland, Norway, Sweden), France, Great Britain, India, Italy, Poland, Eastern Europe (Romania, Slovakia, Ukraine, Croatia, Estonia, Czech Republic), Russia, South Africa, and Spain - as compared to the United States. Results Expressive Deficit: More DIF was observed for items in the Expressive deficit factor than for items relating to experiential deficits. The following regions showed at least moderate to large DIF for all items: Austria-Germany, Nordic, France, and Poland. Of all the items, N3 Poor Rapport showed the most moderate and large DIF (n = 13; 86.67%) across countries, with 7 countries reporting large DIF. Similarly, N6 Lack of Spontaneity and Flow of Conversation showed moderate and large DIF for 66.67% countries (n=10). Experiential Deficit: Item G16 Active Social Avoidance reported negligible DIF for 14 of the 15 countries investigated (93.33%). Large DIF was observed for N2 Emotional Withdrawal and N4 Passive Apathetic Social Withdrawal for Brazil and India. Seven regions demonstrated no DIF across all items of the PANSS experiential deficit factor (South America-Mexico, Belgium-Netherlands, Nordic, Great Britain, Eastern Europe, Russia, and Spain). Overall, there were many fewer observed items with large DIF for PANSS experiential domain. Discussion These results suggest that the PANSS Negative Symptoms Factor can be better represented by a two-factor model than by a single-factor model. Additionally, the results show significant differences in ratings on the PANSS expressive items, but not the experiential items, across regions. This could be due to a lack of equivalence between the original and translated versions, cultural differences in the interpretation of items, rater training, or understanding of scoring anchors. Knowing which items are challenging for raters across regions can help guide PANSS training to improve results of international clinical trials aimed at negative symptoms.

A program evaluation examined a long-term cognitive skills inpatient program (STAIR) in reducing rehospitalization and rearrest rates in mental illness. Psychiatric and criminal histories were obtained. Psychological tests were administered. After discharge, monthly follow-up was obtained. One hundred forty-five patients completed the STAIR program and were followed for a range of six to 60 months after discharge. Thirty-one (21.4%) remained stable, 67 (46.2%) were rehospitalized, and 47 (32.4%) were rearrested and/or rehospitalized. Group membership was predicted by STAIR admission age and outpatient medication compliance. Significantly, fewer arrests, hospitalizations, and days institutionalized occurred post-STAIR. Medication compliance is the single most enduring factor associated with clinical stability and prevention of criminal behavior. Other factors’ impact may vary depending on the length of stay in the community. Long-term inpatient programs (e.g., STAIR) may be helpful to some of these patients.

Background: After noting a significant reduction in aggression and agitation in treatment-refractory patients with molindone augmentation in severely aggressive inpatients, the authors conducted a retrospective medical records review to assess the possible anti-aggressive role of molindone treatment in a larger cohort of treatment-refractory inpatients. Method: Twenty-four weeks of data from thirty inpatients who were consecutively augmented with molindone, including progress notes, orders for seclusion, chemical restraint, and scores on the Agitation-Calmness Evaluation Scale (ACES) were systematically collected. The number of seclusions, number of as-needed medications (PRNs) and ACES scores were used to tabulate the frequency of aggression and agitation episodes during the 8-week period before, 8 weeks after, and 9 through 16 weeks after the initiation of molindone augmentation treatment. Results: Over the observation period of twenty-four weeks, the number of episodes of PRN medication administration ...

OBJECTIVE Primary negative symptoms are intrinsic to the pathology of schizophrenia and are associated with significant deficits in motivation, verbal and nonverbal communication, affect, and cognitive and social functioning. Overall, atypical antipsychotic medications have been found to be more efficacious than conventional antipsychotics in the treatment of negative symptoms, based on studies with acute patients. Results have been confounded by concomitant improvements in positive, depressive, and extrapyramidal symptoms. This 12-week, double-blind, controlled study aimed to examine the effects of the atypical antipsychotic olanzapine versus haloperidol on persistent, primary negative symptoms and neurocognitive functions in stable schizophrenic patients with the deficit syndrome and low levels of concomitant positive, depressive, and extrapyramidal symptoms. METHOD Thirty-five patients with DSM-IV-TR schizophrenia and predominant negative symptoms were randomly assigned in a 12-week double-blind study to either olanzapine (15-20 mg/day) or haloperidol (15-20 mg/day). Patients taking haloperidol received additional blinded benztropine. Inclusion criteria were Positive and Negative Syndrome Scale (PANSS) negative score of >or=20, PANSS positive score < 20, and fulfilling the criteria for the Schedule for the Deficit Syndrome. The PANSS, Clinical Global Impressions, Hamilton Rating Scale for Depression (HAM-D), Simpson-Angus Scale, and Abnormal Involuntary Movement Scale were assessed at regular subsequent intervals. A neuropsychological battery examining declarative verbal learning memory, attention and processing speed, executive functioning, and simple motor functioning domains of cognition was assessed at baseline and endpoint. The study ran from September 1998 through May 2005. RESULTS CLINICAL RESULTS There was a statistically significant difference for PANSS negative symptoms (F = 5.44, df = 1,15; p

Background: Significant increase in life expectancy has been observed in patients with β-thalassemia in recent years. The improved survival, however, is accompanied by significant ongoing healthcare needs related to the chronic condition; therefore, quality of life (QoL) has emerged as a fundamental focus of comprehensive patient care. We compared QoL outcomes between transfusion-dependent (TD) and non-transfusion-dependent (NTD) patients with β-thalassemia in the routine clinical care setting. Method: Adult patients with β-thalassemia were prospectively enrolled in an observational study in Italy, Greece, Lebanon, and Thailand. All patients completed Short Form 36 Health Survey version 2 (SF-36v2) and Functional Assessment of Cancer Therapy (FACT)-Anemia (An) questionnaires at baseline, and then once every 3 weeks using a hand-held electronic device. This analysis evaluated QoL between TD and NTD patients at study entry. Transfusion dependent was defined as receiving ≥ 6 red blood cell (RBC) units in the 24 weeks prior to study entry and no transfusion-free period for ≥ 35 days during that period. Results: A total of 102 patients with β-thalassemia were enrolled, of which 52 were TD and 50 NTD. The mean age of patients was 31.2 years and 70 (68.6%) were females. On average, patients with TD β-thalassemia were 3.6 years younger (P= 0.06) and had moderately higher hemoglobin values at baseline (8.8 vs 8.2 g/dL; P= 0.02). At study entry, all (100%) patients with TD β-thalassemia had received RBC transfusions within the 24 weeks prior to study entry, as per inclusion criteria, versus 5 (10%) patients with NTD β-thalassemia who had received RBC transfusions during the same time period. Patients with NTD β-thalassemia reported lower QoL on all domains and summary scores as captured by the SF-36v2 questionnaire, except for Role-Physical. On average, patients with NTD β-thalassemia experienced statistically significant lower QoL versus their TD counterparts on the domains of General Health (39.5 vs 44.0; P= 0.01), Vitality (49.3 vs 53.7; P= 0.01), and Mental Health (46.8 vs 50.8; P= 0.01), and in the Mental Component Summary Score (46.5 vs 50.8; P= 0.01). Similarly, patients with NTD β-thalassemia reported worse QoL scores from the FACT-An questionnaire on all domains and statistically significant differences were observed for Emotional Well-Being (18.5 vs 20.0; P= 0.02), Functional Well-Being (20.0 vs 23.2; P < 0.01), and FACT-General (82.9 vs 89.4; P= 0.01). Conclusions: In the routine clinical care setting, there are critical unmet medical needs for patients with NTD β-thalassemia as they experience worse QoL on many domains compared with patients with TD β-thalassemia. There is a need for new interventions to treat patients with NTD β-thalassemia and reduce their burden of disease. Disclosures Cappellini: Vifor: Honoraria; Novartis: Speakers Bureau; Celgene: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding, Speakers Bureau. Kattamis: National and Kapodistrian University of Athens: Employment; Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy. Viprakasit: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Siriraj Hospital: Employment; Shire: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding. Sutcharitchan: Celgene: Research Funding; Chulalongkorn University: Consultancy, Employment. Mahmoud: Celgene: Employment. Pariseau: Celgene: Employment. Laadem: Celgene: Employment, Equity Ownership. Khan: Nathan S. Kline Institute for Psychiatric Research; Manhattan Psychiatric Center: Employment. Hu: Celgene: Employment, Equity Ownership. Taher: Novartis Pharmaceuticals: Honoraria, Research Funding; Celgene: Research Funding.

Impairments in social and cognitive functioning are some of the most disabling features of the schizophrenia. They result in poorer communication with others, difficulties in maintaining employment status and decrease in community involvement. Recently, cognitive remediation therapy (CRT), which relies on computer-based drill and practice exercises, has emerged as a nonpharmacological intervention that aims to target and improve cognitive and social functions. Given the recent success of CRT based approaches, the question arises: can other nonpharmacological interventions which aim to augment and improve socio-cognitive functions be effective? Building upon Vygotsky's (1934) theorizing, we conducted an 8-week long study involving 19 participants. The study uses the methodology of narrative inquiry to examine participants’ ability to employ varied socio-cognitive functions (affect, causation, perceptive-taking, logical/hypothetical inference, etc.) when writing about everyday activities and attempting to resolve conflicts in narratives. Prompts employed in this study directed participants to write about three different socio-cultural contexts: (1) inpatient; (2) outpatient and (3) a fictional context. The fictional context aimed to examine participant's ability to imagine and express alternative futures/scenarios. Data show significantly higher frequency of occurrence of linguistic devices tied to cognitive functions in (3) fictional narrative context when compared to either (1) inpatient or (2) outpatient context. Use of affect was the only statistically significant difference between contexts (1) and (2). Findings indicate that individuals diagnosed with schizophrenia are able to vary the use of social and cognitive functions across narrative contexts, suggesting that future socio-cognitive interventions can be anchored in mindfully planned narrative activities.Disclosure of interestThe authors have not supplied their declaration of competing interest.