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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: Clinical trials for schizophrenia are increasingly using electronic methods to collect patient-reported outcomes (ePRO). Hence, several ePROs have been developed to better understand patients’ experience with their own illness. Lack of insight into illness is a core feature of schizophrenia that is multidimensional,and related to poor compliance with treatment and relapse. Assessing insight into illness via an ePRO, and attaining patient perception may provide supplemental information to the clinician as data is collected in real-time to facilitate functional and risk assessment. Core questions are whether it is feasible for patients with schizophrenia to complete an ePRO on their smartphone, and will the results obtained from patient’s perception of insight compare to clinician assessed insight, and passive digital biomarkers of psychiatric morbidity. The aim is to (1) develop a short, multidimensional self-report measure of insight (Awareness of Insight Scale, AIS), (2) assess validity and reliability, and (3) evaluate feasibility in schizophrenia study context. METHODS: A Delphi method was used to facilitate expert participation and ensure face and content validity for development of the AIS. The SUMD and SCI-PANSS G12 Lack of Insight were used as a reference for scale development. A new scale with 8 items incorporating David’s (1990) dimensions of insight was developed consisting of: (1) awareness of having a mental illness, 2) relabel unusual mental events as pathological, and 3) adherence to treatment. The scale was presented as a smartphone app for 6 months via a parent study assessing passive digital biomarkers of psychiatric morbidity (Mindstrong Health). Feasibility was assessed based on the rate of completion of the ePRO. Internal consistency, test-retest reliability and validity were assessed by comparing with PANSS: G12 and Disorganization Factor in a sample of 16 outpatients. The ePRO was designed with push messages suggesting patients complete the scale once per week. RESULTS: The 8 items selected for inclusion in the AIS assessed awareness of psychiatric illness, need to take medications, attributing being sad or upset to unusual experiences, and belief that s/he is always correct. Of the 22 subjects enrolled, data is presented for 16 subjects, as the remaining 6 subjects were not active on their smartphones. Of the 16 subjects, all completed at least 2 weeks of AIS assessments on their smartphone with 68.75% completing all weekly assessments since enrollment with an average of 3.66 minutes to complete. Internal Consistency was high (α = 0.79). Preliminary findings show scores on AIS correlated with PANSS G12 (r = 0.51, p = 0.03) and with the PANSS Disorganization Factor (r = 0.39, p = 0.04). Test-retest reliability are moderate with ICCs = 0.72. DISCUSSION: Preliminary findings show the AIS is a short, reliable and valid measure of insight in schizophrenia. Findings support its feasibility in a small sample of outpatients with chronic and treatment resistant schizophrenia with multiple relapses.

BACKGROUND: A patient’s readiness for discharge can be assessed from the perspectives of the clinician, patient, and family. Criterion-based assessment by the clinician is the most commonly reported method, but there is no ecologically valid method available to assess readiness for discharge while in the hospital. The Virtual Reality Functional Capacity Assessment Tool (VRFCAT) is a novel game-based program, that provides a sequence of objectives related to activities involved in a multi-level shopping task. The aim of the present study was (1) to examine the feasibility of administering the VRFCAT in a population of very low functioning patients with chronic schizophrenia, (2) to relate the performance of the study patients to standardized VRFCAT performance data of higher functioning patients (Keefe et al. 2016), (3) to assess the concurrent validity of the VRFCAT in this population, and (4) to correlate the performance measures to measures of community adjustment 4 weeks after hospital discharge. METHODS: The VRFCAT was administered after informed consent to inpatients with DSM 5 diagnosis of chronic schizophrenia, who were eligible for discharge from a long-term inpatient psychiatric facility. Independent variables included the VRFCAT time to completion (adjusted total time), number of errors on 12 VRFCAT objectives, and the number of times that an individual failed to complete a task (forced progression). The SLOF, the UPSA-B and the PSP were completed for concurrent validity. Patients were followed for one month after their discharge to assess the level of their community adjustment as measured by the SLOF, the UPSA-B and the PSP. RESULTS: Of the 80 subjects enrolled, a total of 72 subjects had evaluable data with a mean age of 41.23 years (SD = 10.11). 55.56% of subjects also had an axis I substance use diagnosis. The mean level of education was 9.89 (SD = 2.69) and 56.94% of patients had a history of incarceration. When compared to higher functioning patients’, participants performed 2.5 standard deviations below the mean for the adjusted total time (Mean T Score = 24.89, SD = 16.56), total errors (T = 24.11, SD = 22.69), and 2 SDs below the mean for total forced progressions (T = 29.56, SD = 14.311). VRFCAT test-retest reliability showed unchanged mean T scores: total time (T Score = 23.11, SD = 16.23), total errors (T = 23.56, SD = 22.00). Pearson correlations at baseline for 4 of 12 VRFCAT objectives with concurrent SLOF Activities (Pay for the Bus, Shop for Groceries, Pay for Groceries), and Work Skills (Shop for Groceries, Pay for Groceries) domain scores were statistically significant (p < 0.001). At 4-week follow-up, significant correlation was found with the change in PSP Domain A of socially useful activities and change in VRFCAT Adjusted Total Time [r = 0.586, p = 0.044]. There were no significant correlations between the SLOF and VRFCAT for change from baseline. There was no difference in VRFCAT scores between the subjects who were re-hospitalized and those who missed clinic appointments. Non-relapsing participants had a higher score on adjusted total time, which indicates worst functional outcomes. DISCUSSION: Results indicate that the VRFCAT is feasible in schizophrenia patients with low levels of functioning and delivers meaningful functional concurrent data. Both concurrent and test-retest validity were good. The VRFCAT performance level was not useful for measurement of readiness for discharge for clinical purposes.

BACKGROUND: One of the key risk factors for relapse in schizophrenia is poor insight. Genetic influences on poor insight have not yet been studied despite growing evidence to the extent of genetic contributions in schizophrenia. There is evidence of genetic associations for psychopathology symptom domains (Arnedo et al., 2015) and these domains are strongly associated with insight. Dysfunction of the catechol-O-methyltransferase (COMT) gene is shown to confer susceptibility to schizophrenia because of its catalytic activity for dopamine degradation. COMT Val allele more rapidly inactivates released dopamine than the Met allele, and is shown to be associated with cognitive performance such as working memory and attention, and influences ToM functioning by modulating the dopamine pathways. Since the role of COMT in schizophrenia remains questionable, we determined whether any association exists between COMT genotypes and clinical symptomatology (Lack of Insight and Judgment) in a large cohort of schizophrenia subjects. METHODS: 145 subjects with DSM-IV-TR schizophrenia or schizoaffective disorder were genotyped via saliva sampling. Subjects were evaluated on clinical symptoms (PANSS). Genotyping of the COMT Val158Met polymorphism was evaluated compared to PANSS Marder factors, including PANSS items Lack of Insight and Judgment. RESULTS: Of 145 subjects, data from 138 subjects were usable. Distribution of COMT genotype: Met/Met: 28 (20.29%), Val/Met: 61 (44.20%), and Val/Val: 49 (35.51%). There was no significant difference between mean PANSS total score Met/Met: 76.053 (SD 13.011), Met/Val: 78.001 (SD 12.489), Val/Val: 79.596 (SD 11.286). Patients with the COMT Val/Val genotype had significantly higher total score on the PANSS Item Lack of Insight than those with the Val/Met or Met/Met genotypes (p = 0.041). Patients with the COMT Val/Val genotype also had significantly higher scores on the PANSS Disorganized Factor than those with the COMT Val/Met genotype (p = 0.043). As an exploratory analysis, COMT Val/Met showed significant association with Blunted Affect (p = 0.039), but no other items of the negative symptom factor. DISCUSSION: Our findings support hypotheses regarding associations between COMT polymorphisms and lack of insight and judgment in schizophrenia. It is important that the exact mechanisms of genetic contribution to insight are delineated to aid the development of effective treatments and to identify prevention strategies.

BACKGROUND: The association between schizophrenia and violence is an important issue in psychiatry. The impact of several factors (social cognition, neurocognition, alexithymia, emotion regulation capacity, and the therapeutic milieu) on aggression in schizophrenia creates an opportunity for the development and evaluation of novel treatments for aggression. Previous studies show that cognitive remediation training (CRT) and social cognitive training (SCT) help to decrease hostility. The parent study examined whether cognitive training leads to improvements in cognition emotion regulation capacity, and impulse control in participants with a history of impulsive aggression. The current study examined the effectiveness of CRT alone versus a combination of CRT and SCT in terms of emotion recognition and cognitive improvement. METHODS: The study recruited participants with schizophrenia or schizoaffective disorder with a past year history of at least 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 from two inpatient sites (Manhattan Psychiatric Center and New York Hospital, Westchester Division). Participants were randomized to two groups of 36 one-hour sessions. Participants in the control group had 24 sessions of CRT (BrainHQ) and 12 sessions of Encyclopedia readings. Participants in the treatment group had 24 sessions of CRT (BrainHQ) and 12 sessions of computerized SCT (MindReading). To assess neurocognition, mentalizing, and facial affect recognition abilities, participants were administered the MATRICS Consensus Cognitive Battery (MCCB), Reading the Mind in the Eyes Task (Eyes Task), and the Emotion Recognition-40 (ER-40) respectively. Negative emotionality was captured using the Positive and Negative Affect Schedule (PANAS). RESULTS: The study data included 49 completers and 5 intent-to-treat samples, with 24 and 25 per group, respectively (CRT+ SCT and CRT alone). Results indicated no significant differences between groups at baseline. Significant overall improvements were observed in the ER-40 for all subjects across time (Mean Time 1 = 25.06 (SD = 25.023), Time 2 Mean = 30.86 (SD = 6.849), p < 0.001), the Mind in the Eyes Test - Revised (Time 1 Mean = 19.70 (SD = 7.407), Time 2 Mean = 26.15 (SD = 7.830), p < 0.001), and the PANAS Negative affect Score (Time 1 Mean = 29.40 (SD = 11.836), Time 2 Mean = 18.47 (SD = 2.688), p < 0.001). Both cognitive groups showed improvements from baseline on the composite cognition score of the MCCB composite (F (1,47)=74.51, p

Virtual Reality (VR) approaches have had considerable success in measurement of functional capacity. However, it is not clear if factors other than cognitive impairment influence performance on VR measures. Many people with schizophrenia have significant negative symptoms and they could reduce engagement in assessment. 158 patients with schizophrenia performed the VRFCAT, were tested with the MCCB, were rated with the PANSS, and were rated on everyday functioning. Scores for reduced emotional experience and reduced expression were derived. Reduced emotional experience, but not reduced expression, was correlated with socially relevant VRFCAT subtasks and real-world social functioning. Performance on the socially relevant subtasks, but not the solitary subtasks, shared variance with work outcomes. MCCB performance was associated with both subdomains, but socially relevant subtasks shared more variance. Patients with higher reduced emotional experience validly engaged in socially relevant VR simulations, as indexed by correlations with outcome measures. These patients had poorer performance on socially relevant tasks than on solitary tasks. The differential validity of solitary vs. socially relevant simulations was supported by differences in correlates, suggesting that assessments with a focus on performance of simulated socially relevant tasks could be developed.

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​.

Background: Following both meta-analysis and extensive resequencing, the single-nucleotide polymorphism of allele A, rs1344706, located in intron 2 of the zinc-finger protein gene ZNF804A, continues to be the common variant most strongly associated with schizophrenia risk (P = 1.1_10–13). ZNF804a is highly expressed in adult brain and functional effects on both protein expression, and altered DNA–protein interaction have been reported. In addition, the ZNF804A rs1344706 A allele has recently been reported to be associated with worse clinical outcome. We were interested in examining whether another proxy for worse clinical outcome, the Positive and Negative Syndrome Scale (PANSS) excitement factor, is associated with a ZNF804a genotype. We hypothesized that a single-nucleotide polymorphism in ZNF804a could be associated with impulsivity. The aim of this study was to assess the association of a single-nucleotide polymorphism rs1344706 with the PANSS excitement factor.

Background: The Brief Assessment of Cognition in Schizophrenia (BACS) is a pen-and-paper cognitive assessment tool that has been used in hundreds of research studies and clinical trials, and has normative data available for generating age- and gender-corrected standardized scores. A tablet-based version of the BACS called the BAC App has been developed to allow standardized presentation of task instructions and stimuli, audio-recording of subject responses, and automatized scoring and data management. Development of the BAC App was aimed at reducing rater burden and variability. Our validation study compared performance on the traditional BACS and the BAC App in patients with schizophrenia and healthy controls. Test equivalency was assessed, and the applicability of paper-based normative data was evaluated. An ongoing follow-up study examines BAC App performance in large-scale census-matched normative sample.

Background: Assessment of functional capacity is vital in establishing an understanding of real world functioning in patients with cognitive impairment in schizophrenia. Most available tests of functional capacity are paper and pencil tests, or are not fully computerized. The Virtual Reality Functional Capacity Assessment Tool (VRFCAT), developed by NeuroCog Trials, is a novel VR program, which provides a sequence of typical and real life community tasks. It offers ecological validity and complements the clinical assessment of functional capacity The aim of the present study was (1) to examine the feasibility of the VRFCAT in a population of very low functioning patients with Treatment resistance schizophrenia (TRS), (2) to relate the performance of the study patients to standardized VRFCAT performance data of higher functioning patients (Keefe et al,. 2016) and (3) to validate the performance level with other concurrent function measures.

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 The Self-Evaluation of Negative Symptoms (SNS), a 20-item self-rating scale,was developed to assess the subjective experience of negative symptoms by schizophrenia patients. The reliability and validity of the translated French version of the SNS was examined in a sample of outpatients in an US site with schizophrenia and schizoaffective disorders (Dollfus et al., 2015). The author found that the SNS had good psychometric properties and demonstrated that the patients’ ratings were highly correlated with observer ratings, which contradicts the expected lack of reliability of patient reported symptoms in patients with schizophrenia. However, the patients included in the study were stable outpatients with high levels of functioning as compared to lower functioning patients. It remains to be explored whether patients with lower levels of functioning are equally able to identify their negative symptoms in a reliable fashion. The aim of the present study was to first evaluate the reliability of the novel tool of self-evaluation of Negative Symptoms (SNS) and to examine its correlation with observer ratings of negative symptoms in a sample of inpatients with ICD 10 schizophrenia or schizo-affective disorder who function at a low level of overall cognition. It was our goal to examine if chronic, low functioning patients are able to complete the instrument without assistance, providing clinically meaningful information with respect to their own perception of negative symptoms. Methods Patients who met DSM-5 criteria for schizophrenia or schizoaffective disorder were included in the study. All patients will provide written informed consent. Patients were administered the SNS assessment at two time points, separated by 1 one week, followed by other concurrent evaluations: the 16-Item Negative Symptom Assessment (NSA-16), a validated clinical assessment for negative symptoms, the CGI-S, WRAT, BACS, and the CDSS. To examine the internal consistency of the SNS. Cronbach’s alpha was calculated for the 20 items and the 5 sub scores at both times. Correlation analyses were performed to examine the convergent validity of the SNS with the observer rated negative symptom scale. Convergent and discriminant validities were tested with Pearson’s correlations. The test-retest reliability of the SNS will be tested by intraclass correlation coefficients (ICCs). Results Fourteen patients with schizophrenia or schizoaffective disorder according to DSM-5, and a mean age of 43.00 (12.48) were evaluated. 66.67% of subjects were African American. Cronbach’s coefficient of the SNS (α = 0.791) showed good internal consistency. The SNS did not show significant correlations with the NSA-16 (r = 0.207, p = 0.497), the NSA global score (r = 0.390, p = 0.296), nor the Clinician Global Impression on the severity of negative symptoms (r = -0.264, p = 0.383). SNS scores did not correlate with level of insight as measured by the SUMD (r = -0.51, p = 0.870), Motor Functioning deficits as measured by the SAS (r = 0.227, p = 0.456). The intrasubject reliability of the SNS revealed good intraclass correlation coefficients (ICC = 0.780). Test-Retest was significant at 0.791, p = 0.004, with a significant change at t(12) = 3.923, p = 0.002. Discussion Our pilot study suggests that the agreement between self-rating and observer-rating of negative symptoms in patients with treatment resistant schizophrenia is rather low as. Patients also evaluated the severity of their negative symptoms rather differently. Reasons for this discrepancy will be discussed, in particular, in the context of low levels of illness insight as well as the psychometric qualities if the SNS.

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.

Background Patients with schizophrenia commonly show both depressive and negative symptoms that can differentially affect the prognosis and course of treatment. The Calgary Depression Scale for Schizophrenia (CDSS) was designed to distinguish between depression and negative symptoms in patients with schizophrenia. The purpose of this study is to validate an Arabic version of the CDSS among patients with schizophrenia. Methods The diagnosis of schizophrenia was confirmed using the Arabic Mini International Neuropsychiatric Interview 6 (MINI 6). A standardized translation back-translation process was adopted. One rater administered the Arabic CDSS to subjects with schizophrenia as well as to a control group who should not have any psychiatric disorder except for depression. Another rater, blinded to the results administered the already validated Arabic version of Beck Depression Inventory-II (BDI-II). Results We recruited 102 patients and 102 controls subjects. The CDSS showed good internal consistency in the active group (Cronbach’s alpha = 0.82). The Intraclass Coefficient correlations (ICC) for the inter-rater reliability (n = 21) was 0.90, p

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.