Utilizing Technology to Enhance the Ecological Validity of Cognitive and Functional Assessments in Schizophrenia: An Overview of the State-of-the-Art.

Cognitive impairment is a core feature of schizophrenia and a key determinant of functional outcome. Although conventional paper-and-pencil based cognitive assessments used in schizophrenia remained relatively static during most of the 20th century, this century has witnessed the emergence of innovative digital technologies that aim to enhance the ecological validity of performance-based assessments. This narrative review provides an overview of new technologies that show promise for enhancing the ecological validity of cognitive and functional assessments.

The Impact of Xanomeline and Trospium Chloride on Cognitive Impairment in Acute Schizophrenia: Replication in Pooled Data From Two Phase 3 Trials.

Objective: Xanomeline and trospium chloride (formerly known as KarXT), a novel M/M muscarinic receptor agonist, demonstrated efficacy across phase 2 and 3 trials as monotherapy for the treatment of inpatients with acute schizophrenia on the Positive and Negative Syndrome Scale total score primary endpoint. In the phase 2 trial, xanomeline/trospium improved performance on a cognitive outcome measure in the subgroup of participants with clinically significant baseline cognitive impairment. The authors sought to confirm this finding using data from two phase 3 trials.

Rationale and Challenges for a New Instrument for Remote Measurement of Negative Symptoms.

There is a broad consensus that the commonly used clinician-administered rating scales for assessment of negative symptoms share significant limitations, including (1) reliance upon accurate self-report and recall from the patient and caregiver; (2) potential for sampling bias and thus being unrepresentative of daily-life experiences; (3) subjectivity of the symptom scoring process and limited sensitivity to change. These limitations led a work group from the International Society of CNS Clinical Trials and Methodology (ISCTM) to initiate the development of a multimodal negative symptom instrument. Experts from academia and industry reviewed the current methods of assessing the domains of negative symptoms including diminished (1) affect; (2) sociality; (3) verbal communication; (4) goal-directed behavior; and (5) Hedonic drives.

The potential of muscarinic M and M receptor activators for the treatment of cognitive impairment associated with schizophrenia.

Cognitive impairment is a core symptom of schizophrenia and a major determinant of poor long-term functional outcomes. Despite considerable efforts, we do not yet have any approved pharmacological treatments for cognitive impairment associated with schizophrenia (CIAS). A combination of advances in pre-clinical research and recent clinical trial findings have led to a resurgence of interest in the cognition-enhancing potential of novel muscarinic acetylcholine receptor (mAChR) agonists in schizophrenia.

Efficacy of KarXT on negative symptoms in acute schizophrenia: A post hoc analysis of pooled data from 3 trials.

Background: Currently approved antipsychotics do not adequately treat negative symptoms (NS), which are a major determinant of functional disability in schizophrenia. KarXT, an M /M preferring muscarinic receptor agonist, has shown efficacy as a broad-spectrum monotherapy for the treatment of schizophrenia in participants with acute psychosis. Post hoc analyses evaluated the possibility that NS improve independently of positive symptoms with KarXT in a subgroup of participants with moderate-to-severe NS and no predominance of positive symptoms.

Location-based differences in cognition and functional capacity: Consistent levels of impairment in participants with schizophrenia compared to healthy controls.

Cognitive performance manifests regional differences, correlated with education. There is less information available about regional differences in performance-based measures of functional capacity. In multi-national trials focused on cognitive enhancement, it may be impossible to validate every measure in all locations.

Current and Emerging Technologies to Address the Placebo Response Challenge in CNS Clinical Trials: Promise, Pitfalls, and Pathways Forward.

Excessive placebo response rates have long been a major challenge for central nervous system (CNS) drug discovery. As CNS trials progressively shift toward digitalization, decentralization, and novel remote assessment approaches, questions are emerging about whether innovative technologies can help mitigate the placebo response. This article begins with a conceptual framework for understanding placebo response.

Social cognition and social motivation in schizophrenia and bipolar disorder: are impairments linked to the disorder or to being socially isolated?

Background: People with schizophrenia on average are more socially isolated, lonelier, have more social cognitive impairment, and are less socially motivated than healthy individuals. People with bipolar disorder also have social isolation, though typically less than that seen in schizophrenia. We aimed to disentangle whether the social cognitive and social motivation impairments observed in schizophrenia are a specific feature of the clinical condition social isolation generally.

An ERP Study of Face Processing in Schizophrenia, Bipolar Disorder, and Socially Isolated Individuals from the Community.

People with schizophrenia (SCZ) and bipolar disorder (BD) have impairments in processing social information, including faces. The neural correlates of face processing are widely studied with the N170 ERP component. However, it is unclear whether N170 deficits reflect neural abnormalities associated with these clinical conditions or differences in social environments.

Qualitative Analysis of the Content Validity of the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) in Schizophrenia: A Multi-Stakeholder Perspective.

The US Food and Drug Agency (FDA) requires clinical trials targeting cognitive impairment associated with schizophrenia (CIAS) to demonstrate the functional relevance of cognitive improvements by employing a functional co-primary measure. Although quantitative evidence supports the suitability of the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) for this purpose, FDA guidelines for qualification of clinical outcome assessments require evidence of content validity, defined as qualitative evidence that key stakeholders view the measure as relevant and important. To collect this important qualitative data, semi-structured interviews were conducted with outpatients with schizophrenia ( = 24), caregivers ( = 12), and professional peer support specialists ( = 12) to elicit their views about the definition and importance of functional independence, the importance of the functional domains assessed by the VRFCAT (meal planning, using transportation, handling money, shopping), and the relevance of the VRFCAT tasks to these domains.

Neuroimaging of social motivation during winning and losing: Associations with social anhedonia across the psychosis spectrum.

Background: Individuals with psychosis spectrum disorders (PSD) have difficulty developing social relationships. This difficulty may reflect reduced response to social feedback involving functional alterations in brain regions that support the social motivation system: ventral striatum, orbital frontal cortex, insula, dorsal anterior cingulate cortex, and amygdala. Whether these alterations span PSD is unknown.

Neurophysiological indices of face processing in people with psychosis and their siblings: An event-related potential study.

People with schizophrenia experience difficulties with social interactions. One contributor to these social deficits is dysfunction in processing facial features and facial emotional expressions. However, it is not known whether face processing deficits are evident in those with other psychotic disorders or in those genetically at-risk for psychosis (i.

A Bayesian Network Approach to Social and Nonsocial Cognition in Schizophrenia: Are Some Domains More Fundamental than Others?

Objectives: Social and nonsocial cognition are defined as distinct yet related constructs. However, the relative independence of individual variables-and whether specific tasks directly depend on performance in other tasks-is still unclear. The current study aimed to answer this question by using a Bayesian network approach to explore directional dependencies among social and nonsocial cognitive domains.

Aberrant reward processing to positive versus negative outcomes across psychotic disorders.

Several studies of reward processing in schizophrenia have shown reduced sensitivity to positive, but not negative, outcomes although inconsistencies have been reported. In addition, few studies have investigated whether patients show a relative deficit to social versus nonsocial rewards, whether deficits occur across the spectrum of psychosis, or whether deficits relate to negative symptoms and functioning. This study examined probabilistic implicit learning via two visually distinctive slot machines for social and nonsocial rewards in 101 outpatients with diverse psychotic disorders and 48 community controls.

An Update on Treatment of Cognitive Impairment Associated with Schizophrenia.

Cognitive impairment associated with schizophrenia (CIAS) is widely regarded as a critically important treatment target for schizophrenia. Despite major efforts and a number of promising findings, we do not yet have an approved drug for CIAS. Similarly, promising cognitive remediation approaches are limited in their ability to help patients achieve real-world functional gains on a wide scale.

Intact differentiation of responses to socially-relevant emotional stimuli across psychotic disorders: An event-related potential (ERP) study.

Event-related potential (ERP) studies of motivated attention in schizophrenia typically show intact sensitivity to affective vs. non-affective images depicting diverse types of content. However, it is not known whether this ERP pattern: 1) extends to images that solely depict social content, (2) applies across a broad sample with diverse psychotic disorders, and (3) relates to self-reported trait social anhedonia.

Social cognition and social problem solving skills training to improve job functioning and tenure in veterans with psychotic disorders.

Objective: Veterans with psychotic disorders often experience employment difficulties. Job tenure is highly variable with shorter tenure frequently tied to interpersonal difficulties in the workplace. The present study sought to address this problem by examining the efficacy of social cognition skills training (SCST) and social problem solving skills training (SPSST) interventions, implemented sequentially, and added to usual VA employment services (augmented vocational rehabilitation [VR]).

Using Artificial Intelligence-based Methods to Address the Placebo Response in Clinical Trials.

The placebo response is a highly complex psychosocial-biological phenomenon that has challenged drug development for decades, particularly in neurological and psychiatric disease. While decades of research have aimed to understand clinical trial factors that contribute to the placebo response, a comprehensive solution to manage the placebo response in drug development has yet to emerge. Advanced data analytic techniques, such as artificial intelligence (AI), might be needed to take the next leap forward in mitigating the negative consequences of high placebo-response rates.

Examining racial differences in community integration between black and white homeless veterans.

Black Americans are overrepresented in Veteran and non-Veteran homeless populations. Community integration remains a problem for many Veterans after they obtain housing, and Black Veterans may encounter additional difficulties due to systemic racism. However, no prior study has specifically examined whether there are racial differences in community integration; similarly, no study has considered racial differences in psychosocial correlates of community integration in homeless Veterans.

The effect of sex on social cognition and functioning in schizophrenia.

Social cognitive impairment is a core feature of schizophrenia and plays a critical role in poor community functioning in the disorder. However, our understanding of the relationship between key biological variables and social cognitive impairment in schizophrenia is limited. This study examined the effect of sex on the levels of social cognitive impairment and the relationship between social cognitive impairment and social functioning in schizophrenia.

Placebo response mitigation with a participant-focused psychoeducational procedure: a randomized, single-blind, all placebo study in major depressive and psychotic disorders.

The remarkably high and growing placebo response rates in clinical trials for CNS indications, such as depression and schizophrenia, constitute a major challenge for the drug development enterprise. Despite extensive literature on participant expectancies and other potent psychosocial factors that perpetuate placebo response, no empirically validated participant-focused strategies to mitigate this phenomenon have been available. This study evaluated the efficacy of the Placebo-Control Reminder Script (PCRS), a brief interactive procedure that educates participants about factors known to cause placebo response, which was administered prior to the primary outcome assessments to subjects with major depressive or psychotic disorders who had at least moderate depression.

Factor structure of cognitive performance and functional capacity in schizophrenia: Evidence for differences across functional capacity measures.

Background: Cognition and functional capacity predict functional outcomes in mental illness. Traditional approaches conceptualize cognition as comprised of domains, but many studies support a unifactorial structure. Some functional capacity measures may share a single-factor structure with cognition.

Benefits of social cognitive skills training within routine community mental health services: Evidence from a non-randomized parallel controlled study.

Although social cognitive impairments are evident in patients with schizophrenia across many cultures, psychosocial interventions are less used in Eastern countries. Despite a growing emphasis on community care in mental health services in Eastern countries, the synergistic effects of social cognitive intervention strategies on routine community mental health services are not well documented. This study aimed to adapt a group-based social cognitive skills training (SCST) program for use in a Korean context and evaluate its feasibility and preliminary effects among community-dwelling individuals with schizophrenia.