Cognition in MCI has responded poorly to pharmacological interventions, leading to use of computerized training. Combining computerized cognitive training (CCT) and functional skills training software (FUNSAT) produced improvements in 6 functional skills in MCI, with effect sizes >0.75. However, 4% of HC and 35% of MCI participants failed to master all 6 tasks. We address early identification of characteristics that identify participants who do not graduate, to improve later interventions.

NC participants (n = 72) received FUNSAT and MCI (n = 92) participants received FUNSAT alone or combined FUNSAT and CCT on a fully remote basis. Participants trained twice a week for up to 12 weeks. Participants “graduated” each task when they made one or fewer errors on all 3–6 subtasks per task. Tasks were no longer trained after graduation.

Between-group comparisons of graduation status on baseline completion time and errors found that failure to graduate was associated with more baseline errors on all tasks but no longer completion times. A discriminant analysis found that errors on the first task (Ticket purchase) uniquely separated the groups, F = 41.40, p < .001, correctly classifying 94% of graduators. An ROC analysis found an AUC of .83. MOCA scores did not increase classification accuracy.

More baseline errors, but not completion times, predicted failure to master all FUNSAT tasks. Accuracy of identification of eventual mastery was exceptional. Detection of risk to fail to master training tasks is possible in the first 15 minutes of the baseline assessment. This information can guide future enhancements of computerized training.

Suicide risk among individuals with psychosis is elevated compared to the general population (e.g., higher rates of suicide attempts [SA] and completions, more severe lethality of means). Importantly, suicidal ideation (SI) seems to be more predictive of near-term and lifetime SAs in people with psychosis than in the general population. Yet, many randomized controlled trials in psychosis have excluded individuals with suicidality. Additionally, research suggests better cognitive and functional abilities are associated with greater suicide risk in psychotic disorders, which is dissimilar to the general population, but studies examining the link between cognition and suicidality are scarce. Because neuropsychological abilities can affect how individuals are able to attend to their environment, solve problems, and inhibit behaviors, further work is needed to consider how they may contribute to suicide risk in people with psychotic disorders. We sought to examine associations between neuropsychological performance and current SI and SA history in a large sample of individuals with psychosis.

176 participants with diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder with psychotic features completed clinical interviews, a neuropsychological assessment (MATRICS Consensus Cognitive Battery subtests), and psychiatric symptom measures (Positive and Negative Syndrome Scale [PANSS]; Montgomery-Asberg Depression Rating Scale [MADRS]. First, participants were divided into groups based on their current endorsement of SI in the past month on the Colombia Suicide Severity Rating scale (C-SSRS): those with current SI (SI+; n=86) and without current SI (SI-; n=90). We also examined lifetime history of SA (n=114) vs. absence of lifetime SA (n=62). Separate t-tests, chi-square tests, and logistic regressions were used to examine associations between neuropsychological performance and the two dichotomous outcome variables (current SI; history of SA).

The SI groups did not differ on diagnosis, demographics (e.g., age, gender, race, ethnicity, years of education, premorbid functioning), or on positive and negative symptoms. The SI+ group reported more severe depressive symptoms (t(169)= -5.90, p<.001) and had significantly worse performance on working memory tests than the SI- group (t(173)=2.28, p=.024). Logistic regression revealed that working memory performance uniquely predicted current SI+ group membership above and beyond depressive symptoms (B= -.040; OR= .96; 95% CI [.93, .99]; p= .034). The SA groups did not significantly differ on demographic variables or on positive/negative symptoms, but those with a history of SA had more severe depressive symptoms (t(169)= -2.80, p=.006) and worse performance on tests of working memory (t(173)=2.16, p=.033) and processing speed (t(166)=2.28, p=.024) than did those without a history of SA. Logistic regression demonstrated that after controlling for depressive symptom severity, working memory and processing speed did not predict unique variance in SA history (p=.25).

Worse working memory performance was associated with SI in the past month in individuals with psychotic disorders. Although our finding is consistent with literature in other psychiatric populations, it conflicts with existing psychosis literature. Thus, a more nuanced examination of how cognition relates to SI/SA in psychosis is warranted to identify and/or develop optimal interventions.

Life engagement represents a holistic concept that encompasses outcomes reflecting life-fulfilment, well-being and participation in valued and meaningful activities, which is recently gaining attention and scientific interest. Despite its conceptual importance and its relevance, life engagement represents a largely unexplored domain in schizophrenia. The aims of the present study were to independently assess correlates and predictors of patient life engagement in a large and well-characterized sample of schizophrenia patients.

To assess the impact of different demographic, clinical, cognitive and functional parameters on life engagement in a large sample of patients with schizophrenia, data from the social cognition psychometric evaluation project were analyzed.

Overall schizophrenia and depressive symptom severity, premorbid IQ, neurocognitive performance, social cognition performance both in the emotion processing and theory of mind domains, functional capacity, social skills performance and real-world functioning in different areas all emerged as correlates of patient life engagement. Greater symptom severity and greater impairment in real-world interpersonal relationships, social skills, functional capacity and work outcomes emerged as individual predictors of greater limitations in life engagement.

Life engagement in people living with schizophrenia represents a holistic and complex construct, with several different clinical, cognitive and functional correlates. These features represent potential treatment targets to improve the clinical condition and also facilitate the process of recovery and the overall well-being of people living with schizophrenia.

Schizophrenia (SZ) and autism spectrum disorders (ASD) are characterized by difficulties in theory of mind (ToM). We examined group differences in performance on a ToM-related test and associations with an estimated IQ.

Participants [N = 1227, SZ (n = 563), ASD (n = 159), and controls (n = 505), 32.2% female] completed the Reading the Mind in the Eyes Test (RMET) and assessments of cognitive ability. Associations between IQ and group on RMET were investigated with regression analyses.

SZ (d = 0.73, p < 0.001) and ASD (d = 0.37, p < 0.001) performed significantly worse on the RMET than controls. SZ performed significantly worse than ASD (d = 0.32, p = 0.002). Adding IQ to the model, SZ (d = 0.60, p < 0.001) and ASD (d = 0.44, p < 0.001) continued to perform significantly worse than controls, but no longer differed from each other (d = 0.13, p = 0.30). Small significant negative correlations between symptom severity and RMET performance were found in SZ (PANSS positive: r = −0.10, negative: r = −0.11, both p < 0.05). A small non-significant negative correlation was found for Autism Diagnostic Observation Schedule scores and RMET in ASD (r = −0.08, p = 0.34).

SZ and ASD are characterized by impairments in RMET. IQ contributed significantly to RMET performance and accounted for group differences in RMET between SZ and ASD. This suggests that non-social cognitive ability needs to be included in comparative studies of the two disorders.

There are currently no approved pharmacotherapies to treat cognitive impairment associated with schizophrenia (CIAS). Iclepertin (BI 425809) is a novel glycine transporter-1 inhibitor under development for treatment of CIAS. A previous study demonstrated pro-cognitive effects of iclepertin in patients with schizophrenia; however, concurrent cognitive stimulation could in theory enhance any pro-cognitive pharmacological effects on neuroplasticity. We present preliminary demographics and baseline data from a trial exploring the efficacy of iclepertin together with at-home computerized cognitive training (CCT).

This is an ongoing Phase II, double-blind, placebo-controlled, parallel-group trial in patients with schizophrenia on stable antipsychotic therapy across ~58 centers in 6 countries. Patients aged 18–50 years, compliant with CCT during the run-in period (completing ≥2 hours/week for 2 weeks), were randomized (1:1) to receive once-daily iclepertin 10 mg or placebo together with CCT for 12 weeks. Thereafter, minimum compliance for at-home CCT is 1 hour/week, with a target of ~30 hours across 3–5 sessions totaling 2.5 hours/week. Patients have been stratified to balance potential effects of age (18–40; 41–50 years). Primary endpoint is change from baseline (CfB) in neurocognitive composite T-score of the MATRICS Consensus Cognitive Battery (MCCB) at Week 12. Secondary endpoints include CfB in the Schizophrenia Cognition Rating Scale (SCoRS) total score, MCCB overall composite T-score, and Positive and Negative Syndrome Scale (PANSS) total scores. Novel exploratory endpoints include the Virtual Reality Functional Capacity Assessment Tool to assess daily functioning and the Balloon Effort Task to assess motivation in cognitive performance.

Of the planned sample of 200 randomized patients, the overall treated population currently includes 183: 67% (n=122) are male; mean (standard deviation [SD]) age and time since first diagnosis are 38.2 (7.9) years and 13.5 (8.5) years. Overall, 49% (n=89) are White and 43% (n=79) are Black or African American; 80% (n=147) are from North America, 15% (n=28) from Europe, and 4% (n=8) from Australia/New Zealand. Mean (SD) baseline MCCB neurocognitive composite and overall T-scores (n=178) are 33.7 (11.9) and 32.5 (12.6). Mean (SD) baseline SCoRS total score (n=167) is 35.2 (8.7). Mean (SD) baseline PANSS total and negative symptom scale scores (n=183) are 64.7 (14.6) and 17.3 (5.4). Median (Q1, Q3) CCT compliance over the on-treatment period for patients who have completed or discontinued early is 2.00 (1.21, 2.51) hours/week.

This trial is, to our knowledge, the largest of its kind combining daily pharmacotherapy for CIAS with at-home CCT. It will indicate whether iclepertin together with concurrent cognitive stimulation provides enhanced cognitive benefit, and whether any improvements in neurocognition can translate into improved measures of daily functioning in patients.

Boehringer Ingelheim International GmbH (NCT03859973/1346-0038)

Inaccurate self-assessment of performance is common among people with serious mental illness, and it is associated with poor functional outcomes independent from ability. However, the temporal interdependencies between judgments of performance, confidence in accuracy, and feedback about performance are not well understood.

We evaluated two tasks: the Wisconsin Card Sorting Test (WCST) and the Penn Emotion recognition task (ER40). These tasks were modified to include item-by-item confidence and accuracy judgments, along with feedback on accuracy. We evaluated these tasks as time series and applied network modeling to understand the temporal relationships between momentary confidence, accuracy judgments, and feedback. The sample constituted participants with schizophrenia (SZ; N = 144), bipolar disorder (BD; N = 140), and healthy controls (HC; N = 39).

Network models for both WCST and ER40 revealed denser and lagged connections between confidence and accuracy judgments in SZ and, to a lesser extent in BD, that were not evidenced in HC. However, associations between feedback regarding accuracy with subsequent accuracy judgments and confidence were weaker in SZ and BD. In each of these comparisons, the BD group was intermediate between HC and SZ. In analyses of the WCST, wherein incorporating feedback is crucial for success, higher confidence predicted worse subsequent performance in SZ but not in HC or BD.

While network models are exploratory, the results suggest some potential mechanisms by which challenges in self-assessment may impede performance, perhaps through hyperfocus on self-generated judgments at the expense of incorporation of feedback.

The COVID-19 pandemic substantially impacted care of patients with schizophrenia treated with long-acting injectable antipsychotics (LAIs). This study examined how clinics adapted operations to maintain a standard of care for these patients after pandemic onset.

Online surveys were completed in October-November 2020 by one principal investigator (PI) or PI-appointed designee at 35 clinics participating in OASIS (NCT03919994). Items concerned pandemic impacts on clinic operations, particularly telepsychiatry, and on the care of patients with schizophrenia treated with LAIs.

All 35 clinics reported using telepsychiatry; 20 (57%) implemented telepsychiatry after pandemic onset. Telepsychiatry visits increased from 12%-15% to 45%-69% across outpatient visit types after pandemic onset; frequency of no-show and/or canceled telepsychiatry visits decreased by approximately one-third. Nearly half of clinics increased the frequency of telepsychiatry visits for patients with schizophrenia treated with LAIs. Approximately one-third of participants each reported switching patients treated with LAIs to longer injection interval LAIs or to oral antipsychotics. The most common system/clinic- and patient-related barrier for telepsychiatry visits was lower reimbursement rate and access to technology/reliable internet, respectively. Almost all participants (94%) were satisfied with telepsychiatry for maintaining care of patients with schizophrenia treated with LAIs; most predicted a hybrid of telepsychiatry and office visits post-pandemic.

Changes made by clinics after pandemic onset were viewed by almost all participants as satisfactory for maintaining a standard of care for patients with schizophrenia treated with LAIs. Most participants predicted continuing telepsychiatry to support patient care post-pandemic; equitable access to telepsychiatry will be important in this regard.

Alkermes, Inc.

Cognitive tasks delivered during ecological momentary assessment (EMA) may elucidate the short-term dynamics and contextual influences on cognition and judgements of performance. This paper provides initial validation of a smartphone task of facial emotion recognition in serious mental illness.

A total of 86 participants with psychotic disorders (non-affective and affective psychosis), aged 19–65, were administered in-lab ‘gold standard’ affect recognition, neurocognition, and symptom assessments. They subsequently completed 10 days of the mobile facial emotion recognition task, assessing both accuracy and self-assessed performance, along with concurrent EMA of psychotic symptoms and mood. Validation focused on task adherence and predictors of adherence, gold standard convergent validity, and symptom and diagnostic group variation.

The mean rate of adherence to the task was 79%; no demographic or clinical variables predicted adherence. Convergent validity was observed with in-lab measures of facial emotion recognition, and no practice effects were observed on the mobile facial emotion recognition task. EMA reports of more severe voices, sadness, and paranoia were associated with worse performance, whereas mood more strongly associated with self-assessed performance.

The mobile facial emotion recognition task was tolerated and demonstrated convergent validity with in-lab measures of the same construct. Social cognitive performance, and biased judgements previously shown to predict function, can be evaluated in real-time in naturalistic environments.

Performance monitoring entails rapid error detection to maintain task performance. Impaired performance monitoring is a candidate pathophysiological process in psychotic disorders, which may explain the broader deficit in executive function and its known associations with negative symptoms and poor functioning. The current study models cross-sectional pathways bridging neurophysiological measures of performance monitoring with executive function, symptoms, and functioning.

Data were from the 20-year assessment of the Suffolk County Mental Health Project. Individuals with psychotic disorders (N = 181) were originally recruited from inpatient psychiatric facilities. Data were also collected from a geographically and demographically matched group with no psychosis history (N = 242). Neural measures were the error-related negativity (ERN) and error positivity (Pe). Structural equation modeling tested mediation pathways.

Blunted ERN and Pe in the clinical cohort related to impaired executive function (r = 0.26–0.35), negative symptom severity (r = 0.17–0.25), and poor real-world functioning (r = 0.17–0.19). Associations with executive function were consistent across groups. Multiple potential pathways were identified in the clinical cohort: reduced ERN to inexpressivity was mediated by executive function (β = 0.10); reduced Pe to global functioning was mediated by executive function and avolition (β = 0.10).

This supports a transdiagnostic model of psychotic disorders by which poor performance monitoring contributes to impaired executive function, which contributes to negative symptoms and poor real-world functioning. If supported by future longitudinal research, these pathways could inform the development of targeted interventions to address cognitive and functional deficits that are central to psychotic disorders.

Autism spectrum disorder (ASD) and schizophrenia (SCZ) are separate neurodevelopmental disorders that are both characterized by difficulties in social cognition and social functioning. Due to methodological confounds, the degree of similarity in social cognitive impairments across these two disorders is currently unknown. This study therefore conducted a comprehensive comparison of social cognitive ability in ASD and SCZ to aid efforts to develop optimized treatment programs.

In total, 101 individuals with ASD, 92 individuals with SCZ or schizoaffective disorder, and 101 typically developing (TD) controls, all with measured intelligence in the normal range and a mean age of 25.47 years, completed a large battery of psychometrically validated social cognitive assessments spanning the domains of emotion recognition, social perception, mental state attribution, and attributional style.

Both ASD and SCZ performed worse than TD controls, and very few differences were evident between the two clinical groups, with effect sizes (Cohen's d) ranging from 0.01 to 0.34. For those effects that did reach statistical significance, such as greater hostility in the SCZ group, controlling for symptom severity rendered them non-significant, suggesting that clinical distinctions may underlie these social cognitive differences. Additionally, the strength of the relationship between neurocognitive and social cognitive performance was of similar, moderate size for ASD and SCZ.

Findings largely suggest comparable levels of social cognitive impairment in ASD and SCZ, which may support the use of existing social cognitive interventions across disorders. However, future work is needed to determine whether the mechanisms underlying these shared impairments are also similar or if these common behavioral profiles may emerge via different pathways.