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Cognitive enhancement therapy (CET) is an 18-month comprehensive cognitive remediation intervention designed to improve cognition and functioning among patients with schizophrenia. The current study sought to confirm previously observed benefits of CET on cognitive and behavioral outcomes in the early course of the condition in a large multisite trial.Overall, 102 outpatients with early-course schizophrenia were randomly assigned to 18 months of CET (N=58) or enriched supportive therapy (EST; N=44). Participants completed cognitive, social adjustment, and symptom assessments at baseline and at 9 and 18 months. Composite indices were calculated for these outcomes. Mixed-effects models investigated differential changes in outcomes between CET and EST. Because of a high attrition rate, sensitivity analyses of data from treatment completers (N=49) were conducted.The effects of CET on improved overall cognition were confirmed and tentatively confirmed for social cognition in both intent-to-treat and completer analyses, and beneficial effects on attention/vigilance were also observed. An effect of CET on social adjustment was not confirmed in the analyses, because both CET and EST groups had considerably improved social adjustment. Although not statistically significant, the between-group effect size for CET's effect on social adjustment doubled from the intent-to-treat (Cohen's d=0.23) to completer analyses (Cohen's d=0.51) (p=0.057). Both groups displayed similar symptom improvements.CET effectively improved cognition among patients with early-course schizophrenia. The functional benefits of CET appeared to increase with treatment retention. Further research is needed to understand predictors of attrition and mechanisms of change during CET for this population.

The percentage of individuals who are functionally bilingual in the United States has grown substantially in the last 3 to 4 decades. Nevertheless, bilingual mental health providers remain relatively scarce and bilingualism in psychosis or schizophreniaspectrum disorders remains relatively unexplored. Here, we present a clinical case study of a man with schizophrenia who presented his psychotic symptoms differently in his primary and secondary languages. We also consider this case in the context of other published cases with similar themes. Based on our review, we hypothesize that the presentation of psychotic symptoms may be influenced by the language a person uses, and more specifically, by their cognitive abilities to speak that language and/or their emotional attachment to that language. We outline the importance of obtaining a thorough language background of each patient with psychosis and investigate the ways in which a second language could serve as a protective factor against functional decline in psychotic and healthy populations. We suggest that attempts to engage bilingual patients with psychosis clinically in each language could lead to a more holistic evaluation of psychotic and disorganized symptoms and thus lead to more multidimensional intervention strategies.

The integrity and function of catecholamine neurotransmitter systems can be assessed using neuromelanin-sensitive MRI (NM-MRI). The relevance of this method to neurodegenerative and psychiatric disorders is becoming increasingly evident, and it has potential as a clinical biomarker.To support future application of NM-MRI as a clinical biomarker by defining the normative range of NM-MRI signal and volume metrics in cognitively normal older adults.Prospective.A total of 152 cognitively normal older adults aged 53-86 years old, including 41 participants who had follow-up NM-MRI data collected 9-16 months later.A 3.0 T; NM-MRI turbo spin echo and T1-weighted magnetization-prepared rapid acquisition with gradient echo sequences.NM-MRI images were processed to yield summary measures of volume and signal (contrast-to-noise ratio, CNR) for the substantia nigra (SN) and locus coeruleus (LC) using a recently developed software employing a fully automated algorithm. Change in these metrics over time was also assessed.Mean and standard deviation of NM-MRI metrics were calculated; change over time was tested for significance using 1-sample t-tests. P values 0.05 were considered statistically significant.At baseline SN signal (CNR) was 10.02% (left) and 10.28% (right) and LC signal was 24.71% (left) and 20.42% (right). Baseline SN volume was 576 mmWe report normative values for NM-MRI signal and volume in the SN and LC of cognitively normal older adults and explore their change over time. These values may help future efforts to use NM-MRI as a clinical biomarker by facilitating identification of patients with extreme NM-MRI values.1.

Background: Individuals with major depressive disorder often experience cognitive deficits. Cognitive remediation (CR) is an intervention aimed at improving cognition in psychiatric disorders. However, its efficacy on global and specific domains of cognition in adults with depression requires systematic investigation. Further, given individual differences in treatment outcome, moderators of CR effects in depression need to be identified.Methods: We performed a systematic review and meta-analysis of published controlled trials of CR in adults with depression. We analyzed results from eight studies to estimate the efficacy of CR on global cognition and on six cognitive domains. We also examined three potential moderators, namely session format (individual vs. group), treatment duration, and participants’ age.Results: CR was found to improve global cognition (g = 0.44), verbal memory (g = 0.60), attention/processing speed (g = 0.41), working memory (g = 0.35), and executive functioning (g = 0.30). No significant improvements emerged for visuospatial memory and verbal fluency. Furthermore, no significant moderating effect of participant’s age, session duration or session format were observed. Limitations: Conclusions are limited by the small number of studies, the heterogeneity in cognitive measures, and the lack of indicators of everyday functioning. Conclusion: Our meta-analysis supports the use of CR in improving global cognition in adults with major depressive disorder with a moderate effect size and this efficacy varies between cognitive domains.Keywords: Depression; Cognition; Cognitive Remediation; Cognitive Training; Cognitive Rehabilitation; Meta-Analysis.

Purpose: Digital media use has been associated with psychotic experiences in youth from the community, but the direction of association remains unclear. We aimed to examine between- and within-person associations of digital media use and psychotic experiences in youth.Methods: The sample included 425 participants aged 18-25 years (82.5% female) from the community, followed between May 2021 and January 2022 over 3 time points – of which 263 participants (61.9%) completed at least 2. Digital media use was self-reported as time spent daily on TV and streaming platforms, social media, and video games over the past 3 months. Psychotic experiences in the past 3 months were measured with the 15-item Community Assessment of Psychic Experiences. Associations between digital media use and psychotic experiences were estimated using a random-intercept cross-lagged panel model.Results: At the between-person level, greater digital media use was associated with higher levels of psychotic experiences (r=0.34, 95% CI: 0.15, 0.53). However, within-person changes in digital media use were not significantly associated with subsequent changes in psychotic experiences, or vice-versa. Results were similar across TV/streaming, social media and video game use, and after adjusting for age, sex, education, sleep, physical activity, and cannabis use.Conclusion: Individuals with a tendency for higher levels of digital media use also had a tendency for higher levels of psychotic experiences. Understanding this association may help personalize mental health interventions for people with psychotic experiences, which may be offered digitally to promote their accessibility.

BackgroundThe integrity and function of catecholamine neurotransmitter systems can be assessed using MRI sequences often referred to as neuromelanin-sensitive MRI (NM-MRI). The relevance of this method to neurodegenerative and psychiatric disorders is becoming increasingly evident, and it has potential as a clinical biomarker. To support such future applications, we report here the normative range of NM-MRI signal and volume metrics in cognitively normal older adults.Methods3 Tesla NM-MRI images and demographic and cognitive data were available from 152 cognitively normal older adults aged 53-86 years old at baseline; a subsample of 68 participants also had follow-up NM-MRI data collected around one-year later. NM-MRI images were processed to yield summary measures of volume and signal (contrast-to-noise ratio, CNR) for the substantia nigra (SN) and locus coeruleus (LC) using a recently developed software employing a fully automated algorithm. The extent of annual change in these metrics was quantified and tested for significance using 1-sample t-tests.ResultsBaseline SN signal (CNR) was 10.02% (left SN) and 10.28% (right) and baseline LC signal was 24.71% (left) and 20.42% (right). The only NM-MRI metric to show a significant annual change was a decrease in left SN volume.ConclusionWe report normative values for NM-MRI signal and volume in the SN and LC of cognitively normal older adults and normative values for their change over time. These values may help future efforts to use NM-MRI as a clinical biomarker for adults in this age range by facilitating identification of patients with extreme NM-MRI values.

Evidence shows that cognitive remediation therapy improves cognition in individuals with schizophrenia. However, its broader impact on patients’ lives remains unclear. Furthermore, little is known about the motivational factors influencing treatment engagement. This quantitative and qualitative case series study identified factors that influence patients’ experiences while receiving cognitive enhancement therapy (CET). Nine individuals with schizophrenia who received CET completed two questionnaires and participated in semi-structured focus groups or in an individual interview about their experience with CET. Four deductive themes were assessed when analyzing responses: (1) perceived impact, (2) motivational facilitators, (3) motivational barriers, and (4) suggestions to improve CET. All participants reported that CET was helpful, and the majority enjoyed participating in CET. Most participants reported high satisfaction with their work and school, but lower satisfaction with their social life. Results also indicated perceived improvements in negative symptoms, neurocognition, and confidence following CET. Participants identified extrinsic, intrinsic, and program-specific facilitators and barriers motivating their participation in the program. Suggestions to improve CET included changes to treatment design and content. Altogether, these results indicate that the perspective of CET end users can provide useful information on the factors influencing treatment engagement, satisfaction, and perceived impact.

In contrast to cardiac sympathetic activity which can be assessed with established PET tracers, there are currently no suitable radioligands to measure cardiac parasympathetic (cholinergic) activity. A radioligand able to measure cardiac cholinergic activity would be an invaluable clinical and research tool since cholinergic dysfunction has been associated with a wide array of pathologies (e.g., chronic heart failure, myocardial infarction, arrythmias). [18F]Fluoroethoxybenzovesamicol (FEOBV) is a cholinergic radiotracer that has been extensively validated in the brain. Whether FEOBV PET can be used to assess cholinergic activity in the heart is not known. Hence, this study aimed to evaluate the properties of FEOBV for cardiac PET imaging and cholinergic activity mapping. PET data were collected for 40 minutes after injection of 230 ± 50 MBq of FEOBV in four healthy participants (1 female; Age: 37 ± 10; BMI: 25 ± 2). Dynamic LV time activity curves were fitted with Logan graphical, 1-tissue compartment, and 2-tissue compartment models, yielding similar distribution volume estimates for each participant. Our initial data show that FEOBV PET has favorable tracer kinetics for quantification of cholinergic activity and is a promising new method for assessing parasympathetic function in the heart.

Funder: Helmholts International BigBrain Analytics & Learning Laboratory, Neurotransmitter receptors support the propagation of signals in the human brain. How receptor systems are situated within macro-scale neuroanatomy and how they shape emergent function remain poorly understood, and there exists no comprehensive atlas of receptors. Here we collate positron emission tomography data from more than 1,200 healthy individuals to construct a whole-brain three-dimensional normative atlas of 19 receptors and transporters across nine different neurotransmitter systems. We found that receptor profiles align with structural connectivity and mediate function, including neurophysiological oscillatory dynamics and resting-state hemodynamic functional connectivity. Using the Neurosynth cognitive atlas, we uncovered a topographic gradient of overlapping receptor distributions that separates extrinsic and intrinsic psychological processes. Finally, we found both expected and novel associations between receptor distributions and cortical abnormality patterns across 13 disorders. We replicated all findings in an independently collected autoradiography dataset. This work demonstrates how chemoarchitecture shapes brain structure and function, providing a new direction for studying multi-scale brain organization., For the Cambridge authors (Coles, Fryer & Aigbirhio): This work was funded by an MRC PET Neuroscience programme grant (Training and Novel Probes Programme in PET Neurochemistry - MR/K02308X/1) and by an MRC Developmental Pathway Funding Scheme grant (MR/L013215/1). This research in Cambridge was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. JPC was supported by a British Journal of Anaesthesia/Royal College of Anaesthetists grant from the National Institute of Academic Anaesthesia.

Relatives of individuals with schizophrenia have a higher risk of developing the illness compared to the general population. Thus, youth at familial high risk (FHR) offer a unique opportunity to identify neuroimaging-based endophenotypes of psychosis. Previous studies have identified lower amygdalo-hippocampal volume in FHR, as well as lower verbal memory and emotion recognition. However, whether these phenotypes increase the risk of transition to psychosis remains unclear. To determine if individuals who develop psychosis have abnormal neurodevelopmental trajectories of the amygdala and hippocampus, we investigated longitudinal changes of these structures in a unique cohort of 82 youth FHR and 56 healthy controls during a 3-year period. Ten individuals from the FHR group converted to psychosis. Longitudinal changes were compared using linear mixed-effects models. Group differences in verbal memory and emotion recognition performance at baseline were also analyzed. Surface-based morphometry measures revealed variation in amygdalar shape (concave shape of the right dorsomedial region) in those who converted to psychosis. Significantly lower emotion recognition performance at baseline was observed in converters. Percent trial-to-trial transfer on the verbal learning task was also significantly impaired in FHR, independently of the conversion status. Our results identify abnormal shape development trajectories in the dorsomedial amygdala and lower emotion recognition abilities as phenotypes of transition to psychosis. Our findings illustrate potential markers for early identification of psychosis, aiding prevention efforts in youth at risk of schizophrenia.

Background Technology is ever evolving, with more and more diverse activities becoming possible on screen-based devices. However, participating in a heavy screen-based lifestyle may come at a cost. Our hypothesis was that problematic social media use increased the prevalence of mental health outcomes. Objective This study seeks to systematically examine problematic social media use in youth and its association with symptoms of depression, anxiety, and stress. Methods A systematic search was conducted to identify studies in adolescents and young adults, using the databases Engineering Village, Psycinfo, Pubmed, and Web of Science. A total of 18 studies were identified, with a total of 9269 participants in our review and included in the meta-analysis. Results Our metaregression shows moderate but statistically significant correlations between problematic social media use and depression (r=0.273, P Conclusions This study provides further evidence of the association between problematic social media use and negative mental health among adolescents and young adults and supports future research to focus on the underlying mechanisms of problematic use of social media. Trial Registration PROSPERO CRD42021222309; https://tinyurl.com/2p9y4bjx

BACKGROUND Technology is ever evolving, with more and more diverse activities becoming possible on screen-based devices. However, participating in a heavy screen-based lifestyle may come at a cost. Our hypothesis was that problematic social media use increased the prevalence of mental health outcomes. OBJECTIVE This study seeks to systematically examine problematic social media use in youth and its association with symptoms of depression, anxiety, and stress. METHODS A systematic search was conducted to identify studies in adolescents and young adults, using the databases Engineering Village, Psycinfo, Pubmed, and Web of Science. A total of 18 studies were identified, with a total of 9269 participants in our review and included in the meta-analysis. RESULTS Our metaregression shows moderate but statistically significant correlations between problematic social media use and depression (r=0.273, Pr=0.348, Pr=0.313, P CONCLUSIONS This study provides further evidence of the association between problematic social media use and negative mental health among adolescents and young adults and supports future research to focus on the underlying mechanisms of problematic use of social media. CLINICALTRIAL PROSPERO CRD42021222309; https://tinyurl.com/2p9y4bjx

As the potential of smartphone apps and sensors for healthcare and clinical research continues to expand, there is a concomitant need for open, accessible, and scalable digital tools. While many current app platforms offer useful solutions for either clinicians or patients, fewer seek to serve both and support the therapeutic relationship between them. Thus, we aimed to create a novel smartphone platform at the intersection of patient demands for trust, control, and community and clinician demands for transparent, data driven, and translational tools. The resulting LAMP platform has evolved through numerous iterations and with much feedback from patients, designers, sociologists, advocates, clinicians, researchers, app developers, and philanthropists. As an open and free tool, the LAMP platform continues to evolve as reflected in its current diverse use cases across research and clinical care in psychiatry, neurology, anesthesia, and psychology. In this paper, we explore the motivation, features, current progress, and next steps to pair the platform for use in a new digital psychiatry clinic, to advance digital interventions for youth mental health, and to bridge gaps in available mental health care for underserved patient groups. The code for the LAMP platform is freely shared with this paper to encourage others to adapt and improve on our team’s efforts.

Objective Brain-based Biotypes for psychotic disorders have been developed as part of the B-SNIP consortium to create neurobiologically distinct subgroups within idiopathic psychosis, independent from traditional phenomenological diagnostic methods. In the current study, we aimed to validate the Biotype model by assessing differences in volume and shape of the amygdala and hippocampus contrasting traditional clinical diagnoses with Biotype classification. Methods A total of 811 participants from 6 sites were included: probands with schizophrenia (n = 199), schizoaffective disorder (n = 122), psychotic bipolar disorder with psychosis (n = 160), and healthy controls (n = 330). Biotype classification, previously developed using cognitive and electrophysiological data and K-means clustering, was used to categorize psychosis probands into 3 Biotypes, with Biotype-1 (B-1) showing reduced neural salience and severe cognitive impairment. MAGeT-Brain segmentation was used to determine amygdala and hippocampal volumetric data and shape deformations. Results When using Biotype classification, B-1 showed the strongest reductions in amygdala-hippocampal volume and the most widespread shape abnormalities. Using clinical diagnosis, probands with schizophrenia and schizoaffective disorder showed the most significant reductions of amygdala and hippocampal volumes and the most abnormal hippocampal shape compared with healthy controls. Biotype classification provided the strongest neuroanatomical differences compared with conventional DSM diagnoses, with the best discrimination seen using bilateral amygdala and right hippocampal volumes in B-1. Conclusion These findings characterize amygdala and hippocampal volumetric and shape abnormalities across the psychosis spectrum. Grouping individuals by Biotype showed greater between-group discrimination, suggesting a promising approach and a favorable target for characterizing biological heterogeneity across the psychosis spectrum.

The percentage of individuals who are functionally bilingual in the United States has grown substantially in the last 3 to 4 decades. Nevertheless, bilingual mental health providers remain relatively scarce and bilingualism in psychosis or schizophreniaspectrum disorders remains relatively unexplored. Here, we present a clinical case study of a man with schizophrenia who presented his psychotic symptoms differently in his primary and secondary languages. We also consider this case in the context of other published cases with similar themes. Based on our review, we hypothesize that the presentation of psychotic symptoms may be influenced by the language a person uses, and more specifically, by their cognitive abilities to speak that language and/or their emotional attachment to that language. We outline the importance of obtaining a thorough language background of each patient with psychosis and investigate the ways in which a second language could serve as a protective factor against functional decline in psychotic and healthy populations. We suggest that attempts to engage bilingual patients with psychosis clinically in each language could lead to a more holistic evaluation of psychotic and disorganized symptoms and thus lead to more multidimensional intervention strategies.

Many individuals living with severe mental illness, such as schizophrenia, present cognitive deficits and reasoning biases negatively impacting clinical and functional trajectories. Remote cognitive assessment presents many opportunities for advancing research and treatment but has yet to be widely used in psychiatric populations. We conducted a scoping review of remote cognitive assessment in severe mental illness to provide an overview of available measures and guide best practices. Overall, 34 studies (n = 20,813 clinical participants) were reviewed and remote measures, psychometrics, facilitators, barriers, and future directions were synthesized using a logic model. We identified 82 measures assessing cognition in severe mental illness across 11 cognitive domains and four device platforms. Remote measures were generally comparable to traditional versions, though psychometric properties were infrequently reported. Facilitators included standardized procedures and wider recruitment, whereas barriers included imprecise measure adaptations, technology inaccessibility, low patient engagement, and poor digital literacy. Our review identified several remote cognitive measures in psychiatry across all cognitive domains. However, there is a need for more rigorous validation of these measures and consideration of potentially influential factors, such as sex and gender. We provide recommendations for conducting remote cognitive assessment in psychiatry and fostering high-quality research using digital technologies.

BACKGROUND Functional recovery in psychosis remains a challenge despite current evidence-based treatment approaches. To address this problem, innovative interventions using virtual reality (VR) have recently been developed. VR technologies have enabled the development of realistic environments in which individuals with psychosis can receive psychosocial treatment interventions in more ecological settings than traditional clinics. These interventions may therefore increase the transfer of learned psychosocial skills to real-world environments, thereby promoting long-term functional recovery. However, the overall feasibility and efficacy of such interventions within the psychosis population remain unclear. OBJECTIVE This systematic review aims to investigate whether VR-based psychosocial interventions are feasible and enjoyable for individuals with psychosis, synthesize current evidence on the efficacy of VR-based psychosocial interventions for psychosis, and identify the limitations in the current literature to guide future research. METHODS This research followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Literature searches were conducted in PubMed and PsycINFO in May 2021. We searched for peer-reviewed English articles that used a psychosocial intervention with a VR component. Participants in the included studies were diagnosed with schizophrenia, schizoaffective disorder, or another psychotic disorder. The included studies were divided into four categories as follows: cognitive remediation interventions, social skills interventions, vocational skills interventions, and auditory verbal hallucinations and paranoia interventions. The risk of bias assessment was performed for each study. RESULTS A total of 18 studies were included in this systematic review. Of these 18 studies, 4 (22%) studies used a cognitive remediation intervention, 4 (22%) studies used a social skills intervention, 3 (17%) studies used a vocational skills intervention, and 7 (39%) studies implemented an intervention aimed at improving auditory verbal hallucinations or paranoia. A total of 745 individuals with psychosis were included in the study. All the studies that evaluated feasibility showed that VR-based psychosocial interventions were feasible and enjoyable for individuals with psychosis. The preliminary evidence on efficacy included in this review suggests that VR-based psychosocial interventions can improve cognitive, social, and vocational skills in individuals with psychosis. VR-based interventions may also improve the symptoms of auditory verbal hallucinations and paranoia. The skills that participants learned through these interventions were durable, transferred into real-world environments, and led to improved functional outcomes, such as autonomy, managing housework, and work performance. CONCLUSIONS VR-based interventions may represent a novel and efficacious approach for improving psychosocial functioning in psychosis. Therefore, VR-based psychosocial interventions represent a promising adjunctive therapy for the treatment of psychosis, which may be used to improve psychosocial skills, community functioning, and quality of life. CLINICALTRIAL

BackgroundThe ability to manage emotions is an important social-cognitive domain impaired in schizophrenia and linked to functional outcome. The goal of our study was to examine the impact of cognitive enhancement therapy (CET) on the ability to manage emotions and brain functional connectivity in early-course schizophrenia.MethodsParticipants were randomly assigned to CET (n = 55) or an enriched supportive therapy (EST) control group (n = 45). The resting-state functional magnetic resonance imaging scans and measures of emotion management performances were collected at baseline, 9, and 18 months follow-up. The final sample consisted of 37 CET and 25 EST participants, including 19 CET and 12 EST participants with imaging data. Linear mixed-effects models investigated the impact of treatment on emotion management and functional connectivity from the amygdala to ventrolateral and dorsolateral prefrontal cortex (dlPFC).ResultsThe CET group showed significant improvement over time in emotion management compared to EST. Neither functional connectivity changes nor main group differences were observed following treatment. However, a significant between-group interaction showed that improved emotion management ability was associated with increased functional connectivity between the left amygdala and the left dlPFC in the CET group exclusively.ConclusionOur results replicate the previous work demonstrating that CET is effective at improving some aspects of social cognition in schizophrenia. We found evidence that improvement in emotion management may be associated with a change in amygdala-dlPFC connectivity. This fronto-limbic circuit may provide a mechanistic link between the biology of emotion management processes that can be enhanced in individuals with schizophrenia.

Theory of Mind (ToM) refers to the ability to perceive others' mental states. Lower ToM has often been associated with poorer functional outcomes in schizophrenia, making it an important treatment target. However, little is known about the underlying neural mechanisms associated with ToM impairments in early course schizophrenia. This study aimed to validate the False Belief task to measure ToM in schizophrenia and to identify aberrant brain activity associated with impairments. 36 individuals with early course schizophrenia and 17 controls were administered the Hinting Task and performed a functional magnetic resonance imaging (fMRI) False Belief task. Between-group differences were examined in a priori regions of interest (ROIs) known to be associated with ToM tasks: medial prefrontal cortex, ventral medial prefrontal cortex, and both the left and right temporal parietal junction (TPJ). We observed a significant positive association between Hinting Task performance and False Belief accuracy, validating the False Belief task as a measure of ToM. Compared to controls, individuals with schizophrenia exhibited reduced brain activation in all four ROIs during the fMRI False Belief task. Furthermore, task-related activations in bilateral TPJs were shown to be positively associated with ToM abilities regardless of diagnosis. Individuals with schizophrenia with lower performance on the False Belief task showed significant reductions in task-related activation in the bilateral TPJ compared to controls, while reductions were not significant for those with higher performance. Our findings suggest that lower neural activity in the bilateral TPJ are associated with ToM impairments observed in individuals with early course schizophrenia.

In contrast to cardiac sympathetic activity which can be assessed with established PET tracers, there are currently no suitable radioligands to measure cardiac parasympathetic (cholinergic) activity. A radioligand able to measure cardiac cholinergic activity would be an invaluable clinical and research tool since cholinergic dysfunction has been associated with a wide array of pathologies (e.g., chronic heart failure, myocardial infarction, arrythmias). [18F]Fluoroethoxybenzovesamicol (FEOBV) is a cholinergic radiotracer that has been extensively validated in the brain. Whether FEOBV PET can be used to assess cholinergic activity in the heart is not known. Hence, this study aimed to evaluate the properties of FEOBV for cardiac PET imaging and cholinergic activity mapping. PET data were collected for 40 minutes after injection of 230 ± 50 MBq of FEOBV in four healthy participants (1 female; Age: 37 ± 10; BMI: 25 ± 2). Dynamic LV time activity curves were fitted with Logan graphical, 1-tissue compartment, and 2-tissue compartment models, yielding similar distribution volume estimates for each participant. Our initial data show that FEOBV PET has favorable tracer kinetics for quantification of cholinergic activity and is a promising new method for assessing parasympathetic function in the heart.

The B-SNIP consortium identified three brain-based Biotypes across the psychosis spectrum, independent of clinical phenomenology. To externally validate the Biotype model, we used free-water fractional volume (FW) and free-water corrected fractional anisotropy (FAT) to compare white matter differences across Biotypes and clinical diagnoses. Diffusion tensor imaging data from 167 individuals were included: 41 healthy controls, 55 schizophrenia probands, 47 schizoaffective disorder probands, and 24 probands with psychotic bipolar disorder. Compared to healthy controls, FAt reductions were observed in the body of corpus callosum (BCC) for schizoaffective disorder (d = 0.91) and schizophrenia (d = 0.64). Grouping by Biotype, Biotype 1 showed FAt reductions in the CC and fornix, with largest effect in the BCC (d = 0.87). Biotype 2 showed significant FAt reductions in the BCC (d = 0.90). Schizoaffective disorder individuals had elevated FW in the CC, fornix and anterior corona radiata (ACR), with largest effect in the BCC (d = 0.79). Biotype 2 showed elevated FW in the CC, fornix and ACR, with largest effect in the BCC (d = 0.94). While significant diagnosis comparisons were observed, overall greater discrimination from healthy controls was observed for lower FAt in Biotype 1 and elevated FW in Biotype 2. However, between-group differences were modest, with one region (cerebral peduncle) showing a between-Biotype effect. No between-group effects were observed for diagnosis groupings.

Self-initiation of semantic encoding strategies is impoverished in schizophrenia and contributes to memory impairments. Recently, we observed that following a brief training, schizophrenia patients had the potential to increase the self-initiation of these strategies. In this study, we investigated the neural correlates underlying such memory improvements. Fifteen schizophrenia patients with deficits in self-initiation of semantic encoding strategies were enrolled in a Strategy for Semantic Association Memory (SESAME) training. Patients underwent a memory task in an fMRI scanner. Memory performance and brain activity during the task were measured pre- and post- training, and changes following training were assessed. We also investigated if structural preservation measured by the cortical thickness of the left dorsolateral prefrontal cortex (DLPFC) predicted memory improvement post-training. Memory training led to significant improvements in memory performance that were associated with increased activity in the left DLPFC, during a task in which patients needed to self-initiate semantic encoding strategies. Furthermore, patients with more cortical reserve in their left DLPFC showed greater memory improvement. Our findings provide evidence of neural malleability in the left DLPFC in schizophrenia using cognitive strategies training. Moreover, the brain-behavioural changes observed in schizophrenia provide hope that memory performance can be improved with a brief intervention.

This chapter discusses non-pharmacological treatments in schizophrenia and their impact on brain structure and function. The treatment modalities included in this chapter are interventions based on physical activity, cognitive remediation therapy, cognitive behavioral therapy, repetitive transcranial magnetic stimulation, and transcranial direct-current stimulation. Neuroimaging methods such as structural MRI, functional MRI, diffusion tensor imaging, electroencephalography, and magnetoencephalography have been used for examining the impact of various treatment modalities on brain structure and function in schizophrenia. Collectively, findings from these studies suggest potential alterations in brain structure and function of non-pharmacological interventions in schizophrenia, which may underlie therapeutic benefits for patients in conjunction with traditional medication treatment. Additionally, studies examining cognitive remediation therapy and physical activity have been shown to influence brain plasticity, improve cognitive functioning, and alleviate symptoms associated with schizophrenia. Although several neuroimaging studies have examined the effects of cognitive remediation therapy on brain structure and function, there is a limited understanding of the effects of other treatment modalities, such as cognitive behavioral therapy, neuromodulation, and physical activity. Further studies are warranted for understanding the underlying neurobiological mechanisms of non-pharmacological interventions and their improvements for cognition and functional outcomes in schizophrenia.

BACKGROUND: Evidence suggests that clinical phenomenology incompletely captures biologically meaningful differentiations in psychosis. The Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP) consortium has employed cognitive and neurophysiological measures to identify three biologically distinct Biotypes, agnostic to clinical features. Biotype 1, 2, and 3, have distinctive neurobiological characteristics: Biotype 1 cases have significant neurocognitive impairment, high numbers of clinically affected relatives, and poor psychosocial functioning. Biotype 2 cases have high neural reactivity and more modest but significant cognitive impairment. Biotype 3 cases have nearly normal cognition and neural reactivity and better psychosocial functioning. As brain white matter is altered in psychosis, we aimed to externally validate the Biotype model using free-water imaging - an advanced diffusion imaging technique to compare differences across Biotypes, as well as across clinical categorization. METHODS: Diffusion tensor imaging (DTI) data from 69 individuals with schizophrenia, 49 with schizoaffective disorder (SAD), 42 with psychotic bipolar disorder, and 51 healthy controls (HC) from the Baltimore and Hartford sites in the B-SNIP consortium were included. Diffusion within each voxel was modeled using two compartments: isotropic free-water compartment, and a tissue compartment. Measures obtained from this model are the free-water compartment fraction (FW), and the tissue-FA fraction (FAt). Using Tract-based spatial statistics, the ENIGMA-DTI protocols were run on FAt and FW maps. The average FAt and FW within 25 bilateral white matter regions of interest was extracted. A MANCOVA model was used to test for differences in FAt and FW between diagnostic groups and Biotype groups, with age and sex as covariates. RESULTS: A significant group effect for diagnosis was observed in the corpus callosum (CC) (p

Background: Psychiatric disorders (e g , schizophrenia) present cognitive deficits and biases that greatly impact functional outcome Due to the COVID-19 pandemic, traditional in-person assessments and interventions must be adapted for remote delivery, but many clinicians and researchers are rapidly embarking on this path with little guidance We synthesized the literature on remote cognitive assessment in psychiatry to facilitate development of these guidelines Methods: We systematically reviewed the literature via OVID and EBSCO, and searched the grey literature, selecting peer-reviewed research articles reporting on remote cognitive assessment in individuals with mental illness We recorded study parameters, remote measure characteristics, psychometric properties, facilitators, barriers, and future directions Extracted data was synthesized using the logic model methodology Results: Of 25,374 retrieved articles, 32 articles were included Remote measures were available across several cognitive domains (e g , processing speed, attention, verbal/visual/working memory, executive function, social cognition, biases) through various digital platforms Psychometric validation was performed in fewer than half of reviewed articles Facilitators included standardized procedures and automated scoring, while barriers were limited digital literacy, low engagement, and imprecise measure adaptations Conclusions: Our scoping review identified several remote cognitive measures used in psychiatry;however, there is a need for more rigorous validation of these measures The development of open-source alternatives and consideration of potential influential factors, such as sex and gender differences, is encouraged Remote mental health is currently a necessity, yet also a rare opportunity to draw from and contribute to the growing psychiatry digital health literature as well as support more personalized remote interventions Supported By: CIHR Keywords: Neurocognition, Cognitive Bias, Systematic Review, Severe Mental Illness, Remote Assessment

Schizophrenia (SZ) is proposed as a disorder of dysconnectivity underlying cognitive impairments and clinical manifestations. Although previous studies have shown extracellular changes in white matter of first-episode SZ, little is known about the transition period towards chronicity and its association with cognition. Free-water (FW) imaging was applied to 79 early course SZ participants and 29 controls to detect white matter axonal and extracellular differences during this phase of illness. Diffusion-weighted images were collected from two sites, harmonized, and processed using a pipeline separately modeling water diffusion in tissue (FAt) and extracellular space (FW). Tract-Based Spatial Statistics was performed using the ENIGMA-DTI protocols. SZ showed FAt reductions in the posterior thalamic radiation (PTR) and FW elevations in the cingulum compared to controls, suggesting FAt and FW changes in the early course of SZ. In SZ, greater FAt of the fornix & stria terminalis (FXST) was positively associated with Theory of Mind performance; average whole-brain FAt, FAt of the FXST and the PTR were positively associated with greater working memory performance; average whole-brain FAt was positively associated with visual learning. Further studies are necessary to better understand the neurobiological mechanisms of SZ for developing intervention strategies to preserve brain structure and function.

Background Cognitive impairments are a core feature of schizophrenia. Although cognitive impairments have consistently shown to have negative impacts on functional outcomes among individuals with schizophrenia, assessing and treating these symptoms in clinical settings remains a difficult challenge. Interestingly, the growing potential of new digital technologies, such as smartphone applications and virtual reality, hold great promise in alleviating these impairments. Methods This presentation will introduce results from two recent studies using digital technologies to assess and treat cognitive symptoms in schizophrenia. In the first study, smartphone versions of the pen-and-paper Trail Making Tests A and B were developed. These cognitive tests measure speed of processing and cognitive flexibility. We assessed the validity of the smartphone versions of both Trail Making Tests in measuring these cognitive domains in in 37 healthy controls and 26 individuals with schizophrenia. Following the initial assessment, participants were asked to complete the two smartphone cognitive tests once a week for three months. This served as a measure of cognitive performance over time Results Results showed that it was feasible to measure cognition using a smartphone application in schizophrenia. Performances on both smartphone cognitive tests were significantly and positively correlated with the pen-and-paper versions (Parts A: r = 0.65, p < .001; Parts B: r= 0.44, p= .01). Additionally, significant differences were observed between controls and individuals with schizophrenia on both smartphone tests (Part A: t = -3.88, p = .004; Part B: t = -3.29, p = .002). Moreover, longitudinal results showed no significant effect of practice over time on the smartphone cognitive tests. Discussion Digital technologies have the potential to optimize cognitive assessments, monitoring, and care in schizophrenia. Our findings support the feasibility and efficacy of using digital technologies to measure and treat cognitive impairments in schizophrenia. Our research also highlights the importance of including scientists, clinicians, and content experts with schizophrenia in the development of these tools to ensure their validity and facilitate clinical implementation.

Background Social cognitive ability is a significant determinant of functional outcome, and deficits in social cognition are a disabling symptom of psychotic disorders. The neurobiological underpinnings of social cognition are not well understood, hampering our ability to ameliorate these deficits. Objective Using ‘resting state’ functional magnetic resonance imaging (rsfMRI) and a trans-diagnostic, data-driven analytic strategy, we sought to identify the brain network basis of emotional intelligence, a key domain of social cognition. Methods The study included 60 participants with a diagnosis of schizophrenia or schizoaffective disorder and 45 healthy controls. All participants underwent a rsfMRI scan. Emotional Intelligence was measured using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). A connectome-wide analysis examined how each individual brain voxel's connectivity correlated with emotional intelligence using multivariate distance matrix regression (MDMR). Results We identified a region in the left superior parietal lobule (SPL) where individual network topology is linked to emotional intelligence. Specifically, in high scoring individuals, this region is a node of the Default Mode Network and in low scoring individuals, it is a node of the Dorsal Attention Network. This relationship was observed in both schizophrenia and healthy comparison participants. Conclusion Prior studies have demonstrated individual variance in the topology of canonical resting state networks but the cognitive or behavioral relevance of these differences has largely been undetermined. We observe that the left SPL, a region of high individual variance at the cytoarchitectonic level, also demonstrates individual variance in its association with large scale resting-state networks and that network topology is linked to emotional intelligence.

Social cognition is a central contributor to social functioning in schizophrenia. A better understanding of the underlying structure of social cognition in the early course schizophrenia could help us identify more precise targets for intervention in this population. In the present study, we performed an Exploratory Factor Analysis (EFA) on 90 patients within the early course of schizophrenia using 11 validated subtests assessing various domains of social cognitive skills. The factors derived from this analysis were then used to investigate relationships between these distinct domains of social cognition skills and neurocognitive performance, clinical symptoms, and social functioning satisfaction. The results revealed the presence of a 3-factor solution, representing the domains of Emotion Management, Emotion Recognition, and Theory of Mind, together accounting for 55.88% of the variance. Moreover, higher scores on the Theory of Mind factor were significantly related to higher social functioning satisfaction measures as well as with lower clinical symptoms severity. Our findings suggest that social cognitive skills are composed of three separate domains in the early course of schizophrenia and that theory of mind could be an important therapeutic target for early intervention.

BackgroundSocial cognitive ability is a significant determinant of functional outcome and deficits in social cognition are a disabling symptom of psychotic disorders. The neurobiological underpinnings of social cognition are not well understood, hampering our ability to ameliorate these deficits.ObjectiveUsing ‘resting-state’ fMRI (functional magnetic resonance imaging) and a trans-diagnostic, data-driven analytic strategy, we sought to identify the brain network basis of emotional intelligence, a key domain of social cognition.MethodsStudy participants included 60 participants with a diagnosis of schizophrenia or schizoaffective disorder and 46 healthy comparison participants. All participants underwent a resting-state fMRI scan. Emotional Intelligence was measured using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). A connectome-wide analysis of brain connectivity examined how each individual brain voxel’s connectivity correlated with emotional intelligence using multivariate distance matrix regression (MDMR).ResultsWe identified a region in the left superior parietal lobule (SPL) where individual network topology predicted emotional intelligence. Specifically, the association of this region with the Default Mode Network predicted higher emotional intelligence and association with the Dorsal Attention Network predicted lower emotional intelligence. This correlation was observed in both schizophrenia and healthy comparison participants.ConclusionPrevious studies have demonstrated individual variance in brain network topology but the cognitive or behavioral relevance of these differences was undetermined. We observe that the left SPL, a region of high individual variance at the cytoarchitectonic level, also demonstrates individual variance in its association with large scale brain networks and that network topology predicts emotional intelligence.

BACKGROUND: Evidence shows that cognitive remediation therapy helps improve cognition in people with schizophrenia. Previous studies have demonstrated mild to moderate positive effects of cognitive remediation therapy, but often with a high attrition rate. Furthermore, the impact of cognitive remediation therapy on patients’ lives following treatment completion remains unclear. Systematic exploration of patients’ perspectives on cognitive remediation therapy will allow for better understanding of its impact and the factors influencing adherence to treatment. METHODS: This quantitative and qualitative descriptive study aimed to identify factors that influence patients’ experiences going through a comprehensive cognitive remediation treatment called Cognitive Enhancement Therapy (CET). CET is designed to provide enriched cognitive experiences by combining individual therapy with neurocognitive training and skills group therapy. We recruited 9 patients who have completed CET (mean age: 26.8, 8 men) and we performed two semi-structured focus groups, as well as one individual interview. We assessed three inductive themes when analyzing responses: 1) Motivational factors, 2) Experiences with the CET program, and 3) Impacts of the treatment. All participants also answered questionnaires on their current life satisfaction and subjective impression on CET. RESULTS: Patients reported that family support and subjective feeling of improvement during CET were two motivational factors in choosing to attend and complete the treatment. The size and lighting of the room where treatment took place were also reported to influence motivation. When asked about their experiences with the CET program, participants mentioned that they liked learning and being challenged. Participants specifically raised the importance of learning strategies during the computerized exercises portion of the treatment, as well as the importance of receiving feedback overall. Every participant mentioned that carrying the CET educational binder reduced motivation and that it could be improved in the future. When asked about long-term impacts of the treatment, patients reported that CET improved focus and confidence, and helped facilitate successful peer interactions. Patients also mentioned that CET made them more confident to go back to school or apply for a job. All participants reported that CET helped them (a lot: 55.6%, a good amount: 44.4%), and the majority reported enjoying their participation in CET (a good amount: 55.6%, a lot: 33.3%). Most participants who completed CET reported high satisfaction with their current work/school situation (55.6%) but reported less satisfaction with their social life (66.7%). DISCUSSION: Patients’ perspectives on CET can guide future cognitive remediation trials. Simple aspects such as the treatment setting or the quality of the educational materials can make a difference in patients’ motivation and satisfaction. Our results highlight the importance of providing learning strategies and constant feedback to the patients during the course of the treatment. CET seems to improve patients’ self-reported focus and helps them to achieve their professional and academic goals. Our findings also suggest that promoting family support could increase motivation to pursue and complete CET. Further work is needed to help improve patients’ social lives after treatment.

BACKGROUND: Recent studies show that computer-based training enhances cognition in schizophrenia; furthermore, socialization has also been found to improve cognitive functions. It is generally believed that non-social cognitive remediation using computer exercises would be a pre-requisite for therapeutic benefits from social cognitive training. However, it is also possible that social interaction by itself enhances non-social cognitive functions; this possibility has scarcely been explored in schizophrenia patients. This pilot study examined the effects of computer-based neurocognitive training, along with social interaction either with a peer (PSI) or without one (N-PSI). We hypothesized that PSI will enhance cognitive performance during computerized exercises in schizophrenia, as compared with N-PSI. METHODS: Sixteen adult participants diagnosed with schizophrenia or schizoaffective disorder participating in an ongoing trial of Cognitive Enhancement Therapy completed several computerized neurocognitive remediation training sessions (the Orientation Remedial Module©, or ORM), either with a peer or without a peer. RESULTS: We observed a significant interaction between the effect of PSI and performance on the different cognitive exercises (p < 0.05). More precisely, when patients performed the session with PSI, they demonstrated better cognitive performances than with N-PSI in the ORM exercise that provides training in processing speed, alertness, and reaction time (the standard Attention Reaction Conditioner, or ARC) (p < 0.01, corrected). PSI did not significantly affect other cognitive domains such as target detection and spatial attention. CONCLUSION: Our findings suggest that PSI could improve cognitive performance, such as processing speed, during computerized cognitive training in schizophrenia. Additional studies investigating the effect of PSI during cognitive remediation are needed to further evaluate this hypothesis.

Schizophrenia (SZ) patients exhibit deficits in emotion regulation that affect their daily functioning. There is evidence that the prefrontal cortex plays an important role in emotion regulation. However, it remains unclear how this brain region is involved in emotion regulation deficits in SZ, and how such deficits impact performance on cognitively demanding tasks. We examined how happy and fearful emotional distractors impact performance on working memory (WM) tasks of varying difficulty (0-back, 2-back), and brain activity using fMRI. Participants were 20 patients with SZ and 20 healthy controls (HC) matched on age, sex, race, and IQ. A significant 3-way interaction showed that SZ patients had lower performance compared to HC when exposed to fearful and happy distractors, but only during the 2-back task. Second-level fMRI between-group analysis revealed that compared to SZ patients, HC showed significantly greater increase in brain activity with WM load in the left IFG (BA 45) when exposed to fearful distractors. Less brain activity in this region was also associated with reduction in SZ patients' performance during higher WM load and the presence of fearful distractors. SZ patients had difficulty in performing a WM task when regulating emotions, and they failed to show the emotion-specific modulation of the left IFG observed in HC. These results suggest that SZ patients have difficulty with emotion regulation demands during effortful cognitive tasks. This also provides us with potential insight on how emotion regulation could be rehabilitated in SZ using cognitive training.

Abnormalities in the subcortical brain regions that support cognitive functions have been reported in schizophrenia. Relatives of those with schizophrenia often present with psychosis-like traits (schizotypy) and similar cognition as those with schizophrenia. To evaluate the relationships between subcortical structure, schizotypy, and cognitive function, we assessed shape and volume of the hippocampus, amygdala and thalamus in untreated youth at familial high risk for schizophrenia (HRSZ). The sample consisted of 66 HRSZ and 69 age-matched healthy controls (HC). Subjects' cognitive functions and schizotypy were assessed, and T1-weighted brain MRI were analyzed using the FSL software FIRST. The right hippocampus and right amygdala showed significantly increased concavity (inward displacement) in HRSZ compared to HC. While regional subcortical shape displacements were significantly correlated with sustained attention and executive function scores in HC, fewer correlations were seen in HRSZ. This suggests a possible alteration of the local structure-function relationship in subcortical brain regions of HRSZ for these cognitive domains, which could be related to anomalous plasticity.