Schizophrenia Consensus Cognitive Battery Research Articles

Interview Versus Performance Assessment of Cognition as Predictors of Real-World Outcomes in a Large-Scale Cross-Sectional Study in Schizophrenia.

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). It is approved as a coprimary measure of performance-based instruments, such as the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Recent research highlights negative symptoms, social cognition, and functional capacity as mediators of cognitive impairment's impact on functioning. This study compared mediation analysis outcomes using CAI or MCCB scores, providing insights into the utility of interview-based tools in research and clinical practice. The study included 618 individuals diagnosed with schizophrenia, recruited from 24 Italian psychiatric clinics. Neurocognitive assessments utilized both CAI and MCCB. Mediation analyses explored negative symptoms, social cognition, and functional capacity as mediators of the impact of neurocognition on real-life functioning domains. The study's results extend the validation of the CAI as a coprimary measure that provides valid information on the impact of cognitive impairment on real-life functioning and its possible mediators, complementing the information obtained using the MCCB. Interview-based cognitive assessment might be essential for understanding schizophrenia complexity and its impact on various cognitive and functional domains for clinicians, patients, and caregivers.

Measuring Cognitive Impairments Associated With Schizophrenia in Clinical Practice: Overview of Current Challenges and Future Opportunities.

Cognitive impairment associated with schizophrenia (CIAS) negatively impacts daily functioning, quality of life, and recovery, yet effective pharmacotherapies and practical assessments for clinical practice are lacking. Despite the pivotal progress made with establishment of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) for clinical research, implementation of the full MCCB is too time-consuming and cost-ineffective for most clinicians in clinical practice. Here we discuss current assessments in relation to delivery format (interview-based and performance-based), validity, ease of use for clinicians and patients, reliability/reproducibility, cost-effectiveness, and suitability for clinical implementation. Key challenges and future opportunities for improving cognitive assessments are also presented. Current assessments that require 30min to complete would have value in clinical settings, but the associated staff training and time required might preclude their application in most clinical settings. Initial profiling of cognitive deficits may require about 30min to assist in the selection of evidence-based treatments; follow-up monitoring with brief assessments (10-15min in duration) to detect treatment-related effects on global cognition may complement this approach. Guidance on validated brief cognitive tests for the strategic monitoring of treatment effects on CIAS is necessary. With increased advancements in technology-based and remote assessments, development of validated formats of remote and in-person assessment, and the necessary training models and infrastructure required for implementation, are likely to be of increasing clinical relevance for future clinical practice.

Cognitive Impairments in Drug-Naive Patients With First-Episode Negative Symptom–Dominant Psychosis

Available antipsychotic medications are predominantly used to treat positive symptoms, such as hallucinations and delusions, in patients with first-episode psychosis (FEP). However, treating negative and cognitive symptoms, which are closely related to functional outcomes, remains a challenge. To explore the cognitive characteristics of patients with negative symptom-dominant (NSD) psychosis. This large-scale cross-sectional study of patients with FEP was led by the Shanghai Mental Health Center in China from 2016 to 2021, with participants recruited from 10 psychiatric tertiary hospitals. A comprehensive cognitive assessment was performed among 788 patients with FEP who were drug-naive. Symptom profiles were determined using the Positive and Negative Symptoms Scale (PANSS), and NSD was defined as a PANSS score for negative symptoms higher than that for positive and general symptoms. Positive symptom-dominant (PSD) and general symptom-dominant (GSD) psychosis were defined similarly. Data were analyzed in 2023. Psychotic symptoms were categorized into 3 groups: NSD, PSD, and GSD. Neurocognitive performance, assessed using the Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. This study included 788 individuals with FEP (median age, 22 [IQR, 17-28] years; 399 men [50.6%]). Patients with NSD exhibited more-pronounced cognitive impairment than did those with PSD or GSD. Specifically, cognitive differences between the NSD and PSD group, as well as between the NSD and GSD group, were most notable in the processing speed and attention domains (Trail Making [F = 4.410; P = .01], Symbol Coding [F = 4.957; P = .007], Verbal Learning [F = 3.198; P = .04], and Continuous Performance [F = 3.057; P = .05]). Patients with PSD and GSD showed no significant cognitive differences. Cognitive impairment was positively associated with the severity of negative symptoms. Most of the cognitive function tests used were able to differentiate patients with NSD from those with PSD and GSD, with significant differences observed across a range of tests, from Brief Visuospatial Memory Test-Revised (χ2 = 3.968; P = .05) to Brief Assessment of Cognition in Schizophrenia symbol coding (χ2 = 9.765; P = .002). The findings of this cross-sectional study of patients with FEP suggest the presence of a clinical subtype characterized by a predominance of negative symptoms and cognitive impairment.

Sex-differential cognitive performance on MCCB of youth with BD-II depression

BackgroundRecent evidences have shown sex-differential cognitive deficits in bipolar disorder (BD) and differences in cognitions across BD subtypes. However, the sex-specific effect on cognitive impairment in BD subtype II (BD-II) remains obscure. The aim of the current study was to examine whether cognitive deficits differ by gender in youth with BD-II depression.MethodThis cross-sectional study recruited 125 unmedicated youths with BD-II depression and 140 age-, sex-, and education-matched healthy controls (HCs). The Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) was used to assess cognitive functions. Mood state was assessed using the 24-item Hamilton Depression Rating Scale (24-HDRS) and the Young Mania Rating Scale (YMRS). Multivariate analysis of covariance (MANCOVA) was conducted.Result​Compared with HCs, patients with BD-II depression had lower scores on MCCB composite and its seven cognitive domains (all p < 0.001). After controlling for age and education, MANCOVA revealed significant gender-by-group interaction on attention/vigilance (F = 6.224, df = 1, p = 0.013), verbal learning (F = 9.847, df = 1, p = 0.002), visual learning (F = 4.242, df = 1, p = 0.040), and composite (F = 8.819, df = 1, p = 0.003). Post hoc analyses suggested that males performed worse in the above-mentioned MCCB tests than females in BD-II depression.ConclusionOur study demonstrated generalized cognitive deficits in unmedicated youths with BD-II depression. Male patients performed more serious cognitive impairment on attention/vigilance, verbal learning, and visual learning compared to female patients.

Sex-specific associations of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in patients with drug-naïve schizophrenia

This present study aimed to investigate the sex-specific association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in drug-naïve schizophrenia patients for the first time. A total of 204 participants in this study, including 137 drug-naïve schizophrenia (DNS) patients and 67 healthy controls (HCs). All participants completed the Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), and were collected fasting venous blood for NGAL measurement. DNS patients also complete the Positive and Negative Syndrome Scale (PANSS). Partial correlation analysis and multiple linear regression were used to explore sex-specific associations between NGAL and cognition. All dimensions of MCCB scores were significantly lower in both male and female DNS patients than HCs. Sex differences were significant in cognitive performance in both DNS patients and HCs. Female DNS patients experienced poorer working memory and reason& problem solving than male patients. Female HCs performed a better attention/vigilance and visual learning, a poorer reason& problem solving than male HCs. In patients with DNS, NGAL levels were negatively associated with positive subscale of PANSS and positively associated with working memory and visual learning only in female. However, there was no significant correlation between NGAL levels and all cognitive tests in both male and female HCs. Regression model showed that higher level of NGAL was an independent protective factor for cognitive performance in female patients with DNS, whereas there was no such role in male patients. Our findings suggest sex specificity between NGAL levels and cognitive performance in DNS patients.

The Phase III CONNEX programme assessing the efficacy and safety of iclepertin in patients with schizophrenia: Trial design and recruitment update

IntroductionIn a 12-week, Phase II (NCT02832037) trial, iclepertin (BI 425809), an inhibitor of glycine transporter-1, was generally well tolerated and significantly improved cognition in 509 patients with schizophrenia.ObjectivesThe Phase III CONNEX programme aims to confirm the efficacy, safety and tolerability of iclepertin in improving cognition and functioning across a larger cohort of patients with schizophrenia.MethodsThe CONNEX programme includes 3 randomised, double-blind, placebo-controlled parallel group trials in patients with schizophrenia (NCT04846868, NCT04846881, NCT04860830) receiving stable antipsychotic treatment. Each trial aims to recruit ˜586 patients, 18–50 years old, treated with 1–2 antipsychotic medications (≥12 weeks on current drug and ≥35 days on current dose before treatment) who have functional impairment in day-to-day activities and interact ≥1 hour per week with a designated study partner. Patients with cognitive impairment due to developmental, neurological or other disorders, with a current DSM-5 diagnosis other than schizophrenia or receiving cognitive remediation therapy within 12 weeks prior to screening, will be excluded. Patients will be recruited from multiple centres across 41 countries in Asia, North and South America, Europe and the Asia-Pacific Region, and randomised 1:1 to receive either iclepertin 10 mg (oral administration; n=293), or placebo (n=293) once daily for 26 weeks. The primary endpoint is change from baseline in overall composite T-score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. The key secondary endpoints are change from baseline in total score on the Schizophrenia Cognition Rating Scale and change from baseline in the adjusted total time T-score in the Virtual Reality Functional Capacity Assessment Tool.ResultsThe CONNEX programme is currently recruiting (Table); the first patients were enrolled in Aug–Sept 2021 and completion is expected in Q1 2025. The presentation will describe the current study status, information relating to screening failures, and the experience of collecting these data as part of a large multi-country, multicentre study.Table.The number of patients recruited by 31 August 2023CONNEX 1CONNEX 2CONNEX 3Screened565521493Randomised409360350Completed trial medication202184191ConclusionsIclepertin may represent the first efficacious medication for cognitive impairment associated with schizophrenia.FundingBoehringer IngelheimDisclosure of InterestC. Reuteman-Fowler Employee of: Boehringer Ingelheim, Z. Blahova Employee of: Boehringer Ingelheim, S. Ikezawa Consultant of: Boehringer Ingelheim Pharma GmbH, Lundbeck, Takeda Pharma, Sumitomo Dainippon Pharma, Employee of: International University of Health and Welfare, Mita Hospital, Tokyo, Japan, S. Marder Consultant of: Boehringer Ingelheim Pharma GmbH, Merck, Biogen and Sunovion, P. Falkai Consultant of: Boehringer Ingelheim Pharma GmbH, Boehringer Ingelheim Pharma Advisory Board, J. H. Krystal Shareolder of: Freedom Biosciences, Inc., Biohaven Pharmaceuticals, Sage Pharmaceuticals, Spring Care, Biohaven Pharmaceuticals Medical Sciences, EpiVario, RBNC Therapeutics, Terran Biosciences and Tempero Bio, Consultant of: Aptinyx, Atai Life Sciences, AstraZeneca Pharmaceuticals, Biogen, Biomedisyn Corporation, Bionomics, Boehringer Ingelheim International, Cadent Therapeutics, Clexio Bioscience, COMPASS Pathways, Concert Pharmaceuticals, Epiodyne, EpiVario, Greenwich Biosciences, Heptares Therapeutics, Janssen, Jazz Pharmaceuticals, Otsuka America Pharmaceutical, Perception Neuroscience Holdings, Spring Care, Sunovion Pharmaceuticals, Takeda Industries, Taisho Pharmaceutical Co.; Biohaven Pharmaceuticals, BioXcel Therapeutics, Cadent Therapeutics, Cerevel Therapeutics, Delix Therapeutics, EpiVario, Eisai, Jazz Pharmaceuticals, Novartis, PsychoGenics, RBNC Therapeutics, Tempero Bio and Terran Biosciences Advisory Boards

Improvement of social functioning in patients with first-episode schizophrenia using blonanserin treatment: a prospective, multi-centre, single-arm clinical trial.

This clinical trial primarily aimed to investigate the effects of blonanserin on social functioning in patients with first-episode schizophrenia. In this prospective, multi-centre, single-arm clinical trial study, blonanserin (flexible oral dose ranging from 8mg to 24mg per day) was given 26 weeks. Outcome measures included the Personal and Social Performance (PSP) scale for evaluating social functioning, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) for measuring neurocognitive performance, and the Positive and Negative Syndrome Scale (PANSS) for assessing symptom severity. The primary endpoint was social function improvement evaluated by PSP scale at the end of blonanserin treatment. And the secondary endpoint was to validate the efficacy and neurocognitive effects of blonanserin. Adverse drug reactions (ADRs) were also recorded and analysed. A total of 96 patients with first-episode schizophrenia were recruited and proceeded to analysis. Fifty-one participants (53.1%) completed the PSP scale measurements at baseline and week 26. Following 26 weeks of blonanserin treatment, all outcome measurements demonstrated significant improvement during the follow-up period. Notably, PSP scores exhibited a continuous increase up to 68.1% ± 103.7% at the end of the treatment (46.6 ± 14.6 at baseline, 69.4 ± 17.4 at week 26, p<0.001), indicating positive effects on social functioning that were already noticeable by week 8. Blonanserin treatment exhibited favourable effects on social functioning in individuals with first-episode schizophrenia. The results suggest that blonanserin was effective treatment options for patients with schizophrenia encountering functional impairments.

Diagnostic significance and potential function of miR-320d in schizophrenia.

Schizophrenia is a chronic brain disorder and needs objective diagnostic biomarkers. MicroRNAs are highly expressed in the nervous system. The study investigated the expression and clinical values of serum miR-320d in schizophrenia patients. In addition, the underlying mechanism was preliminarily examined via bioinformatic analysis. Serum samples were collected from 57 patients with first-episode schizophrenia and 62 healthy controls. The cognitive function of patients was assessed via Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) consisting of seven domains. Serum miR-320d levels were tested via qRT-PCR. The miRNA target predictions were obtained from Target Scan, and annotated through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Based on the GSE167630 dataset, downregulated serum miR-320d in schizophrenia was identified, which was determined in the serum of schizophrenia patients. Serum miR-320d presented a conspicuous relationship with MCCB score in both the control group and the schizophrenia group. After adjusting for age, sex, BMI, and education, serum miR-320d was still independently related to the occurrence of schizophrenia. It can identify schizophrenia cases from healthy ones with an AUC of 0.931. The Go enrichment analysis indicated that the target genes were mainly enriched in homophilic cell adhesion and cell-cell adhesion via plasma-membrane adhesion molecules, and GTPase activity and guanosine diphosphate (GDP) binding. Rap1 signaling pathway was enriched via KEGG analysis. Serum miR-320d can be taken as a candidate marker for the diagnosis of schizophrenia. Its regulatory role in neuronal cell adhesion and Rap1 signaling pathway might be the potential underlying mechanism of miR-320d in schizophrenia.

Cognitive Function and Variability in Antipsychotic Drug–Naive Patients With First-Episode Psychosis

Cognitive impairment contributes significantly to clinical outcome and level of function in individuals with psychotic disorders. These impairments are present already at psychosis onset at a group level; however, the question of heterogeneity in cognitive function among patients has not been systematically investigated. To provide an updated quantification of cognitive impairment at psychosis onset before patients receive potentially confounding antipsychotic treatment, and to investigate variability in cognitive function compared with healthy controls. In this systematic review and meta-analysis, PubMed articles were searched up to September 15, 2022. Original studies reporting data on cognitive function in antipsychotic drug-naive patients with first-episode psychosis (FEP) were included. Data were independently extracted by 2 researchers. Cognitive tasks were clustered according to 6 domains of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery and the domain of executive function. Random-effects model meta-analyses of mean differences and coefficient of variation ratios (CVRs) were performed, as well as meta-regressions, assessment of study quality, and publication bias. The main outcome measure was Hedges g for mean differences in cognition and CVR for within-group variability. Fifty studies were included in the analysis with a total of 2625 individuals with FEP (mean [SD] age, 25.2 [3.6] years, 60% male; 40% female) and 2917 healthy controls (mean [SD] age, 26.0 [4.6]; 55% male; 45% female). In all cognitive domains, the FEP group displayed significant impairment compared with controls (speed of processing: Hedges g = -1.16; 95% CI, -1.35 to -0.98; verbal learning: Hedges g = -1.08; 95% CI, -1.28 to -0.88; visual learning: Hedges g = -1.05; 95% CI, -1.27 to -0.82; working memory: Hedges g = -1.04; 95% CI, -1.35 to -0.73; attention: Hedges g = -1.03; 95% CI, -1.24 to -0.82; reasoning/problem solving: Hedges g = -0.90; 95% CI, -1.12 to -0.68; executive function: Hedges g = -0.88; 95% CI, -1.07 to -0.69). Individuals with FEP also exhibited a larger variability across all domains (CVR range, 1.34-1.92). Results of this systematic review and meta-analysis identified cognitive impairment in FEP before the initiation of antipsychotic treatment, with large effect sizes. The high variability within the FEP group suggests the need to identify those individuals with more severe cognitive problems who risk worse outcomes and could benefit the most from cognitive remediation.

The relationship between serum prolactin levels and cognitive function in drug-naïve schizophrenia patients: a cross-sectional study.

This study aimed to investigate the association between serum prolactin levels and psychiatric symptoms and cognitive function in drug-naïve schizophrenia patients. The study recruited 91 drug-naïve schizophrenia patients and 67 healthy controls. Sociodemographic and clinical data were collected, and cognitive function was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). Serum prolactin levels were measured, and statistical analyses were performed to examine the relationship between prolactin levels, clinical symptoms, and cognitive function. The study found that drug-naïve schizophrenia patients had severe cognitive deficits compared to healthy controls across all seven domains of the MCCB. However, no correlation was found between these patients' serum prolactin levels and clinical severity or cognitive function. The drug-naïve schizophrenia patients had significant cognitive deficits compared to healthy controls. However, there was no significant relationship between prolactin levels and symptomatology and cognition in drug-naïve schizophrenia patients.

Latent classes of symptom trajectories among major depressive disorder patients in China

ObjectiveThis study aimed to understand the long-term symptom trajectories of Chinese patients with major depressive disorder (MDD) using piecewise latent growth modeling and growth mixture modeling. The investigation also aimed to identify the baseline characteristics indicative of poorer treatment outcomes. MethodsA total of 558 outpatients with MDD were assessed using a sequence of surveys. The Hamilton Rating Scale for Depression (HRSD), Hamilton Anxiety Rating Scale (HAMA), and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) were used to evaluate baseline depression, anxiety, and cognitive function. Depression symptom severity was subsequently measured at the 1-month, 2-month, 6-month, 1-year, and 2-year follow-ups. ResultsResults indicated three depressive symptomology trajectories, including (a) severe, improving class (12.72 %), (b) partially responding, later deteriorating class (6.09 %), and (c) moderate, improving class (81.18 %). Logistic regression analyses showed that a history of cardiovascular disease (CVD) increased the odds of belonging to the partially responding, later deteriorating class, whereas higher baseline depression increased the odds of belonging to the severe, improving class compared to the moderate, improving class. Patients who experienced less depression relief during the first month of treatment had a lower probability of belonging to the moderate, improving class. LimitationsParticipant attrition in this study may have inflated the estimated rate of treatment-resistant patients. ConclusionsThe burden of CVD and poorer initial treatment response are plausible risk factors for poorer treatment outcomes, highlighting targets for intervention in Chinese MDD patients.

Negative symptoms and neurocognition in drug-naïve schizophrenia: moderating role of plasma neutrophil gelatinase-associated lipocalin (NGAL) and interferon-gamma (INF-γ).

Previous studies reported that peripheral inflammation was associated with cognitive performance and brain structure in schizophrenia. However, the moderating effect of inflammation has not been extensively studied. This study investigated whether inflammation markers moderated the association between negative symptoms and neurocognition in schizophrenia. This cross-sectional study included 137 drug-naïve schizophrenia patients (DNS) and 67 healthy controls (HC). We performed the Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) for cognitive assessment and the Positive and Negative Syndrome Scale (PANSS) for psychiatric symptoms. Plasma concentrations of interferon-gamma (IFN-γ), neutrophil gelatinase-associated lipocalin (NGAL), and nuclear factor kappa B (NF-κB) were measured. The MCCB neurocognition score, social cognition score, and total score; the plasma concentrations of NGAL, IFN-γ, and NF-κB were significantly decreased in DNS than in HC (all P's < 0.001). PANSS negative subscale (PNS), PANSS reduced expressive subdomain (RES) negatively correlated with neurocognition score (P = 0.007; P = 0.011, respectively). Plasma concentrations of IFN-γ and NGAL positively correlated with neurocognition score (P = 0.043; P = 0.008, relatively). The interactions of PNS × NGAL; PNS × IFN-γ; RES × IFN-γ accounted for significant neurocognition variance (P = 0.025; P = 0.029, P = 0.007, respectively). Simple slope analysis showed that all the above moderating effects only occurred in patients with near normal IFN-γ and NGAL levels. Plasma concentrations of IFN-γ and NGAL moderated the relationship between negative symptoms (especially RES) and neurocognition in schizophrenia. Treatment targeting inflammation may contribute to neurocognition improvement in schizophrenia.

Spatial and Temporal Abnormalities of Spontaneous Fixational Saccades and Their Correlates With Positive and Cognitive Symptoms in Schizophrenia.

Visual fixation is a dynamic process, with the spontaneous occurrence of microsaccades and macrosaccades. These fixational saccades are sensitive to the structural and functional alterations of the cortical-subcortical-cerebellar circuit. Given that dysfunctional cortical-subcortical-cerebellar circuit contributes to cognitive and behavioral impairments in schizophrenia, we hypothesized that patients with schizophrenia would exhibit abnormal fixational saccades and these abnormalities would be associated with the clinical manifestations. Saccades were recorded from 140 drug-naïve patients with first-episode schizophrenia and 160 age-matched healthy controls during ten separate trials of 6-second steady fixations. Positive and negative symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Cognition was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Patients with schizophrenia exhibited fixational saccades more vertically than controls, which was reflected in more vertical saccades with angles around 90° and a greater vertical shift of horizontal saccades with angles around 0° in patients. The fixational saccades, especially horizontal saccades, showed longer durations, faster peak velocities, and larger amplitudes in patients. Furthermore, the greater vertical shift of horizontal saccades was associated with higher PANSS total and positive symptom scores in patients, and the longer duration of horizontal saccades was associated with lower MCCB neurocognitive composite, attention/vigilance, and speed of processing scores. Finally, based solely on these fixational eye movements, a K-nearest neighbors model classified patients with an accuracy of 85%. Conclusions: Our results reveal spatial and temporal abnormalities of fixational saccades and suggest fixational saccades as a promising biomarker for cognitive and positive symptoms and for diagnosis of schizophrenia.

Time discrimination in psychosis: findings from a neuroimaging study

IntroductionPrevious functional neuroimaging studies have demonstrated a brain network responsible of time discrimination (TD) processes, which may play a significant mediating role in other cognitive processes, such as change detection and cognitive control. The study of TD and its dysfunction in psychosis has become a matter of growing interest. We hypothesize that the impairment of the TD network is involved both in the mechanisms of psychosis and in the cognitive deficit presented by patients.Objectives1.To delimit the brain regions involved in TD.2.To examine the dysfunction in TD brain network in patients diagnosed with psychosis.3.To sudy the integrity of brain white matter pathways in psychosis.4.To verify whether the neuroimaging findings and TD test performance predict the neurocognitive profile of the patients.MethodsParticipants included 20 patients with psychosis (PSY group) and 13 healthy controls (HC group). PSY group participants met remission criteria for 6 months prior to the study. Participants were interviewed for sociodemographic information and clinical assessments. They underwent a detailed cognitive assesment using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). Neuroimaging study was performed on a 3 Tesla MRI scanner. We designed an experimental task including a test tool to assess TD and Oddbal detection (OD) paradigms with a cognitive control component. The task was conducted under functional magentic resonance imaging (fMRI). We used the general linear model analysis of the individual data of the fMRI images and the random effects model for group inference. Group differences in DTI were tested using tract-based spatial statistics (TBSS).ResultsWe find statistically significant differences (fMRI) in the activity related to TD (in HC), with greater activity in frontal cortical regions, the insular cortex and the cerebellum. In the PSY group, differences in the functionality and activation pattern of brain networks responsible for TD are observed, although voxel clustering does not reach the cluster significance limit when compared to HC. Compared to the HC, the PSY group has a significant deficit of fractional anisotropy (DTI) in the whole brain and in 21 specific brain regions. The PSY group has significantly lower scores in six of the seven cognitive domains than the control group, as well as in the overall composite. We correlated FA values in the groups of interest with MCCB scores.Image:Image 2:Image 3:ConclusionsWe have defined the TD network, its relationship with other brain networks and cognitive processes of more complexity. The inclusion of participants with stable psychosis allowed us to analyze de TD disfunction in the PSY group. We compared the integrity of TD related brain pathways and correlated the findings with various clinical characteristics and the cognitive impairment present in psychotic patients.Disclosure of InterestNone Declared

Cognitive dysfunction and neurometabolic alternations in major depressive disorder with gastrointestinal symptoms

BackgroundBrain biochemical abnormalities have been associated with major depressive disorder (MDD) and cognitive impairments. However, the cognitive performance and neurometabolic alterations of MDD patients accompanied by gastrointestinal (GI) symptoms remain to be elucidated. We aimed to reveal the features and correlation between cognitive impairments and brain biochemical abnormalities of depressed patients with GI symptoms. MethodsFifty MDD patients with GI symptoms (GI group), 46 patients without GI symptoms (NGI group) and 50 demographically matched healthy controls (HCs) underwent Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) assessments. In addition, proton magnetic resonance spectroscopy (1H-MRS) was used to obtain ratios of N-acetyl aspartate to creatine (NAA/Cr) and choline-containing compounds to creatine (Cho/Cr) in the thalamus, putamen and anterior cingulate cortex (ACC). Finally, association analysis was conducted to investigate the relationships of these measurements. ResultsCompared to HCs, participants in both the GI and NGI groups had significantly reduced performance in the six MCCB cognitive domains (all p < 0.05), except for reasoning and problem solving. Higher Cho/Cr ratios in the right thalamus (p < 0.05) and lower NAA/Cr ratios in the left putamen (p < 0.05) were found in the NGI group than in the GI group. The severity of GI symptoms was negatively correlated with Cho/Cr ratios in the right ACC (r = −0.288, p = 0.037). In addition, the T-scores of visual learning were negatively correlated with NAA/Cr ratios in the right ACC (r = −0.443, p = 0.001) and right thalamus (r = −0.335, p = 0.015). ConclusionOur findings suggest that MDD patients with GI symptoms may exhibit greater neurometabolic alternations than those without GI symptoms, while both show similar cognitive dysfunction. In addition, neurometabolic alterations in the ACC and thalamus may underlie the neural basis of GI symptoms and cognitive impairment in MDD.

Ultrarare Coding Variants and Cognitive Function in Schizophrenia

Impaired cognitive function in schizophrenia is associated with poor functional outcomes, but the role of rare coding variants is unclear. To determine whether ultrarare constrained variants (URCVs) are associated with cognition in patients with schizophrenia. Linear regression was used to perform a within-case genetic association study of URCVs and current cognition and premorbid cognitive ability. A multivariable linear regression analysis of the outcomes associated with URCVs, schizophrenia polygenic risk score, polygenic risk score for intelligence and schizophrenia associated copy number variants on cognitive ability was performed. Exome sequencing data from 802 participants with schizophrenia were assessed for current cognition using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery and for estimated premorbid IQ using the National Adult Reading Test. Individuals were recruited from clinical and voluntary mental health services in the UK. Those with a diagnosis of intellectual disability or a neurological disorder known to affect cognition were excluded. Data collection occurred between 2007 and 2015. Data were analyzed between April 2020 and March 2022. Association between URCVs, current cognition, and current cognition adjusted for premorbid IQ. Of the 802 participants, 499 (62%) were men and 303 (38%) were women; mean (SD) age at interview was 43.36 (11.87) years. Ultrarare constrained variants (n = 400) were associated with lower current cognition scores (β = -0.18; SE = 0.07; P = .005). In the univariable analysis, premorbid IQ was associated with URCVs (β = -0.12; SE = 0.05; P = .02) and partly attenuated the association with current cognition (β = -0.09; SE = 0.05; P = .08). Multivariable analysis showed that measured genetic factors combined accounted for 6.2% of variance in current cognition, 10.3% of variance in premorbid IQ, and supported outcomes of URCVs associated with current cognition independent of premorbid IQ (β = -0.10; SE = 0.05; P = .03). The findings of this study suggest that URCVs contribute to variance in cognitive function in schizophrenia, with partly independent associations before and after onset of the disorder. Although the estimated effect sizes were small, future studies may show that the effect sizes will be greater with better annotation of pathogenic variants. Genomic data may contribute to identifying those at particularly high risk of cognitive impairment in whom early remedial or preventive measures can be implemented.

Serum hyperhomocysteine and cognitive impairment in first-episode patients with schizophrenia: Moderated by brain cortical thickness

The mechanism by which high homocysteine (HCY) may aggravate cognitive impairment in patients with schizophrenia is not well understood. We aimed to test the hypothesis that hyperhomocysteinaemia may exacerbate cognitive deficits by mediating the decrease in cortical thickness in patients with schizophrenia. One hundred and sixty-seven first-episode patients with schizophrenia (FEPS) and 120 healthy controls (HCs) were included. Psychopathology and cognitive function were assessed using the Positive and Negative Symptom Scale and Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB), respectively. Brain cortical thickness was measured by 3.0 T high-resolution magnetic resonance imaging. Serum HCY levels were tested using a sandwich enzyme-linked immunosorbent assay. Our findings showed that HCY levels in the FEPS were significantly higher than those in the HCs (P < 0.001). The MCCB total and subtest scores in the patients were significantly lower than those in the HCs (P < 0.001). The HCs had significantly higher cortical thickness than the patients (P < 0.001). Serum HCY levels were negatively correlated with Working Memory, Attention/Vigilance, and MCCB total scores in the FEPS (P < 0.05). Brain cortical thickness had positive moderating effects on cognitive impairment in FEPS with high HCY after controlling for sex, age, and education (P < 0.05). In HCs with high HCY, brain cortical thickness had no mediating or moderating effects on cognitive impairment. Compared with HCs, FEPS had thinner grey matter thickness, furthermore, the grey matter thickness might play a crucial role in relationship between high HCY and cognitive deficits.

Cognitive Function Mediates the Anti-suicide Effect of Repeated Intravenous Ketamine in Adult Patients With Suicidal Ideation.

ObjectivePrior research has shown that ketamine has anti-suicide effects. Additional evidence also suggests that ketamine may offer pro-cognitive effects. Herein, we propose that the anti-suicide effects of ketamine are partially mediated via pro-cognitive effects. We aimed to determine whether improvement in cognitive function mediated change in suicidal ideation was associated with ketamine treatment.MethodsUnipolar or bipolar depressive patients (n = 86) with suicidal ideation received six infusions of ketamine (0.5 mg/kg) over 2 weeks. The current severity of suicidal ideation and depression symptoms were assessed with the Beck Scale for Suicide Ideation (SSI) and the Montgomery–Asberg Depression Rating Scale (MADRS), respectively, at baseline, days 13 and 26. Cognitive domains, including processing speed, working memory, visual learning, and verbal learning were measured with the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery at the same time points.ResultsMediation analysis showed a significant total effect of ketamine treatment on SSI score (coef = –1.853, 95%CI [–2.2, –1.5]). The direct and total indirect (MADRS total score and any of cognitive domains) effects of ketamine on suicidal ideation both were statistically significant (direct: coef = –1.064 to –1.352; total indirect: coef = –0.501 to –0.788). MADRS total score and processing speed (but not other cognitive domains) were significant partial mediators of the association between ketamine treatment and improvements in suicidal ideation.ConclusionDepressive symptoms severity and processing speed performance partially mediated improvements in suicidal ideation after repeated ketamine infusions in persons with unipolar or bipolar depressive disorder.

The prevalence and characteristics of MCCB cognitive impairment in unmedicated patients with bipolar II depression and major depressive disorder

BackgroundCognitive impairment has been acknowledged as a core clinical manifestation of bipolar disorder (BD) as well as major depressive disorder (MDD). Determining the prevalence and characteristics of cognitive impairment is important for clinical interventions. This study investigated the prevalence and characteristics of cognitive impairment based on the Measurement and Treatment Research to Improve Cognition Schizophrenia Consensus Cognitive Battery (MCCB) in both BD and MDD. MethodOne hundred and forty-nine BD II depression, 147 MDD, and 124 demographically matched healthy controls (HC) underwent MCCB cognitive assessment. The prevalence of MCCB cognitive impairment and group difference comparisons were performed. Additionally, association analysis was performed to investigate the relationship between cognitive performance and clinical variables. ResultsCompared to the HC group, both BD II depression and MDD groups had a significantly reduced performance for all MCCB cognitive domains (all p < 0.05). The numerical scores for visual learning were lower in the BD II depression group compared to the MDD group. 32.89% of the BD II depression patients had clinically significant impairment (>1.5 SD below the normal mean) in two or more MCCB domains compared to 23.13% for MDD patients. ConclusionsA high percent of patients in the BD II depression and MDD group exhibited MCCB cognitive impairments with clinical significance. Cognitive impairments were more common in BD II depression patients compared to MDD patients, particularly for visual learning. These findings suggest that clinicians should be aware of the severe cognitive impairment in mood disorders and establish effective cognitive screening and intervention strategies.

Reduced temporal activation during a verbal fluency test in clinical high risk of psychosis: a functional near-infrared spectroscopy-based study

BackgroundClinical high risk (CHR) of psychosis is a state in which positive symptoms cause the subjects distress but do not approach a severity level that fulfils the criteria for a...