MATRICS Consensus Cognitive Battery Research Articles

Efficacy and safety of low-frequency repetitive transcranial magnetic stimulation in adolescents with first-episode major depressive disorder: A randomized, double-blind, sham-controlled pilot trial

BackgroundA few sham-controlled studies have examined the efficacy, safety, and tolerability of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) in adolescents with first-episode major depressive disorder (FE-MDD). MethodsForty adolescents (aged 13–17 years) with FE-MDD were randomly assigned to receive active rTMS (n = 20) or sham rTMS (n = 20) for 10 sessions over two weeks. The severity of baseline depressive symptoms and their improvement on the day immediately after the second, fourth, sixth, eighth, and tenth sessions were assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17). Results: After completing 10 rTMS treatment sessions, there was no significant difference in antidepressant response (70.0 % vs. 60.0 %, p > 0.05) and antidepressant remission (55.0 % vs. 35.0 %, p > 0.05) between rTMS groups. The linear mixed model analysis did not show a significant group-by-time interaction (F = 1.26; p > 0.05) in the HAMD-17 scores. There was a significant time main effect on the speed of processing (F = 13.61; p < 0.05), but this did not differ significantly between groups (p > 0.05). There were no other main effects and group-by-time interactions in the other MATRICS Consensus Cognitive Battery domains (all p > 0.05). All adverse event categories, such as fatigue and headache, were similar in the two groups (all p > 0.05). ConclusionsIn this study that compared a combination of LF-rTMS + medication with sham + medication, LF-rTMS had higher response and remission rates than a sham procedure in adolescents with FE-MDD, but the change was not statistically significant. LF-rTMS is generally safe, with mild adverse effects and no negative impact on neurocognitive performance for adolescents with FE-MDD. Registration numberChiCTR2000037878.

Sex differences in the association of overweight with cognitive performance in individuals with first-episode psychosis

Cognitive deficits and overweight are prominent challenges in the treatment of psychosis, which have a direct impact on patients’ quality of life. We aim to determine whether there is an association of overweight with cognitive performance and whether there are sex differences in this association. We included 170 individuals with first-episode psychosis (FEP) (mean age 23.08 years, 32.9% females) attending an early intervention service who underwent clinical, biometric, and cognitive assessments by the MATRICS Consensus Cognitive Battery. A set of two-way analyses of covariance (ANCOVAs) were conducted for each cognitive test. Sex, overweight, and their interaction were included as factors. Nearly 34% of the participants were overweight without differences between males and females. The excess of weight did not exert any main effect on cognition; however, overweight females performed significantly worse than non-overweight females in processing speed, verbal learning and memory, reasoning and problem-solving, and global cognitive function, whereas in males, there were no differences. Our findings highlight that sex matters in the study of metabolic and cognitive factors in FEP to develop targeted interventions based on sex perspectives.

NRN1 genetic variability and methylation changes as biomarkers for cognitive remediation therapy response in schizophrenia

Cognitive remediation therapy (CRT) demonstrates potential in enhancing cognitive function in schizophrenia (SZ), though the identification of molecular biomarkers remains challenging. The Neuritin-1 gene (NRN1) emerges as a promising candidate gene due to its association with SZ, cognitive performance and response to neurotherapeutic treatments. We aimed to investigate whether NRN1 genetic variability and methylation changes following CRT are related to cognitive improvements.Twenty-five SZ patients were randomly assigned to CRT or treatment-as-usual (TAU) groups, with cognitive function and NRN1 methylation assessed pre- and post-intervention using the MATRICS Consensus Cognitive Battery and EpiTYPER. Besides, eleven NRN1 polymorphisms were genotyped. Methylation changes (Δm = post - pre) were analyzed via sparse Partial Least Square Discriminant Analysis (sPLS-DA) to identify latent components (LCs) distinguishing CRT from TAU. To further explore methylation patterns of these LCs, CpG units were grouped into two subsets, yielding Δm means for those with increased and decreased methylation. Cognitive changes (Δcog = post - pre) were used to identify CRT improvers (CRTI, Δcog ≥1), and the association between methylation changes and cognitive improvements post-therapy was also tested.We identified two LCs that differentiated CRT from TAU with a classification error rate of 0.28. The main component, LC1, included 25 CpG units. The subsets of CpG units with increased and decreased post-therapy methylation differed significantly between the two treatment arms, suggesting that differences were not merely data-driven but reflected meaningful biological variation. Additionally, CpG units linked to therapy were also associated with cognitive improvement, with LC1 and the subset of CpG units showing increased methylation post-therapy distinguishing CRT-I from the rest of the patients across multiple cognitive domains. Furthermore, the effect of LC1 on speed processing improvement after CRT was enhanced by considering the NRN1-rs9405890 polymorphism. Notably, these CpG units, particularly those with increased methylation after CRT, overlapped with key gene regulatory elements.Our model, integrating genetics and epigenetics, boosts the understanding of CRT response variability and highlights this multi-level approach as a promising strategy for identifying potential NRN1-related biomarkers of CRT effects, though further studies with larger samples are needed.

Comparative study about the therapeutic effect of cTBS and rTMS in the treatment of auditory verbal hallucinations in schizophrenia.

This study aims to compare the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) and continuous theta-burst stimulation (cTBS) treatment in schizophrenia patients with auditory verbal hallucinations (AVHs). We enrolled 64 schizophrenia patients with AVHs who were treated with either rTMS (n = 32) or cTBS (n = 32), and we compared the clinical outcomes by evaluating parameters from motor evoked potentials, Positive and Negative Syndrome Scale (PANSS), Auditory Hallucination Rating Scale (AHRS), and MATRICS Consensus Cognitive Battery (MCCB), as well as the changes of serum neurotrophic factors before and after the treatment. After the treatment, both treatments resulted in reduced PANSS scores, with the cTBS group showing more substantial symptom improvement across positive, negative, and general symptoms, highlighting the enhanced efficacy of cTBS. Cognitive functions assessed by MCCB also improved in both groups, with cTBS showing a generally higher therapeutic effect. Serum levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) increased following treatment in both groups, with a more notable increase after cTBS, while GABA and glutamate levels remained unchanged. Cardiovascular indices were unaffected by either treatment, suggesting no significant impact on cardiovascular health. Our study found that both rTMS and cTBS treatment can exhibit therapeutic effects in the management of AVHs in patients with schizophrenia. However, cTBS treatment generally shows a higher therapeutic effect than rTMS treatment.

Abnormal resting-state functional connectivity of the right anterior cingulate cortex in chronic ketamine users and its correlation with cognitive impairments

BackgroundChronic ketamine use leads to cognitive impairments, however, the neural mechanisms underpinning these impairments are still unclear. AimsMany studies showed Anterior cingulate cortex (ACC)is strongly involved in cognition and drug addiction, as supported by our previous studies. The objective of this study was to assess the variations in resting-state functional connectivity (FC) changes in the right anterior cingulate cortex (ACC) of chronic ketamine users (CKUs) and their relationship with cognitive performance. MethodsThe study enrolled 28 chronic ketamine users (CKUs) and 30 healthy controls (HCs). Resting-state functional magnetic resonance imaging (fMRI) data were gathered from both groups. Cognitive functions were evaluated using the MATRICS Consensus Cognitive Battery (MCCB). ResultsCKUs demonstrated significantly poorer cognitive performance than HCs in various cognitive domains, including Visual Learning, Speed of Processing, Working Memory, and the composite score of MCCB. Group-level comparisons revealed that CKUs exhibited enhanced functional connectivity between the right ACC and the right postcentral gyrus (PCG) compared to HCs. There was a positive relationship between the connectivity of right ACC-PCG and reasoning and problem-solving score, but there was no significant association with the characteristics of ketamine use. ConclusionCKUs showed enhanced connectivity between the right ACC and the right PCG. This enhanced functional connectivity may indicate functional compensation for cognitive deficits in CKUs, especially for reasoning and problem-solving impairments in CKUs.

Exploring the relationship between lipid metabolism and cognition in individuals living with stable-phase Schizophrenia: a small cross-sectional study using Olink proteomics analysis

BackgroundCognitive impairment is a core symptom of schizophrenia. Metabolic abnormalities impact cognition, and although the influence of blood lipids on cognition has been documented, it remains unclear. We conducted a small cross-sectional study to investigate the relationship between blood lipids and cognition in patients with stable-phase schizophrenia. Using Olink proteomics, we explored the potential mechanisms through which blood lipids might affect cognition from an inflammatory perspective.MethodsA total of 107 patients with stable-phase schizophrenia and cognitive impairment were strictly included. Comprehensive data collection included basic patient information, blood glucose, blood lipids, and body mass index. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the MATRICS Consensus Cognitive Battery (MCCB). After controlling for confounding factors, we identified differential metabolic indicators between patients with mild and severe cognitive impairment and conducted correlation and regression analyses. Furthermore, we matched two small sample groups of patients with lipid metabolism abnormalities and used Olink proteomics to analyze inflammation-related differential proteins, aiming to further explore the association between lipid metabolism abnormalities and cognition.ResultsThe proportion of patients with severe cognitive impairment (SCI) was 34.58%. Compared to patients with mild cognitive impairment (MCI), those with SCI performed worse in the Attention/Alertness (t = 2.668, p = 0.009) and Working Memory (t = 2.496, p = 0.014) cognitive dimensions. Blood lipid metabolism indicators were correlated with cognitive function, specifically showing that higher levels of TG (r = -0.447, p < 0.001), TC (r = -0.307, p = 0.002), and LDL-C (r = -0.607, p < 0.001) were associated with poorer overall cognitive function. Further regression analysis indicated that TG (OR = 5.578, P = 0.003) and LDL-C (OR = 5.425, P = 0.001) may be risk factors for exacerbating cognitive impairment in individuals with stable-phase schizophrenia. Proteomics analysis revealed that, compared to individuals with stable-phase schizophrenia and normal lipid metabolism, those with hyperlipidemia had elevated levels of 10 inflammatory proteins and decreased levels of 2 inflammatory proteins in plasma, with these changes correlating with cognitive function. The differential proteins were primarily involved in pathways such as cytokine-cytokine receptor interaction, chemokine signaling pathway, and IL-17 signaling pathway.ConclusionBlood lipids are associated with cognitive function in individuals with stable-phase schizophrenia, with higher levels of TG, TC, and LDL-C correlating with poorer overall cognitive performance. TG and LDL-C may be risk factors for exacerbating cognitive impairment in these patients. From an inflammatory perspective, lipid metabolism abnormalities might influence cognition by activating or downregulating related proteins, or through pathways such as cytokine-cytokine receptor interaction, chemokine signaling pathway, and IL-17 signaling pathway.

Elevated plasma matrix metalloproteinase 9 in schizophrenia patients associated with poor antipsychotic treatment response and white matter density deficits

Oxidative stress and neuroinflammation contribute to schizophrenia (SCZ) pathology and may influence treatment efficacy. Matrix metalloproteinase 9 (MMP9) is a critical molecular node mediating the interaction between oxidative stress and inflammation, and so may influence treatment efficacy. Here we examined the associations of plasma MMP9 concentration with antipsychotic drug responses, clinical symptoms, and brain structure. A total of 129 healthy controls and 124 patients with SCZ were included in this study. Patients were monitored clinically during 8 weeks of antipsychotic treatment and classified as poor responders (n = 49) or good responders (n = 75). We then compared plasma MMP9 concentrations in healthy controls at baseline and both SCZ responder groups at baseline and after the 8-week antipsychotic treatment regimen. Cognitive function was also examined using the MATRICS Consensus Cognitive Battery. In addition, we extracted regional white matter density from magnetic resonance images of patients. Compared to healthy controls, plasma MMP9 levels were significantly elevated in poor responders at baseline and negatively correlated with both white matter density in the right superior temporal gyrus and the change in cognitive symptoms after treatment. Conversely, there was no significant difference in plasma MMP9 between good responders and healthy controls, and no associations of plasma MMP9 with cognitive symptoms or regional white matter density among good responders. Elevated plasma MMP9 is associated with poor antipsychotic drug efficacy and white matter deficits in SCZ patients, and so may be a useful biomarker to guide personalized treatment.

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

Cognitive performance manifests regional differences, correlated with education. There is less information available about regional differences in performance-based measures of functional capacity. In multi-national trials focused on cognitive enhancement, it may be impossible to validate every measure in all locations. It is unknown if regional differences in healthy controls’ (HC) performance affects relative levels of impairment in participants with schizophrenia (SCZ). A multi-site study comparing SCZ and HC administered the MATRICS Consensus Cognitive Battery (MCCB) and Virtual Reality Functional Capacity Assessment Tool (VRFCAT) to 164 HC participants and 164 with SCZ across three sites (Columbia, SC, Miami, and San Diego) and a representative sample of HC (n = 390) completed the VRFCAT in Durham, NC. Performance was compared between HC and SCZ participants at the validation sites. There were statistically significant cross-site differences in HC performance on both the MCCB and VRFCAT. Differences between HC and SCZ on MCCB and VRFCAT were substantial at all three sites, indicating that regional variations in HC performance did not induce reduced differences from SCZ participants. Regional differences were smaller than diagnostic group differences, suggesting that relative impairments of participants with SCZ is consistently preserved across performance differences in HC.

Correlations between Immunoinflammatory Factor Levels and Cognitive Functions and Brain Structural Magnetic Resonance Imaging Features among Patients with Primary Schizophrenia.

Schizophrenia is associated with significant cognitive impairment. However, the pathophysiological mechanisms underlying cognitive dysfunction in schizophrenia remain unclear. Based on the latest concept of cognition, immunoinflammatory factors and structural magnetic resonance imaging (sMRI) features of the brain are considered markers of schizophrenia. This study explored the correlations between cognitive function and immunoinflammatory factors and sMRI in primary schizophrenia patients. Non-interventional cross-sectional study was conducted, including 21 patients with primary schizophrenia, who were identified based on the Diagnostic and Statistical Manual, Fifth Edition (DSM-V) and grouped under the observation group. Thirty healthy volunteers with age, gender, hand dominance, and education duration matched with those of the primary schizophrenia patients were recruited to the control group. All subjects underwent sMRI examination. MATRICS consensus cognitive battery (MCCB) was employed to assess the cognitive functions among patients with primary schizophrenia. The levels of serum amyloid A (SAA), monocyte chemoattractant protein 1 (MCP-1), and chitinase-3-like protein 1 (YKL-40) were measured by means of enzyme-linked immunosorbent assay (ELISA). Pearson's correlation analysis was carried out to analyze the correlation between immunoinflammatory factor levels and cognitive functions as well as brain sMRI features. The scores for all MCCB items and the total score for the observation group were apparently lower than those for the control group (p < 0.001), while the YKL-40 and SAA levels were notably higher in the observation group (t = 3.406, p < 0.05; t = 5.656, p < 0.001). Compared to the control group, the observation group exhibited reduced volumes of left and right insular lobes, left and right anterior cingulate cortexes, left and right hippocampi, right parahippocampal gyrus, right amygdala, left inferior occipital lobe, left superior temporal lobe, left temporal pole, and left middle and inferior temporal lobes (p < 0.001). The levels of YKL-40 and SAA were both negatively correlated with MCCB score (r = -0.3668, p = 0.004; r = -0.8495, p < 0.001). The volumes of right insular lobe, left and right anterior cingulate cortexes, right parahippocampal gyrus, right amygdala, and gray matter in left middle temporal lobe were all negatively correlated with the levels of YKL-40 and SAA (p < 0.05). Cognitive impairment in patients with primary schizophrenia is associated with increased serum SAA and YKL-40 levels and decreased gray matter volume.

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 impairment in major depressive disorder with non-suicidal self-injury: Association with the functional connectivity of frontotemporal cortex

BackgroundNon-suicidal self-injury (NSSI) may be related to serious cognitive impairment in patients with major depressive disorder (MDD), but the specific mechanism is still unclear. This study attempts to identify the neurobiological process alterations of cognitive impairment in MDD patients with NSSI by examining the functional connectivity of the frontotemporal cortex in MDD patients with or without NSSI. MethodThirty MDD patients with NSSI, 36 MDD patients without NSSI, and 35 healthy controls (HC) were included in the study. The MATRICS Consensus Cognitive Battery (MCCB) was used to comprehensively assess the cognitive function of the subjects and functional near-infrared spectroscopy (fNIRS) was used to detect the functional connectivity of the frontotemporal cortex and its brain regions of interest. ResultsMDD patients with or without NSSI had multi-domain cognitive impairments. MDD patients with NSSI showed the lowest score in performance of attention/alertness and the weakest functional connectivity of frontotemporal when compared with the MDD patients without NSSI and the HC. In addition, the functional connectivity of the bilateral frontotemporal cortex was positively correlated with verbal learning and working memory in MDD patients with NSSI. ConclusionIn MDD patients, the appearance of NSSI is often accompanied by further impairment of attention/alertness and a decline in functional connectivity of the frontotemporal cortex. The impairment of verbal learning and working memory was associated with decreased functional connectivity of the frontotemporal cortex in MDD patients with NSSI.

Increased and sex-differentiated medial prefrontal cortex activation during the MATRICS Consensus Cognitive Battery in schizophrenia: A fNIRS study

Executive impairment in schizophrenia is common, but the mechanism remains unclear. This is the first study to use simultaneously functional near-infrared spectroscopy (fNIRS) to monitor the hemodynamic response in schizophrenia during the MATRICS Consensus Cognitive Battery (MCCB). Here, we monitored relative changes in oxyhemoglobin concentration in the medial prefrontal cortex (mPFC) during Trail Making Test, Symbol Coding Test and Mazes Test of the MCCB in 63 patients (29 females) with schizophrenia and 32 healthy controls (15 females). Results showed that patients with schizophrenia scored lower than healthy controls on all three tests (P < 0.001), but mPFC activation was significantly higher during the test (P < 0.03). Higher activation of the mPFC may reflect abnormal information processing in schizophrenia. In addition, the results also showed sex differences in hemodynamic activation during the task in patients with schizophrenia, and fNIRS has the potential to be a clinical adjunct to screening for cognitive function in schizophrenia.

Cognitive dysfunction in schizophrenia patients caused by down-regulation of γ-aminobutyric acid receptor subunits

BACKGROUND The expression pattern of gamma aminobutyric acid (GABA) receptor subunits are commonly altered in patients with schizophrenia, which may lead to nerve excitation/inhibition problems, affecting cognition, emotion, and behavior. AIM To explore GABA receptor expression and its relationship with schizophrenia and to provide insights into more effective treatments. METHODS This case-control study enrolled 126 patients with schizophrenia treated at our hospital and 126 healthy volunteers who underwent physical examinations at our hospital during the same period. The expression levels of the GABA receptor subunits were detected using 1H-magnetic resonance spectroscopy. The recognized cognitive battery tool, the MATRICS Consensus Cognitive Battery, was used to evaluate the scores for various dimensions of cognitive function. The correlation between GABA receptor subunit downregulation and schizophrenia was also analyzed. RESULTS Significant differences in GABA receptor subunit levels were found between the case and control groups (P &lt; 0.05). A significant difference was also found between the case and control groups in terms of cognitive function measures, including attention/alertness and learning ability (P &lt; 0.05). Specifically, as the expression levels of GABRA1 (α1 subunit gene), GABRB2 (β2 subunit gene), GABRD (δ subunit), and GABRE (ε subunit) decreased, the severity of the patients’ condition increased gradually, indicating a positive correlation between the downregulation of these 4 receptor subunits and schizophrenia (P &lt; 0.05). However, the expression levels of GABRA5 (α5 subunit gene) and GABRA6 (α6 subunit gene) showed no significant correlation with schizophrenia (P &gt; 0.05). CONCLUSION Downregulation of the GABA receptor subunits is positively correlated with schizophrenia. In other words, when GABA receptor subunits are downregulated in patients, cognitive impairment becomes more severe.

Psychometric evaluation of the patient-reported experience of cognitive impairment in schizophrenia (PRECIS) scale

BackgroundCognitive impairment associated with schizophrenia (CIAS) represents a distinct, persistent, and core group of schizophrenia symptoms. Cognitive symptoms have been shown to have an impact on quality of life. There are several published CIAS measures, but none based on direct patient self-report. It is important to capture the patient’s perspective to supplement performancebased outcome measures of cognition to provide a complete picture of the patient’s experience. This paper describes additional validation work on the Patient-Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS) instrument.MethodsData from two large, international, pharmaceutical clinical trials in medically and psychiatrically stable English-speaking patients with schizophrenia and 88 healthy controls were analyzed. An exploratory factor analysis (EFA) was conducted in one trial (n = 215), using the original 35-item PRECIS. The factor structure suggested by EFA was further evaluated using item response theory (IRT; Samejima’s graded response model), and tested using confirmatory factor analysis (CFA). Both EFA and CFA results were tested in a second trial with similar inclusion/exclusion characteristics (n = 410). Additional statistical properties were evaluated in healthy controls.ResultsEFA suggested that the best solution after item reduction suggested a factor structure of 6 factors based on 26 items (memory, communication, self-control, executive function, attention, sharpness of thought), supporting a total score, with an additional 2-item bother score (28 items in all). IRT analysis indicated the items were well-ordered within each domain. The CFA demonstrated excellent model fit, accounting for 69% of the variance. The statistical properties of the 28-item version of the PRECIS were confirmed in the second trial. Evidence for internal consistency and test-retest reliability was robust. Known-groups validity was supported by comparison of healthy controls with patients with schizophrenia. Correlations indicated moderate associations between PRECIS and functioning instruments like the Schizophrenia Cognition Rating Scale (SCoRS), but weak correlations with performance-based outcomes like MATRICS Consensus Cognitive Battery (MCCB).DiscussionUsing two clinical trial samples, we identified a robust factor structure for the PRECIS and were able to replicate it in the second sample. Evaluation of the meaningful score difference (MSD) should be repeated in future studies, as these samples did not show enough change for it to be evaluated.ConclusionsThis analysis provides strong evidence for the reliability and validity of the PRECIS, a 28-item, patient-reported instrument to assess cognitive impairment associated with schizophrenia. The correlation with functioning and the weak correlation with performance on cognitive tasks suggests that patient reports of cognitive impairment measure a unique aspect of patient experience.

Abnormal Global Cortical Responses in Drug-Naïve Patients With Schizophrenia Following Orbitofrontal Cortex Stimulation: A Concurrent Transcranial Magnetic Stimulation–Electroencephalography Study

BackgroundAbnormalities in cortical excitability and plasticity have been considered to underlie the pathophysiology of schizophrenia. Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) can provide a direct evaluation of cortical responses to TMS. Here, we employed TMS-EEG to investigate cortical responses to orbitofrontal cortex (OFC) stimulation in schizophrenia. MethodsIn total, we recruited 92 drug-naïve patients with first-episode schizophrenia and 51 age- and sex-matched healthy individuals. For each participant, one session of 1-Hz repetitive TMS (rTMS) was delivered to the right OFC, and TMS-EEG data were obtained to explore the change in cortical-evoked activities before and immediately after rTMS during the eyes-closed state. The MATRICS Consensus Cognitive Battery was used to assess neurocognitive performance. ResultsThe cortical responses indexed by global mean field amplitudes (i.e., P30, N45, and P60) were larger in patients with schizophrenia than in healthy control participants at baseline. Furthermore, after one session of 1-Hz rTMS over the right OFC, the N100 amplitude was significantly reduced in the healthy control group but not in the schizophrenia group. In the healthy control participants, there was a significant correlation between modulation of P60 amplitude by rTMS and working memory; however, this correlation was absent in patients with schizophrenia. ConclusionsAberrant global cortical responses following right OFC stimulation were found in patients with drug-naïve first-episode schizophrenia, supporting its significance in the primary pathophysiology of schizophrenia.

Neurocognition and NMDAR co-agonists pathways in individuals with treatment resistant first-episode psychosis: a 3-year follow-up longitudinal study

This study aims to determine whether 1) individuals with treatment-resistant schizophrenia display early cognitive impairment compared to treatment-responders and healthy controls and 2) N-methyl-D-aspartate-receptor hypofunction is an underlying mechanism of cognitive deficits in treatment-resistance. In this case‒control 3-year-follow-up longitudinal study, n = 697 patients with first-episode psychosis, aged 18 to 35, were screened for Treatment Response and Resistance in Psychosis criteria through an algorithm that assigns patients to responder, limited-response or treatment-resistant category (respectively resistant to 0, 1 or 2 antipsychotics). Assessments at baseline: MATRICS Consensus Cognitive Battery; N-methyl-D-aspartate-receptor co-agonists biomarkers in brain by MRS (prefrontal glutamate levels) and plasma (D-serine and glutamate pathways key markers). Patients were compared to age- and sex-matched healthy controls (n = 114). Results: patient mean age 23, 27% female. Treatment-resistant (n = 51) showed lower scores than responders (n = 183) in processing speed, attention/vigilance, working memory, verbal learning and visual learning. Limited responders (n = 59) displayed an intermediary phenotype. Treatment-resistant and limited responders were merged in one group for the subsequent D-serine and glutamate pathway analyses. This group showed D-serine pathway dysregulation, with lower levels of the enzymes serine racemase and serine-hydroxymethyltransferase 1, and higher levels of the glutamate-cysteine transporter 3 than in responders. Better cognition was associated with higher D-serine and lower glutamate-cysteine transporter 3 levels only in responders; this association was disrupted in the treatment resistant group. Treatment resistant patients and limited responders displayed early cognitive and persistent functioning impairment. The dysregulation of NMDAR co-agonist pathways provides underlying molecular mechanisms for cognitive deficits in treatment-resistant first-episode psychosis. If replicated, our findings would open ways to mechanistic biomarkers guiding response-based patient stratification and targeting cognitive improvement in clinical trials.

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.

Cognitive functions following initiation of antipsychotic medication in adolescents and adults at clinical high risk for psychosis: a naturalistic sub group analysis using the MATRICS consensus cognitive battery

BackgroundThe effects of antipsychotic (AP) medications on cognitive functions in individuals at clinical high-risk (CHR) of psychosis are poorly understood. This study compared the effects of AP treatment on cognitive improvement in CHR adolescents and adults.MethodsA total of 327 CHR participants, with an age range of 13 to 45 years, who underwent baseline neuropsychological assessments and a 1-year clinical follow-up were included. Participants with CHR were categorized into four groups based on their age: adolescents (aged < 18) and adults (aged ≥ 18), as well as their antipsychotic medication status (AP+ or AP−). Therefore, the four groups were defined as Adolescent-AP−, Adolescent-AP+, Adult-AP−, and Adult-AP+.ResultsDuring the follow-up, 231 CHR patients received AP treatment, 94 converted to psychosis, and 161 completed the 1-year follow-up. The Adolescent-AP+ group had more positive symptoms, lower general functions, and cognitive impairments than the Adolescent-AP− group at baseline, but no significant differences were observed among adults. The Adolescent-AP+ group showed a significant increase in the risk of conversion to psychosis (p < 0.001) compared to the Adolescent-AP− group. The Adult-AP+ group showed a decreasing trend in the risk of conversion (p = 0.088) compared to the Adult-AP− group. The Adolescent-AP− group had greater improvement in general functions (p < 0.001), neuropsychological assessment battery mazes (p = 0.025), and brief visuospatial memory test-revised (p = 0.020), as well as a greater decrease in positive symptoms (p < 0.001) at follow-up compared to the Adolescent-AP+ group. No significant differences were observed among adults.ConclusionsEarly use of AP was not associated with a positive effect on cognitive function in CHR adolescents. Instead, the absence of AP treatment was associated with better cognitive recovery, suggesting that AP exposure might not be the preferred choice for cognitive recovery in CHR adolescents, but may be more reasonable for use in adults.

Long-term neurological and neurocognitive impairments after tick-borne encephalitis in Lithuania - a prospective study

Background The aim of this study was to characterise long-term neurological and neurocognitive sequelae after tick-borne encephalitis (TBE) in adults. Methods 98 prospective consecutive TBE patients, classified by disease severity, were included. Immediate outcomes were evaluated with Glasgow Outcome Scale (GOS) and Rankin Scale (RS). After 6 and 18 months, long-term disability was evaluated using Modified Rankin Scale (MRS) and neurocognitive assessment was performed with Matrics Consensus Cognitive Battery (MCCB), measuring processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving and social cognition. The MCCB results were compared to healthy age, gender and education-matched controls. Results Mild, moderate, and severe TBE was diagnosed in 53.1%, 38.8%, and 8.2% of cases, respectively. At discharge, 25.5% of the patients had major or moderate impairments (GOS) and various levels of disability in 34.7% (RS). Up to 18 months from the onset of TBE, over 20% remained with slight to moderate disability (MRS). GOS, RS and MRS scores correlated with disease severity. At 6 months after the onset, TBE patients scored significantly lower than controls in processing speed, verbal, and visual learning. Two latter domains were significantly more impaired in patients with mild TBE. Patients aged 18-39 performed significantly worse in attention/vigilance and working memory, whereas aged 60+ in verbal learning. A year later, significant improvement was observed in six of seven cognitive domains. Conclusions Long-term neurological sequelae persist in a substantial proportion of TBE patients with significant impairment in several cognitive domains, especially in younger patients and even after mild TBE.

Can neurocognition, brain neurotrophic factor, triglyceride, and total cholesterol predict suicidal ideation in first-episode Han Chinese patients with schizophrenia?

Previous studies have suggested that the suicide rate of patients with schizophrenia is high. This study investigates factors influencing suicidal ideation in first-episode schizophrenia patients, focusing on cognitive function, brain-derived neurotrophic factor (BDNF), triglyceride (TG), and total cholesterol (TC) in patients with first-episode schizophrenia. A total of 123 patients with first-episode schizophrenia and 38 healthy controls were included in the study. The patients were divided into suicidal and nonsuicidal ideation groups based on the Beck Scale for Suicidal Ideation, and they were assessed with Positive and Negative Syndrome Scale(PANSS). Cognitive function was assessed using the Chinese version of the MATRICS consensus cognitive battery (MCCB) and the serum BDNF, TG, and TC were detected. The main statistical methods include t-test, χ2 test, multivariate logistic regression analysis, receiver operating characteristic (ROC) curve analysis, and the DeLong test. 26.02% of patients exhibited suicidal ideation. Higher PANSS and TC levels were risk factors, while higher MCCB scores and BDNF levels were protective factors. ROC analysis indicated AUCs of 0.630, 0.724, and 0.762 for serum BDNF, PANSS, and MCCB, respectively, with a combined AUC of 0.870. Serum BDNF level, PANSS score, and MCCB score can be used as auxiliary predictors of suicidal ideation in schizophrenic patients. Combining these three indicators can effectively predict suicidal ideation in schizophrenic patients.