Building a neurocognitive profile of suicidal risk in severe mental disorders.

BACKGROUND: Research on the influence of neurocognitive factors on suicide risk, regardless of the diagnosis, is inconsistent. Recently, suicide risk studies propose applying a trans-diagnostic framework in line with the launch of the Research Domain Criteria Cognitive Systems model. In the present study, we highlight the extent of cognitive impairment using a standardized battery in a psychiatric sample stratified for different degrees of suicidal risk. We also differentiate in our sample various neurocognitive profiles associated with different levels of risk. MATERIALS AND METHODS: We divided a sample of 106 subjects into three groups stratified by suicide risk level: Suicide Attempt (SA), Suicidal Ideation (SI), Patient Controls (PC) and Healthy Controls (HC). We conducted a multivariate Analysis of Variance (MANOVA) for each cognitive domain measured through the standardized battery MATRICS Consensus Cognitive Battery (MCCB). RESULTS: We found that the group of patients performed worse than the group of healthy controls on most domains; social cognition was impaired in the suicide risk groups compared both to HC and PC. Patients in the SA group performed worse than those in the SI group. CONCLUSION: Social cognition impairment may play a crucial role in suicidality among individuals diagnosed with serious mental illness as it is involved in both SI and SA; noteworthy, it is more compromised in the SA group fitting as a marker of risk severity.

Negative and disorganized symptoms mediate the relationship between verbal learning and global functioning in adolescents with early-onset psychosis.

Neurocognitive deficits are associated with impaired global functioning and psychotic symptoms. However, whether symptoms can mediate the relationship between neurocognition and global functioning in adolescent psychosis is unclear. Here, we investigated if symptoms assessed with the Positive And Negative Syndrome Scale (PANSS), mediated the relationship between neurocognitive performance and global functioning in adolescents with non-affective early-onset psychotic disorders (EOP). Sixty-one adolescent EOP patients (age 12-18 years) from 2 Norwegian clinical cohorts were included. Linear regression models were applied to investigate associations between neurocognitive domains from the MATRICS Consensus Cognitive Battery (MCCB) and global functioning. PANSS symptoms were analyzed using the Wallwork/Fortgang five-factor model. Using the INDIRECT macro for SPSS, mediation effects were tested using bootstrapping with 95% bias corrected confidence intervals. Verbal learning was positively associated with global functioning (P < 0.001) and negatively associated with the disorganized symptom factor (P = 0.002), controlling for age, sex and cohort. Testing of indirect effects, controlling for age, sex and cohort, showed that the Negative (point estimate = 1.56, 95% CI 0.22, 3.47) and Disorganized (point estimate = 1.24, 95% CI 0.05, 3.69) symptom factors significantly mediated the relationship between verbal learning and global functioning. We found that verbal learning, negative and disorganized symptoms influenced global functioning in adolescents with EOP, while reality-distorted positive symptoms did not. These results suggest that assessing these domains in EOP is helpful for planning treatment and rehabilitation programs focusing on functional outcome.

Association of Working Memory With Distributed Executive Control Networks in Schizophrenia.

OBJECTIVE: Working memory impairments represent a core cognitive deficit in schizophrenia, predictive of patients' daily functioning, and one that is unaffected by current treatments. To address this, working memory is included in the MATRICS Consensus Cognitive Battery (MCCB), a standardized cognitive battery designed to facilitate drug development targeting cognitive symptoms. However, the neurobiology underlying these deficits in MCCB working memory is currently unknown, mirroring the poor understanding in general of working memory deficits in schizophrenia. METHODS: Twenty-eight participants with schizophrenia were administered working memory tests from the MCCB and examined with resting-state functional MRI. Intrinsic connectivity networks were estimated with independent component analysis. Each voxel's time series was correlated with each network time series, creating a feature vector for voxel-level connectivity analysis. This feature vector was associated with working memory by using the distance covariance statistic. RESULTS: The neurobiology of MCCB working memory tests largely followed the multicomponent model of working memory but revealed unexpected differences. The dorsolateral prefrontal cortex was not associated with working memory. The central executive system was instead associated with delocalized right and left executive control networks. The phonologic loop within the multicomponent model, a subsystem involved in storing linguistic information, was associated with connectivity to the left temporoparietal junction and inferior frontal gyrus. However, connections to the language network did not predict working memory test performance. CONCLUSIONS: These results provide supporting evidence for the multicomponent model of working memory in terms of the biology underlying MCCB findings.

Effects of cognitive remediation therapy versus other interventions on cognitive functioning in schizophrenia inpatients.

Computerised cognitive remediation therapy (CCRT) has been shown to improve cognitive function in individuals with schizophrenia beyond effects of other forms of therapy. However, results vary between studies, and most are aimed at individuals who are living in the community. Very few studies have investigated its efficacy in psychiatric wards in order to assess whether or not this is a suitable site to start the therapy. This study evaluated CCRT efficacy among schizophrenia inpatients who received a broad range of therapeutic interventions in a psychiatric ward. A randomised controlled trial of CCRT versus an active control in 66 young inpatients with a diagnosis of schizophrenia was conducted. The intervention lasted for 6 weeks and its efficacy was assessed with the composite score of the MATRICS Consensus Cognitive Battery. Both groups improved similarly in cognitive function and psychopathological symptoms. However, the CCRT group improved more than the controls in negative symptoms. This result shows that providing a drill and practice cognitive remediation to inpatients does not produce benefits for cognitive functioning substantially greater than other forms of therapy provided in a ward, but it is more efficient in reduction of negative symptoms. Our results suggest that CRT might be considered as a promising intervention for reducing negative symptoms in schizophrenia individuals.

An approach to directly link ICA and seed-based functional connectivity: Application to schizophrenia.

Independent component analysis (ICA) and seed-based analyses are widely used techniques for studying intrinsic neuronal activity in task-based or resting scans. In this work, we show there is a direct link between the two, and show that there are some important differences between the two approaches in terms of what information they capture. We developed an enhanced connectivity-matrix independent component analysis (cmICA) for calculating whole brain voxel maps of functional connectivity, which reduces the computational complexity of voxel-based connectivity analysis on performing many temporal correlations. We also show there is a mathematical equivalency between parcellations on voxel-to-voxel functional connectivity and simplified cmICA. Next, we used this cost-efficient data-driven method to examine the resting state fMRI connectivity in schizophrenia patients (SZ) and healthy controls (HC) on a whole brain scale and further quantified the relationship between brain functional connectivity and cognitive performances measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery. Current results suggest that SZ exhibit a wide-range abnormality, primarily a decrease, in functional connectivity both between networks and within different network hubs. Specific functional connectivity decreases were associated with MATRICS performance deficits. In addition, we found that resting state functional connectivity decreases was extensively associated with aging regardless of groups. In contrast, there was no relationship between positive and negative symptoms in the patients and functional connectivity. In sum, we have developed a novel mathematical relationship between ICA and seed-based connectivity that reduces computational complexity, which has broad applicability, and showed a specific application of this approach to characterize connectivity changes associated with cognitive scores in SZ.

Right unilateral electroconvulsive therapy does not cause more cognitive impairment than pharmacologic treatment in treatment-resistant bipolar depression: A 6-month randomized controlled trial follow-up study.

OBJECTIVES: Electroconvulsive therapy is an effective treatment for bipolar depression, but there are concerns about whether it causes long-term neurocognitive impairment. METHODS: In this multicenter randomized controlled trial, in-patients with treatment-resistant bipolar depression were randomized to either algorithm-based pharmacologic treatment or right unilateral electroconvulsive therapy. After the 6-week treatment period, all of the patients received maintenance pharmacotherapy as recommended by their clinician guided by a relevant treatment algorithm. Patients were assessed at baseline and at 6 months. Neurocognitive functions were assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, and autobiographical memory consistency was assessed using the Autobiographical Memory Interview-Short Form. RESULTS: Seventy-three patients entered the trial, of whom 51 and 26 completed neurocognitive assessments at baseline and 6 months, respectively. The MATRICS Consensus Cognitive Battery composite score improved by 4.1 points in both groups (P = .042) from baseline to 6 months (from 40.8 to 44.9 and from 41.9 to 46.0 in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively). The Autobiographical Memory Interview-Short Form consistency scores were reduced in both groups (72.3% vs 64.3% in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively; P = .085). CONCLUSIONS: This study did not find that right unilateral electroconvulsive therapy caused long-term impairment in neurocognitive functions compared to algorithm-based pharmacologic treatment in bipolar depression as measured using standard neuropsychological tests, but due to the low number of patients in the study the results should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00664976.

Predicting individualized clinical measures by a generalized prediction framework and multimodal fusion of MRI data.

Neuroimaging techniques have greatly enhanced the understanding of neurodiversity (human brain variation across individuals) in both health and disease. The ultimate goal of using brain imaging biomarkers is to perform individualized predictions. Here we proposed a generalized framework that can predict explicit values of the targeted measures by taking advantage of joint information from multiple modalities. This framework also enables whole brain voxel-wise searching by combining multivariate techniques such as ReliefF, clustering, correlation-based feature selection and multiple regression models, which is more flexible and can achieve better prediction performance than alternative atlas-based methods. For 50 healthy controls and 47 schizophrenia patients, three kinds of features derived from resting-state fMRI (fALFF), sMRI (gray matter) and DTI (fractional anisotropy) were extracted and fed into a regression model, achieving high prediction for both cognitive scores (MCCB composite r=0.7033, MCCB social cognition r=0.7084) and symptomatic scores (positive and negative syndrome scale [PANSS] positive r=0.7785, PANSS negative r=0.7804). Moreover, the brain areas likely responsible for cognitive deficits of schizophrenia, including middle temporal gyrus, dorsolateral prefrontal cortex, striatum, cuneus and cerebellum, were located with different weights, as well as regions predicting PANSS symptoms, including thalamus, striatum and inferior parietal lobule, pinpointing the potential neuromarkers. Finally, compared to a single modality, multimodal combination achieves higher prediction accuracy and enables individualized prediction on multiple clinical measures. There is more work to be done, but the current results highlight the potential utility of multimodal brain imaging biomarkers to eventually inform clinical decision-making.

Modafinil and cognitive enhancement in schizophrenia and healthy volunteers: the effects of test battery in a randomised controlled trial.

BACKGROUND: Cognitive deficits in schizophrenia have major functional impacts. Modafinil is a cognitive enhancer whose effect in healthy volunteers is well-described, but whose effects on the cognitive deficits of schizophrenia appear to be inconsistent. Two possible reasons for this are that cognitive test batteries vary in their sensitivity, or that the phase of illness may be important, with patients early in their illness responding better. METHODS: A double-blind, randomised, placebo-controlled single-dose crossover study of modafinil 200 mg examined this with two cognitive batteries [MATRICS Consensus Cognitive Battery (MCCB) and Cambridge Neuropsychological Test Automated Battery (CANTAB)] in 46 participants with under 3 years' duration of DSM-IV schizophrenia, on stable antipsychotic medication. In parallel, the same design was used in 28 age-, sex-, and education-matched healthy volunteers. Uncorrected p values were calculated using mixed effects models. RESULTS: In patients, modafinil significantly improved CANTAB Paired Associate Learning, non-significantly improved efficiency and significantly slowed performance of the CANTAB Stockings of Cambridge spatial planning task. There was no significant effect on any MCCB domain. In healthy volunteers, modafinil significantly increased CANTAB Rapid Visual Processing, Intra-Extra Dimensional Set Shifting and verbal recall accuracy, and MCCB social cognition performance. The only significant differences between groups were in MCCB visual learning. CONCLUSIONS: As in earlier chronic schizophrenia studies, modafinil failed to produce changes in cognition in early psychosis as measured by MCCB. CANTAB proved more sensitive to the effects of modafinil in participants with early schizophrenia and in healthy volunteers. This confirms the importance of selecting the appropriate test battery in treatment studies of cognition in schizophrenia.

Neurocognitive profile of euthymic Japanese patients with bipolar disorder.

AIM: Neurocognitive impairment is one of the core symptoms of bipolar disorder (BD). The MATRICS Cognitive Consensus Battery (MCCB) is a potential consensus assessment tool to evaluate cognitive function in patients with BD. Here, we report on cognitive deficits evaluated using the MCCB Japanese version (MCCB-J) in euthymic Japanese patients with BD, and compare them with scores in previous studies. METHODS: We compared neurocognitive function in 25 patients with euthymic BD and 53 healthy controls (HC). Additionally, we searched all available databases for studies that have evaluated cognitive function in BD using the MCCB, and conducted a meta-analysis. RESULTS: Canonical discriminant analysis revealed significant differences in MCCB-J domain scores between BD and HC. Patients with BD performed significantly worse on visual learning, social cognition, speed of processing, and MCCB composite scores. Our meta-analysis revealed that patients with BD performed worse than HC, as reflected by MCCB composite scores and scores on all seven cognitive domains. However, there are differences in the cognitive deficits identified in previous studies compared with our participants, particularly social cognition. CONCLUSION: As reported in previous studies, neurocognitive deficits were observed in Japanese euthymic BD patients assessed using the MCCB-J. Further study is needed to clarify whether differences in social cognition between this study and previous studies are a result of coping mechanisms for social settings in Japanese populations.

Factor analyzing the Norwegian MATRICS Consensus Cognitive Battery.

AIM: The MATRICS Consensus Cognitive Battery (MCCB) assesses seven cognitive domains with 10 subtests. This domain structure has not been demonstrated. Three factors have been produced in US samples. We examined the dimensional structure of the Norwegian MCCB. In addition, we studied the contribution of each subtest to the battery sum score. METHODS: The participants were 131 patients with schizophrenia spectrum disorders and 300 healthy controls. Their Norwegian MCCB test scores were subject to exploratory and confirmatory factor analysis and regression analysis. RESULTS: The theoretical MCCB factor structure was not shown. In the patient group, three-factor and two-factor models had acceptable fit. In both groups, the Symbol Coding, Spatial Span, Letter-Number Span, and Visual Learning subtests contributed most to the sum score. CONCLUSION: The theoretical domain structure of the MCCB could not be demonstrated in these Norwegian participants. Consonant with US studies, models with three and two factors had mediocre fit, and in the schizophrenia spectrum disorder group only. In both groups, the subtests Symbol Coding, Working Memory, and Learning were the most sensitive in tapping general neurocognitive performance, supporting US results. We conclude that in both Norway and the USA, the MCCB generates the same cognitive domains through factor analysis, but that these domains are not the ones suggested by the MATRICS project.

An empirical evaluation of the MATRICS Consensus Cognitive Battery in bipolar disorder.

OBJECTIVES: There is a large body of evidence to indicate that neurocognitive impairments in bipolar disorder (BD) may represent viable endophenotypes; however, a standard consensus-based battery of cognitive tests used to measure them is yet to appear. There is potential for a neurocognitive battery which was developed for use in the related disorder, schizophrenia - the MATRICS Consensus Cognitive Battery (MCCB) - to provide a consistent measurement tool with a standard to which the cognitive capacity of BD can be compared to other disorders. However, its suitability for capturing neurocognitive impairment in BD cohorts is not well established. Moreover, neurocognitive tests recently recommended by the International Society for Bipolar Disorders (ISBD) for inclusion in a consensus neurocognitive battery for BD have not been evaluated in the context of the MCCB. An evaluation of (i) the clinical efficacy of the MCCB and (ii) the tests recommended by the ISBD in a BD cohort were the aims of the current study. METHODS: A total of 50 patients with BD (mean age = 38 years) and 52 healthy controls (mean age = 34 years) completed all of the MCCB subtests, in addition to the well-recognized Trail Making Test-Part B and the Colour-Word Stroop. RESULTS: Multivariate analyses of variance of the MCCB domains revealed a significant group effect for overall cognition, and significantly reduced patient performance on speed of processing, working memory, and visual and verbal learning. A second multivariate analysis of variance using a newly created composite score called executive function, comprising scores on an existing MCCB subtest in addition to TMT-B and Colour-Word Stroop, revealed significant differences on this domain as well. Subgroup analysis indicated that there were no differences in any domain score performance between symptomatic and euthymic patients, or bipolar I and II disorder patient groups. CONCLUSIONS: Our findings suggest that the MCCB and two additionally recommended ISBD executive function measures form a promising consensus-based research tool for examining neurocognition in BD.

Relationship of cognitive measures to mRNA levels in lymphocytes from patients with schizophrenia and controls.

Patients with schizophrenia show substantial cognitive deficits and abnormalities in neurotransmitter-related levels of mRNA in brain or peripheral blood lymphocytes. However, the relationship of cognitive deficits as measured by the MATRICS battery and mRNA levels in brain or lymphocytes has not been sufficiently explored. We measured levels of methylation or neurotransmitter-related mRNAs in lymphocytes of 38 patients with chronic schizophrenia (CSZ) and 33 non-psychotic controls (controls) by qPCR using TaqMan probes. We assessed cognitive function in these patients and controls with the MATRICS battery. We used correlation analysis and scatter plots to assess the relationship of lymphocyte mRNA levels to MATRICS domain and composite scores. CSZ subjects had a consistently negative correlation between mRNA levels in lymphocytes and MATRICS cognitive variables of speed of processing, attention-vigilance, working memory, visual learning, and overall composite score. It is uncertain whether these negative correlations represent a causative relation between specific mRNA levels and cognitive deficits. Controls had either positive correlations or non-significant correlations between mRNA and most of the MATRICS variables. There were statistically significant differences in the correlations between mRNA and MATRICS variables between CSZ vs controls for several mRNAs (DNMT1, DNMT3A, BDNF, NR3C1, FPRF3, CNTNAP2). Our data show a different relationship between mRNA levels in peripheral blood lymphocytes and MATRICS cognitive variables in CSZ vs controls. The substantive significance of these differences needs further investigation.

The MATRICS consensus cognitive battery for the assessment of cognitive impairment in schizotypal personality disorder.

Cognitive deficits are a core impairment across the range of schizophrenia (SZ) spectrum disorders, including schizotypal personality disorder (SPD). The MATRICS Consensus Cognitive Battery (MCCB) was developed to be a robust, specific, and valid cognitive assessment battery to assess cognition in clinical trials for treating cognitive impairments in SZ. Despite the similarity of cognitive impairments shown in SPD and SZ and the clear relevance of uniform assessment across a diagnostic spectrum, the MCCB has yet to be validated in SPD. As such, this is the first study to evaluate the sensitivity of the MCCB for the assessment of cognitive function in individuals with SPD. Participants were 30 individuals with SPD and 54 healthy controls (HC) assessed with the MCCB and supplemental neurocognitive assessments (Trails B, DOT test, Paced Auditory Serial Addition Test (PASAT), AX Continuous Performance Task (AX-CPT), and N-back). Individuals with SPD performed worse than HC participants on all MCCB subtests, as well as on converging supplemental tasks including Trails B, DOT test, PASAT, AX-CPT, and N-back. These results indicate that the MCCB was sensitive to cognitive impairment in SPD compared to controls. SPD participants demonstrate impairments similar to data of SZ participants within the literature, although to a slightly lesser degree of severity. Taken together, these results highlight the generalizability of using the MCCB across SZ spectrum diagnostic groups to assess cognition. Such findings allow for further comparison across disorders, greater understanding of the cognitive characteristics in the spectrum, and use of uniform assessment within cognitive intervention research.

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.

National Institute of Mental Health Support for Cognitive Treatment Development in Schizophrenia: A Narrative Review.

For several decades the National Institute of Mental Health (NIMH) has supported basic and translational research into cognitive impairment in schizophrenia. This article describes the Institute's ongoing commitment to cognitive assessment and intervention research, as reflected by three signature initiatives-Measurement and Treatment Research to Improve Cognition in Schizophrenia; Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia; and Research Domain Criteria-and related funding announcements that span basic experimental studies, efficacy and comparative effectiveness trials, and implementation research designed to promote cognitive healthcare in real-world treatment settings. We discuss how trends in science and public health policy since the early 2000s have influenced NIMH treatment development activities, resulting in greater attention to (1) inclusive teams that reflect end-user perspectives on the utility of proposed studies; (2) measurement of discrete neurocognitive processes to inform targeted interventions; (3) clinical trials that produce useful information about putative illness mechanisms, promising treatment targets, and downstream clinical effects; and (4) "productive urgency" in pursuing feasible and effective cognitive interventions for psychosis. Programs employing these principles have catalyzed cognitive measurement, drug development, and behavioral intervention approaches that aim to improve neurocognition and community functioning among persons with schizophrenia. NIMH will maintain support for innovative and impactful investigator-initiated research that advances patient-centered, clinically effective, and continuously improving cognitive health care for persons with psychotic disorders.

The MATRICS Consensus Cognitive Battery: An Update.

Through a series of NIMH-supported consensus-building meetings of experts and empirical comparisons of candidate tests, the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative developed a battery of standardized cognitive measures to allow reliable evaluation of results from clinical trials of promising interventions for core cognitive deficits in this disorder. Ten tests in seven cognitive domains were selected for the MATRICS Consensus Cognitive Battery (MCCB). The MCCB has now been translated into 39 languages/dialects and has been employed in more than 145 clinical trials. It has become the standard cognitive change measure for studies of both pharmacological and training-based interventions seeking to improve cognitive deficits in schizophrenia. We summarize its applications and its relationship to the subsequent development of the NIMH RDoC Matrix.

Deficits in odor discrimination versus odor identification in patients with schizophrenia and negative correlations with GABAergic and DNA methyltransferase mRNAs in lymphocytes.

Introduction: People with schizophrenia have been reported to show deficits in tests of olfactory function. DNA methylation and GABAergic input have been implicated in biochemical processes controlling odor in animal studies, but this has not been investigated in human studies. Methods: In a study of measures of DNA methylation and GABAergic mRNAs in lymphocytes, we also measured odor identification and discrimination with the Sniffin' Sticks battery in 58 patients with chronic schizophrenia (CSZ) and 48 controls. mRNAs in lymphocytes were assessed by qPCR using TaqManTM probes. Cognition was assessed by the MATRICS battery (Measurement and Treatment Research to Improve Cognition in Schizophrenia) in CSZ and controls, and symptoms in CSZ were assessed by PANSS scale (Positive and Negative Symptom Scale). The relationships of odor deficits with mRNA, cognition, and symptoms were explored by correlation analysis. Variables which significantly differentiated CSZ from controls were explored by logistic regression. Results: Overall, CSZ showed significantly (P≤.001) lower scores on odor discrimination compared to controls, with a moderate effect size, but no difference in odor identification. Deficits in odor discrimination, which has not been standardly assessed in many prior studies, strongly differentiated CSZ from controls. In logistic regression analysis, odor discrimination, but not odor identification, was a significant variable predicting schizophrenia versus control class membership. This is the first study to report relationship between odor deficits and DNA methylation and GABAergic mRNAs in blood cells of human subjects. There were negative correlations of odor identification with DNA methylation enzymes mRNAs and significant negative correlations with odor discrimination and GABAergic mRNAs. Lower odor scores were significantly associated with lower cognitive scores on the MATRICS battery in CSZ but not control subjects. In CSZ, lower odor scores were significantly associated with negative symptom scores, while higher odor identification scores were associated with PANNS Excitement factor. Discussion: Odor discrimination was a more powerful variable than odor identification in discriminating CSZ from controls and should be used more regularly as an odor measure in studies of schizophrenia. The substantive meaning of the negative correlations of odor discrimination and GABAergic mRNA variables in peripheral lymphocytes of CSZ needs more investigation and comparison with results in neural tissue.

Visuospatial Learning Selectively Enhanced by Personalized Transcranial Magnetic Stimulation over Parieto-Hippocampal Network among Patients at Clinical High-Risk for Psychosis.

BACKGROUND AND HYPOTHESIS: Cognitive deficits in visuospatial learning (VSL) are highly associated with an increased risk of developing psychosis among populations with clinical high risk (CHR) for psychosis. Early interventions targeting VSL enhancement are warranted in CHR but remain rudimentary. We investigated whether personalized transcranial magnetic stimulation (TMS) over the left parieto-hippocampal network could improve VSL performance in CHR patients and if it could reduce the risk of psychosis conversion within 1 year. STUDY DESIGN: Sixty-five CHR patients were randomized to receive active or sham TMS treatments using an accelerated TMS protocol, consisting of 10 sessions of 20 Hz TMS treatments within 2 days. TMS target was defined by individual parieto-hippocampal functional connectivity and precisely localized by individual structural magnetic resonance imaging. VSL performance was measured using Brief Visuospatial Memory Test-Revised included in measurement and treatment research to improve cognition in schizophrenia consensus cognitive battery (MCCB). Fifty-eight CHR patients completed the TMS treatments and MCCB assessments and were included in the data analysis. STUDY RESULTS: We observed significant VSL improvements in the active TMS subgroup (Cohen's d = 0.71, P < .001) but not in the sham TMS subgroup (Cohen's d = 0.07, P = .70). In addition, active TMS improved the precision of VSL performance. At a 1-year follow-up, CHR patients who received active TMS showed a lower psychosis conversion rate than those who received sham TMS (6.7% vs 28.0%, χ2 = 4.45, P = .03). CONCLUSIONS: Our findings demonstrate that personalized TMS in the left parieto-hippocampal network may be a promising preventive intervention that improves VSL in CHR patients and reduces the risk of psychosis conversion at follow-up.

Montreal Cognitive Assessment (MoCA) and Digit Symbol Substitution Test (DSST) as a screening tool for evaluation of cognitive deficits in schizophrenia.

Cognitive deficit is one of the core features of schizophrenia and is associated with poor functional outcomes. There is a lack of validated criteria to screen and monitor cognitive deficits in schizophrenia. This study aimed to evaluate the concurrent validity and sensitivity of MoCA (Montreal Cognitive Assessment) and DSST (Digit Symbol Substitution Test) in identifying cognitive deficits in Schizophrenia comparing with a comprehensive MCCB [MATRICS (Measurement And Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery] equivalent battery. We did clinical and cognitive assessments on 30 patients with schizophrenia and 30 age and gender-matched healthy controls. The Cronbach's Alpha of MoCA was 0.839, and on adding the DSST, it increased to 0.859. In stepwise binary logistic regression, adding DSST to MoCA improved the prediction of cognitive impairment as defined by a comprehensive battery with 86.7% classification accuracy. Receiver operating characteristic curve analysis suggested a score of 25 of MoCA and 59 of DSST as an optimal cut-off in identifying severe cognitive deficits with an additional MoCA cut-off of 27 for identifying mild cognitive deficits. Combined MoCA and DSST is a sensitive and quick method to screen for neurocognitive deficits in schizophrenia.

The Relationship between Cognitive Functions and Psychopathological Symptoms in First Episode Psychosis and Chronic Schizophrenia.

Impairments in cognitive functions are one of the main features of schizophrenia. A variety of factors can influence the extent of cognitive deficits. In our study, we examined the severity of cognitive deficits at different stages of the disease and the relationship between psychopathological symptoms and cognitive functions. We recruited 32 patients with first-episode psychosis (FEP), 70 with chronic schizophrenia (CS), and 39 healthy controls (HC). Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS) and cognitive functions were measured with the MATRICS Cognitive Consensus Battery (MCCB). Cognitive deficits were present in both FEP and CS participants. CS individuals had lower overall scores and poorer working memory; however, clinical variables appeared to play a significant role in these scores. In FEP, disorganization correlated negatively with verbal and visual learning and memory, social cognition, and overall score; negative symptoms negatively correlated with social cognition. In CS participants, disorganization correlated negatively with speed of processing, reasoning, problem solving, and overall score; negative symptoms were negatively correlated with speed of processing, visual learning, memory, and overall score; positive symptoms were negatively correlated with reasoning and problem solving. Our findings indicate that psychopathological symptoms have a significant impact on cognitive functions in FEP and CS patients.