Assessment Of Cognition In Schizophrenia Research Articles

A-89 Age at First Psychiatric Hospitalization Predicts Deviation from Expected Cognitive Ability in Psychosis Spectrum Disorders

Abstract Objective The present study investigated whether clinical variables related to illness onset (age at symptom onset, diagnosis, first psychiatric hospitalization) predict deviation from expected cognitive ability. Additionally, we examined the potential moderating effect of psychosis groups (“biotypes”). Method Cognitive ability was predicted based on demographic variables and estimated premorbid intelligence modeled in controls. The degree to which current cognitive ability (based on Brief Assessment of Cognition in Schizophrenia) deviated from predicted ability was computed in 362 schizophrenia, schizoaffective, and bipolar with psychosis patients recruited from the community (Mage = 39.11; 52.2% male; 41.7% White, 41.4% Black, 16.9% Other). Linear regression assessed the relationship between illness onset and deviation scores and moderation analysis was performed using moderated multiple regression. Results Only age at first psychiatric hospitalization predicted deviation scores (F(1,328) = 3.93, p < 0.05), such that younger individuals had a greater deviation from expected cognitive ability. The full moderated regression model significantly predicted deviation scores (F(5,330) = 14.05, p < 0.001), and there was a significant effect of age at first psychiatric hospitalization and deviation scores only for biotype 3 (t = 7.37, p < 0.001). Discussion Findings suggest that severity of illness at a younger age (requiring hospitalization), rather than earlier symptom onset, may be a risk factor for greater disruption of cognitive development. The association between group membership in biotype 3 (characterized by less cognitive impairment) and lower deviation scores may reflect reduced variability in deviation scores and less disruption of cognitive abilities than other biotypes. When assessing psychosis spectrum patients, clinicians should consider how factors related to illness onset and severity may impact developmental cognitive trajectories.

Deficits in generalized cognitive ability, visual sensorimotor function, and inhibitory control represent discrete domains of neurobehavioral deficit in psychotic disorders

Psychotic disorders are characterized by impaired cognition, yet some reports indicate specific deficits extend beyond reduced general cognitive ability. This study utilized exploratory and confirmatory factor analytic methods to evaluate the latent structure of a broad neurocognitive battery used in the Bipolar-Schizophrenia Network of Intermediate Phenotypes (B-SNIP) study, which included neuropsychological and neurophysiological measures in psychotic disorder probands and their unaffected first-degree relatives. Findings indicate that the factor structure of data from this set of assessments is more complex than the unitary factor of global cognitive ability underlying the Brief Assessment of Cognition in Schizophrenia (BACS). In addition to assessing generalized cognitive ability, two other factors were identified: visual sensorimotor function and inhibitory behavioral control. This complex cognitive architecture, derived in controls, generalized to patients across the psychosis spectrum and to their unaffected relatives. These findings highlight the need for a more differentiated assessment of neurobehavioral functions in studies designed to test for diagnostically specific biomarkers, endophenotypes for gene discovery and beneficial effects of therapeutics on cognitive function.

The Impact of Negative Symptoms and Neurocognition on Functioning in MDD and Schizophrenia.

Introduction: Negative symptoms, neurocognitive deficits and functional impairment are prevalent in individuals with major depressive disorder (MDD) and schizophrenia (SCZ). However, unlike neurocognitive deficits, little is known about the role of negative symptoms toward functioning in individuals with MDD. On the other hand, both factors are well-studied in individuals with SCZ. Thus, this study aimed to examine the contributions of negative symptoms and neurocognitive impairments in functioning in individuals with MDD, compared to individuals with SCZ.Methods: Participants included 50 individuals with MDD, 49 individuals with SCZ and 49 healthy controls. The following measures were administered—Negative Symptom Assessment (NSA-16), Brief Assessment of Cognition in Schizophrenia (BACS), Patient Health Questionnaire (PHQ-9), and MIRECC-Global Assessment of Functioning (MIRECC-GAF) to evaluate negative symptoms, neurocognition, depressive symptoms, and functioning respectively.Results: Both MDD and SCZ groups had significantly more severe negative symptoms, depressive symptoms, and poorer functioning than healthy controls. Individuals with SCZ performed significantly poorer on the BACS than the other two groups. Both negative symptoms and neurocognition were significantly correlated with social and occupational functioning in SCZ. Motivation subdomain of the negative symptoms was significantly correlated with occupational functioning, while depressive symptoms correlated with functioning in MDD.Conclusion: Both negative symptoms and neurocognitive deficits appear to play differential roles on individual domains of functioning between MDD and SCZ. Future longitudinal studies with larger sample sizes should be done for a better understanding about the associations between the factors and functioning.

Genome-wide association study accounting for anticholinergic burden to examine cognitive dysfunction in psychotic disorders.

Identifying genetic contributors to cognitive impairments in psychosis-spectrum disorders can advance understanding of disease pathophysiology. Although CNS medications are known to affect cognitive performance, they are often not accounted for in genetic association studies. In this study, we performed a genome-wide association study (GWAS) of global cognitive performance, measured as composite z-scores from the Brief Assessment of Cognition in Schizophrenia (BACS), in persons with psychotic disorders and controls (N = 817; 682 cases and 135 controls) from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study. Analyses accounting for anticholinergic exposures from both psychiatric and non-psychiatric medications revealed five significantly associated variants located at the chromosome 3p21.1 locus, with the top SNP rs1076425 in the inter-alpha-trypsin inhibitor heavy chain 1 (ITIH1) gene (P = 3.25×E-9). The inclusion of anticholinergic burden improved association models (P < 0.001) and the number of significant SNPs identified. The effect sizes and direction of effect of the top variants remained consistent when investigating findings within individuals receiving specific antipsychotic drugs and after accounting for antipsychotic dose. These associations were replicated in a separate study sample of untreated first-episode psychosis. The chromosome 3p21.1 locus was previously reported to have association with the risk for psychotic disorders and cognitive performance in healthy individuals. Our findings suggest that this region may be a psychosis risk locus that is associated with cognitive mechanisms. Our data highlight the general point that the inclusion of medication exposure information may improve the detection of gene-cognition associations in psychiatric genetic research.

Circulating inflammatory markers impact cognitive functions in bipolar depression

BackgroundCognitive impairment is a core feature of bipolar disorder, with a prevalence of about 64.4% during episodes and 57.1% in euthymia. Recent evidences suggest that cognitive deficits in BD may follow immune dysfunction and elevated levels of inflammatory cytokines have been reported during periods of depression, mania and euthymia, suggesting the presence of a chronic, low-grade inflammatory state. The aim of the study is to investigate if immune/inflammatory markers and especially chemokines associate to cognitive performances. MethodsSeventy-six consecutively admitted inpatients with a depressive episode in course of bipolar disorder performed a neuropsychological evaluation with the Brief Assessment of Cognition in Schizophrenia and plasma blood levels of cytokines, chemokines and growth factors were analyzed with Luminex technology. ResultsHigher levels of IL-1β, IL-6, CCL2, CCL4, CCL5, CXCL10, and bFGF are associated with the likelihood of having a poor cognitive performance. LimitationsLimitation include the lack of a group of healthy controls and the lack of information regarding previous psychopharmacological treatments, alcohol and tobacco use. ConclusionsOur results confirm the importance of chemokines in bipolar disorder and suggest that inflammatory markers suggestive of a low-grade inflammatory state could contribute to the neurocognitive deficits observed in depressed patients.

Brain glutamate concentration in men with early psychosis: a magnetic resonance spectroscopy case\u2013control study at 7\u2009T

Abnormalities in glutamate neurotransmission are linked to psychotic symptoms and cognitive dysfunction in schizophrenia. magnetic resonance spectroscopy (MRS) provides an acceptable means of measuring glutamate in the human brain but findings from patient studies at conventional magnetic field strength show considerable heterogeneity. Ultra-high-field MRS offers greater precision in glutamate measurement, particularly in delineation of glutamate from its precursor and metabolite, glutamine. This study aimed to use high-field (7 T) MRS to measure concentrations of glutamate and glutamine in three brain regions, anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC) and putamen (PUT), in young men with early psychosis. MRS was performed in 17 male participants with early psychosis and 18 healthy age-matched controls. Neurometabolite levels were calculated with unsuppressed water signal as the reference and corrected for individual grey matter, white matter and cerebrospinal fluid concentration. Cognitive function was measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Compared to controls, patients with early psychosis had lower concentrations of glutamate and glutamine in ACC. No differences were apparent in the DLPFC and PUT. In patients with early psychosis, there was a highly significant correlation between glutamate concentration in ACC and performance on the BACS, though the numbers available for this analysis were small. Our finding of lower glutamate levels in ACC in patients with schizophrenia is consistent with a recent meta-analysis of 7 T studies and suggests that this abnormality is present in both patients with early psychosis and those with longer-established illness. The possible link between ACC glutamate and cognitive performance requires replication in larger studies.

The effects of JNJ-39393406 a positive allosteric nicotine modulator on mood and cognition in patients with unipolar depression: A double-blind, add-on, placebo-controlled trial

Nicotinic agonists have been shown to improve cognition and mood, but this improvement is inconsistent and short-lived, possibly due to receptor desensitization. Positive Allosteric Modulators (PAMs) of the nicotinic alpha-7 nicotinic-acetyl-choline receptor (a7nAChR) are hypothesized to change the configuration of the nicotinic receptor and delay desensitization, potentially increasing the duration of the activation of the receptor, and improving clinical efficacy. This was a randomized controlled trial (RCT) adding JNJ-39393406 9 (a PAM of the a7nAChR) (n=35) or placebo (n=36) to treatment as usual for two weeks in 71 patients with unipolar depression. Mixed models for repeated measures analyses were performed Primary outcome measures were the Brief Assessment of Cognition in Schizophrenia (BACS) composite and the Montgomery-Asperg Depression Rating Scale (MADRS) scores. The drug was well tolerated, however mixed models for repeated measures comparing JNJ-39393406 to placebo showed no significant difference for MADRS total score (p=0.78), BACS composite score (p=0.34), or any of the secondary outcome measures. There was no significant difference in adverse events between the study groups (p=0.44). In conclusion, this study's findings do not support the hypothesis that a positive nicotinic receptor modulator can improve cognitive or depressive symptomatology in patients with unipolar depression.

Screening for cognitive impairment in schizophrenia: Psychometric properties of the German version of the Screen for Cognitive Impairment in Psychiatry (SCIP-G)

BackgroundThe Screen for Cognitive Impairment in Psychiatry (SCIP) is a brief scale designed for detecting cognitive deficits in patients with psychiatric disorders including schizophrenia. In this preliminary study the psychometric properties of the German version of the SCIP are examined in a sample of patients with schizophrenia and schizoaffective psychosis (DSM-IV) as well as in healthy controls. MethodsThirty patients and thirty matched controls were asked to complete two versions of the SCIP separated by two-week intervals in addition to psychiatric and neurocognitive instruments including assessments to measure psychosocial functioning. Feasibility, reliability and validity of the SCIP were examined in order to determine parallel reliability. The convergent validity was assessed by the BACS (Brief Assessment of Cognition in Schizophrenia) and the MMSE (Mini-Mental-State-Examination). ResultsSignificant differences in cognitive performance between patients and healthy controls were detected in both versions of the SCIP. The SCIP effectively discriminated between patients and the control sample. The reliability of the parallel versions of the SCIP was supported by high correlations between the alternate forms, and by the high internal consistency of SCIP subtests within the patient sample. Construct validity of the SCIP was supported by high correlations between the SCIP and the BACS total scores, and by high correlations with common cognitive domain scores from the two tests. ConclusionsOur data show that the German version of the SCIP (SCIP-G) is a brief, valid and reliable assessment tool for the detection of cognitive impairment in patients with schizophrenia or schizoaffective psychosis.

Cross-cultural adaptation and validation of the Arabic version of the BACS scale (the brief assessment of cognition in schizophrenia) among chronic schizophrenic inpatients

BackgroundAssessment of cognitive disorders in schizophrenia is becoming a part of clinical and research practice by using batteries that differ widely in their content. The Brief Assessment of Cognition in Schizophrenia (BACS) was developed to cover the main cognitive deficits of schizophrenia. The objective of this study was to assess concurrent validity of the Arabic version of the BACS with a standard neurocognitive battery of tests in Lebanese patients with schizophrenia and healthy controls.MethodsA sample of 120 stable inpatients diagnosed with schizophrenia and 60 healthy controls received the Arabic version of the BACS in a first session, and a standard battery in a second session.ResultsMean duration of completion for the BACS was 31.2 ± 5.4 min in patients with schizophrenia. All tests demonstrated significant differences between controls and patients (p < .01). Principal components analysis demonstrated that a one-factor solution best fits our dataset (64.8% of the variance). High Cronbach alpha was found (.85). The BACS composite scores were significantly correlated with the standard battery composite scores in patients (r = .73, p < .001) and healthy controls (r = .78, p < .001). Also, correlation analysis between the BACS sub-scores and the standard battery sub-scores showed significant results (p < .05).ConclusionResults showed that the Arabic version of the BACS demonstrated high ability to discriminate patients with schizophrenia from healthy controls and it is a useful tool for assessing cognition in patients with schizophrenia and could be used in clinical practice in Lebanon.

Prolonged P300 Latency in Antipsychotic-Free Subjects with At-Risk Mental States Who Later Developed Schizophrenia.

We measured P300, an event-related potential, in subjects with at-risk mental states (ARMS) and aimed to determine whether P300 parameter can predict progression to overt schizophrenia. Thirty-three subjects with ARMS, 39 with schizophrenia, and 28 healthy controls participated in the study. All subjects were antipsychotic-free. Subjects with ARMS were followed-up for more than two years. Cognitive function was measured by the Brief assessment of Cognition in Schizophrenia (BACS) and Schizophrenia Cognition Rating Scale (SCoRS), while the modified Global Assessment of Functioning (mGAF) was used to assess global function. Patients with schizophrenia showed smaller P300 amplitudes and prolonged latency at Pz compared to those of healthy controls and subjects with ARMS. During the follow-up period, eight out of 33 subjects with ARMS developed overt psychosis (ARMS-P) while 25 did not (ARMS-NP). P300 latency of ARMS-P was significantly longer than that of ARMS-NP. At baseline, ARMS-P elicited worse cognitive functions, as measured by the BACS and SCoRS compared to ARMS-NP. We also detected a significant relationship between P300 amplitudes and mGAF scores in ARMS subjects. Our results suggest the usefulness of prolonged P300 latency and cognitive impairment as a predictive marker of later development of schizophrenia in vulnerable individuals.

Efficacy and Safety of Multi-Session Transcranial Direct Current Stimulation on Social Cognition in Schizophrenia: A Study Protocol for an Open-Label, Single-Arm Trial.

Backgrounds: Social cognition is defined as the mental operations underlying social behavior. Patients with schizophrenia elicit impairments of social cognition, which is linked to poor real-world functional outcomes. In a previous study, transcranial direct current stimulation (tDCS) improved emotional recognition, a domain of social cognition, in patients with schizophrenia. However, since social cognition was only minimally improved by tDCS when administered on frontal brain areas, investigations on the effect of tDCS on other cortical sites more directly related to social cognition are needed. Therefore, we present a study protocol to determine whether multi-session tDCS on superior temporal sulcus (STS) would improve social cognition deficits of schizophrenia. Methods: This is an open-label, single-arm trial, whose objective is to investigate the efficacy and safety of multi-session tDCS over the left STS to improve social cognition in patients with schizophrenia. The primary outcome measure will be the Social Cognition Screening Questionnaire. Neurocognition, functional capacity, and psychotic symptoms will also be evaluated by the Brief Assessment of Cognition in Schizophrenia, UCSD Performance-Based Skills Assessment-Brief, and Positive and Negative Syndrome Scale, respectively. Data will be collected at baseline, and 4 weeks after the end of intervention. If social cognition is improved in patients with schizophrenia by tDCS based on this protocol, we may plan randomized controlled trial.

Disentangling Cognitive Heterogeneity in Psychotic Spectrum Disorders

Neuropsychological impairments represent a central feature of psychosis-spectrum disorders. It is characterized by a great both within- and between-subjects variability (i.e. cognitive heterogeneity), which needs to be better disentangled. The present study aimed to describe the distribution of performance on the Brief Assessment of Cognition in Schizophrenia (BACS) by using the Equivalent Scores, in order to balance statistical methodological problems. To do so, cognitive performance groups were branded, identifying the main factors contributing to cognitive heterogeneity. A sample of 583 patients with a diagnosis of Schizophrenia or Psychotic Disorder Not Otherwise Specified was enrolled and assessed for neurocognition and intellectual level. K-means cluster analysis was performed based on BACS Equivalent Scores. Differences among clusters were analyzed throughout Analysis of Variance and Discriminant Function Analysis in order to identify the most significant predictors of cluster membership. For each cognitive task, roughly 40% of patients displayed poor performance, while up to 63% displayed a symbol-coding deficit. K-means cluster analysis depicted three profiles characterized by "near-normal" cognition, widespread impairment, and "borderline" profile. Discriminant analysis selected Verbal IQ and diagnosis as predictors of cluster membership. Our findings support the usefulness of Equivalent Scores and cluster analysis to explain cognitive heterogeneity, and tailor better interventions.

Reasoning, problem solving, attention/vigilance, and working memory are candidate phenotypes of non-suicidal self-injury in Chinese Han nationality

BackgroundNon-suicidal self-injury (NSSI) is an act of deliberately hurting one’s body without the purpose of death. Internal phenotypes have been used in numerous studies of mental disorders, suicide, and self-injury. This research aimed to evaluate the cognitive function of patients with NSSI and determine their potential endophenotype. MethodsThis study used a comparative control design and included 61 patients with NSSI, 55 healthy siblings (HS), and 53 healthy controls. Visual learning, reasoning and problem, verbal learning, attention/vigilance, working memory, and speed of processing were used to evaluate the cognitive function of the subjects. ResultsPatients with NSSI and their HS showed cognitive defects in reasoning and problem, attention/vigilance, and working memory. Substantial differences were observed in verbal learning among the three groups, but no significant difference was recorded in the scores in Brief Assessment of Cognition in Schizophrenia. ConclusionsThe results suggest that reasoning and problem, attention/vigilance, and working memory may be potential endophenotypes in early identification of Chinese Han people with NSSI behavior.

Cross-cultural adaptation and validation of the lebanese arabic version of the BACS scale (the brief assessment of cognition in schizophrenia) among stable schizophrenic inpatients

IntroductionThe assessment of cognitive disorders in schizophrenia is becoming a part of clinical and research practice by using batteries that differ widely in their content. The Brief Assessment of Cognition in Schizophrenia (BACS) was developed to cover the main cognitive deficits of schizophrenia.ObjectivesThe objective of this study was to assess concurrent validity of the Arabic version of the BACS with a standard neurocognitive battery of tests in Lebanese patients with schizophrenia and healthy controls.MethodsA sample of 120 stable inpatients diagnosed with schizophrenia and 60 healthy controls received the Arabic version of the BACS in a first session, and a standard battery in a second session.ResultsThe mean duration of completion for the BACS was 31.2 ± 5.4 min in patients with schizophrenia. All tests demonstrated significant differences between controls and patients (p&lt;0.01). A principal components analysis demonstrated that a one-factor solution best fits our dataset (64.8% of the variance). A high Cronbach alpha was found (0.85). The BACS composite scores were significantly correlated with the standard battery composite scores in patients (r=0.78, p &lt; 0.001) and healthy controls (r=0.77, p &lt; 0.001). Also, the correlation analysis between the BACS sub-scores and the standard battery sub-scores showed significant results (p &lt; 0.05). The Arabic-BACS demonstrated high ability to discriminate patients with schizophrenia from healthy controls.ConclusionsThe results showed that the Arabic version of the BACS is a useful tool for assessing cognition in patients with schizophrenia and could be used in clinical practice in Lebanon.

Usefulness of a psychomotor function test as a cognitive function scale for patients with schizophrenia: A pilot study

As cognitive dysfunction due to schizophrenia is strongly associated with patients' social rehabilitation, cognitive functions have been examined as a therapeutic target. Although the Brief Assessment of Cognition in Schizophrenia (BACS) has been used to evaluate cognitive function, it is difficult to administer in routine clinical practice due to its time-consuming nature. Therefore, a novel tool is needed to facilitate the assessment of cognitive function. In the present study, we examined whether cognitive function can be assessed effectively by testing psychomotor function in patients with schizophrenia. Test batteries consisting of choice reaction time (CRT) and compensatory tracking task (CTT) and the BACS were examined in 20 schizophrenic patients to evaluate the correlation between the scales by Pearson correlation coefficient. Of the test batteries, the CRT was significantly correlated with attention functions, a subtest of the BACS (r = -0.506, p = 0.023), and the CTT was strongly correlated with attention functions (r = -0.716, p < 0.001) and working memory (r = -0.633, p = 0.003). A multiple regression analysis was performed to clarify the association between psychomotor function tests and the total BACS score, and peripheral awareness task, a component of CTT, was independently associated with the total BACS score (β = -0.59, p = 0.004) with an R2 of 0.37. Thus, of the psychomotor function tests, the CRT and the CTT are highly useful in assessing cognitive functions in schizophrenic patients. However, no having large sample size in this study is a limitation.

Planning impairment in schizophrenia: The possible role of abstract thinking and short-term memory

IntroductionThe planning impairment is one of the basic aspect of cognitive dysfunction, but its mechanisms in schizophrenia remain unclear.ObjectivesTo assess the links between planning and cognitive functioning in schizophrenic patients and in norm.Methods50 patients with schizophrenia (age 34.92±8.54; illness duration 8.34±5.87) and 50 healthy volunteers (age 32.42±7.26) were examined. Brief Assessment of Cognition in Schizophrenia, Benton’s test for short-term memory assessment; sub-test Similarity (from WAIS) to assess abstract thinking were used.ResultsPatients showed significantly worse results in all parameters (Tab.1). Table 1: Differences of planning between groups.SchizophreniaNormp-levelTOL-DX92,64±14,48102,52±11,970,00033Similarity16,92±3,9719,76±2,850,00009BVTR Score6,73±1,787,60±1,320,00709In healthy subjects, significant relationship was found between planning and abstract thinking, and there was no relationship between planning and short-term memory (Tab.2). Table 2: Correlations in the Norm groupSpearman Rp-levelTOL-DX &amp; Similarity0,3925300,004809TOL-DX &amp; BVTR0,1864940,194710In patients with schizophrenia, the opposite picture was observed (Tab.3). Table 3: Correlations in the Schizophrenia group.Spearman Rp-levelTOL-DX &amp; Similarity0,2623890,071596TOL-DX &amp; BVTR0,3445660,015331The effectiveness of planning in patients was significantly associated with short-term memory, but not with abstract thinking.ConclusionsStudy results indicate a possible role of basic aspects of mental activity such as short-term memory in planning impairment in patients with schizophrenia. Problem solving and reasoning disorders represent two relatively independent forms of thought disorders in schizophrenia.

Lowered serum cesium levels in schizophrenia: association with immune-inflammatory biomarkers and cognitive impairments.

Objectives:A previous study has shown that schizophrenia (SCZ) is accompanied by lowered levels of trace/metal elements, including cesium. However, it is not clear whether changes in cesium, rubidium, and rhenium are associated with activated immune-inflammatory pathways, cognitive impairments, and the symptomatology of SCZ.Methods:This study measured cesium, rubidium, and rhenium, cognitive impairments (using the Brief Assessment of Cognition in Schizophrenia [BACS]), and the levels of cytokines/chemokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and eotaxin (CCL11) in 120 patients with SCZ and 54 healthy controls. Severity of illness was assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) Scale, and the Hamilton Depression Rating Scale (HAM-D).Results:Serum cesium was significantly lower in patients with SCZ as compared with controls. Further, serum cesium was significantly and inversely associated with CCL11 and TNF-α, but not IL-1β, in patients with SCZ; significant inverse associations were also noted between serum cesium levels and BPRS, FF, HAM-D, and SANS scores. Finally, cesium was positively correlated with neurocognitive probe results including the Tower of London, Symbol Coding, Controlled Word Association, Category Instances, Digit Sequencing Task, and List Learning tests.Conclusion:The results suggest that lowered serum cesium levels may play a role in the pathophysiology of SCZ, contributing to specific symptom domains including negative, depressive and fatigue symptoms, neurocognitive impairments (spatial working, episodic, and semantic memory and executive functions), and neuroimmune pathways.

Predicting Real-World Functioning in Schizophrenia: The Relative Contributions of Neurocognition, Functional Capacity, and Negative Symptoms

Neurocognition and functional capacity are commonly reported predictors of real-world functioning in schizophrenia. However, the additional impact of negative symptoms, specifically its subdomains, i.e., diminished expression (DE) and avolition-apathy (AA), on real-world functioning remains unclear. The current study assessed 58 individuals with schizophrenia. Neurocognition was assessed with the Brief Assessment of Cognition in Schizophrenia, functional capacity with the UCSD Performance-based Skills Assessment (UPSA-B), and negative symptoms with the Negative Symptom Assessment-16. Real-world functioning was assessed with the Multnomah Community Ability Scale (MCAS) with employment status as an additional objective outcome. Hierarchical regressions and sequential logistic regressions were used to examine the associations between the variables of interest. The results show that global negative symptoms contribute substantial additional variance in predicting MCAS and employment status above and beyond the variance accounted for by neurocognition and functional capacity. In addition, both AA and DE predict the MCAS after controlling for cognition and functional capacity. Only AA accounts for additional variance in employment status beyond that by UPSA-B. In summary, negative symptoms contribute substantial additional variance in predicting both real-world functioning and employment outcomes after accounting for neurocognition and functional capacity. Our findings emphasize both DE and AA as important treatment targets in functional recovery for people with schizophrenia.

Biomarker Profiles in Psychosis Risk Groups Within Unaffected Relatives Based on Familiality and Age.

Investigating biomarkers in unaffected relatives (UR) of individuals with psychotic disorders has already proven productive in research on psychosis neurobiology. However, there is considerable heterogeneity among UR based on features linked to psychosis vulnerability. Here, using the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) dataset, we examined cognitive and neurophysiologic biomarkers in first-degree UR of psychosis probands, stratified by 2 widely used risk factors: familiality status of the respective proband (the presence or absence of a first- or second-degree relative with a history of psychotic disorder) and age (within or older than the common age range for developing psychosis). We investigated biomarkers that best differentiate the above specific risk subgroups. Additionally, we examined the relationship of biomarkers with Polygenic Risk Scores for Schizophrenia (PRSSCZ) in a subsample of Caucasian probands and healthy controls (HC). Our results demonstrate that the Brief Assessment of Cognition in Schizophrenia (BACS) score, antisaccade error (ASE) factor, and stop-signal task (SST) factor best differentiate UR (n = 169) from HC (n = 137) (P = .013). Biomarker profiles of UR of familial (n = 82) and non-familial (n = 83) probands were not significantly different. Furthermore, ASE and SST factors best differentiated younger UR (age ≤ 30) (n = 59) from older UR (n = 110) and HC from both age groups (age ≤ 30 years, n=49; age > 30 years, n = 88) (P < .001). In addition, BACS (r = -0.175, P = .006) and ASE factor (r = 0.188, P = .006) showed associations with PRSSCZ. Taken together, our findings indicate that cognitive biomarkers-"top-down inhibition" impairments in particular-may be of critical importance as indicators of psychosis vulnerability.

Investigating potential associations between neurocognition/social cognition and oxidative stress in schizophrenia

IntroductionDeficits in neurocognition and social cognition play a critical role in the functional impairment of patients with schizophrenia. Increased oxidative stress has been evidenced in schizophrenia. Increased oxidative stress can affect neuronal function and lead to impairments in neurocognitive functions (especially working memory) and social cognition. ObjectiveTo investigate deficits in neurocognition and social cognition and their potential association with oxidative stress biomarkers in schizophrenia. Material and methodsEight-five clinically stable patients with schizophrenia and 75 controls were enrolled in this study. Neurocognition was evaluated through the Brief Assessment of Cognition in Schizophrenia (BACS). Social cognition was assessed through the Hinting Task – a test of theory of mind – and an emotion processing test, Facial Emotion Recognition Test (FERT-100). Oxidative stress was assessed by measuring serum levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). ResultsPatients had decreased serum levels of GSH (Z=3.56; p<0.001) and increased TBARS (Z=5.51; P<0.001) when compared with controls. TBARS levels are higher in patients using first generation antipsychotics. Higher serum levels of TBARS in patients were associated with poor performance in working memory test (r=-0.39; p=0.002), even when controlling for age and negative symptoms (Standard Beta: -0.36; CI= -2.52 a -13.71). DiscussionThe association between greater lipid peroxidation, as assessed by TBARS, and worse performance in working memory corroborates theoretical models of greater vulnerability of schizophrenia to oxidative stress.