Cognitive Function In Schizophrenia Research Articles

The association between exposure to herpes simplex virus type 1 (HSV-1) and cognitive functioning in schizophrenia: A meta-analysis

Cognitive deficits are characteristic of schizophrenia but their etiology is not understood. Previous studies show an association between viral exposures and cognitive impairment. This meta-analysis was undertaken to determine the relationship of herpes simplex virus type 1 (HSV-1) exposure and cognitive functioning in schizophrenia. A systematic search was performed for studies comparing the cognitive functioning of HSV-1 seropositive vs. seronegative persons with schizophrenia. The primary outcome was the standardized mean difference (SMD) in composite cognitive score using Hedges’ g. Secondary outcomes were SMDs in 9cognitive domains. Study heterogeneity was estimated using the I2 index and formal tests of heterogeneity using Cochran's Q. In a sample of 3516 individuals from 9 studies the SMD was negative for the composite score and all 9 domains indicating a significant deficit for seropositive individuals in 8 domains. The SMDs ranged from -0.11 (Working Memory) to -0.36 (Visual Spatial). Cochran's Q test indicated heterogeneity for one domain. The I2 index of heterogeneity was in the low -moderate range for all but one domain. Exposure to HSV-1 is associated with decreased cognitive functioning in schizophrenia. An increased understanding of HSV-1 exposure might lead to improved methods for the prevention and treatment of cognitive deficits in schizophrenia.

Increased Plasma Level of Longevity Protein Klotho as a Potential Indicator of Cognitive Function Preservation in Patients With Schizophrenia

Cognitive impairments are a core feature of schizophrenia. Klotho is an anti-aging protein with demonstrated cognitive-enhancing effects on the brain. The purpose of this study was to investigate the differences in levels of plasma klotho between patients with schizophrenia and healthy controls, as well as the relationship between klotho level and cognitive function in patients. Forty patients with schizophrenia and 40 gender- and age-matched healthy individuals were recruited. Positive and Negative Syndrome Scale (PANSS) was used to assess the psychopathology of patients. A neuropsychological battery was performed to evaluate the cognitive function of participants. Plasma klotho was measured using enzyme-linked immunosorbent assay. We show that patients with schizophrenia performed worse in the neurocognitive tests than the healthy controls. The levels of plasma klotho were significantly higher in schizophrenia patients than in healthy controls (p < 0.001). In patients, plasma klotho levels were positively correlated with cognitive function with regard to attention (p = 0.010), working memory (p < 0.001), verbal memory (p = 0.044), executive function (p < 0.001), and composite cognitive score (p < 0.001). Stepwise linear regression analysis shows that executive function had the highest correlation with plasma klotho levels (β = 0.896, t = 8.290, p < 0.001). Collectively, these results indicate that anti-aging protein klotho may be implicated in the pathogenesis of schizophrenia, and increased klotho may act as a compensatory factor for the preservation of cognitive function in schizophrenia. Further studies are needed to investigate the dynamic changes of klotho and the mechanisms by which klotho modulates cognition in schizophrenia.

The relationship between plasma levels of clozapine and N-desmethyclozapine as well as M1 receptor polymorphism with cognitive functioning and associated cortical activity in schizophrenia

Studies that examined the effect of clozapine on cognitive functions in schizophrenia provided contradictory results. N-desmethylclozapine (NDMC) is the major metabolite of clozapine and have procognitive effects via agonistic activity in the M1 cholinergic receptors. The rs2067477 polymorphism in the M1 receptors may play role in cognitive profile in schizophrenia. We investigated the association of plasma clozapine (PClz), NDMC (PNdmc) levels and the rs2067477 polymorphism with cognitive functions and cortical activity measured by functional near infrared spectroscopy during the N-Back task in subjects with schizophrenia (N = 50) who are under antipsychotic monotherapy with clozapine. We found that PClz and PNdmc levels were negatively, PNdmc/PClz ratio was positively correlated with immediate recall score in the Rey Auditory Verbal Learning Test. PNdmc/PClz ratio was positively correlated with cortical activity during the N-back task. M1 wild-type group (CC: wild-type) produced higher cortical activity than M1 non wild-type group (CA: heterozygote / AA: mutant) in cortical regions associated with working memory (WM). These results suggest that individual differences in clozapine's effect on short term episodic memory may be associated with PClz and PNdmc. Higher activity in the M1 wild-type group may indicate inefficient use of cortical resources and/or excessive use of certain cognitive strategies during WM performance.

Peripheral inflammatory and neurotrophic biomarkers of cognitive impairment in schizophrenia: a meta-analysis - CORRIGENDUM.

BackgroundSchizophrenia is associated with significant cognitive impairment. However, the pathophysiological mechanisms underlying cognitive dysfunction in schizophrenia remain unclear. Brain-derived neurotrophic factor (BDNF) and C-reactive protein (CRP) are among the most commonly investigated peripheral markers of cognition in schizophrenia.MethodsA systematic review in PubMed and Scopus databases was performed until 31 January 2019 to assess the relationship between cognitive impairment, CRP and BDNF levels in schizophrenia. A random-effects meta-analysis was conducted.ResultsCurrent meta-analysis included 21 studies including 2449 patients with schizophrenia-spectrum disorders. Overall, both BDNF [r = 0.12, confidence interval (CI) 0.04–0.19] and CRP (r = −0.13, CI 0.08–0.18) levels were very modestly but significantly related to cognitive functioning in schizophrenia (r = 0.12, CI 0.04–0.19). In meta-analyses of cognitive domains, BDNF levels were significantly associated with verbal memory (r = 0.16, CI 0.09–0.23), working memory (r = 0.14, CI 0.06–0.22), processing speed (r = 0.18, CI 0.10–0.26) and verbal fluency (r = 0.09, CI 0–0.18) performances. Elevated CRP levels were related to all cognitive domains (r = −0.09 to −0.13) except for fluency. Subgroup analyses suggested that the relationship between cognitive and BDNF levels were more pronounced in chronic samples.ConclusionsCurrent findings suggest that cognitive impairment in schizophrenia is significantly related to elevated CRP and reduced BDNF levels in schizophrenia, particularly in chronic samples. However, small effect sizes of these correlations suggest that inflammation and decreased BDNF levels do not play a major role in cognitive dysfunction in most patients with schizophrenia. Further studies are needed to investigate the potential intermediating and confounding factors which can influence the level of relationship between inflammation, neurotrophic factors and cognition in schizophrenia.

Does childhood trauma influence cognitive functioning in schizophrenia? The association of childhood trauma and cognition in schizophrenia spectrum disorders.

Childhood trauma (CT) is a risk factor for schizophrenia spectrum disorders (SSDs), and cognitive impairment is a core feature and a vulnerability marker of SSDs. Studies of the relationship between CT and cognitive impairment in SSDs are inconclusive. In addition, few studies have examined differential effects of CT subtypes, e.g. physical, sexual or emotional abuse/neglect, on cognitive functioning. The present study therefore aimed to examine the effects of CT and CT subtypes on cognitive impairment in SSD. Participants (n = 78) with SSDs completed a comprehensive neuropsychological test battery and the Childhood Trauma Questionnaire Short-Form (CTQ-SF). We compared global cognitive performance as well as scores in seven subdomains (verbal abilities, visuospatial abilities, learning, memory, attention/working memory, executive abilities and processing speed) between participants reporting no CT and those reporting CT experiences using independent samples t-tests as well as linear regression analyses to control for possible confounders. CT subtype physical neglect was associated with attention and working memory after controlling for positive and negative psychosis symptoms, years of education, antipsychotics, gender and age, and adjustment of multiple testing. Our results indicate that the observed heterogeneity in cognitive impairment in SSDs, especially attention/working memory abilities, may in part be associated with childhood physical neglect.

Self-Assessments of Cognitive Performance in Schizophrenia: The Role of Impaired Momentary Judgement

Self-Assessments of Cognitive Performance in Schizophrenia: The Role of Impaired Momentary Judgement

Metabolic Syndrome and Cognitive Functions in Schizophrenia-Implementation of Dietary Intervention.

IntroductionThe co-existence of schizophrenia and metabolic syndrome is a widely described phenomenon that contributes to the worse functioning of patients in everyday life. A relatively new area of research is the relationship between metabolic syndrome (MS) and cognitive function in patients with schizophrenia. The aim of the study was to verify the relationship between the presence of metabolic syndrome and cognitive function of patients with schizophrenia and to assess the possibility of changing cognitive function by introducing appropriate dietary intervention.Materials and MethodsThe study involved 87 individuals diagnosed with schizophrenia according to ICD-10 criteria, aged 19 to 67 years (M = 41.67; SD = 11.87). Patients were in the remission phase of schizophrenia, all using antipsychotics for pharmacological treatment. From a group of 83 patients with schizophrenia and diagnosed metabolic syndrome (according to IDF criteria) 30 patients were randomly assigned to an experimental group—with dietary intervention, 29 patients—to group without dietary intervention, 24 patients with schizophrenia without metabolic syndrome was a comparison group. All groups were evaluated for cognitive function using Stroop Test, Trail Making Test (TMT), Verbal Fluency Test, Digit Span Backwards Test. In the experimental group a dietary intervention was applied, which was to provide the examined person with a 7-day dietary plan with reduced calorie content, in compliance with the Mediterranean diet.ResultsAfter the dietary intervention there was a significant improvement in the number of errors made in the third Stroop Test (p <0.001), the time taken to complete the Point Linking Test was shortened (Test B; p = 0.005), there was an improvement in Verbal Fluency Test in “animals” category (p = 0.006) “sharp objects” category (p = 0.009), the number of repeated digits has increased in Digit Span Test in “forward” category (p = 0.001) and overall completion of the test (p = 0.021). In the group of patients with MS without dietary intervention, the results of cognitive tests remained mostly unchanged.ConclusionsChange of eating habits may be a significant element of a holistic approach to the problems of treatment of schizophrenia.

DNA Methylation Analysis of AKT1 Promoter and HTR2A EXON-I of Malaysian Schizophrenia Multiplex Families with Lower Cognitive Performance

Dysfunction of cognitive performance in schizophrenia has been associated with aberrant alteration of DNA methylation of several schizophrenia-risk genes. AKT1 and HTR2A are among the candidate genes for schizophrenia. Their expressions were found reduced in schizophrenia patients. Thus, we aimed to study the methylation status of AKT1 promoter and HTR2A exon-I in Malaysian schizophrenia patients and their affected family members. In this study, each participant was required to perform Trail Making Test (TMT) part A and B to measure their cognitive performance. Genomic DNA extracted from the peripheral blood of 12 Malaysian schizophrenia families and 12 controls families, was subjected to bisulfite conversion. The methylation status of CpG sites of AKT1 promoter at Chr14: 104796054 and HTR2A exon-I at Chr13: 46896918 were identified using methylation-specific polymerase chain reaction (MSP). Our results showed that schizophrenia patients performed worse in both TMT-A and B (p<0.0001) than healthy controls. The patients also displayed significantly (p=0.023) high level of methylation in AKT1 promoter compared to controls. Meanwhile, no significant difference (p=0.248) in methylation status was observed in HTR2A exon-I between schizophrenia and control groups. Therefore, methylation of AKT1 promoter in peripheral bloods of patients may involve in cognitive impairment and schizophrenia pathology. In addition, we were able to demonstrate the heritability of DNA methylation status across family members.

Plasticity of DNA methylation, functional brain connectivity and efficiency in cognitive remediation for schizophrenia

Cognitive remediation (CR) is predicated on principles of neuroplasticity, but the actual molecular and neurocircuitry changes underlying cognitive change in individuals with impaired neuroplastic processes is poorly understood. The present study examined epigenetic-neurocircuitry-behavioral outcome measures in schizophrenia, before and after participating in a CR program that targeted higher-order cognitive functions. Outcome measures included DNA methylation of genes central to synaptic plasticity (CpG sites of Reelin promoter and BDNF promoter) from buccal swabs, resting-state functional brain connectivity and topological network efficiency, and global scores of a cognitive battery from 35 inpatients in a rehabilitative ward (18 CR, 17 non-CR) with similar premorbid IQ to 15 healthy controls. Baseline group differences between healthy controls and schizophrenia, group-by-time effects of CR in schizophrenia, and associations between the outcome measures were tested. Baseline functional connectivity abnormalities within the frontal, fronto-temporal and fronto-parietal regions, and trending decreases in global efficiency, but not DNA methylation, were found in schizophrenia; the frontal and fronto-temporal connectivity, and global efficiency correlated with global cognitive performance across all individuals. Notably, CR resulted in differential changes in Reelin promoter CpG methylation levels, altered within-frontal and fronto-temporal functional connectivity, increasing global efficiency and improving cognitive performance in schizophrenia, when compared to non-CR. In the CR inpatients, positive associations between the micro to macro measures: Reelin methylation changes, higher global efficiency and improving global cognitive performance were found. Present findings provide a neurobiological insight into potential CR-led epigenetics-neurocircuitry modifications driving cognitive plasticity.

The Relationship Between White Matter Microstructure and General Cognitive Ability in Patients With Schizophrenia and Healthy Participants in the ENIGMA Consortium.

Schizophrenia has recently been associated with widespread white matter microstructural abnormalities, but the functional effects of these abnormalities remain unclear. Widespread heterogeneity of results from studies published to date preclude any definitive characterization of the relationship between white matter and cognitive performance in schizophrenia. Given the relevance of deficits in cognitive function to predicting social and functional outcomes in schizophrenia, the authors carried out a meta-analysis of available data through the ENIGMA Consortium, using a common analysis pipeline, to elucidate the relationship between white matter microstructure and a measure of general cognitive performance, IQ, in patients with schizophrenia and healthy participants. The meta-analysis included 760 patients with schizophrenia and 957 healthy participants from 11 participating ENIGMA Consortium sites. For each site, principal component analysis was used to calculate both a global fractional anisotropy component (gFA) and a fractional anisotropy component for six long association tracts (LA-gFA) previously associated with cognition. Meta-analyses of regression results indicated that gFA accounted for a significant amount of variation in cognition in the full sample (effect size [Hedges' g]=0.27, CI=0.17-0.36), with similar effects sizes observed for both the patient (effect size=0.20, CI=0.05-0.35) and healthy participant groups (effect size=0.32, CI=0.18-0.45). Comparable patterns of association were also observed between LA-gFA and cognition for the full sample (effect size=0.28, CI=0.18-0.37), the patient group (effect size=0.23, CI=0.09-0.38), and the healthy participant group (effect size=0.31, CI=0.18-0.44). This study provides robust evidence that cognitive ability is associated with global structural connectivity, with higher fractional anisotropy associated with higher IQ. This association was independent of diagnosis; while schizophrenia patients tended to have lower fractional anisotropy and lower IQ than healthy participants, the comparable size of effect in each group suggested a more general, rather than disease-specific, pattern of association.

Aerobic exercise and cognitive functioning in schizophrenia: Results of a 1-year follow-up from a randomized controlled trial

We previously reported that adding combined, individual, and group aerobic exercise (AE) interventions to the treatment as usual (TAU) for schizophrenia showed significant improvements in cognition and other outcomes compared to those with TAU alone in a randomized controlled trial. Following the promising results of our previous study, this 1-year follow-up study evaluated the improvements in cognition and other outcomes with TAU + AE compared to those with TAU alone. Of 41 randomized patients, 40 were included in the intent-to-treat population—20 in the TAU + AE and 20 in the TAU alone; all patients completed the 1-year follow-up. Mixed models were applied to assess changes in outcome measures over time from baseline to 1-year follow-up. At 1-year follow-up, the TAU + AE demonstrated significant group by time interaction effects in several cognitive domains, intrinsic motivation, negative symptom, interpersonal relations, and functional outcome compared with the TAU alone. Our results demonstrate that the improvements in cognition and other outcomes with TAU + AE were maintained and that functional outcome improved over 1-year follow-up. These findings show that the improvements sustained for each outcome over 1 year have the potential to offer opportunities for greater transitions to improvement of functional outcome.

Add-on spironolactone as antagonist of the NRG1-ERBB4 signaling pathway for the treatment of schizophrenia: Study design and methodology of a multicenter randomized, placebo-controlled trial

BackgroundPreclinical studies recently showed that the mineralocorticoid antagonist spironolactone acts also as an antagonist of the NRG1-ERBB4 signaling pathway and improves schizophrenia-like behaviour in Nrg1 transgenic mouse model. As this signaling pathway is critically linked to the pathophysiology of schizophrenia, especially in the context of working-memory dysfunction, spironolactone may be a novel treatment option for patients with schizophrenia targeting cognitive impairments. AimsTo evaluate whether spironolactone added to an ongoing antipsychotic treatment improves cognitive functioning in schizophrenia. MethodsThe add-on spironolactone for the treatment of schizophrenia trial (SPIRO-TREAT) is a multicenter randomized, placebo-controlled trial with three arms (spironolactone 100 mg, spironolactone 200 mg and placebo). Schizophrenia patients are treated for three weeks and then followed-up for additional nine weeks. As primary outcome, we investigate changes in working memory before and at the end of the intervention phase. We will randomize 90 patients. Eighty-one patients are intended to reach the primary endpoint measure at the end of the three-week intervention period. Secondary endpoints include other measures of cognition, psychopathology, safety measures and biological measures. ConclusionsSPIRO-TREAT is the first study evaluating the efficacy of the mineralocorticoid receptor antagonist spironolactone to improve cognitive impairments in schizophrenia patients targeting the NRG1-ERBB4 signaling pathway. With SPIRO-TREAT, we intend to investigate a novel treatment option for cognitive impairments in schizophrenia that goes beyond the established concepts of interfering with dopaminergic neurotransmission as key pathway in schizophrenia treatment. Clinical trial registrationInternational Clinical Trials Registry Platform: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2014-001968-35-DE

P.405 Ketamine modulates synaptic plasticity by interneuron disinhibition and AMPA-current augmentation

Cognitive deficits and visual impairment in the magnocellular (M) pathway, have been independently reported in schizophrenia. The current study examined the association between neuropsychological (NPS) performance and visual evoked potentials (VEPs: N80/P1 to M- and P(parvocellular)-biased visual stimuli) in schizophrenia and healthy controls.NPS performance and VEPs were measured in n = 44 patients and n = 34 matched controls. Standardized NPS-scores were combined into Domains and a PCA (Principal Component Analysis) generated Composite. Group differences were assessed via (M)ANOVAs, association between NPS and VEP parameters via PCA, Pearson’s coefficient and bootstrapping. Logistic regression was employed to assess classification power.Patients showed general cognitive impairment, whereas group differences for VEP-parameters were non-significant. In patients, N80 latency across conditions loaded onto one factor with cognitive composite, showed significant negative correlations of medium effect sizes with NPS performance for M/P mixed stimuli and classified low and high performance with 70% accuracy.The study provides no evidence for early visual pathway impairment but suggests a heightened association between early visual processing and cognitive performance in schizophrenia.Our results lend support to bottom-up models of cognitive function in schizophrenia and implicate visual N80 latency as a potential biomarker of cognitive deficits in schizophrenia.

Behavioral abnormalities and phosphorylation deficits of extracellular signal-regulated kinases 1 and 2 in rat offspring of the maternal immune activation model

Extracellular signal-regulated kinase (ERK) signal transduction is known to be associated with neurogenesis and neuronal differentiation and as such may be related to the synaptic plasticity associated with cognitive function. Although antipsychotic drug studies have suggested a potential role for the ERK cascade in schizophrenia, the mechanistic basis is unknown. The maternal immune activation (MIA) rat model is a well-known to simulate many of the clinical symptoms of schizophrenia, including cognitive deficits, but a role in this model for dynamic changes in ERK has not been established. In this study, polyinosinic:polycytidylic acid was administered to rats intravenously at a dose of 10 mg/kg on embryonic day 9.5 to produce MIA. The effect of MIA on behavior and ERK phosphorylation within the prefrontal cortex and the hippocampus of adolescent and adult offspring were explored. We also examined neurofilaments, a marker of neurogenesis, which have been reported to be modulated by ERK signaling. The results demonstrate an age- and region-specific profile of ERK expression and phosphorylation and suggest possible relationships among ERK, neurofilament expression, and cognitive performance in schizophrenia.

The internal noise of the visual system and cognitive functions in schizophrenia

Abstract In this study, we report the existence of correlation between the ability of the object perception in the presence of the external noise and the cognitive functioning in schizophrenia. The level of the internal noise of the visual system have been measured for the 41 healthy volunteers and for the 68 schizophrenia patients in the task of distinguishing the location of the rupture of the Landolt ring, under the conditions of external interference. The collected evidence demonstrated an increase in the level of internal noise of the visual system in the patients with schizophrenia.

Development and Evaluation of a Visual Remediation Intervention for People with Schizophrenia.

It is now well documented that schizophrenia is associated with impairments in visual processing at all levels of vision, and that these disturbances are related to deficits in multiple higher-level cognitive and social cognitive functions. Visual remediation methods have been slow to appear in the literature as a potential treatment strategy to target these impairments, however, in contrast to interventions that aim to improve auditory and higher cognitive functions in schizophrenia. In this report, we describe a National Institute of Mental Health (NIMH)-funded R61/R33 grant that uses a phased approach to optimize and evaluate a novel visual remediation intervention for people with schizophrenia. The goals of this project are: (1) in the R61 phase, to establish the optimal components and dose (number of sessions) of a visual remediation intervention from among two specific visual training strategies (and their combination) for improving low and mid-level visual functions in schizophrenia; and (2) in the R33 phase, to determine the extent to which the optimal intervention improves not only visual processing but also higher-level cognitive and role functions. Here we present the scientific background for and innovation of the study, along with our methods, hypotheses, and preliminary data. The results of this study will help determine the utility of this novel intervention approach for targeting visual perceptual, cognitive, and functional impairments in schizophrenia.

Evaluation of cognitive deficits in schizophrenia using event-related potentials and rehabilitation influences using EEG Biofeedback in patients diagnosed with schizophrenia.

Cognitive deficits in schizophrenic patients have a chronic and negative effect on patients' social functioning. Antipsychotic drugs do not sufficiently improve cognitive functions. In this study, an analysis of previous studies on cognitive functions using event-related potentials in schizophrenia patients was conducted on the basis of available publications (Pubmed, Scopus). The studies indicate numerous deviations at various stages of information processing in patients diagnosed with schizophrenia when compared to healthy subjects, and this justifies the need for the development of new methods influencing the bioelectric brain activity in cognitive rehabilitation of these patients. EEG Biofeedback is a method which could be used for rehabilitation of cognitive functions in schizophrenia patients. Despite it being used in practice, the importance of EEG Biofeedback as a rehabilitation influence on cognitive functions in schizophrenia has not been fully ascertained. This paper analyses the results of previous studies on the effect of EEG Biofeedback therapy on cognitive functions as a possible method to be used in the rehabilitation of schizophrenia patients. Currently, the body of research that may prove the value of this method in the rehabilitation of patients with schizophrenia appears to be insufficient, and there is no scientific evidence from randomized studies for the usefulness of EEG Biofeedback in schizophrenia treatment. At the moment, the recommendation of this method in the cognitive rehabilitation of patients is a therapeutic experiment. The researchers, on the basis of an analysis of clinical cases, currently propose that EEG Biofeedback is conducted in patients diagnosed with schizophrenia by experienced practitioners, paying particular attention to strengthening alpha in the right parietal region.

A randomized study on the effect of tDCS on cognitive function in schizophrenia

Psychiatrist Dr Tomiki Sumiyoshi is the Director of Preventive Intervention for Psychiatric Disorders at National Centre of Neurology and Psychiatry, with extensive experience in clinical and basic research on schizophrenia and mood disorders. His deep interest in schizophrenia is driven by his background investigating neurobiological substrates responsible for cognitive impairment, but also in discovering effective therapeutics to facilitate social outcomes in patients with psychiatric conditions. Sumiyoshi explains that the connection between psychiatric disorders and cognitive impairment is well-established. Yet, limited efforts have been made towards implementing novel approaches that can truly help psychiatric patients to overcome this impairment, and hence live a normal life. He believes it is critical that current research needs to shift its focus on investigating innovative methods such as transcranial direct current stimulation (tDCS) that can facilitate cognitive enhancement in patients with schizophrenia.

Autistic symptoms predict social cognitive performance in patients with schizophrenia.

Schizophrenia spectrum disorders and Autism Spectrum Disorders (ASD) share many similarities. Among those features, social cognitive impairment is recognized as a key characteristic of both ASD and schizophrenia. In this study, the role of ASD symptoms, measured with the PANSS Autism Severity Score (PAUSS), was investigated as a predictor of social cognitive performance in patients with Schizophrenia spectrum disorders. Existent databases from 2 studies (SCOPE Phase 3 and SCOPE Phase 5), in which a total of 361 patients (mean age 41.7 years; 117 females) were assessed with tests of mental state attribution and emotion recognition, were analyzed. Less severe ASD symptoms, as well as younger age, better premorbid IQ, and neurocognition were identified as individual predictors of better social cognitive performance. These results suggest a role of ASD symptoms in affecting social cognitive performance in schizophrenia.

Deviation from expected cognitive ability is a core cognitive feature of schizophrenia related to neurophysiologic, clinical and psychosocial functioning

Cognitive functioning in schizophrenia is characterized by a generalized impairment in current cognitive ability based on traditional population-based norms. However, these norms assume a normal cognitive trajectory and do not directly account for illness-related declines from expected cognitive potential. Indeed, schizophrenia patients exhibit even greater deviation between their observed and expected cognitive functioning based on expanded norms that leverage premorbid variables resistant to illness-related features. The current study further quantified the extent to which illness-related features account for this deviation from expectation and assessed its relationship to neurophysiologic (mismatch negativity, P3a, theta oscillations), clinical, and psychosocial functioning in schizophrenia patients. Expected cognitive ability (PENN-CNB global cognition) in patients (n = 684) was calculated using healthy comparison subject (n = 660) weighted regression based on premorbid variables resistant to illness-related decline (demographics, single-word reading, parental education). The magnitude of any deviation between current (observed) and regression-predicted (expected) cognitive ability was calculated. Results indicated that 24% (n = 164) of the total patient population exhibited significant (≥-1.96 SD) deviation between observed and expected global cognitive ability. Interestingly, 20% of the total patient population (n = 136) had “normal” range cognitive performance when using traditional population-based norms, but also had significant deviation from expected cognitive ability. The magnitude of this deviation was associated with more severe neurophysiologic abnormalities, longer illness duration, higher levels of negative symptoms, and worse psychosocial functioning. Assessment of cognitive deviation is thus a complementary metric for characterizing the severity of illness-related cognitive declines in patients, while also reflecting the expression and severity of key endophenotypes of schizophrenia.