Cognitive Deficits In Schizophrenia Research Articles

Bifactor model of cognition in schizophrenia: Evidence for general and specific abilities

BackgroundDespite extensive study of cognition in schizophrenia, it remains unclear as to whether cognitive deficits and their latent structure are best characterized as reflecting a generalized deficit, specific deficits, or some combination of general and specific constructs. MethodTo clarify latent structure of cognitive abilities, confirmatory factor analysis was used to examine the latent structure of cognitive data collected for the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) for Schizophrenia study. Baseline assessment data (n = 813) were randomly divided into calibration (n = 413) and cross-validation samples (n = 400). To examine whether generalized or specific deficit models provided better explanation of the data, we estimated first-order, hierarchical, and bifactor models. ResultsA bifactor model with seven specific factors and one general factor provided the best fit to the data for both the calibration and cross-validation samples. ConclusionsThese findings lend support for a replicable bifactor model of cognition in schizophrenia, characterized by both a general cognitive factor and specific domains. This suggests that cognitive deficits in schizophrenia might be best understood by separate general and specific contributions.

Visual N80 latency as a marker of neuropsychological performance in schizophrenia: Evidence for bottom-up cognitive models

ObjectiveCognitive 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. MethodsNPS 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. ResultsPatients 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. ConclusionThe study provides no evidence for early visual pathway impairment but suggests a heightened association between early visual processing and cognitive performance in schizophrenia. SignificanceOur 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.

Allostatic Load Effects on Cortical and Cognitive Deficits in Essentially Normotensive, Normoweight Patients with Schizophrenia.

Reduced cortical gray matter integrity and cognitive abilities are among core deficits in schizophrenia. We hypothesized that higher allostatic load (AL) that accounts for exposure to chronic stress is a contributor to structural and cognitive deficits in schizophrenia. One hundred and sixty-seven schizophrenia patients who were on average with normal weight, normal systolic, and diastolic blood pressure and 72 healthy controls were enrolled in the study. Group differences in subclinical cardiovascular, metabolic, immune, and neuroendocrine biological markers as indexed by AL and contribution of AL components to the structural and cognitive deficits in schizophrenia were explored. Compared with controls, schizophrenia patients who were normotensive, normoweight, and had low total cholesterol levels still had significantly higher AL mainly due to lower high-density lipoprotein cholesterol and higher heart rate, waist-hip ratio, hemoglobinA1c, hypersensitive C-reactive protein, and overnight-urine cortisol levels. Patients also had decreased whole-brain mean cortical thickness, and lower cognition assessed by the MATRICS consensus cognitive battery. AL was inversely correlated with mean cortical thickness and cognition in schizophrenia, while none of these relationships existed in controls. Mediation analyses showed the effect of AL on cognitive deficits in schizophrenia was significantly mediated by cortical thinning, and the most significant mediating cortical area was the left superior frontal gyrus. Cortical thickness may act as a mediator between AL and cognitive deficits in schizophrenia. Early intervention strategies to reduce cortical thinning and cognitive dysfunction in schizophrenia should target specific aspects of their high AL in addition to weight gain, hypertension and high cholesterol levels.

Prefrontal α7nAChR Signaling Differentially Modulates Afferent Drive and Trace Fear Conditioning Behavior in Adolescent and Adult Rats.

Increased level of kynurenic acid is thought to contribute to the development of cognitive deficits in schizophrenia through an α7nAChR-mediated mechanism in the prefrontal cortex (PFC). However, it remains unclear to what extent disruption of PFC α7nAChR signaling impacts afferent transmission and its modulation of behavior. Using male rats, we found that PFC infusion of methyllycaconitine (MLA; α7nAChR antagonist) shifts ventral hippocampal-induced local field potential (LFP) suppression to LFP facilitation, an effect only observed in adults. Hippocampal stimulation can also elicit a GluN2B-mediated LFP potentiation (when PFC GABAAR is blocked) that is insensitive to MLA. Conversely, PFC infusion of MLA diminished the gain of amygdalar transmission, which is already enabled by postnatal day (P)30. Behaviorally, the impact of prefrontal MLA on trace fear-conditioning and extinction was also age related. While freezing behavior during conditioning was reduced by MLA only in adults, it elicited opposite effects in adolescent and adult rats during extinction as revealed by the level of reduced and increased freezing response, respectively. We next asked whether the late-adolescent onset of α7nAChR modulation of hippocampal inputs contributes to the age-dependent effect of MLA during extinction. Data revealed that the increased freezing behavior elicited by MLA in adult rats could be driven by a dysregulation of the GluN2B transmission in the PFC. Collectively, these results indicate that distinct neural circuits are recruited during the extinction of trace fear memory in adolescents and adults, likely because of the late-adolescent maturation of the ventral hippocampal-PFC functional connectivity and its modulation by α7nAChR signaling.SIGNIFICANCE STATEMENT Abnormal elevation of the astrocyte-derived metabolite kynurenic acid in the prefrontal cortex (PFC) is thought to impair cognitive functions in schizophrenia through an α7nAChR-mediated mechanism. Here, we found that prefrontal α7nAChR signaling is recruited to control the gain of hippocampal and amygdalar afferent transmission in an input-specific, age-related manner during the adolescent transition to adulthood. Behaviorally, prefrontal α7nAChR modulation of trace fear memory was also age-related, likely because of the late-adolescent maturation of the ventral hippocampal pathway and its recruitment of PFC GABAergic transmission enabled by local α7nAChR signaling. Collectively, these results reveal that distinct α7nAChR-sensitive neural circuits contribute to regulate behavior responses in adolescents and adults, particularly those requiring proper integration of hippocampal and amygdalar inputs by the PFC.

Prevalence of antipsychotic-induced extrapyramidal symptoms and their association with neurocognition and social cognition in outpatients with schizophrenia in the “real-life”

First generation antipsychotics (FGAs) are more likely to induce extrapyramidal side-effects (EPS) than second generation antipsychotics (SGAs), and EPS have been shown associated to cognitive deficits in schizophrenia. So far, no study has explored the relationships between EPS and social cognition (SC) in people with schizophrenia. Therefore, we assessed the prevalence of EPS in a large sample of drug-treated community-dwelling persons with schizophrenia and explored their relationships with patients' neurocognitive and SC abilities.875 patients underwent EPS, psychopathological, neurocognitive and SC assessments by means of standardized measures. Relationships between EPS, psychopathology and neurocognitive and SC measures were investigated by correlation tests. Moreover, a partial correlation network was computed by means of a network analysis.256 patients were treated with FGAs alone or in combination with SGA and 619 with SGAs. EPS were significantly more frequent in FGA-treated group than in the SGA-treated one. Patients with EPS disclosed a more severe psychopathology and were more impaired in neurocognitive and SC measures compared to those without EPS. Disorganization, expressive deficit, and duration of illness were significantly associated to both neurocognitive and SC measures while EPS were associated to neurocognitive measures only. The network analysis showed that parkinsonism was the sole EPS directly connected to both psychopathological and neurocognitive indices whereas no direct connection emerged between EPS and SC measures.Present findings confirm that EPS are still present in the era of SGAs and contribute, together with other clinical variables, to the neurocognitive but not to the SC impairment of patients with schizophrenia.

Association between global visual scanning and cognitive function in schizophrenia.

Abnormalities of global visual scanning have been well-recognized in schizophrenia patients. However, its relevance to various cognitive domains is still understudied. In the present study, we identified the association between global visual scanning and cognitive function in schizophrenia. Eye movement was captured and analyzed in 28 individuals with schizophrenia and 21 healthy controls in free viewing test. The MATRICS consensus cognitive battery (MCCB) was applied to evaluate cognitive function. Consistent with previous reports, schizophrenia patients exhibited several eye movement abnormalities during global visual scanning and showed cognition deficits in MCCB test as compared with healthy controls. Fixation duration was significantly related to cognitive dysfunction in schizophrenia. Moreover, there was a potential that eye movement measures during landscape scanning, rather than face scanning, were preferentially related to cognitive dysfunction. This study indicated the association between free visual scanning and various cognitive functions in schizophrenia, shedding light on the possibility that some eye movement measures during visual exploration could be a biomarker for cognitive deficits in schizophrenia.

Exposure to Epstein Barr virus and cognitive functioning in individuals with schizophrenia

Cognitive deficits are a central feature of schizophrenia whose etiology is not fully understood. Epstein Barr Virus (EBV) is a potentially neurotropic infectious agent that can generate persistent infections with immunomodulatory effects. Previous studies have found an association between EBV antibodies and cognitive functioning in different populations, but there has been limited investigation in schizophrenia. In this study, 84 individuals with schizophrenia were administered a comprehensive neuropsychological battery, the MATRICS Consensus Cognitive Battery (MCCB). Participants also provided a blood sample, from which antibodies to the EBV whole virion and specific proteins were measured. Multivariate models were constructed to determine the association between these antibodies and cognitive performance on the MCCB overall and domain scores. Using these models, we found a significant association between the MCCB overall percent composite score and level of antibodies to the EBV Nuclear Antigen-1 (EBNA-1) protein, the Viral Capsid Antigen (VCA) protein, and the EBV whole virion. A significant association was also found for the MCCB social cognition domain with the level of antibodies to the EBV Nuclear Antigen-1 (EBNA-1) protein, the Viral Capsid Antigen (VCA) protein, and the EBV whole virion. In all cases, a higher level of antibodies was associated with a lower level cognitive performance. These findings suggest that exposure to EBV may contribute to cognitive deficits in schizophrenia, a finding which may have implications for new methods of prevention and treatment.

White Matter Alterations Between Brain Network Hubs Underlie Processing Speed Impairment in Patients With Schizophrenia.

Processing speed (PS) impairment is one of the most severe and common cognitive deficits in schizophrenia. Previous studies have reported correlations between PS and white matter diffusion properties, including fractional anisotropy (FA), in several fiber bundles in schizophrenia, suggesting that white matter alterations could underpin decreased PS. In schizophrenia, white matter alterations are most prevalent within inter-hub connections of the rich club. However, the spatial and topological characteristics of this association between PS and FA have not been investigated in patients. In this context, we tested whether structural connections comprising the rich club network would underlie PS impairment in 298 patients with schizophrenia or schizoaffective disorder and 190 healthy controls from the Australian Schizophrenia Research Bank. PS, measured using the digit symbol coding task, was largely (Cohen’s d = 1.33) and significantly (P < .001) reduced in the patient group when compared with healthy controls. Significant associations between PS and FA were widespread in the patient group, involving all cerebral lobes. FA was not associated with other cognitive measures of phonological fluency and verbal working memory in patients, suggesting specificity to PS. A topological analysis revealed that despite being spatially widespread, associations between PS and FA were over-represented among connections forming the rich club network. These findings highlight the need to consider brain network topology when investigating high-order cognitive functions that may be spatially distributed among several brain regions. They also reinforce the evidence that brain hubs and their interconnections may be particularly vulnerable parts of the brain in schizophrenia.

The relationship between visual dysfunction and cognitive deficit in schizophrenia

To investigate whether visual processing abnormalities are the result of visual dysfunction involving cognitive impairment or independent abnormalities and to identify the relationship of visual impairments with cognitive functions and severity of psychopathological symptoms. We compared results of visual size perception and actions on objects (motor assessment) in patients with schizophrenia (n=37), including patients with non-resistant schizophrenia (n=19) and healthy individuals (n=20). Cognitive impairments were assessed with BACS. Severity of schizophrenia symptoms was assessed with PANSS. The error in the visual size perception test was smaller in healthy controls compared with non-resistant patients (p<0.03). There are no significant differences between non-resistant patients and other groups. Also, there are no significant differences in motor assessment between healthy controls and patients with schizophrenia. In the visual size perception test, the amount of error correlates with cognitive impairments (r= -0.84, p<0.001), and the severity of psychotic symptoms on PANSS (r=0.55, p<0.05). Changes in visual threshold in patients with schizophrenia are correlated with cognitive dysfunction and reflect dysfunction in the parvocellular system.

Exploratory study of selected nucleotide variants in GRIN1, GRIN2A and GRIN2B encoding subunits of the NMDA receptor in a targeted group of schizophrenia patients with chronic cognitive impairment

BackgroundSchizophrenia is a mental disease that affects approximately 1% of the population. Despite over 100 years of research, its pathomechanism has still not been clarified. Cognitive deficits, which are one of the symptomatic dimensions of schizophrenia, usually appear a few years before the first psychotic episode. Therefore, this is why they are probably the clinical manifestation of the primary pathomechanism of schizophrenia. It is also supposed that N-methyl-d-aspartate receptor (NMDA-R) insufficiency in the prefrontal cortex is responsible for cognitive deficits in schizophrenia. The study aimed to examine whether four selected single nucleotide variants in GRIN1, GRIN2A and GRIN2B encoding NMDA-R subunits, of which two have not been tested before, are linked with the selected clinical phenotype of cognitive dysfunction in schizophrenia.MethodsThe study included the targeted group of 117 patients diagnosed with schizophrenia, all with cognitive deficits and in symptomatic remission. DNA fragments including the studied polymorphisms of the NMDA receptors subunit genes were amplified by polymerase chain reaction and subjected to sequencing.ResultsThe study did not confirm the presence of any of the four selected single nucleotide variants in GRIN1, GRIN2A and GRIN2B subunits of NMDA-R.ConclusionsThe finding indicates that selected single nucleotide variants in GRIN2A and GRIN2B encoding subunits of the NMDA receptor are not associated with the presence of cognitive deficits in schizophrenia.

Social cognitive deficits in schizophrenia and their neurocognitive correlates across the different phases of illness.

This study aimed to assess the relationship between neurocognition (NC) and social cognition (SC) in patients with schizophrenia during the symptomatic phase and the phase of clinical remission. Thirty-two patients were assessed on Color trail test (CTT), Hopkins verbal learning test (HVLT), Controlled oral word association (COWA) test, Wisconsin card sorting test (WCST), Ravens standard progressive matrices (SPM) and Social cognition rating tool in Indian setting (SOCRATIS) during symptomatic and remission phases of illness at least 3 months apart. Compared to baseline assessment, even after controlling for PANSS scores except for social perception index all other domains of SC showed significant improvement at the time of remission. Although there was significant improvement in a few subtests of verbal learning, IQ and number of correct responses of COWA, colour trail test, no significant difference was seen in performance on WCST. Although second order theory of mind task had some association with IQ at the baseline assessment, no association was seen between SC and NC in the remission phase. To conclude, present study suggests that impairments in all the domains of SC (except for social perception index) and NC (except for WCST) improve in the remission phase.

Anomalous self-experiences are related to general cognition deficits in schizophrenia.

Anomalous self-experiences (ASEs) are prevalent in schizophrenia, but its underpinnings are not completely understood. Given the likely complex substrate of the experience of the self, neurocognitive functions requiring coordinate cerebral activity may relate to ASEs. Moreover, cognitive deficits functioning may be involved in the link between self-experience disturbances and some aspects of social dysfunction in schizophrenia. We have assessed ASEs in 41 schizophrenia patients (11 first episodes) using the Inventory of Psychotic-Like Anomalous Self-Experiences (IPASE), and the general cognition using the Brief Assessment of Cognition in Schizophrenia (BACS). Besides, social cognition was assessed using two complementary tools Meyer, Salovey and Caruso Emotional Intelligence Test (MSCEIT) and GEOPTE (Grupo Español para la Optimización del Tratamiento de la Esquizofrenia). The results revealed that Self-awareness/presence and Somatization IPASE scores were inversely explained by motor speed in the BACS; Consciousness IPASE scores were inversely explained by problem solving performance in the BACS. These data reveal a significant relationship between certain domains of general cognition and anomalous self-experiences, that may be useful in further investigation on the substrates of ASEs.

Assessment of brain cholesterol metabolism biomarker 24S-hydroxycholesterol in schizophrenia

Plasma 24S-hydroxycholesterol mostly originates in brain tissue and likely reflects the turnover of cholesterol in the central nervous system. As cholesterol is disproportionally enriched in many key brain structures, 24S-hydroxycholesterol is a promising biomarker for psychiatric and neurologic disorders that impact brain structure. We hypothesized that, as schizophrenia patients have widely reported gray and white matter deficits, they would have abnormal levels of plasma 24S-hydroxycholesterol, and that plasma levels of 24S-hydroxycholesterol would be associated with brain structural and functional biomarkers for schizophrenia. Plasma levels of 24S-hydroxycholesterol were measured in 226 individuals with schizophrenia and 204 healthy controls. The results showed that levels of 24S-hydroxycholesterol were not significantly different between patients and controls. Age was significantly and negatively correlated with 24S-hydroxycholesterol in both groups, and in both groups, females had significantly higher levels of 24S-hydroxycholesterol compared to males. Levels of 24S-hydroxycholesterol were not related to average fractional anisotropy of white matter or cortical thickness, or to cognitive deficits in schizophrenia. Based on these results from a large sample and using multiple brain biomarkers, we conclude there is little to no value of plasma 24S-hydroxycholesterol as a brain metabolite biomarker for schizophrenia.

Molecular imaging of schizophrenia: Neurochemical findings in a heterogeneous and evolving disorder

The past four decades have seen enormous efforts placed on a search for molecular markers of schizophrenia using positron emission tomography (PET) and single photon emission computed tomography (SPECT). In this narrative review, we cast a broad net to define and summarize what researchers have learned about schizophrenia from molecular imaging studies. Some PET studies of brain energy metabolism with the glucose analogue FDGhave have shown a hypofrontality defect in patients with schizophrenia, but more generally indicate a loss of metabolic coherence between different brain regions. An early finding of significantly increased striatal trapping of the dopamine synthesis tracer FDOPA has survived a meta-analysis of many replications, but the increase is not pathognomonic of the disorder, since one half of patients have entirely normal dopamine synthesis capacity. Similarly, competition SPECT studies show greater basal and amphetamine-evoked dopamine occupancy at post-synaptic dopamine D2/3 receptors in patients with schizophrenia, but the difference is likewise not pathognomonic. We thus propose that molecular imaging studies of brain dopamine indicate neurochemical heterogeneity within the diagnostic entity of schizophrenia. Occupancy studies have established the relevant target engagement by antipsychotic medications at dopamine D2/3 receptors in living brain. There is evidence for elevated frontal cortical dopamine D1 receptors, especially in relation to cognitive deficits in schizophrenia. There is a general lack of consistent findings of abnormalities in serotonin markers, but some evidence for decreased levels of nicotinic receptors in patients. There are sparse and somewhat inconsistent findings of reduced binding of muscarinic, glutamate, and opioid receptors ligands, inconsistent findings of microglial activation, and very recently, evidence of globally reduced levels of synaptic proteins in brain of patients. One study reports a decline in histone acetylase binding that is confined to the dorsolateral prefrontal cortex. In most contexts, the phase of the disease and effects of past or present medication can obscure or confound PET and SPECT findings in schizophrenia.

Key role for lipids in cognitive symptoms of schizophrenia

Schizophrenia (SZ) is a psychiatric disorder with a convoluted etiology that includes cognitive symptoms, which arise from among others a dysfunctional dorsolateral prefrontal cortex (dlPFC). In our search for the molecular underpinnings of the cognitive deficits in SZ, we here performed RNA sequencing of gray matter from the dlPFC of SZ patients and controls. We found that the differentially expressed RNAs were enriched for mRNAs involved in the Liver X Receptor/Retinoid X Receptor (LXR/RXR) lipid metabolism pathway. Components of the LXR/RXR pathway were upregulated in gray matter but not in white matter of SZ dlPFC. Intriguingly, an analysis for shared genetic etiology, using two SZ genome-wide association studies (GWASs) and GWAS data for 514 metabolites, revealed genetic overlap between SZ and acylcarnitines, VLDL lipids, and fatty acid metabolites, which are all linked to the LXR/RXR signaling pathway. Furthermore, analysis of structural T1-weighted magnetic resonance imaging in combination with cognitive behavioral data showed that the lipid content of dlPFC gray matter is lower in SZ patients than in controls and correlates with a tendency towards reduced accuracy in the dlPFC-dependent task-switching test. We conclude that aberrations in LXR/RXR-regulated lipid metabolism lead to a decreased lipid content in SZ dlPFC that correlates with reduced cognitive performance.

Social Cognition and Neuro-cognition in Patients with Bipolar Disorder, Their First-Degree Relatives and Healthy Controls.

Background:Studies focusing on assessing social cognition deficits in schizophrenia have been expanded to bipolar disorder considering the similarities shared between the two conditions. Existing research has identified significant deficits in social cognitive skills independent of mood states and neurocognitive deficits, which could indicate the potentiality of this domain to be an endophenotype for bipolar disorder.Methods:The current study assesses the impairments in social cognition in patients with bipolar disorder and their first degree relatives, simultaneously testing for neurocognition as well, and comparing their performance to healthy controls. Fifty four participants were recruited, with 18 participants in each group. MATRICS Consensus Cognitive Battery was used to test neurocognition and Social Cognition Rating Tool in Indian Setting was administered for testing social cognition.Results:Significant deficits were found in social cognition and neurocognition (at p<.01) in the patient group when compared to both probands and healthy controls but no difference between probands and healthy controls. This finding established impairments in socio-cognitive functioning in remitted patients. Conclusion: The study has identified persistent deficits in social and neuro-cognition despite remission, having significant clinical implications in terms developing remediation programs for social cognition and planning early intervention as social cognition deficits have been identified as potential risk factors.

P.552 Acylcarnitine levels in paranoid schizophrenia with metabolic syndrome during treatment of second-generation antipsychotics

Individuals with schizophrenia have been found to display neurocognitive deficits on the order of 1 standard deviation below the mean of healthy controls on a range of cognitive domains, with no clear pattern of deficits that characterizes the majority of individuals with schizophrenia. Such findings have led some to suggest that schizophrenia is characterized by a “generalized” neurocognitive deficit, implying that a common underlying etiology impacts all cognitive domains. Central nervous system accounts of the generalized deficit have been proposed (e.g., NMDA and GABA interneuron receptor dysfunction); however, there may also be more diffuse “general systems” abnormalities that affect brain function. The current study evaluated the role of one type of general systems abnormality, metabolic dysfunction, on global cognitive functioning in a sample of outpatients with schizophrenia (n = 27) and demographically matched healthy controls (n = 33). Participants completed a battery of neuropsychological tests, as well as metabolic measurements to assess blood glucose, blood pressure, and abdominal obesity. Results indicated that higher pulse pressure predicted the generalized neurocognitive deficit in schizophrenia, but not healthy controls; however, blood glucose and abdominal obesity did not predict cognitive performance in either group. These findings provide support for the role of metabolic abnormalities in the generalized neurocognitive deficit in schizophrenia, and suggest that treatment of hypertension may be a novel adjunctive treatment target for remediating cognitive deficits in schizophrenia.

Impaired Frontal Midline Theta During Periods of High Reaction Time Variability in Schizophrenia

BackgroundImpairment in cognitive control is one of the most significant cognitive deficits in schizophrenia. Although it has generally been associated with altered engagement of lateral and medial prefrontal cortices, how attention fluctuations affect this engagement is still not known. In this context, we explored sustained (or proactive) and transient (or reactive) control engagement by investigating frontal theta-band oscillations during periods of low- and high-performance instability, assumed to represent intraindividual attentional fluctuations. MethodsA total of 25 patients with schizophrenia (16 males) and 25 healthy matched control subjects (18 males) performed a long-sustained Go/NoGo task coupled with electroencephalographic recording. Proactive control was explored through frontal lateral theta during trial-by-trial conflict (Go N−1/Go N+1), whereas reactive control was explored through frontal midline theta and the N2 component during current-trial conflict (Go/NoGo). Variance in the time course of reaction time (RT) was computed to identify periods of low and high RT variability in each subject. ResultsPatients with schizophrenia exhibited no frontal lateral theta activity regardless of the RT variability periods, whereas in control subjects, this activity was preserved only during periods of low RT variability (less error prone). During these periods, patients exhibited preserved midline frontal theta activity and N2. However, during high RT variability periods (more error prone), the midline theta activity was impaired in patients but preserved in control subjects. ConclusionsOur results reveal that the efficient engagement of reactive control in patients with schizophrenia and of proactive control in control subjects was state dependent. The findings highlight the importance of accounting for attentional fluctuations when investigating cognitive control impairment in schizophrenia.

The interactive effect of genetic polymorphisms of IL-10 and COMT on cognitive function in schizophrenia

Dopaminergic and inflammatory systems have been proven to play an important role in the cognitive deficits of schizophrenia. Although increasing evidence indicates two systems have strong interaction, the relevant research on this interaction is still limited. Catechol-o-methyltransferase (COMT) and Interleukin-10 (IL-10) play critical functions in dopaminergic and inflammatory systems respectively, and their genetic polymorphisms are both associated with cognitive function. However, the interactive effect of their genetic polymorphisms has not been investigated. In this study, COMT Val158Met (rs4680) and IL-10 -592A/C (rs1800872) polymorphisms were measured in patients with chronic schizophrenia (n = 244) and healthy controls (n = 396), and their cognitive functions were assessed using the “Repeatable Battery for the Assessment of Neuropsychological Status” (RBANS). We found that IL-10 alone had no effect on cognitive function, while COMT affected language ability and interacted with the schizophrenia (case vs control) or sex in multiple RBANS indexes. Additionally, we found there was a significant interactive effect between IL-10 and COMT polymorphisms on multiple cognitive indexes of RBANS. In detail, the analysis showed that the IL-10 polymorphism had opposite effects on cognitive function in different COMT genotype carriers; meanwhile, the polymorphism of COMT only had a significant effect on cognitive function in IL-10 C carriers. And this interaction was more significant in schizophrenia than in controls. Our study discovered for the first time, there is an interactive effect between IL-10 and COMT genetic polymorphisms on cognitive function, which is valuable for further investigations and drug administrations associated with both systems.

Social Cognition Training for Enhancing Affective and Cognitive Theory of Mind in Schizophrenia: A Systematic Review and a Meta-Analysis

People with schizophrenia disorder show the presence of a deficit in social cognition (SC). Several proposals of intervention for social cognitive deficits in schizophrenia have been raised. The present study aimed to provide an update to the state-of-the-art of SC training in schizophrenia, with specific analysis on their efficacy on ToM, which is deeply involved with social dysfunction in this disorder. Furthermore, we proposed to investigate the efficacy of SC training both on ToM cognitive and affective components. We conducted a systematic review, screening 5251 articles; 26 studies met our inclusion criteria. Interventions included were very heterogeneous. To test the efficacy of SC training on ToM domain, we conducted a meta-analysis. Our results showed that SC multidimensional training programs have a positive effect on ToM domain, with a moderate effect on both cognitive and affective ToM subcomponents. Future investigations about which could be the best option for the enhancement of SC in schizophrenia are needed, contributing to expanding the state-of-the-art of SC training in this disorder.