Neurocognitive and social cognitive predictors of interpersonal skill in schizophrenia

Social dysfunction is among the major criteria for receiving a diagnosis of schizophrenia, and research indicates that the impairments in social functioning experienced by individuals with schizophrenia are strongly related to deficits in interpersonal skills. In turn, these deficits in interpersonal skills have been linked to impairments in general cognitive abilities and impairments in social cognition. This study explored the relationship between neurocognition, social cognition, and interpersonal skills in 49 outpatients with schizophrenia and 44 non-clinical control participants. Results indicate that individuals with schizophrenia demonstrated impaired performance across several domains of neurocognitive and social cognitive functioning as well as interpersonal skills. In addition, among the participants with schizophrenia, social cognition significantly contributed unique variance to interpersonal skill beyond that of neurocognition. This pattern was not observed in the non-clinical control sample. These findings have implications for the treatment of the disorder and represent an important step in understanding the role of social cognition in schizophrenia.     

An Event-Related Potential Investigation of Early Visual Processing Deficits During Face Perception in Youth at Clinical High Risk for Psychosis

Impairments in early visual face perception are well documented in patients with schizophrenia. Specifically, event-related potential (ERP) research in patients with schizophrenia has demonstrated deficits in early sensory processing of stimulus properties (P1 component) and the structural encoding of faces (N170 component). However, it is not well understood if similar impairments are present in individuals at clinical high risk (CHR) for psychosis (ie, those in the putative prodromal stage of the illness). Thus, it is unknown if face perception deficits are the result of illness onset or are present in the high-risk period for the illness. The present study used the ERP technique to examine neural activation when viewing facial emotion expressions and objects in 44 CHR and 47 control adolescents and young adults (N = 91). P1 amplitude was similar across groups, indicating that early sensory processing impairments did not substantially contribute to face perception deficits in CHR youth. CHR youth exhibited reduced N170 amplitude compared to controls when viewing faces but not objects, implicating a specific deficit in the structural encoding of faces rather than a general perceptual deficit. Further, whereas controls demonstrated the expected face-selective N170 effect (ie, larger amplitude for faces than objects), CHR youth did not, which suggests that facial emotion expressions do not elicit the expected preferential perceptual processing for critical social information in individuals at CHR for psychosis. Together, these findings provide valuable information regarding the specific impairments contributing to face perception deficits in the high-risk period where treatment stands to aid in preventing illness progression.     

Cortical Kynurenine Pathway Metabolism: A Novel Target for Cognitive Enhancement in Schizophrenia

The brain concentration of kynurenic acid (KYNA), a metabolite of the kynurenine pathway of tryptophan degradation and antagonist at both the glycine coagonist site of the N-methyl-D-aspartic acid receptor (NMDAR) and the α7 nicotinic acetylcholine receptor (α7nAChR), is elevated in the prefrontal cortex (PFC) of individuals with schizophrenia. This increase may be clinically relevant because hypofunction of both the NMDAR and the α7nAChR are implicated in the pathophysiology, and especially in the cognitive deficits associated with the disease. In rat PFC, fluctuations in endogenous KYNA levels bidirectionally modulate extracellular levels of 3 neurotransmitters closely related to cognitive function (glutamate, dopamine, and acetylcholine). Moreover, behavioral studies in rats have demonstrated a causal link between increased cortical KYNA levels and neurocognitive deficits, including impairment in spatial working memory, contextual learning, sensory gating, and prepulse inhibition of the startle reflex. In recent human postmortem studies, impairments in gene expression and activity of kynurenine pathway enzymes were found in cortical areas of individuals with schizophrenia. Additional studies have revealed an interesting association between a sequence variant in the gene of one of these enzymes, kynurenine 3-monooxygenase, and neurocognitive deficits seen in patients. The emerging, remarkable confluence of data from humans and animals suggests an opportunity for developing a rational pharmacology by targeting cortical kynurenine pathway metabolism for cognition enhancement in schizophrenia and beyond.     

Social cognitive bias and neurocognitive deficit in paranoid symptoms: evidence for an interaction effect and changes during treatment

Persistent paranoid symptoms are best understood as having multiple causal mechanisms. An enhanced multidimensional understanding of paranoia may result from the convergence of two distinct measurement paradigms, experimental psychopathology and social cognitive research. This study investigated the role of neurocognitive deficits and emotion misperception bias as they relate to paranoid symptoms at two different time points in a sample of individuals with severe mental illness (primarily schizophrenia spectrum disorders [N=91]) undergoing intensive psychosocial rehabilitation. Before intensive rehabilitation (but after initial stabilization), paranoid symptoms were related to a tendency to misperceive emotion as disgust. The impact of this social cognitive bias was amplified by perseveration (as measured by the COGLAB Card Sorting Task). Perseverative errors were associated with paranoid symptoms at both time points. After 6 months of treatment, there were significant reductions in paranoid symptoms and perseverative errors but no significant changes in emotion misperception biases. This study is one of few to date to evaluate the contribution of both neurocognitive deficits and social cognitive biases to paranoid symptoms. The results demonstrate how social cognitive biases can interact with neurocognitive deficits in expression of paranoid symptoms, and how these relationships change during treatment.     

Attention deficits in the development of schizophrenia: Recent evidence from genetic high-risk and prodromal studies

Schizophrenia is a complex, heterogeneous disorder marked by a range of psychopathologic features, from positive and negative symptoms to deficits in social and occupational functioning. Impaired cognition also is a core component of schizophrenia. Understanding the role of cognitive deficits in the developmental processes leading to the full illness will clarify its causes and possible prevention. Attention, especially as measured by continuous performance tests, is a well-studied cognitive domain associated with schizophrenia. In this review, the most recent findings about attention dysfunctions measured in affected patients, their relatives (including genetically at-risk offspring and young siblings) and more recently, in young adults in the prodromal (or prepsychotic stage) of illness, are summarized and evaluated.     

Social cognition in schizophrenia, Part 1: performance across phase of illness

Social cognitive impairments are consistently reported in schizophrenia and are associated with functional outcome. We currently know very little about whether these impairments are stable over the course of illness. In the current study, 3 different aspects of social cognition were assessed (emotion processing, Theory of Mind [ToM], and social relationship perception) at 3 distinct developmental phases of illness: prodromal, first episode, and chronic. In this cross-sectional study, participants included 50 individuals with the prodromal risk syndrome for psychosis and 34 demographically comparable controls, 81 first-episode schizophrenia patients and 46 demographically comparable controls, and 53 chronic schizophrenia patients and 47 demographically comparable controls. Outcome measures included total and subtest scores on 3 specialized measures of social cognition: (1) emotion processing assessed with the Mayer-Salovey-Caruso Emotional Intelligence Test, (2) ToM assessed with The Awareness of Social Inference Test, and (3) social relationship perception assessed the Relationships Across Domains Test. Social cognitive performance was impaired across all domains of social cognition and in all clinical samples. Group differences in performance were comparable across phase of illness, with no evidence of progression or improvement. Age had no significant effect on performance for either the clinical or the comparison groups. The findings suggest that social cognition in these 3 domains fits a stable pattern that has outcome and treatment implications. An accompanying article prospectively examines the longitudinal stability of social cognition and prediction of functional outcome in the first-episode sample.     

Neural bases for impaired social cognition in schizophrenia and autism spectrum disorders

Schizophrenia and autism both feature significant impairments in social cognition and social functioning, but the specificity and mechanisms of these deficits remain unknown. Recent research suggests that social cognitive deficits in both disorders may arise from dysfunctions in the neural systems that underlie social cognition. We explored the neural activation of discrete brain regions implicated in social cognitive and face processing in schizophrenia subgroups and autism spectrum disorders during complex social judgments of faces. Twelve individuals with autism spectrum disorders (ASD), 12 paranoid individuals with schizophrenia (P-SCZ), 12 non-paranoid individuals with schizophrenia (NP-SCZ), and 12 non-clinical healthy controls participated in this cross sectional study. Neural activation, as indexed by blood oxygenation level dependent (BOLD) contrast, was measured in a priori regions of interest while individuals rated faces for trustworthiness. All groups showed significant activation of a social cognitive network including the amygdala, fusiform face area (FFA), superior temporal sulcus (STS), and ventrolateral prefrontal cortex (VLPFC) while completing a task of complex social cognition (i.e. trustworthiness judgments). ASD and P-SCZ individuals showed significantly reduced neural activation in the right amygdala, FFA, and left VLPFC as compared to controls and in the left VLPFC as compared to NP-SCZ individuals during this task. These findings lend support to models hypothesizing well-defined neural substrates of social cognition and suggest a specific neural mechanism that may underlie social cognitive impairments in both autism and paranoid schizophrenia.     

The Effect of Context Processing on Different Aspects of Social Cognition in Schizophrenia

Background: It is well known that individuals with schizophrenia have impaired social cognition. The construct of social cognition involves several components, including perception, interpretation, and the ability to integrate context (Adolphs R. The neurobiology of social cognition. Curr Opin Neurobiol. 2001;11:231–239; Brothers L. The social brain: a project for integrating primate behavior and neurophysiology in a new domain. Concepts Neurosci. 1990;1:27–61). Importantly, a number of studies have suggested that deficits in context processing underlie cognitive dysfunction in schizophrenia (Penn DL, Corrigan PW, Bentall RP, Racenstein JM, Newman L. Social cognition in schizophrenia. Psychol Bull. 1997;121(1):114–132; Green MF, Nuechterlein KH. Should schizophrenia be treated as a neurocognitive disorder? Schizophr Bull. 1999;25:309–319). Thus, the purpose of the current study was to investigate the relationship between context processing and different aspects of social cognition in schizophrenia. Method: Individuals with schizophrenia (n = 41) and the healthy controls (n = 32) participated in this study. The participants completed 2 sections of The Awareness of Social Inference Test: (1) social inference minimal (SI-M) and (2) social inference enriched (SI-E). They also completed face and voice emotion discrimination tasks. In addition, we used the AX-Continuous Performance Test (AX-CPT) to measure context processing and the n-back task to measure working memory more generally. Results: AX-CPT performance in schizophrenia was positively correlated with both SI-M and SI-E performance but not with either the face or the voice discrimination. Furthermore, the correlation between AX-CPT performance and SI-M/SI-E performance was significantly stronger in individuals with schizophrenia than in controls. Conclusion: These results suggest that impairments in context processing are related to inferential components of social cognition in schizophrenia but not to the ability to recognition facial or vocal emotion. As such, deficits in context processing may contribute to deficits in both “hot” and “cold” aspects of cognition in schizophrenia.     

Cognition sociale dans la schizophrénie et les troubles du spectre de l’autisme : points de convergences et différences fonctionnelles

Introduction

Schizophrenia and autistic spectrum disorder (ASD) are two neurodevelopmental disorders that have different symptom presentations, ages of onset and developmental courses. Both schizophrenia and ASD are characterized by marked deficit in communication, social interactions, affects and emotions. Social cognitive impairments in ASD and schizophrenia were demonstrated separately in both disorders. It was reported that these impairments have direct relation with social deficits of both disorders. The apparent similarity between social cognition impairments in ASD and schizophrenia highlights questions about the existence of common or different neurocognitive mechanisms related to social dysfunctions. In order to examine these questions, the present article provides a comprehensive review of all published studies which directly compare individuals with ASD and schizophrenia on the same cognitive tasks of social cognition.

Facial recognition deficits and cognition in schizophrenia

Previous investigations have found impaired recognition of facial affect and cognition in schizophrenia. We compared patients with schizophrenia and healthy control volunteers on computerized tasks of emotion recognition, to determine whether emotion processing deficits were correlated with neurocognitive performance. A Computerized Neuropsychological Test Battery (CNP) was administered to 40 patients (25 male, 15 female, mean age+/-S.D. 30.4+/-8.1) with schizophrenia (DSM-IV, 15 first episode and 25 chronically ill patients) treated with atypical neuroleptics and 43 healthy volunteers. A German version of the PENN Facial Discrimination, Differentiation and Memory Test, including happy, sad and neutral faces was used. Additionally, all patients were tested with a standard neuropsychological battery and rated for positive and negative symptoms. Patients with schizophrenia performed worse than control subjects on all emotion recognition tasks (p<0.01). We found higher error rates for discrimination of emotion in happy (p<0.02) and happy female faces (p<0.01), for differentiation of sad versus happy faces (p<0.001) and for facial memory (p<0.04). Poorer performance in emotion discrimination and facial memory correlated with severity of negative symptoms, abstraction-flexibility (p<0.001), verbal memory (p<0.01) and language processing (p<0.001). The study did not reveal a specific deficit for emotion recognition in schizophrenia. These findings lend support to the notion that difficulties in emotion recognition are associated in schizophrenia with key cognitive deficits.     

Social cognition and quality of life in schizophrenia

Schizophrenia is associated with poor quality of life (QOL). Whereas the effects of neurocognitive deficits and psychopathology on QOL of schizophrenia patients have recently been elucidated, little is known about social cognitive deficits in this regard. This study investigated the influence of social cognition on QOL in schizophrenia. A sample of 1032 patients, 1011 of their siblings, and 552 healthy controls was recruited from the Dutch Genetic Risk and Outcome in Psychosis (GROUP) study. Participants completed a battery of cognitive tests, including social cognitive tests on theory of mind and emotion perception. To assess QOL the World Health Organization QOL Assessment-BREF (WHOQOL-BREF) was used. Schizophrenia symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Social cognitive performance was significantly worse in patients compared to siblings and healthy controls. Patients had the poorest QOL, while QOL in healthy controls was better than in siblings. Theory of mind but not emotion perception or neurocognition was associated with QOL in patients, whereas neurocognition was the only significant predictor of QOL in siblings and healthy controls. There was a significant interaction between theory of mind and symptom severity with respect to QOL. Our study indicates that social cognition is associated with QOL in schizophrenia. Theory of mind rather than emotion perception is associated with QOL, and this association is moderated by schizophrenia symptoms. In particular, patients with relatively unimpaired theory of mind and more severe schizophrenia symptoms have poor QOL and could therefore benefit from therapeutic intervention.     

Cognitive functioning in schizophrenia

This paper reviews the literature on cognition in schizophrenia from the past 2 years. Themes of key interest such as the course of impairments throughout the lifespan in schizophrenia, the relationship between cognitive functioning and the clinical symptoms of schizophrenia, neurocognitive subtyping of schizophrenia, treatment of cognitive deficits, social cognition in schizophrenia, and the association between cognition and functional outcome are reviewed. Additionally, future directions for these and other topic areas are proposed as the field continues to progress.     

Facial emotion perception differs in young persons at genetic and clinical high-risk for psychosis

A large body of literature has documented facial emotion perception impairments in schizophrenia. More recently, emotion perception has been investigated in persons at genetic and clinical high-risk for psychosis. This study compared emotion perception abilities in groups of young persons with schizophrenia, clinical high-risk, genetic risk and healthy controls. Groups, ages 13–25, included 24 persons at clinical high-risk, 52 first-degree relatives at genetic risk, 91 persons with schizophrenia and 90 low risk persons who completed computerized testing of emotion recognition and differentiation. Groups differed by overall emotion recognition abilities and recognition of happy, sad, anger and fear expressions. Pairwise comparisons revealed comparable impairments in recognition of happy, angry, and fearful expressions for persons at clinical high-risk and schizophrenia, while genetic risk participants were less impaired, showing reduced recognition of fearful expressions. Groups also differed for differentiation of happy and sad expressions, but differences were mainly between schizophrenia and control groups. Emotion perception impairments are observable in young persons at-risk for psychosis. Preliminary results with clinical high-risk participants, when considered along findings in genetic risk relatives, suggest social cognition abilities to reflect pathophysiological processes involved in risk of schizophrenia.     

RGS4 Polymorphisms Associated With Variability of Cognitive Performance in a Family-Based Schizophrenia Sample

Polymorphisms of the gene encoding the regulator of G protein signaling, subtype 4 (RGS4), may be associated with schizophrenia. Among first-episode schizophrenia patients, they are also associated with dorsolateral prefrontal cortex (DLPFC) volume. The DLPFC is a key region that regulates heritable cognitive functions implicated in schizophrenia pathogenesis. To further understand the relationship of RGS4 variants to schizophrenia, we examined their associations with cognitive functions among schizophrenia patients and their relatives. We analyzed 31 multiplex, multigenerational Caucasian families with schizophrenia recruited on the basis of 2 affected first-degree relatives. All participants underwent a computerized neurocognitive battery that evaluates accuracy and speed (response time) of performance on abstraction/mental flexibility; attention; verbal, spatial, and face memory; and spatial ability. “Tag” single-nucleotide polymorphisms (SNPs) representing common polymorphisms were genotyped. Measured genotype analyses accounting for family relationships were performed using Sequential Oligogenic Linkage Analysis Routines. SNPs rs10917670 (“SNP1”) and rs951439 (“SNP7”) were associated with face memory speed (P = .0003) at a significance level that survived Bonferroni correction (P = .039). The same SNPs have earlier been reported to be associated with schizophrenia. There also were uncorrected associations with rs10917670 (“SNP1”) and rs951439 (“SNP7”) on face memory efficiency (P = .03) and verbal memory efficiency (P = 0.02), rs28757217 on abstraction/mental flexibility speed (P = .02) and verbal memory efficiency (P = .03), SNP18 (rs2661319) on spatial memory accuracy (P = 0.02) and face memory speed (P = .03). RGS4 polymorphisms are associated with variations in cognitive functions and contribute a small but statistically significant proportion of variance in a family-based sample.     

Modulation of affective face processing deficits in Schizophrenia by congruent emotional sounds

Schizophrenia is a psychiatric disorder resulting in prominent impairments in social functioning. Thus, clinical research has focused on underlying deficits of emotion processing and their linkage to specific symptoms and neurobiological dysfunctions. Although there is substantial research investigating impairments in unimodal affect recognition, studies in schizophrenia exploring crossmodal emotion processing are rare. Therefore, event-related potentials were measured in 15 patients with schizophrenia and 15 healthy controls while rating the expression of happy, fearful and neutral faces and concurrently being distracted by emotional or neutral sounds. Compared with controls, patients with schizophrenia revealed significantly decreased P1 and increased P2 amplitudes in response to all faces, independent of emotion or concurrent sound. Analyzing these effects with regard to audiovisual (in)congruence revealed that P1 amplitudes in patients were only reduced in response to emotionally incongruent stimulus pairs, whereas similar amplitudes between groups could be observed for congruent conditions. Correlation analyses revealed a significant negative correlation between general symptom severity (Brief Psychiatric Rating Scale-V4) and P1 amplitudes in response to congruent audiovisual stimulus pairs. These results indicate that early visual processing deficits in schizophrenia are apparent during emotion processing but, depending on symptom severity, these deficits can be restored by presenting concurrent emotionally congruent sounds.     

A multidimensional assessment of social cognition in psychometrically defined schizotypy

Individuals with schizophrenia exhibit impairments in multiple social cognitive domains. There is evidence that these impairments may be trait-related vulnerability markers for schizophrenia. However, the literature focusing on individuals vulnerable to developing schizophrenia-spectrum disorders, referred to as schizotypy, has produced inconsistent findings. This study's primary aim was to provide a more comprehensive understanding of social cognitive functioning within schizotypy than previous studies by employing a broad array of measures to assess multiple social cognitive domains, and examine how these domains relate to specific schizotypy traits (i.e., positive, negative, and disorganized) and Quality of Life (QOL). Facial emotion recognition, Theory of Mind (ToM), and aspects of emotional intelligence related to regulating one's own emotions (emotion management) and other's emotions (social management) were measured. Individuals with psychometrically defined schizotypy (n=36) and controls (n=26) were examined. The schizotypy group performed significantly worse than controls on facial emotion recognition, ToM, and emotion management, but not social management. Generally speaking, poorer social cognition performance was not a function of specific schizotypy traits. However, negative traits were associated with poorer facial emotion recognition, and disorganized traits were associated with better social management. Facial emotion recognition was associated with QOL in the schizotypy group.     

Deficits in Domains of Social Cognition in Schizophrenia: A Meta-Analysis of the Empirical Evidence

Objective: Social cognition is strongly associated with functional outcome in schizophrenia, making it an important target for treatment. Our goal was to examine the average magnitude of differences between schizophrenia patients (SCs) and normal comparison (NCs) patients across multiple domains of social cognition recognized by the recent NIMH consensus statement: theory of mind (ToM), social perception, social knowledge, attributional bias, emotion perception, and emotion processing. Method: We conducted a meta-analysis of peer-reviewed studies of social cognition in schizophrenia, published between 1980 and November, 2011. Results: 112 studies reporting results from 3908 SCs and 3570 NCs met our inclusion criteria. SCs performed worse than NCs across all domains, with large effects for social perception (g = 1.04), ToM (g = 0.96), emotion perception (g = 0.89), and emotion processing (g = 0.88). Regression analyses showed that statistically significant heterogeneity in effects within domains was not explained by age, education, or gender. Greater deficits in social and emotion perception were associated with inpatient status, and greater deficits in emotion processing were associated with longer illness duration. Conclusions: Despite the limitations of existing studies, including lack of standardization or psychometric validation of measures, the evidence for deficits across multiple social cognitive domains in schizophrenia is clear. Future research should examine the role of neurobiological and psychosocial factors in models linking various aspects of deficit in schizophrenia, including social cognition, in order to identify targets for intervention.     

Emotion recognition, 'theory of mind,' and social behavior in schizophrenia

Several studies have demonstrated that patients with schizophrenia are impaired in recognizing emotions from facial expressions and in appreciating other people's mental states--the latter commonly referred to as 'theory of mind.' The question as to how social cognitive skills relate to patients' actual social behavior is, however, largely unanswered. This study examined emotion recognition, 'theory of mind,' and social behavior in schizophrenia. Emotion recognition, 'theory of mind,' executive functioning, 'crystallized' verbal intelligence, psychopathology, and social behavior were assessed in patients with schizophrenia compared with a healthy control group. Patients were significantly impaired on all tasks involving executive functioning, emotion recognition, and 'theory of mind.' Impaired executive functioning did, however, only partially account for the deficits in social perception and social cognition. Social perception and cognition in schizophrenia predicted the odds of being a patient significantly better than nonsocial cognition. Severe social behavioral abnormalities were linked to the duration of the illness, and even more so to 'theory of mind' deficits. Considering impaired social perception and social cognition significantly contributes to the understanding of social behavioral problems in schizophrenia.     

An integrated psychobiological predictive model of emergent psychopathology among young relatives at risk for schizophrenia

Objective

Studies of young relatives at elevated risk for schizophrenia have pointed to the importance of a variety of neurobiological, cognitive, and clinical risk factors for the disorder; yet few have employed integrated models to estimate the joint contribution of these factors to heightened schizophrenic risk. We tested the predictive power of an integrated psychobiological model of schizophrenia risk to subsequent psychopathology development among young relatives at risk for the disorder.

Methods

Young first (n = 66) and second (n = 20) degree relatives of schizophrenia probands were followed for an average of 3 (SD = 1.13) years to examine their trajectories toward psychopathology development. Neurobiologic, cognitive, and clinical measures were employed in an integrated structural equation model to estimate their contribution to the prospective emergence of psychopathology.

Results

Results indicated that neurobiological, neurocognitive, and psychosis proneness factors at baseline were all uniquely predictive of subsequent psychopathology development, and that an integrated model of psychopathology development that took into account these factors provided an excellent fit to the observed data. Subsequent classification analyses of model accuracy using likelihood ratios adjusting for the base-rate of psychopathology development in this sample revealed that individuals identified by this model had a 71% chance of developing psychopathology in the future.

Conclusions

An integrated model of biobehavioral risk factors may provide a powerful method for predicting psychopathology and schizophrenia risk in at-risk samples. If validated, this model may be useful for early detection and intervention programs. Future research will need to focus particularly on predicting schizophrenia development and refining models to further enhance sensitivity.     

Deficits in social cognition: a marker for psychiatric disorders?

Research on social cognition focuses on several human abilities with a huge diversity in the approaches to tap the different functions. Empathy, for instance, is a rather elaborated human ability, and several recent studies point to significant impairments in patients suffering from psychiatric disorders, such as schizophrenia or autism. Neuroimaging data from these patients commonly indicate neural dysfunctions accompanying the behavioral deficits. Studying the neural correlates of social cognition is of particular importance, because deficits in these domains may explain the major dysfunctions in psychiatric disorders that prevent effective (re) integration into work and social life. It has also become clearer that social cognition deficits, similar to emotion dysfunctions, may represent trait markers and endophenotypes of the diseases. However, there are several challenges for future studies on social cognitive dysfunctions: on the one hand, the complexity of the constructs and thus the variety of definitions which make it hard to develop adequate tasks. On the other hand, results are needed that particularly address the disorder specificity of these impairments, as well as their potential as endophenotypes via analyzing people at high-risk and their relatives.