BACKGROUND: The relationship between cognition and age at onset of schizophrenia is largely unknown. AIMS: To compare cognitive deficits in individuals with youth-onset and late-onset schizophrenia with those in adults with first-episode schizophrenia. METHOD: Twenty-nine databases (including EMBASE, MEDLINE and PsycINFO) were searched from 1980 to 2008. Selected publications had to include healthy controls and analyse separately individuals diagnosed with schizophrenia or a related disorder and individuals with first-episode, youth-onset or late-onset schizophrenia. Descriptive and cognitive data were extracted and the latter aggregated into 22 cognitive measures. Cohen's effect size raw and weighted means of cognitive deficits were generated and compared in the three groups. RESULTS: Individuals with youth-onset and first-episode schizophrenia demonstrate large deficits (mean effect size >or=0.8) on almost all cognitive measures. Individuals with youth-onset schizophrenia demonstrate larger deficits than those with first-episode schizophrenia on arithmetic, executive function, IQ, psychomotor speed of processing and verbal memory. In contrast, those with late-onset schizophrenia demonstrate minimal deficits on arithmetic, digit symbol coding and vocabulary, but larger ones on attention, fluency, global cognition, IQ and visuospatial construction. CONCLUSIONS: Individuals with youth-onset schizophrenia have severe cognitive deficits, whereas those with late-onset schizophrenia have some relatively preserved cognitive functions. This finding supports the view that severity of the disease process is associated with different ages at onset. In addition, the cognitive pattern of people with late-onset schizophrenia suggests that their deficits are specific rather than solely as a result of ageing and related factors.
Cognitive impairment in schizophrenia involves a broad array of nonsocial and social cognitive domains. It is a core feature of the illness, and one with substantial implications for treatment and prognosis. Our understanding of the causes, consequences and interventions for cognitive impairment in schizophrenia has grown substantially in recent years. Here we review a range of topics, including: a) the types of nonsocial cognitive, social cognitive, and perceptual deficits in schizophrenia; b) how deficits in schizophrenia are similar or different from those in other disorders; c) cognitive impairments in the prodromal period and over the lifespan in schizophrenia; d) neuroimaging of the neural substrates of nonsocial and social cognition, and e) relationships of nonsocial and social cognition to functional outcome. The paper also reviews the considerable efforts that have been directed to improve cognitive impairments in schizophrenia through novel psychopharmacology, cognitive remediation, social cognitive training, and alternative approaches. In the final section, we consider areas that are emerging and have the potential to provide future insights, including the interface of motivation and cognition, the influence of childhood adversity, metacognition, the role of neuroinflammation, computational modelling, the application of remote digital technology, and novel methods to evaluate brain network organization. The study of cognitive impairment has provided a way to approach, examine and comprehend a wide range of features of schizophrenia, and it may ultimately affect how we define and diagnose this complex disorder.
OBJECTIVE: The study of social cognition in schizophrenia has received growing attention in recent years. At the same time, a large body of work has explored the neural basis of social cognition in both nonclinical and clinical groups, other than those with schizophrenia. The gap between these two literatures is considerable and may slow progress in creating a comprehensive social cognitive model of schizophrenia. This article attempts to bridge this gap by discussing how the neural basis of social cognition may inform future clinical research in schizophrenia. METHOD: PsycINFO and MEDLINE were systematically searched for articles pertaining to the neural basis of social cognition and social cognition in schizophrenia. Relevant studies were obtained and synthesized into a comprehensive review and integrative formulation. RESULTS: Striking parallels between these two areas of research were found. CONCLUSIONS: These parallels might help to better elucidate the underlying mechanisms for social cognitive and social behavioral impairments in schizophrenia as well as provide potential targets for treatment and drug development.
Cognitive impairments are currently regarded as important determinants of functional domains and are promising treatment goals in schizophrenia. Nevertheless, the exact nature of the interdependent relationship between neurocognition and social cognition as well as the relative contribution of each of these factors to adequate functioning remains unclear. The purpose of this article is to systematically review the findings and methodology of studies that have investigated social cognition as a mediator variable between neurocognitive performance and functional outcome in schizophrenia. Moreover, we carried out a study to evaluate this mediation hypothesis by the means of structural equation modeling in a large sample of 148 schizophrenia patients. The review comprised 15 studies. All but one study provided evidence for the mediating role of social cognition both in cross-sectional and in longitudinal designs. Other variables like motivation and social competence additionally mediated the relationship between social cognition and functional outcome. The mean effect size of the indirect effect was 0.20. However, social cognitive domains were differentially effective mediators. On average, 25% of the variance in functional outcome could be explained in the mediation model. The results of our own statistical analysis are in line with these conclusions: Social cognition mediated a significant indirect relationship between neurocognition and functional outcome. These results suggest that research should focus on differential mediation pathways. Future studies should also consider the interaction with other prognostic factors, additional mediators, and moderators in order to increase the predictive power and to target those factors relevant for optimizing therapy effects.
The topic of social cognition has attracted considerable interest in schizophrenia over the last several years. This construct generally refers to the detection, processing, and utilization of social information and, within the field of schizophrenia, includes several skills such as recognizing emotion, understanding the thoughts and intentions of others, and interpreting social cues. Individuals with schizophrenia show significant impairments in social cognition, and these impairments are strongly related to functional outcome. Treating social cognition yields significant improvements in real-world outcomes, including social functioning and social skill. Importantly, social cognitive abilities are linked to specific neural circuits that have been shown to be abnormal in individuals with schizophrenia. Investigations of these neural networks in patients have also demonstrated that brain activation is significantly correlated with social functioning, which suggests that abnormal activation in social cognitive networks may serve as a mechanism for social dysfunction in schizophrenia. Among the many challenges in this area is the issue of measurement. There is disagreement about which tasks best measure social cognition and many existing measures show poor psychometric properties. A recent project, called the Social Cognition Psychometric Evaluation (SCOPE) study, aims to address these problems by providing the field with a well-validated battery of social cognitive tasks that can be used in treatment outcome trials. Research is honing in on the potential mechanisms of social cognitive impairment in patients, and with improved measurement, there is promise for optimizing behavioral and pharmacologic interventions and remediation strategies.
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.
The purpose of this column is to provide an overview of social cognition in schizophrenia. The column begins with a short introduction to social cognition. Then, we describe the application of social cognition to the study of schizophrenia, with an emphasis on key domains (i.e., emotion perception, Theory of Mind, and attributional style). We conclude the column by discussing the relationship of social cognition to neurocognition, negative symptoms, and functioning, with an eye toward strategies for improving social cognition in schizophrenia.
This article summarizes the discussion from a breakout group at the National Institute of Mental Health-Measurement and Treatment Research to Improve Cognition in Schizophrenia New Approaches Conference on social cognition in schizophrenia. During this discussion, the reasons for the recent growth of research on social cognition in schizophrenia were examined. The discussion group established consensus on several points, including the importance of viewing social cognition from interdisciplinary perspectives (including outcomes research, social psychology, cognitive psychology, cognitive neuroscience, and animal models) and the need for clearer definition of terms. There was also general agreement that social cognition is a valuable construct for understanding the nature and disability of schizophrenia. One of the objectives of this group was to generate recommendations for subsequent human and animal studies, and these research agendas are summarized in this report.
This study examined the criterion and construct validity of a brief computerized cognitive test battery (CogState Schizophrenia Battery) compared to a conventional cognitive test battery recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus. The CogState and MATRICS batteries yielded comparable effect sizes in comparing patients with schizophrenia to healthy controls (Cohen's ds = -1.50 for both batteries). Moderate to large correlations were observed between CogState and MATRICS measures of processing speed, attention/vigilance, working memory, verbal and visual learning, reasoning/problem solving, and social cognition (rs = .56-.79). CogState and MATRICS composite scores also correlated strongly with scores on the University of California at San Diego (UCSD) Performance-Based Skills Assessment (UPSA; rs = .76 and .79, respectively) in patients with schizophrenia. Results of this study suggest that the CogState Schizophrenia Battery provides valid measurement of the cognitive domains nominated by the MATRICS consensus group as being important to consider in the context of pharmacological treatments for cognitive impairment in schizophrenia.
Social cognition has become a high priority area for the study of schizophrenia. However, despite developments in this area, progress remains limited by inconsistent terminology and differences in the way social cognition is measured. To address these obstacles, a consensus-building meeting on social cognition in schizophrenia was held at the National Institute of Mental Health in March 2006. Agreement was reached on several points, including definitions of terms, the significance of social cognition for schizophrenia research, and suggestions for future research directions. The importance of translational interdisciplinary research teams was emphasized. The current article presents a summary of these discussions.
BACKGROUND: Cognitive and functional impairments occur in patients diagnosed with bipolar disorder (BPD), although they are usually less severe and far less studied than in schizophrenia. There may be value in applying approaches developed in schizophrenia research to study cognitive functioning among BPD patients in areas including performance-based disability assessment, cognitive remediation treatments, enhancement of the accuracy of real-world functioning, and studying cognition and disability in relatives. METHODS: We reviewed current research on cognitive and functional disability in BPD, noted areas of similarity and discrepancy to research on schizophrenia, and highlighted methods and approaches used to study schizophrenia that can be applied to study unmet needs of BPD patients. RESULTS: Research in schizophrenia increasingly separates potential functional capacity from real-world outcome status, and has assessed contributions of cognitive impairment and other illness factors to functional outcomes. For schizophrenia, various behavioral and pharmacological treatments aimed at cognitive enhancement have been attempted, with moderate success, compared to rare studies of treatment effects on cognitive impairment in BPD. Very little research has been performed in the occurrence of cognitive impairments in first-degree relatives of people with BPD, despite evidence that cognitive impairments may be stable traits across symptomatic status in people with BPD. CONCLUSIONS: Research and treatment approaches developed for schizophrenia can productively be applied to the study and treatment of patients diagnosed with BPD, notably including studies of the characteristics of and treatments for functional impairment related to cognitive deficits.
Deficits in a wide array of functional outcome areas (eg, social functioning, social skills, independent living skills, etc) are marked in schizophrenia. Consequently, much recent research has attempted to identify factors that may contribute to functional outcome; social cognition is one such domain. The purpose of this article is to review research examining the relationship between social cognition and functional outcome. Comprehensive searches of PsycINFO and MEDLINE/PUBMED were conducted to identify relevant published manuscripts to include in the current review. It is concluded that the relationship between social cognition and functional outcome depends on the specific domains of each construct examined; however, it can generally be concluded that there are clear and consistent relationships between aspects of functional outcome and social cognition. These findings are discussed in light of treatment implications for schizophrenia.
BACKGROUND: Deficits in social cognition and neurocognition are believed to underlie schizophrenia disability. Attempts at rehabilitation have had circumscribed effects on cognition, without concurrent improvement in broad aspects of behavior and adjustment. OBJECTIVE: To determine the differential effects of cognitive enhancement therapy (a recovery-phase intervention) on cognition and behavior compared with state-of-the-art enriched supportive therapy. DESIGN: A 2-year, randomized controlled trial with neuropsychological and behavioral assessments completed at baseline and at 12 and 24 months. SETTING: An outpatient research clinic housed in a medical center's comprehensive care service for patients with severe mental illness. PATIENTS: A total of 121 symptomatically stable, non-substance-abusing but cognitively disabled and chronically ill patients with schizophrenia or schizoaffective disorder. INTERVENTIONS: Cognitive enhancement therapy is a multidimensional, developmental approach that integrates computer-assisted training in neurocognition with social cognitive group exercises. Enriched supportive therapy fosters illness management through applied coping strategies and education. MAIN OUTCOME MEASURES: Six highly reliable summary measures--Processing Speed, Neurocognition, Cognitive Style, Social Cognition, Social Adjustment and Symptoms--were tested using analysis of covariance and linear trend analysis. RESULTS: At 12 months, robust cognitive enhancement therapy effects were observed on the Neurocognition and Processing Speed composites (P<.003), with marginal effects observed on the behavioral composites. By 24 months, differential cognitive enhancement therapy effects were again observed for the 2 neuropsychological composites and for Cognitive Style (P=.001), Social Cognition (P=.001), and Social Adjustment (P=.01). As expected, no differences were observed on the residual Symptoms composite. Effects were unrelated to the type of antipsychotic medication received. Enriched supportive therapy also demonstrated statistically significant within-group effect sizes, suggesting that supportive psychotherapy can also have positive, although more modest, effects on cognitive deficits. CONCLUSION: Many cognitive deficits and related behaviors of patients with stable schizophrenia are improved when sufficient exposure to relevant rehabilitation is provided.
Social cognition has become a topic of widespread interest in experimental and treatment research in schizophrenia over the past 15 years. This explosion of interest largely reflects the robust evidence that social cognition is among the strongest known correlates of poor community functioning throughout the course of schizophrenia. While progress has been impressive, we consider several fundamental questions about the scope, structure, and optimal measurement of social cognition that remain unanswered and point to the need for continued method development. We also consider more recently emerging questions about individual differences, ecological and cross-cultural validity, and intervention approaches, as well as broader technological changes that impact how we understand and use social cognition at a societal level. Continued efforts to creatively grapple with the complexities and challenges the field now faces hold great promise for helping us understand and more effectively treat a major source of functional disability in schizophrenia.
Cognitive tasks and concepts are used increasingly in schizophrenia science and treatment. Recent meta-analyses show that across a spectrum of research domains only cognitive measures distinguish a majority of schizophrenia patients from healthy people. Average effect sizes derived from common clinical tests of attention, memory, language, and reasoning are twice as large as those obtained in structural magnetic resonance imaging and positron emission tomography studies. Chronic stress, genes, brain disturbances, task structure, gender, and sociocultural background may all enhance the sensitivity of cognitive performance to schizophrenia. At the same time, disease heterogeneity and the presence of endophenotypes and subtypes within the patient population may place upper limits on the strength of any specific cognitive finding. Schizophrenia is a complex biobehavioral disorder that manifests itself primarily in cognition.
Schizophrenia and autism spectra disorders are currently conceptualized as distinct clinical categories. However, the relationship between these two nosological entities has been revisited in recent years due to the evidence that they share some important clinical and neurobiological features, putting into question the nature and the extent of their commonalities and differences. In this respect, some core symptoms that are present in both disorders, such as social cognitive deficits, could be a primary target of investigation. This review briefly summarizes the commonalities and overlapping features between schizophrenia and autism spectra disorders in social cognitive functions, considering this construct in a Research Domain Criteria perspective. The clinical manifestation of deficits in social cognition are similar in schizophrenia spectrum disorders and autism spectrum disorders, and brain areas that appear to be altered in relation to these impairments are largely shared; however, the results of various studies suggest that, in some cases, the qualitative nature of these alterations may be different in the two spectra. Moreover, relevant differences could be present at the level of brain networks and connections. More research is required in this field, regarding molecular and genetic aspects of both spectra, to better define the neurobiological mechanisms involved in social cognition deficits, with the objective of developing specific and targeted treatments.
This preliminary study was performed to test the reliability and validity of the Brief Assessment of Cognition in Schizophrenia (BACS) as an assessment tool in a Japanese-language version (BACS-J). The subjects for the present study were 30 outpatients with chronic schizophrenia. Each subject gave written informed consent to participate in the research. Cronbach's alpha for the BACS-J was 0.77. The BACS-J composite score was significantly correlated with all primary measures of BACS-J (verbal memory, working memory, motor speed, verbal fluency, attention, and executive function). All BACS-J primary measures and the composite score were significantly correlated between two assessments. The mean score of the Digit Sequencing Task and composite score on the second assessment were significantly larger than those on the first assessment. All BACS-J primary measures except the Symbol Coding Task were significantly correlated with relevant standard neurocognitive tests. Also, the BACS-J composite score was significantly correlated with all standard neurocognitive tests except the Continuous Performance Test. A principal components analysis with varimax rotation resulted in a three-factor solution (executive function and memory; motor speed and general cognitive functions; and working memory). This preliminary study indicates that the BACS-J is a reliable and practical scale to evaluate cognitive function.
CONTEXT: The alpha7 nicotinic acetylcholine receptor gene, CHRNA7, is associated with genetic transmission of schizophrenia and related cognitive and neurophysiological sensory gating deficits. Cognitive dysfunction is responsible for significant psychosocial disability in schizophrenia. Nicotine, a low-potency agonist at the alpha7 receptor, has some positive effects on neurophysiological and neurocognitive deficits associated with schizophrenia, which suggests that more effective receptor activation might meaningfully enhance cognition in schizophrenia. OBJECTIVES: To determine if 3-[(2,4-dimethoxy)benzylidene]anabaseine (DMXB-A), a natural alkaloid derivative and a partial alpha7 nicotinic cholinergic agonist, significantly improves neurocognition, and to assess, by effects on P50 auditory evoked potential inhibition, whether its neurobiological actions are consistent with activation of alpha7 nicotinic receptors. DESIGN: Randomized, double-blind crossover trial of 2 drug doses and 1 placebo. SETTING: General clinical research center. PATIENTS: Twelve persons with schizophrenia who did not smoke and were concurrently treated with antipsychotic drugs. One person was withdrawn because of a transient decrease in white blood cell count. INTERVENTION: Administration of DMXB-A. MAIN OUTCOME MEASURES: Total scale score of the Repeatable Battery for the Assessment of Neuropsychological Status and P50 inhibitory gating. RESULTS: Significant neurocognitive improvement was found on the Repeatable Battery for the Assessment of Neuropsychological Status total scale score, particularly for the lower DMXB-A dose compared with placebo. Effects were greater than those of nicotine in a similar study. Significant improvement in P50 inhibition also occurred. Patients generally tolerated the drug well. CONCLUSIONS: An alpha7 nicotinic agonist appears to have positive effects on neurocognition in persons with schizophrenia. Longer trials are needed to determine the clinical utility of this novel treatment strategy.
The pharmacological modulation of glutamatergic neurotransmission to improve cognitive function has been a focus of intensive research, particularly in relation to the cognitive deficits seen in schizophrenia. Despite this effort, there has been little success in the clinical use of glutamatergic compounds as procognitive drugs. Here, we review a selection of the drugs used to modulate glutamatergic signalling and how they impact on cognitive function in rodents and humans. We highlight how glutamatergic dysfunction, and NMDA receptor hypofunction in particular, is a key mechanism contributing to the cognitive deficits observed in schizophrenia and outline some of the glutamatergic targets that have been tested as putative procognitive targets for this disorder. Using translational research in this area as a leading exemplar, namely, models of NMDA receptor hypofunction, we discuss how the study of functional brain network connectivity can provide new insight into how the glutamatergic system impacts on cognitive function. Future studies characterizing functional brain network connectivity will increase our understanding of how glutamatergic compounds regulate cognition and could contribute to the future success of glutamatergic drug validation. Linked Articles This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc.
Dopamine is an inhibitory neurotransmitter involved in the pathology of schizophrenia. The revised dopamine hypothesis states that dopamine abnormalities in the mesolimbic and prefrontal brain regions exist in schizophrenia. However, recent research has indicated that glutamate, GABA, acetylcholine, and serotonin alterations are also involved in the pathology of schizophrenia. This review provides an in-depth analysis of dopamine in animal models of schizophrenia and also focuses on dopamine and cognition. Furthermore, this review provides not only an overview of dopamine receptors and the antipsychotic effects of treatments targeting them but also an outline of dopamine and its interaction with other neurochemical models of schizophrenia. The roles of dopamine in the evolution of the human brain and human mental abilities, which are affected in schizophrenia patients, are also discussed.