Amy E. Pinkham

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.

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.

The Social Cognition Psychometric Evaluation Study: Results of the Expert Survey and RAND Panel

BACKGROUND In schizophrenia, social cognition is strongly linked to functional outcome and is increasingly seen as a viable treatment target. The goal of the Social Cognition Psychometric Evaluation (SCOPE) study is to identify and improve the best existing measures of social cognition so they can be suitably applied in large-scale treatment studies. Initial phases of this project sought to (1) develop consensus on critical domains of social cognition and (2) identify the best existing measures of social cognition for use in treatment studies. METHODS Experts in social cognition were invited to nominate key domains of social cognition and the best measures of those domains. Nominations for measures were reduced according to set criteria, and all available psychometric information about these measures was summarized and provided to RAND panelists. Panelists rated the quality of each measure on multiple criteria, and diverging ratings were discussed at the in-person meeting to obtain consensus. RESULTS Expert surveys identified 4 core domains of social cognition-emotion processing, social perception, theory of mind/mental state attribution, and attributional style/bias. Using RAND panel consensus ratings, the following measures were selected for further evaluation: Ambiguous Intentions Hostility Questionnaire, Bell Lysaker Emotion Recognition Task, Penn Emotion Recognition Test, Relationships Across Domains, Reading the Mind in the Eyes Test, The Awareness of Social Inferences Test, Hinting Task, and Trustworthiness Task. DISCUSSION While it was possible to establish consensus, only a limited amount of psychometric information is currently available for the candidate measures, which underscores the need for well-validated and standardized measures in this area.

Emotion perception and social skill over the course of psychosis: A comparison of individuals “at-risk” for psychosis and individuals with early and chronic schizophrenia spectrum illness

Introduction. Deficits in emotion perception and social skill have been well established in schizophrenia; however, little is known about the extent of these deficits across the course of the illness; that is, prior to illness onset and as the duration of the illness increases. Method. We compared emotion perception (i.e., the Face Emotion Identification Task [FEIT] and Face Emotion Discrimination Task [FEDT]; Kerr & Neale, 1993) and social skill (Conversation Probe role-play test) performance in four groups: individuals “at risk” for psychosis who met criteria for a prodromal state, individuals early in the course of a schizophrenia spectrum illness (SSI), individuals with a chronic SSI, and healthy control individuals. Results. At-risk individuals did not significantly differ from control participants on emotion perception measures; however, early and chronic SSI groups performed significantly worse than controls, although not different from one another. Conversely, there was evidence that deficits in social skill are present prior to illness onset. Consistent with the findings for the emotion perception tasks, early and chronic SSI groups showed comparable levels of social skill impairment. Conclusion. Social skill deficits may be a vulnerability marker for schizophrenia, and it appears that the initial psychotic episode represents a critical point for the emergence of emotion perception deficits in schizophrenia spectrum illnesses.

CNTRICS Final Task Selection: Social Cognitive and Affective Neuroscience–Based Measures

This article describes the results and recommendations of the third Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia meeting related to measuring treatment effects on social and affective processing. At the first meeting, it was recommended that measurement development focuses on the construct of emotion identification and responding. Five Tasks were nominated as candidate measures for this construct via the premeeting web-based survey. Two of the 5 tasks were recommended for immediate translation, the Penn Emotion Recognition Task and the Facial Affect Recognition and the Effects of Situational Context, which provides a measure of emotion identification and responding as well as a related, higher level construct, context-based modulation of emotional responding. This article summarizes the criteria-based, consensus building analysis of each nominated task that led to these 2 paradigms being recommended as priority tasks for development as measures of treatment effects on negative symptoms in schizophrenia.

Social Cognition Psychometric Evaluation: Results of the Initial Psychometric Study

Measurement of social cognition in treatment trials remains problematic due to poor and limited psychometric data for many tasks. As part of the Social Cognition Psychometric Evaluation (SCOPE) study, the psychometric properties of 8 tasks were assessed. One hundred and seventy-nine stable outpatients with schizophrenia and 104 healthy controls completed the battery at baseline and a 2-4-week retest period at 2 sites. Tasks included the Ambiguous Intentions Hostility Questionnaire (AIHQ), Bell Lysaker Emotion Recognition Task (BLERT), Penn Emotion Recognition Task (ER-40), Relationships Across Domains (RAD), Reading the Mind in the Eyes Task (Eyes), The Awareness of Social Inferences Test (TASIT), Hinting Task, and Trustworthiness Task. Tasks were evaluated on: (i) test-retest reliability, (ii) utility as a repeated measure, (iii) relationship to functional outcome, (iv) practicality and tolerability, (v) sensitivity to group differences, and (vi) internal consistency. The BLERT and Hinting task showed the strongest psychometric properties across all evaluation criteria and are recommended for use in clinical trials. The ER-40, Eyes Task, and TASIT showed somewhat weaker psychometric properties and require further study. The AIHQ, RAD, and Trustworthiness Task showed poorer psychometric properties that suggest caution for their use in clinical trials.

Resting quantitative cerebral blood flow in schizophrenia measured by pulsed arterial spin labeling perfusion MRI

Arterial spin labeling (ASL) perfusion MRI is a relatively novel technique that can allow for quantitative measurement of cerebral blood flow (CBF) by using magnetically labeled arterial blood water as an endogenous tracer. Available data on resting CBF in schizophrenia primarily come from invasive and expensive nuclear medicine techniques that are often limited to small samples and yield mixed results. The noninvasive nature of ASL offers promise for larger-scale studies. The utility of this approach was examined in 24 healthy controls and 30 patients with schizophrenia. Differences between groups in quantitative CBF were assessed, as were relationships between CBF and psychiatric symptoms. Group comparisons demonstrated greater CBF for controls in several regions including bilateral precuneus and middle frontal gyrus. Patients showed increased CBF in left putamen/superior corona radiata and right middle temporal gyrus. For patients, greater severity of negative symptoms was associated with reduced CBF in bilateral superior temporal gyrus, cingulate gyrus, and left middle frontal gyrus. Increased severity of positive symptoms was related to both higher CBF in cingulate gyrus and superior frontal gyrus and decreased CBF in precentral gyrus/middle frontal gyrus. These findings support the feasibility and utility of implementing ASL in schizophrenia research and expand upon previous results.

The benefit of directly comparing autism and schizophrenia for revealing mechanisms of social cognitive impairment

Autism and schizophrenia share a history of diagnostic conflation that was not definitively resolved until the publication of the DSM-III in 1980. Though now recognized as heterogeneous disorders with distinct developmental trajectories and dissociative features, much of the early nosological confusion stemmed from apparent overlap in certain areas of social dysfunction. In more recent years, separate but substantial literatures have accumulated for autism and schizophrenia demonstrating that abnormalities in social cognition directly contribute to the characteristic social deficits of both disorders. The current paper argues that direct comparison of social cognitive impairment can highlight shared and divergent mechanisms underlying pathways to social dysfunction, a process that can provide significant clinical benefit by informing the development of tailored treatment efforts. Thus, while the history of diagnostic conflation between autism and schizophrenia may have originated in similarities in social dysfunction, the goal of direct comparisons is not to conflate them once again but rather to reveal distinctions that illuminate disorder-specific mechanisms and pathways that contribute to social cognitive impairment.

An Investigation of the Relationship Between Activation of a Social Cognitive Neural Network and Social Functioning

Previous work examining the neurobiological substrates of social cognition in healthy individuals has reported modulation of a social cognitive network such that increased activation of the amygdala, fusiform gyrus, and superior temporal sulcus are evident when individuals judge a face to be untrustworthy as compared with trustworthy. We examined whether this pattern would be present in individuals with schizophrenia who are known to show reduced activation within these same neural regions when processing faces. Additionally, we sought to determine how modulation of this social cognitive network may relate to social functioning. Neural activation was measured using functional magnetic resonance imaging with blood oxygenation level dependent contrast in 3 groups of individuals--nonparanoid individuals with schizophrenia, paranoid individuals with schizophrenia, and healthy controls--while they rated faces as either trustworthy or untrustworthy. Analyses of mean percent signal change extracted from a priori regions of interest demonstrated that both controls and nonparanoid individuals with schizophrenia showed greater activation of this social cognitive network when they rated a face as untrustworthy relative to trustworthy. In contrast, paranoid individuals did not show a significant difference in levels of activation based on how they rated faces. Further, greater activation of this social cognitive network to untrustworthy faces was significantly and positively correlated with social functioning. These findings indicate that impaired modulation of neural activity while processing social stimuli may underlie deficits in social cognition and social dysfunction in schizophrenia.

Social cognition in schizophrenia.

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.