Loneliness is associated with mentalizing and emotion recognition abilities in schizophrenia, but only in a cluster of patients with social cognitive deficits.

OBJECTIVE: Loneliness is a concern for patients with schizophrenia. However, the correlates of loneliness in patients with schizophrenia are unclear; thus, the aim of the study is to investigate neuro- and social cognitive mechanisms associated with loneliness in individuals with schizophrenia. METHOD: Data from clinical, neurocognitive, and social cognitive assessments were pooled from two cross-national samples (Poland/USA) to examine potential predictors of loneliness in 147 patients with schizophrenia and 103 healthy controls overall. Furthermore, the relationship between social cognition and loneliness was explored in clusters of patients with schizophrenia differing in social cognitive capacity. RESULTS: Patients reported higher levels of loneliness than healthy controls. Loneliness was linked to increased negative and affective symptoms in patients. A negative association between loneliness and mentalizing and emotion recognition abilities was found in the patients with social-cognitive impairments, but not in those who performed at normative levels. CONCLUSIONS: We have elucidated a novel mechanism which may explain previous inconsistent findings regarding the correlates of loneliness in individuals with schizophrenia.

Childhood adversity and cognitive function in schizophrenia spectrum disorders and healthy controls: evidence for an association between neglect and social cognition.

BACKGROUND: Childhood adversity is associated with cognitive impairments in schizophrenia. However, findings to date are inconsistent and little is known about the relationship between social cognition and childhood trauma. We investigated the relationship between childhood abuse and neglect and cognitive function in patients with a first-episode of schizophrenia or schizophreniform disorder (n = 56) and matched healthy controls (n = 52). To the best of our knowledge, this is the first study assessing this relationship in patients and controls exposed to similarly high levels of trauma. METHODS: Pearson correlational coefficients were used to assess correlations between Childhood Trauma Questionnaire abuse and neglect scores and cognition. For the MCCB domains displaying significant (p < 0.05) correlations, within group hierarchical linear regression, was done to assess whether abuse and neglect were significant predictors of cognition after controlling for the effect of education. RESULTS: Patients and controls reported similarly high levels of abuse and neglect. Cognitive performance was poorer for patients compared with controls for all cognitive domains except working memory and social cognition. After controlling for education, exposure to childhood neglect remained a significant predictor of impairment in social cognition in both patients and controls. Neglect was also a significant predictor of poorer verbal learning in patients and of attention/vigilance in controls. However, childhood abuse did not significantly predict cognitive impairments in either patients or controls. CONCLUSION: These findings are cross sectional and do not infer causality. Nonetheless, they indicate that associations between one type of childhood adversity (i.e. neglect) and social cognition are present and are not illness-specific.

Familial aggregation of MATRICS Consensus Cognitive Battery scores in a large sample of outpatients with schizophrenia and their unaffected relatives.

BACKGROUND: The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative-control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands' scores. METHODS: Multivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands' MCCB scores predicted REL neurocognitive performance. RESULTS: SCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning. CONCLUSIONS: In a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors.

Developing an international scoring system for a consensus-based social cognition measure: MSCEIT-managing emotions.

BACKGROUND: Measures of social cognition are increasingly being applied to psychopathology, including studies of schizophrenia and other psychotic disorders. Tests of social cognition present unique challenges for international adaptations. The Mayer-Salovey-Caruso Emotional Intelligence Test, Managing Emotions Branch (MSCEIT-ME) is a commonly-used social cognition test that involves the evaluation of social scenarios presented in vignettes. METHOD: This paper presents evaluations of translations of this test in six different languages based on representative samples from the relevant countries. The goal was to identify items from the MSCEIT-ME that show different response patterns across countries using indices of discrepancy and content validity criteria. An international version of the MSCEIT-ME scoring was developed that excludes items that showed undesirable properties across countries. RESULTS: We then confirmed that this new version had better performance (i.e. less discrepancy across regions) in international samples than the version based on the original norms. Additionally, it provides scores that are comparable to ratings based on local norms. CONCLUSIONS: This paper shows that it is possible to adapt complex social cognitive tasks so they can provide valid data across different cultural contexts.

Latent structure of cognition in schizophrenia: a confirmatory factor analysis of the MATRICS Consensus Cognitive Battery (MCCB).

BACKGROUND: The number of separable cognitive dimensions in schizophrenia has been debated. Guided by the extant factor analytic literature, the NIMH Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative selected seven cognitive domains relevant to treatment studies in schizophrenia: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. These domains are assessed in the MATRICS Consensus Cognitive Battery (MCCB). The aim of this study was to conduct a confirmatory factor analysis (CFA) of the beta battery of the MCCB to compare the fit of the MATRICS consensus seven-domain model to other models in the current literature on cognition in schizophrenia. METHOD: Using data from 281 schizophrenia outpatients, we compared the seven correlated factors model with alternative models. Specifically, we compared the 7-factor model to (a) a single-factor model, (b) a three correlated factors model including speed of processing, working memory, and general cognition, and (c) a hierarchical model in which seven first-order factors loaded onto a second-order general cognitive factor. RESULTS: Multiple fit indices indicated the seven correlated factors model was the best fit for the data and provided significant improvement in model fit beyond the comparison models. CONCLUSIONS: These results support the assessment of these seven cognitive dimensions in clinical trials of interventions to improve cognition in schizophrenia. Because these cognitive factors are separable to some degree, it is plausible that specific interventions may have differential effects on the domains.

Impaired emotion regulation in schizophrenia: evidence from event-related potentials.

BACKGROUND: Although several aspects of emotion seem to be intact in schizophrenia, there is emerging evidence that patients show an impaired ability to adaptively regulate their emotions. This event-related potential (ERP) study examined whether schizophrenia is associated with impaired neural responses to appraisal frames, that is when negative stimuli are presented in a less negative context. METHOD: Thirty-one schizophrenia out-patients and 27 healthy controls completed a validated picture-viewing task with three conditions: (1) neutral pictures preceded by neutral descriptions ('Neutral'), (2) unpleasant pictures preceded by negative descriptions ('Preappraised negative'), and (3) unpleasant pictures preceded by more neutral descriptions ('Preappraised neutral'). Analyses focused on the late positive potential (LPP), an index of facilitated attention to emotional stimuli that is reduced following cognitive emotion regulation strategies, during four time windows from 300 to 2000 ms post-picture onset. RESULTS: Replicating prior studies, controls showed smaller LPP in Preappraised neutral and Neutral versus Preappraised negative conditions throughout the 300-2000-ms time period. By contrast, patients showed (a) larger LPP in Preappraised neutral and Preappraised negative versus Neutral conditions in the initial period (300-600 ms) and (b) an atypical pattern of larger LPP to Preappraised neutral versus Preappraised negative and Neutral conditions in the 600-1500-ms epochs. CONCLUSIONS: Modulation of neural responses by a cognitive emotion regulation strategy seems to be impaired in schizophrenia during the first 2 s after exposure to unpleasant stimuli.

Event-related potential examination of facial affect processing in bipolar disorder and schizophrenia.

BACKGROUND: Patients with bipolar disorder exhibit consistent deficits in facial affect identification at both behavioral and neural levels. However, little is known about which stages of facial affect processing are dysfunctional. METHOD: Event-related potentials (ERPs), including amplitude and latency, were used to evaluate two stages of facial affect processing: N170 to examine structural encoding of facial features and N250 to examine decoding of facial features in 57 bipolar disorder patients, 30 schizophrenia patients and 30 healthy controls. Three conditions were administered: participants were asked to identify the emotion of a face, the gender of a face, or whether a building was one or two stories tall. RESULTS: Schizophrenia patients' emotion identification accuracy was lower than that of bipolar patients and healthy controls. N170 amplitude was significantly smaller in schizophrenia patients compared to bipolar patients and healthy controls, which did not differ from each other. Both patient groups had significantly longer N170 latency compared to healthy controls. For N250, both patient groups showed significantly smaller amplitudes compared with controls, but did not differ from each other. Bipolar patients showed longer N250 latency than healthy controls; patient groups did not differ from each other. CONCLUSIONS: Bipolar disorder patients have relatively intact structural encoding of faces (N170) but are impaired when decoding facial features for complex judgments about faces (N250 latency and amplitude), such as identifying emotion or gender.

The causal relationships between neurocognition, social cognition and functional outcome over time in schizophrenia: a latent difference score approach.

BACKGROUND: Social cognition has been identified as a significant construct for schizophrenia research with relevance to diagnosis, assessment, treatment and functional outcome. However, social cognition has not been clearly understood in terms of its relationships with neurocognition and functional outcomes. The present study sought to examine the empirical independence of social cognition and neurocognition; to investigate the possible causal structure among social cognition, neurocognition and psychosocial functioning. METHOD: The sample consists of 130 individuals diagnosed with schizophrenia. All participants were recruited as they were admitted to four community-based psychosocial rehabilitation programs. Social cognition, neurocognition and psychosocial functioning were measured at baseline and 12 months. The empirical independence of social cognition and neurocognition was tested using confirmatory factor analysis (CFA) and the possible causal structure among social cognition, neurocognition and psychosocial functioning was investigated using latent difference score (LDS) analysis. RESULTS: A two-factor model of social cognition and neurocognition fit the data very well, indicating the empirical independence of social cognition, whereas the longitudinal CFA results show that the empirical independence of neurocognition and social cognition is maintained over time. The results of the LDS analysis support a causal model that indicates that neurocognition underlies and is causally primary to social cognition, and that neurocognition and social cognition are causally primary to functional outcome. CONCLUSIONS: Social cognition and neurocognition could have independent and distinct upward causal effects on functional outcome. It is also suggested that the approaches for remediation of neurocognition and social cognition might need to be distinct.

Impaired neural response to internal but not external feedback in schizophrenia.

BACKGROUND: Accurate monitoring and integration of both internal and external feedback is crucial for guiding current and future behavior. These aspects of performance monitoring are commonly indexed by two event-related potential (ERP) components: error-related negativity (ERN) and feedback negativity (FN). The ERN indexes internal response monitoring and is sensitive to the commission of erroneous versus correct responses, and the FN indexes external feedback monitoring of positive versus negative outcomes. Although individuals with schizophrenia consistently demonstrate a diminished ERN, the integrity of the FN has received minimal consideration. METHOD: The current research sought to clarify the scope of feedback processing impairments in schizophrenia in two studies: study 1 examined the ERN elicited in a flanker task in 16 out-patients and 14 healthy controls; study 2 examined the FN on a simple monetary gambling task in expanded samples of 35 out-patients and 33 healthy controls. RESULTS: Study 1 replicated prior reports of an impaired ERN in schizophrenia. By contrast, patients and controls demonstrated comparable FN differentiation between reward and non-reward feedback in study 2. CONCLUSIONS: The differential pattern across tasks suggests that basic sensitivity to external feedback indicating reward versus non-reward is intact in schizophrenia, at least under the relatively simple task conditions used in this study. Further efforts to specify intact and impaired reward-processing subcomponents in schizophrenia may help to shed light on the diminished motivation and goal-seeking behavior that are commonly seen in this disorder.

Pathways between early visual processing and functional outcome in schizophrenia.

BACKGROUND: Early visual processing deficits are reliably detected in schizophrenia and show relationships to poor real-world functioning. However, the nature of this relationship is complex. Theoretical models and recent studies using statistical modeling approaches suggest that multiple intervening factors are involved. We previously reported that a direct and significant association between visual processing and functional status was mediated by a measure of social perception. The present study examined the contribution of negative symptoms to this model. METHOD: We employed structural equation modeling (sem) to test several models of outcome, using data from 174 schizophrenia out-patients. Specifically, we examined the direct and indirect relative contributions of early visual processing, social perception and negative symptoms to functional outcome. RESULTS: First, we found that, similar to social perception, a measure of negative symptoms mediated the association between visual information processing and functional status. Second, we found that the inclusion of negative symptoms substantially enhanced the explanatory power of the model. Notably, it was the experiential aspect of negative symptoms (avolition and anhedonia) more than the expressive aspect (affective flattening and alogia) that accounted for significant variance in functional outcome, especially in the social component of the construct of functional outcome. CONCLUSIONS: Social perception and negative symptoms play relevant roles in functional impairment in schizophrenia. Both social perception and negative symptoms statistically mediate the connection between visual processing and functional outcome. However, given the lack of association between social perception and negative symptoms, these constructs appear to have an impact on functioning through separate pathways.

Schizophrenia patients are impaired in empathic accuracy.

BACKGROUND: Empathy is crucial for successful social relationships. Despite its importance for social interactions, little is known about empathy in schizophrenia. This study investigated the degree to which schizophrenia patients can accurately infer the affective state of another person (i.e. empathic accuracy). METHOD: A group of 30 schizophrenia patients and 22 healthy controls performed an empathic accuracy task on which they continuously rated the affective state of another person shown in a video (referred to as the 'target'). These ratings were compared with the target's own continuous self-rating of affective state; empathic accuracy was defined as the correlation between participants' ratings and the targets' self-ratings. A separate line-tracking task was administered to measure motoric/attentional factors that could account for group differences in performance. Participants' self-rated empathy was measured using the Interpersonal Reactivity Index, and targets' self-rated emotional expressivity was measured using the Berkeley Expressivity Questionnaire. RESULTS: Compared with controls, schizophrenia patients showed lower empathic accuracy although they performed the motoric tracking task at high accuracy. There was a significant group×target expressivity interaction such that patients showed a smaller increase in empathic accuracy with higher levels of emotional expressivity by the target, compared with controls. Patients' empathic accuracy was uncorrelated with self-reported empathy or clinical symptoms. CONCLUSIONS: Schizophrenia patients showed lower empathic accuracy than controls, and their empathic accuracy was less influenced by the emotional expressivity of the target. These findings suggest that schizophrenia patients benefit less from social cues of another person when making an empathic judgement.

Visual masking by object substitution in schizophrenia.

BACKGROUND: Schizophrenia patients demonstrate impairment on visual backward masking, a measure of early visual processing. Most visual masking paradigms involve two distinct processes, an early fast-acting component associated with object formation and a later component that acts through object substitution. So far, masking paradigms used in schizophrenia research have been unable to separate these two processes. METHOD: We administered three visual processing paradigms (location masking with forward and backward masking, four-dot backward masking and a cuing task) to 136 patients with schizophrenia or schizoaffective disorder and 79 healthy controls. A psychophysical procedure was used to match subjects on identification of an unmasked target prior to location masking. Location masking interrupts object formation, four-dot masking task works through masking by object substitution and the cuing task measures iconic decay. RESULTS: Patients showed impairment on location masking after being matched for input threshold, similar to previous reports. After correcting for age, patients showed lower performance on four-dot masking than controls, but the groups did not differ on the cuing task. CONCLUSIONS: Patients with schizophrenia showed lower performance when masking was specific to object substitution. The difference in object substitution masking was not due to a difference in rate of iconic decay, which was comparable in the two groups. These results suggest that, despite normal iconic decay rates, individuals with schizophrenia show impairment in a paradigm of masking by object substitution that did not also involve disruption of object formation.

Neurocognitive change, functional change and service intensity during community-based psychosocial rehabilitation for schizophrenia.

BACKGROUND: This study examined the magnitude of neurocognitive change during 1 year of community-based psychosocial intervention, whether neurocognitive change and functional change were linked, and how neurocognitive change combined with service intensity to facilitate functional change. METHOD: A total of 130 individuals diagnosed with schizophrenia were recruited upon admission to four community-based psychosocial rehabilitation programs. Subjects were assessed at baseline, 6 and 12 months on role functioning and symptom measures. Neurocognition was measured at baseline and 12 months. Service intensity was the number of days of treatment attendance during the study period. Latent mean difference tests and Latent Growth Curve Models (LCGMs) were used to examine the study hypotheses. RESULTS: There was statistically and clinically significant functional improvement over 12 months. Neurocognition improved significantly over time. Seventy-six (58%) of the sample showed neurocognitive improvement and 54 (42%) did not. There was a significant rate of functional enhancement in the neurocognitive improver group. There was a non-significant rate of functional change in the neurocognitive non-improver group. Neurocognitive improvers showed functional improvement that was 350% greater than neurocognitive non-improvers. Service intensity did not vary between neurocognitive improvers and non-improvers but there was a strong interaction between neurocognitive improvement, service intensity and rate of functional improvement such that service intensity was strongly related to functional improvement for neurocognitive improvers but not for neurocognitive non-improvers. Medication usage and symptomatology did not confound these findings. CONCLUSIONS: These findings suggest that neurocognitive improvement may be a foundation for functional change and treatment responsiveness during community-based psychosocial rehabilitation for individuals with schizophrenia.

MCCB cognitive profile in Spanish first episode schizophrenia patients.

The objective of the study was to examine the cognitive profile of Spanish patients with a first episode of schizophrenia (FESz) and to compare that to the profile of patients with a chronic schizophrenia (CSz) and non-psychiatric (NP) control subjects. The study included 106 FESz, 293 CSz, and 210 NP, assessed with the Spanish version of the MATRICS Consensus Cognitive Battery (MCCB). The MCCB cognitive profile in a Spanish sample of FESz was similar to the cognitive profile of CSz with some discrepancies in select domains. The scores of both patient samples were about 1-2 SD below the scores of non-psychiatric control subjects.

Repurposing Drugs for Cognition in Schizophrenia.

Currently approved treatments for schizophrenia only minimally affect the cognitive features of the illness that are the most closely related to disability. Hence, there is now considerable effort to repurpose drugs for schizophrenia, and to seek agents that can improve cognition by targeting receptor systems other than the dopaminergic system. The results of these studies have been mixed thus far; however, this continues to be a high-priority area of schizophrenia research and an important unmet need.

Backward masking in schizophrenia and mania. I. Specifying a mechanism.

BACKGROUND: Backward masking is a neuropsychological procedure that involves the earliest phases of visual processing. Compared with normal controls, the performance of schizophrenic patients is more disrupted by a visual mask. Masking procedures used previously with schizophrenic patients have combined two separate masking mechanisms (interruption and integration), which prevent interpretation of the nature of the abnormality. The current study systematically limited the masking mechanism to interruption to specify the underlying mechanisms. Manic patients were included to examine diagnostic specificity. METHODS: Sixty-three schizophrenic inpatients, 31 manic inpatients, and 48 normal controls received three versions of the backward masking procedure. One version used a high-energy mask that combines both integration and interruption mechanisms. Another procedure used a low-energy mask that works mainly through interruption. A final condition altered the features of the mask so that masking was almost entirely through interruption. RESULTS: Schizophrenic patients showed performance deficits across masking conditions, even in procedures that were largely limited to masking by interruption. The masking performance of the patients did not appear to fit a simple generalized deficit. Manic patients performed significantly worse than normal controls and comparably with the schizophrenic patients. CONCLUSIONS: Schizophrenic patients have abnormalities at least with interruptive mechanisms. The results suggest that deficits on masking procedures are not entirely specific to schizophrenia because comparable masking deficits were found in manic inpatients with chronic disease. The current study addresses the neuropsychological mechanisms of the masking deficit. The next step will be to investigate the contributions of two distinct neuroanatomical visual pathways to the masking abnormality in schizophrenia.

Backward masking in schizophrenia and mania. II. Specifying the visual channels.

BACKGROUND: The backward masking procedures that have been used in psychopathology research have confounded two types of masking mechanisms (integration and interruption) and two types of visual channels (transient and sustained). In an earlier study, we attempted to limit the masking mechanism to interruption. The current study limited the role of sustained (parvocellular) visual channels to masking performance. METHODS: Masking procedures were altered in the following two ways to reduce reliance on sustained visual channels: (1) the spatial frequency was lowered by blurring the target and (2) a location task was used instead of an identification task. Manic patients were included to examine the specificity of deficits on these tasks to schizophrenia and to test the hypothesis that mania is associated with abnormalities on visuospatial tasks. RESULTS: Schizophrenic patients differed significantly from normal controls on both masking conditions. Manic patients also showed deficits relative to normal controls. Manic patients showed a significantly different masking function from that of schizophrenic patients on the location condition. CONCLUSIONS: Schizophrenic deficits within masking paradigms may involve abnormalities in transient, as opposed to sustained, visual channels. Masking performance deficits were also found in manic patients, but the underlying processes are probably different. A reformulation is offered concerning the nature of early visual processing deficits in schizophrenia.

Backward masking performance in unaffected siblings of schizophrenic patients. Evidence for a vulnerability indicator.

BACKGROUND: Visual masking is a procedure that is used to assess the earliest components of visual processing. In backward masking, the identification of an initial stimulus (the target) is disrupted by a later stimulus (the mask). The masking function can be divided into an early component (e.g., up to about 60 ms) that reflects the involvement of sensory-perceptual processes, and a later component that reflects susceptibility to attentional disengagement as the mask diverts processing away from the representation of the target. Schizophrenic patients show anomalies on both masking components. It is not known whether backward masking deficits reflect enduring genetic vulnerability to schizophrenia. METHODS: We assessed 32 unaffected siblings of schizophrenic patients and 52 normal control subjects on the early and late components of 4 masking conditions. The conditions differentially involved the sustained and transient visual pathways. RESULTS: The unaffected siblings showed poorer overall performance than control subjects on the masking procedures. More specifically, siblings showed anomalies on the early, sensory-perceptual component, but not on the later, attentional disengagement component. CONCLUSIONS: The backward masking performance deficits that have been observed in schizophrenic patients appear to reflect enduring vulnerability to the disorder rather than only the symptoms of the illness. This vulnerability appears to be associated with early, sensory-perceptual processes.

The MCCB impairment profile in a Spanish sample of patients with schizophrenia: Effects of diagnosis, age, and gender on cognitive functioning.

The MATRICS Consensus Cognitive Battery (MCCB) was administered to 293 schizophrenia outpatients and 210 community residents in Spain. Our first objective was to identify the age- and gender-corrected MCCB cognitive profile of patients with schizophrenia. The profile of schizophrenia patients showed deficits when compared to controls across the seven MCCB domains. Reasoning and Problem Solving and Social Cognition were the least impaired, while Visual Learning and Verbal Learning showed the greatest deficits. Our second objective was to study the effects on cognitive functioning of age and gender, in addition to diagnosis. Diagnosis was found to have the greatest effect on cognition (Cohen's d>0.8 for all MCCB domains); age and gender also had effects on cognitive functioning, although to a lesser degree (with age usually having slightly larger effects than gender). The effects of age were apparent in all domains (with better performance in younger subjects), except for Social Cognition. Gender had effects on Attention/Vigilance, Working Memory, Reasoning and Problem Solving (better performance in males), and Social Cognition (better performance in females). No interaction effects were found between diagnosis and age, or between diagnosis and gender. This lack of interactions suggests that age and gender effects are not different in patients and controls.