The Association Between Emotion Recognition, Affective Empathy, and Structural Connectivity in Schizophrenia Patients

INTRODUCTION: Emotion processing deficits often occur in patients with schizophrenia. We investigate whether patients and controls differ in the association between facial emotion recognition and experience of affective empathy and whether performance on these emotion processing domains differently relates to white matter connectivity. MATERIALS AND METHODS: Forty-seven patients with schizophrenia and 47 controls performed an emotion recognition and affective empathy task. T1-weighted and diffusion-tensor images (DTI) of the brain were acquired. Using Tracula 5.3, ten fibers were reconstructed and fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were extracted. Groups were compared on task performance, white matter measures and their interactions using ANCOVAs. Correction for multiple comparisons was applied. RESULTS: Patients scored lower on emotion recognition (p = 0.037) and reported higher levels of affective empathy (p < 0.001) than controls. Patients with poor emotion recognition (PT-low) experienced stronger affective empathy than patients with similar emotion recognition performance as controls (PT-normal; p = 0.011), who in turn reported stronger affective empathy than controls (p = 0.043). We found a significant interaction between emotion recognition, affective empathy and anterior thalamic radiation AD (p = 0.017, d = 0.43). Post hoc analyses revealed that the correlation between AD and empathy differed significantly between all groups (empathy/AD in PT-low < empathy/AD in PT-normal < empathy/AD in controls). DISCUSSION: In patients with poor emotion recognition, the negative association between anterior thalamic radiation AD and affective empathy was stronger than in patients with normal emotion recognition capacity. Possibly, axonal damage in fronto-thalamic structural connections, as part of a larger frontotemporal network, underlies the association between poor emotion recognition and higher levels of affective empathy in schizophrenia patients

Efficacy of different types of cognitive enhancers for patients with schizophrenia:a meta-analysis

Cognitive impairment is a core feature of schizophrenia, which is predictive for functional outcomes and is, therefore, a treatment target in itself. Yet, literature on efficacy of different pharmaco-therapeutic options is inconsistent. This quantitative review provides an overview of studies that investigated potential cognitive enhancers in schizophrenia. We included pharmacological agents, which target different neurotransmitter systems and evaluated their efficacy on overall cognitive functioning and seven separate cognitive domains. In total, 93 studies with 5630 patients were included. Cognitive enhancers, when combined across all different neurotransmitter systems, which act on a large number of different mechanisms, showed a significant (yet small) positive effect size of 0.10 (k = 51, p = 0.023; 95% CI = 0.01 to 0.18) on overall cognition. Cognitive enhancers were not superior to placebo for separate cognitive domains. When analyzing each neurotransmitter system separately, agents acting predominantly on the glutamatergic system showed a small significant effect on overall cognition (k = 29, Hedges' g = 0.19, p = 0.01), as well as on working memory (k = 20, Hedges' g = 0.13, p = 0.04). A sub-analysis of cholinesterase inhibitors (ChEI) showed a small effect on working memory (k = 6, Hedges' g = 0.26, p = 0.03). Other sub-analyses were positively nonsignificant, which may partly be due to the low number of studies we could include per neurotransmitter system. Overall, this meta-analysis showed few favorable effects of cognitive enhancers for patients with schizophrenia, partly due to lack of power. There is a lack of studies involving agents acting on other than glutamatergic and cholinergic systems, especially of those targeting the dopaminergic system.</p

Efficacy of different types of cognitive enhancers for patients with schizophrenia:a meta-analysis

Cognitive impairment is a core feature of schizophrenia, which is predictive for functional outcomes and is, therefore, a treatment target in itself. Yet, literature on efficacy of different pharmaco-therapeutic options is inconsistent. This quantitative review provides an overview of studies that investigated potential cognitive enhancers in schizophrenia. We included pharmacological agents, which target different neurotransmitter systems and evaluated their efficacy on overall cognitive functioning and seven separate cognitive domains. In total, 93 studies with 5630 patients were included. Cognitive enhancers, when combined across all different neurotransmitter systems, which act on a large number of different mechanisms, showed a significant (yet small) positive effect size of 0.10 (k = 51, p = 0.023; 95% CI = 0.01 to 0.18) on overall cognition. Cognitive enhancers were not superior to placebo for separate cognitive domains. When analyzing each neurotransmitter system separately, agents acting predominantly on the glutamatergic system showed a small significant effect on overall cognition (k = 29, Hedges' g = 0.19, p = 0.01), as well as on working memory (k = 20, Hedges' g = 0.13, p = 0.04). A sub-analysis of cholinesterase inhibitors (ChEI) showed a small effect on working memory (k = 6, Hedges' g = 0.26, p = 0.03). Other sub-analyses were positively nonsignificant, which may partly be due to the low number of studies we could include per neurotransmitter system. Overall, this meta-analysis showed few favorable effects of cognitive enhancers for patients with schizophrenia, partly due to lack of power. There is a lack of studies involving agents acting on other than glutamatergic and cholinergic systems, especially of those targeting the dopaminergic system

In search of the self : On self-disturbances and social cognition in schizophrenia

For most patients with schizophrenia it is difficult to sufficiently participate in the community, largely due to deficits in social interaction. The decreased ability to interact with other people and understand them is affected by the way patients perceive themselves. As schizophrenia is seen as a disorder of fundamental self-disturbances, in this thesis a series of empirical studies explore how schizophrenia is related to components that are crucial for making a distinction between oneself and others, hereby focusing on the concepts of body ownership, self-agency, and empathy. The feeling of body-ownership and the feeling of self-agency are considered the most important aspects for basic self-experience and contribute to a feeling of presence and being. Therefore, using a Rubber Hand Illusion paradigm, we provide insight into disturbances in the feeling of body ownership in patients with schizophrenia and in adolescents at increased familial risk to develop the disease. Second, self-agency inferences can result from implicitly associated cues or situations that can unconsciously pre-activate or prime an outcome representation in the agent’s mind. As previous studies found that patients with schizophrenia show specific impairments in these prime-based self-agency inferences, which are particularly important in social behavior, the current thesis provides insight in this topic. Third, as empathic abilities are an important predictor for functional outcome in schizophrenia, our research aims to increase knowledge about its etiology by focusing on the role of the self-reflection network in the brain. Summarizing, this thesis contributes to our understanding of self-disturbances in patients with schizophrenia by using experimental set-ups

Self-other integration and distinction in schizophrenia : A theoretical analysis and a review of the evidence

Difficulties in self-other processing lie at the core of schizophrenia and pose a problem for patients’ daily social functioning. In the present selective review, we provide a framework for understanding self-other integration and distinction, and impairments herein in schizophrenia. For this purpose, we discuss classic motor prediction models in relation to mirror neuron functioning, theory of mind, mimicry, self-awareness, and self-agency phenomena. Importantly, we also discuss the role of more recent cognitive expectation models in these phenomena, and argue that these cognitive models form an essential contribution to our understanding of self-other integration and distinction. In doing so, we bring together different lines of research and connect findings from social psychology, affective neuropsychology, and psychiatry to further our understanding of when and how people integrate versus distinguish self and other, and how this goes wrong in schizophrenia patients

The effect of raloxifene augmentation in men and women with a schizophrenia spectrum disorder: a systematic review and meta-analysis

Abstract Recognizing the robust sex differences in schizophrenia prevalence, the selective estrogen receptor modulator (SERM) raloxifene is a likely candidate for augmentation therapy in this disorder. Therefore, a systematic search was performed using PubMed (Medline), Embase, PsychInfo, and Cochrane Database of Systematic Reviews. Randomized controlled trials investigating the effect of raloxifene in schizophrenia spectrum disorders were included in the quantitative analyses. Outcome measures were psychotic symptom severity, depression, and cognition. Meta-analyses were performed using Comprehensive Meta-Analysis software. A random-effects model was used to compute overall weighted effect sizes in Hedges’ g. Nine studies were included, investigating 561 patients with a schizophrenia spectrum disorder. Raloxifene was superior to placebo in improving total symptom severity (N = 482; Hedge’s g = .57, p = 0.009), as well as positive (N = 561; Hedge’s g = 0.32, p = 0.02), negative (N = 561; Hedge’s g = 0.40, p = 0.02), and general (N = 526; Hedge’s g = 0.46, p = 0.01) subscales, as measured by the Positive and Negative Syndrome Scale. No significant effects were found for comorbid depression and cognitive functioning. Altogether, these results confirm the potential of raloxifene augmentation in the treatment of schizophrenia

Impaired self-agency inferences in schizophrenia: The role of cognitive capacity and causal reasoning style

Background The sense of self-agency, i.e., experiencing oneself as the cause of one's own actions, is impaired in patients with schizophrenia. Normally, inferences of self-agency are enhanced when actual outcomes match with pre-activated outcome information, where this pre-activation can result from explicitly set goals (i.e., goal-based route) or implicitly primed outcome information (i.e., prime-based route). Previous research suggests that patients show specific impairments in the prime-based route, implicating that they do not rely on matches between implicitly available outcome information and actual action-outcomes when inferring self-agency. The question remains: Why? Here, we examine whether neurocognitive functioning and self-serving bias (SSB) may explain abnormalities in patients’ agency inferences. Methods Thirty-six patients and 36 healthy controls performed a commonly used agency inference task to measure goal- and prime-based self-agency inferences. Neurocognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS) and the SSB was assessed with the Internal Personal and Situational Attributions Questionnaire. Results Results showed a substantial smaller effect of primed outcome information on agency experiences in patients compared with healthy controls. Whereas patients and controls differed on BACS and marginally on SSB scores, these differences were not related to patients’ impairments in prime-based agency inferences. Conclusions Patients showed impairments in prime-based agency inferences, thereby replicating previous studies. This finding could not be explained by cognitive dysfunction or SSB. Results are discussed in the context of the recent surge to understand and examine deficits in agency experiences in schizophrenia

Individual differences in action co-representation : not personal distress or subclinical psychotic experiences but sex composition modulates joint action performance

Successful social interaction requires the ability to integrate as well as distinguish own and others’ actions. Normally, the integration and distinction of self and other are a well-balanced process, occurring without much effort or conscious attention. However, not everyone is blessed with the ability to balance self–other distinction and integration, resulting in personal distress in reaction to other people’s emotions or even a loss of self [e.g., in (subclinical) psychosis]. Previous research has demonstrated that the integration and distinction of others’ actions cause interference with one’s own action performance (commonly assessed with a social Simon task). The present study had two goals. First, as previous studies on the social Simon effect employed relatively small samples (N < 50 per test), we aimed for a sample size that allowed us to test the robustness of the action interference effect. Second, we tested to what extent action interference reflects individual differences in traits related to self–other distinction (i.e., personal distress in reaction to other people’s emotions and subclinical psychotic symptoms). Based on a questionnaire study among a large sample (N = 745), we selected a subsample (N = 130) of participants scoring low, average, or high on subclinical psychotic symptoms, or on personal distress. The selected participants performed a social Simon task. Results showed a robust social Simon effect, regardless of individual differences in personal distress or subclinical psychotic symptoms. However, exploratory analyses revealed that the sex composition of interaction pairs modulated social Simon effects. Possible explanations for these findings are discussed

Abnormalities in the experience of self-agency in schizophrenia: A replication study

People usually experience agency over their actions and subsequent outcomes. These agency inferences over action-outcomes are essential to social interaction, and occur when an actual outcome corresponds with either a specific goal (goal-based), and matches with action-outcome information that is subtly pre-activated in the situation at hand (prime-based). Recent research showed that schizophrenia patients exhibit goal-based inferences, but not prime-based inferences. Intrigued by these findings, and underscoring their potential role in explaining poor social functioning, we replicate patients’ deficit in prime-based agency inferences. Additionally, we exclude the account that patients are unable to visually process and attend to primed information

Multisensory integration underlying body-ownership experiences in schizophrenia and offspring of patients : A study using the rubber hand illusion paradigm

Background: Schizophrenia is a disorder of basic self-disturbance. Evidence suggests that people with schizophrenia may have aberrant experiences of body ownership: they may feel that they are not the subject of their own body experiences. However, little is known about the development of such disturbances. Methods: Using a rubber hand illusion paradigm, we assessed body ownership in patients with schizophrenia (n = 54), healthy controls (n = 56), children/adolescents at increased familial risk of developing schizophrenia (n = 24) or mood disorders (n = 33), and children/adolescents without this risk (n = 18). In this paradigm, a rubber hand (visible) and a participant’s real hand (invisible) were stroked synchronously and asynchronously; we then measured subjective illusory experiences and proprioceptive drift. Results: All groups showed the expected effect of the rubber hand illusion: stronger proprioceptive drift and increased subjective illusory experiences after synchronous versus asynchronous stroking. The effect of synchronicity on subjective experiences was significantly weaker in patients with schizophrenia than in healthy controls, and subjective ratings were positively correlated with delusions in patients. We found no significant differences between children/adolescents with and without increased familial risk. Limitations: Large individual differences raised questions for future research. Conclusion: We found subtle disturbances in body-ownership experiences in patients with schizophrenia, which were associated with delusions. We found no evidence for impairments in children/adolescents at increased familial risk of developing schizophrenia or a mood disorder. Longitudinal data might reveal whether impairments in body ownership are predictive of psychosis onset