Social Cognition and Metacognition in Schizophrenia

Psychopathology and Treatment Approaches

Paul Lysaker, Giancarlo Dimaggio, Martin Brüne

• Publisher: Academic Press
• Year: 2014
• Print ISBN: 9780124051720
• eBook ISBN: 9780124051744
• Topic: Psychology
• Subtopic: Clinical Psychology
• Index: Psychology

Deficits in social cognition and metacognition in schizophrenics makes it difficult for them to understand the speech, facial expressions and hence emotion and intention of others, as well as allowing little insight into their own mental state. These deficits are associated with poor social skills, fewer social relationships, and are predictive of poorer performance in a work setting. Social Cognition and Metacognition in Schizophrenia reviews recent research advances focusing on the precise nature of these deficits, when and how they manifest themselves, what their effect is on the course of schizophrenia, and how each can be treated. These deficits may themselves be why schizophrenia is so difficult to resolve; by focusing on the deficits, recovery may be quicker and long lasting. This book discusses such deficits in early onset, first episode, and prolonged schizophrenia; how the deficits relate to each other and to other forms of psychopathology; how the deficits affect social, psychological, and vocational functioning; and how best to treat the deficits in either individual or group settings. - Summarizes the types of social cognitive and metacognitive deficits present in schizophrenia - Discusses how deficits are related to each other and to other forms of psychopathology - Describes how deficits impact function and affect the recovery process - Provides treatment approaches for these deficits

Chapter 1

Neurobiologic Underpinnings of Social Cognition and Metacognition in Schizophrenia Spectrum Disorders

Elliot C. Brown^1,2, Cumhur Tas^1,3, Cristina Gonzalez^1,3 and Martin Brüne¹, ¹LWL-University Hospital Bochum, Bochum, Germany, ²International Graduate School of Neuroscience (IGSN), Ruhr-University Bochum, Bochum, Germany, ³Ruhr-University Bochum, Bochum, Germany

With the contribution of social neuroscience in neuropsychiatry, a large body of literature has suggested that schizophrenia is a product of a dysfunction in the ‘social brain’. The rising interest in the field of social neuroscience has provided an instrumental foundation for understanding how the social brain may be going wrong in schizophrenia, and how neurobiologic abnormalities may help to explain deficits in social cognition. So far, work using animal disease models and neuroimaging in patients has already made progress in uncovering some of the neurobiologic factors related to social cognitive deficits in schizophrenia. This chapter will summarize the work to date in this area, while also raising some crucial unresolved issues in this field by taking a critical view on the literature, and making future suggestions for research.

Keywords

animal models; biomarker; neurotransmitter; neuroimaging; fMRI; EEG; emotion processing; theory of mind

Chapter Outline

Introduction 1

Animal Studies on Basic Social Cognition and Social Behavior with Schizophrenia Models 2

Neurotransmitters and Receptors Related to Social Cognition 4

Social Cognition in Schizophrenia: Neuroimaging Research 5

Neuroimaging of Emotion Processing 6

Neuroimaging of Theory of Mind 9

Action Observation and the Mirror Neuron System in Schizophrenia 11

Neuroimaging of Social Decision-Making 13

The Neurobiology of Metacognition 15

Biomarkers for Deficits in Social Cognition 16

Limitations and Future Suggestions 17

References 18

Introduction

As the field of psychiatry is currently becoming more focused on the brain as the target organ for treatment, it is natural then to search for the neurobiologic factors that play a role in the pathologic features of mental illness and disorder. In schizophrenia, potential dysfunctions of the ‘social brain’ provide a tangible starting point to explore the underlying neurobiology of deficits in social cognition. This line of inquiry is particularly pertinent due to the growing work on animal models of schizophrenia, as well as with the rise of social neuroscience as a discipline that utilizes neuroimaging and brain stimulation techniques to uncover the neural substrates of the cognitive processes underlying human social interaction.

The aim of this chapter is to present the current state of research in the neurobiology of social cognition in schizophrenia. As animal studies provide the initial steps that lead to human studies, we first focus on rodents as animal models of schizophrenia and social cognition. The translation of these findings, as well as the neurobiologic evidence on social cognition in schizophrenia, is also summarized with current limitations and future suggestion in the following sections.

Animal Studies on Basic Social Cognition and Social Behavior with Schizophrenia Models

In order to understand the most fundamental neural underpinnings of social behavior in humans, many scientists have opted for animal models owing to the opportunity to explore and alter and measure the brain mechanisms and the resulting behavior. Furthermore, while sociocognitive tasks for humans are usually designed in experimental settings and involve large machinery or cables (e.g., magnetic resonance imaging (MRI) or electroencephalography (EEG)), that is in non-natural circumstances, social behavior and basic social cognition assessed in animals reduces the effects of, or at least controls, laboratory influence. Lastly, neurotransmitter networks can be more easily explored in the brains of animals, while brain networks in low- and high-level social cognition are better investigated in humans.

A variety of animal models of schizophrenia, mostly in rodents, have been developed and have brought new insights into the neurobiologic underpinnings that lead to social dysfunction in this psychiatric disorder. One of the greatest challenges in neuropsychiatric animal research is to reproduce and relate the clinical characteristics observed in humans to less complex animals. Given the heterogeneity of symptoms in schizophrenia, most animal models do not recreate the whole psychopathology of the disease, but instead, present certain aspects of the disorder (Brüne, 2009). Therefore, some models embody positive symptoms, while others try to characterize some of the negative symptoms, such as social isolation.

Interestingly, some of the behavioral abnormalities common to patients with schizophrenia also occur and can be assessed in rodents, and these are thus widely used to determine face and predictive validity of the psychiatric animal models. These behaviors can be examined by using sensorimotor gating experiments and by measuring social withdrawal. Sensorimotor gating refers to the filtering of external information that is trivial or unnecessary, such as the background noise of a party. Deficits in sensorimotor gating lead to an overload of sensory and cognitive processes that have been associated with impaired social behavior in patients with schizophrenia and in rodent models of schizophrenia (Duncan et al., 2004; Koh et al., 2007; Lijam et al., 1997). For instance, Wynn and colleagues showed that patients with schizophrenia who performed better in a sensorimotor gating test also performed better in a social perception task (Wynn et al., 2005). Thus, assessing the levels of sensorimotor gating is greatly informative in terms of social cognition and social behavior in both humans and animals. Sensorimotor gating impairments have been consistently found in patients with schizophrenia as well as their first-degree relatives (Kumari et al., 2005), and even though these deficits are not disease-specific, it has been repeatedly demonstrated to be a key characteristic of this group of psychiatric disorders. Moreover, most of the literature on sensorimotor gating has been addressed in schizophrenia given the reliability to replicate the results in this disease and its relationship to social cognition. However, patients diagnosed with other disorders, such as obsessive-compulsive disorder (Ahmari et al., 2012), Huntington disease (Swerdlow et al., 1995), or bipolar disorder with acute psychotic mania (Perry et al., 2001) have also been shown to exhibit deficits in sensorimotor gating, although all of these disorders present dysfunctions in sensory, motor, and/or cognitive information processing (Geyer, 2006). The most widely used test to assess the levels of sensorimotor gating is through pre-pulse inhibition (PPI), which occurs when the startle reaction to a particular stimulus (usually auditory but also visual and tactile) is decreased by presenting a weaker pre-stimulus before. Therefore, animals or people who do not display a decrease (or inhibition) of their startle reaction when a weak tone precedes a strong tone, as compared with when only a strong tone is presented, are considered to have reduced PPI, which is related to deficits in social cognition. The benefit of this test is that it can be measured in both humans and rodents and thus offers the possibility for translational approaches. In the case of social performance, several behavioral measures are used in rodents, such as mating behavior, nest building, and playful behavior. Hence, animal models that present deficits in these behaviors may help us learn the underlying mechanisms responsible for the social cognitive deficits found in schizophrenia.

Animal studies have found that several factors, including neurodevelopment (during and after pregnancy), brain lesions, genetic predisposition, and exposure to certain substances, induce abnormalities in PPI responses. For instance, neonatal rats exposed to epidermal growth factor (EGF), rats with lesions in the ventral and caudodorsal striatum (Kodsi and Swerdlow, 1995), rats treated with the adrenoreceptor agonist ciralozine (Carasso et al., 1998), and rats that are reared in isolation (Wilkinson et al., 1994) present deficits in this test. Neonatal lesions to the ventral part of the hippocampus (Sams-Dodd et al., 1997), basal amygdala (Decker et al., 1995; Wan and Swerdlow, 1997), and prefrontal cortex (PFC) (Schneider and Koch, 2005) in rats causes social interaction abnormalities as well as other schizophrenia-related behavioral malfunctions in juvenile and adults, as occurs in people with this disorder. Studies have shown that respiratory or immune infection of a pregnant mouse induces PPI deficits and social withdrawal in the offspring once they reach adulthood (Bitanihirwe et al., 2010; Shi et al., 2003; Wolff and Bilkey, 2008). Finally, several genes suggested to be partly responsible for the etiology of schizophrenia in humans (e.g., DISC 1, Neuregulin 1, ErbB4, Dysbindin) have been manipulated in animal models and have been linked to social deficits (Ehrlichman et al., 2009; Feng et al., 2008; Moy et al., 2009; O’Tuathaigh et al., 2007; Pletnikov et al., 2008). These studies emphasize the importance of environmental as well as genetic factors in the modulation of the PPI startle response and the ensuing induction of sociocognitive deficits in schizophrenia.

Neurotransmitters and Receptors Related to Social Cognition

Compatible with lesion, genetic, and immunodevelopmental manipulations, numerous animal studies have demonstrated a dysfunction in distinct neurotransmitter networks to explain the social deficits in schizophrenia. Altering the dopaminergic system by exposing rodents to direct and indirect dopamine agonists such as apomorphine, D-amphetamine, and cocaine disrupts PPI, and this effect has been suggested to be driven by the dopamine D₂-receptor family. The atypical antipsychotics clozapine, quetiapine, and olanzapine reverse the apomorphine-induced PPI deficits in both animals and humans with schizophrenia, implying the involvement of similar dopamine-dependent mechanisms for the induction of this dysfunction (Geyer and Moghaddam, 2001; Swerdlow and Geyer, 1998). Despite the evidence toward hyperactivity of the dopaminergic system, some authors have more recently suggested that the hyperdopaminergia is restricted to subcortical mesolimbic regions and mostly explains positive symptoms, while mesocortical projections to the PFC might indeed be characterized by dopamine hypofunction and may be related to the cognitive and negative symptomatology (Abi-Dargham and Moore, 2003; Kondiziella et al., 2007; Laruelle et al., 2003).

In addition to manipulation of the dopaminergic system, acute and chronic administration of the N-methyl-D-aspartate (NMDA) receptor noncompetitive antagonist phencyclidine (PCP) in rats and mice induces PPI deficits and social withdrawal (Lee et al., 2005; Mansbach and Geyer, 1989; Qiao et al., 2001; Sams-Dodd, 1995; Sams-Dodd, 1996). Some atypical antipsychotics, such as clozapine and olanzapine, but not typical ones, partially reverse the NMDA blocker-induced social disturbances (Qiao et al., 2001; Sams-Dodd, 1996). Other NMDA antagonists such as ketamine and MK-801 are also widely used in animal research to induce PPI deficits (Bast et al., 2000; Geyer and Moghaddam, 2001; Swerdlow et al., 1998). Interestingly, a mouse model where the NMDAR1 (NR1) has been knocked down (i.e., expressed in lower amounts) displays disturbances in both PPI and social behavior (Mohn et al., 1999). This is supported by findings showing that NMDA receptors and intracellular NMDA receptor-interacting proteins are dysregulated in patients with schizophrenia (Gao et al., 2000; Kristiansen et al., 2007). Finally, the con...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Preface
• Chapter 1. Neurobiologic Underpinnings of Social Cognition and Metacognition in Schizophrenia Spectrum Disorders
• Chapter 2. Cross-Cultural Aspects of Social Cognitive Abilities in Schizophrenia
• Chapter 3. Social Cognition during the Early Phase of Schizophrenia
• Chapter 4. Empathy
• Chapter 5. Memory-Related Metacognition in Patients with Schizophrenia
• Chapter 6. Metacognition in Schizophrenia Spectrum Disorders: Methods of Assessment and Associations with Psychosocial Function, Neurocognition, Symptoms, and Cognitive Style
• Chapter 7. The Impact of Metacognition on the Development and Maintenance of Negative Symptoms
• Chapter 8. Metacognition as a Framework to Understanding the Occurrence of Aggression and Violence in Patients with Schizophrenia
• Chapter 9. Social Cognition and Interaction Training: The Role of Metacognition
• Chapter 10. An Overview of Social Cognitive Treatment Interventions
• Chapter 11. Metacognitive Training and Therapy: An Individualized and Group Intervention for Psychosis
• Chapter 12. Metacognitively Focused Psychotherapy for People with Schizophrenia: Eight Core Elements That Define Practice
• Chapter 13. Adapted-Metacognitive Interpersonal Therapy Applied to Paranoid Schizophrenia: Promoting Higher Levels of Reflection on One’s and Others’ Minds, Awareness of Interpersonal Schemas, Differentiation, and Mastery of Social Problems
• Chapter 14. Triumphs and Tribulations in the Psychotherapy of Schizophrenia: Reflections from a Pilot Study of Metacognitive Narrative Psychotherapy
• Chapter 15. A Mentalization-Based Treatment Approach to Disturbances of Social Understanding in Schizophrenia
• Chapter 16. The Relationship Between Metacognitive Profile, Attachment Pattern, and Intersubjective Process in Psychotherapy of a Person Recovering from First-Episode Schizophrenia
• Chapter 17. Metacognition-Oriented Social Skills Training
• Chapter 18. Experimental Usage of Oxytocin to Combat Deficits in Social Cognition in Schizophrenia
• Chapter 19. Social Cognition and Metacognition in Schizophrenia: Research to Date and Directions for the Future
• Index