A glimpse forward regarding psychopathology of psychotic disorders

Issues related to early detection and intervention, primary prevention, and re-conceptualizing therapeutic targets are important current themes in psychosis research. Extensive heterogeneity within each diagnostic class and overlap in clinical features, risk factors and associated features between diagnostic classes, all result in critical limitations in clinical care and research. In this chapter, concrete approaches are suggested to make progress in psychosis research. Each partial solution has a different profile of strengths and weaknesses. New knowledge will be needed to make progress, and that knowledge will be acquired incrementally.

Health in a connected world

This chapter is about a redesign of mental healthcare, as it evolves in a changing world. It focuses on digital transformations and their impact on social relationships, networks, and communities. It intends to demonstrate better responses to the needs of service users in society. It first defines terminologies to access the changing world and focus on how to understand health, recovery, and well-being in people with lived experience of psychosis. These central elements can be accessed or maintained using eHealth, including mHealth, virtual reality, and eCommunities. It also discuss strengths, challenges, and pitfalls in developing and applying innovative interventions in the context of daily life. It reviews these trends and how these relate to the therapeutic relationship in general, and the mental health practitioner’s role in particular.

AVATAR therapy

AVATAR therapy is a newly developed treatment for auditory verbal hallucinations (AVH) that uses virtual reality technology to allow a three-way interaction between therapist, participant, and the entity the person believes is the source of their distressing auditory verbal hallucinations with the aim of reducing the perceived power and hostility of the persecutory voices. Two controlled trials, one a preliminary proof of concept and the second a larger powered clinical trial comparing AVATAR therapy with a supportive counseling control intervention, have demonstrated effectiveness in terms of reduced frequency, omnipotence, and associated distress of targeted AVH. This chapter reviews the present evidence and speculates on possible mechanism of action and future developments.

Family interventions in psychosis

Families can play an important role in supporting individuals living with psychosis disorders and helping to facilitate their improved outcomes. This chapter, offered by Juliana Onwumere and Elizabeth Kuipers, provides an overview of the literature reporting on family involvement in the care of adults with lived experiences of psychosis, the impact of the caregiving role on carer well-being, and the predictive links between caregiving relationships and key patient outcomes including relapse. The chapter reports on the application of family interventions, the evidence base supporting its application and inclusion in treatment guidelines, and implementation issues.

Glutamate in the pathophysiology of schizophrenia

Glutamate theories of schizophrenia were first proposed over 30 years ago and since that time have become increasingly accepted. Theories are supported by the ability of N-methyl-D-aspartate receptor (NMDAR) antagonists such as phencyclidine (PCP) or ketamine to induce symptoms that closely resemble those of schizophrenia. Moreover, NMDAR antagonists uniquely reproduce the level of negative symptoms and cognitive deficits observed in schizophrenia, suggesting that such models may be particularly appropriate to poor outcome forms of the disorder. As opposed to dopamine, which is most prominent within frontostriatal brain regions, glutamate neurons are present throughout cortex and subcortical structures. Thus, NMDAR theories predict widespread disturbances across cortical and thalamic pathways, including sensory brain regions. In auditory cortex, NMDAR play a critical role in the generation of mismatch negativity (MMN), which may therefore serve as a translational marker of NMDAR dysfunction across species. In the visual system, NMDAR play a critical role in function of the magnocellular visual system. Deficits in both auditory and visual processing contribute to social and communication deficits, which, in turn, lead to poor functional outcome. By contrast, NMDAR dysfunction within the frontohippocampal system may contribute to well described deficits in working memory, executive processing and long-term memory formation. Deficits in NMDAR function may be driven by disturbances in presynaptic glutamate release, impaired metabolism of NMDAR modulators such as glycine or D-serine, or intrinsic abnormalities in NMDAR themselves.

Self-awareness in schizophrenia

Unawareness of illness has been known to be a feature of schizophrenia since the first descriptions of the condition in the early 1900s. Recently it has become clear that unawareness, accompanied by perception biases, also extends to awareness of cognitive abilities, social cognition, and social competence, and the ability to perform everyday activities. These problems in awareness, referred to as introspective accuracy (IA), have several correlates, including depression, reduced life experience, and some elements of cognitive impairment. This chapter reviews the characteristics and correlates of IA impairments as well as their major functional implications. Although IA is also inaccurate in healthy people, the concurrent cognitive and environmental challenges experienced by people with schizophrenia increase their impact. Treatment of IA and related biases has been attempted, with some success in improving everyday outcomes in people with schizophrenia. Future challenges include identification of the neurobiological substrates of these impairments.

Understanding sex differences in psychosis through the exploration of hormonal contributions

Sex appears to modulate the risk, clinical presentation, and course of schizophrenia as well as other psychotic disorders. Sex differences in neuroendocrine and/or genetic factors may contribute to these sex differences as well as in social/emotional and cognitive functioning. The goal of this chapter is to better understand these sex differences through the exploration of hormonal contributions to this brain disorder. We specifically focus on sex steroid hormones (e.g., estrogen) as well as sexually dimorphic neurohormones—oxytocin and vasopressin.

Animal models of psychosis

The creation of a valid animal model is of crucial importance to the study of the biological mechanisms underlying disease pathophysiology. This becomes difficult when studying psychiatric illness, most especially psychosis, as humans’ mental state is a strictly internally experienced phenomenon, and thus the biological readout of these conditions is often a behavioral assessment. Therefore, when designing appropriate animal model systems and behavioral assessments for the study of psychiatric illness, it is necessary that appropriate measures be taken to ensure the systems and tasks used fulfill rigorous demands of validity. This chapter discusses different forms of validity, expanding on the classical validity measures of face, predictive, and construct validity. Specific examples of behavioral assessments and animal preparations that adhere to these specific definitions of validity are presented. These include specific experimental paradigms that can be similarly assessed in humans with psychosis and animal models, methods to create an animal preparation based on known psychosis triggers and risk factors, and pharmacological means to demonstrate relevance to the human condition. The chapter argues for a systematic approach to design, verify, and validate an animal model system for research into psychosis specifically, and other psychiatric disorders more generally, based on these different classes of validity.

Aberrant salience attribution and psychosis

Nearly two decades ago, Berridge and Robinson conceptualized a role for dopamine in motivational salience, and in 2003 it was invoked as an explanation for psychosis in schizophrenia. In the years since, research developing and testing the “aberrant salience hypothesis” has grown steadily. However even basic questions remain: How is salience calculated and attributed in the brain, and how can we measure it? How does it involve dopamine signaling and how does it go wrong? How does it change with the course of psychosis and with treatment? Does abnormal salience attribution underlie all psychoses? This chapter reviews fifteen years of research into aberrant salience processing in psychosis. It compares the different operationalizations of salience processing in online and offline tasks in controls and in various patient groups. It provides an up-to-date picture of the state of the art, and suggest directions for future research.

First-episode psychosis

Psychosis in the schizophrenia spectrum constitutes a major public health problem. There is convincing evidence for positive effects of 2-year specialized early intervention programs with intensive care, assertive outreach, and family involvement. Follow-up studies indicate a risk of loss of positive clinical effects after termination of specialized programs, but clinical effects can be sustained or even improved with prolonged specialized treatment or transfer to standard treatment, including assertive community treatment (ACT) for the most disabled patients. Long-term studies show substantial heterogeneity in clinical and functional outcomes, resulting in a very diverse picture. Ten-year follow-up studies of the OPUS and the AESOP cohort indicate that more than half of the patients will achieve stable remission of psychotic symptoms and that half of those patients can maintain remission in the long run without antipsychotic medication.