Soundless voices, silenced selves: are auditory verbal hallucinations in schizophrenia truly perceptual?

In much contemporary psychiatric training and practice, there is a strong emphasis on the audible or perceptual quality and externality of auditory verbal hallucinations in clinical assessments. A typical question during clinical assessment is asking whether the voices that a person hears sound identical to the way the clinician's voice is heard. In this Personal View, we argue that the most important factor in auditory verbal hallucinations in schizophrenia spectrum psychoses is a loss of first-person authority, and that a perceptual quality is not required for it to be this kind of hallucination. We draw on evidence from cognitive neuroscience showing that the activation of brain networks retrieved during capture of auditory verbal hallucinations that were experienced when a patient was in a functional MRI scanner does not match activation of networks retrieved during auditory perception. We propose that, despite early writings by Esquirol and Schneider that defined auditory verbal hallucinations as beliefs in perception rather than true perception, cognitive neuroscience, psychiatric training and practice, and patients adopting clinical vocabulary have been strongly influenced by the progression of the diagnostic criteria for schizophrenia, which increasingly place emphasis on language, such as the "full force" of a true perception. We hold that this change has resulted in an unhelpful top-down influence on the field, imposing perceptual qualities on auditory verbal hallucinations, and leading to misunderstandings and inaccuracies in clinical practice and patients' self-reports, and misinterpretations in cognitive neuroscience. We encourage a revision of the definition of auditory verbal hallucinations to move away from the necessity for auditory perception, and towards beliefs in perception due to the loss of first-person authority.

Measurement of brain glutathione with magnetic Resonance spectroscopy in Schizophrenia-Spectrum disorders - A systematic review and Meta-Analysis.

Oxidative stress may contribute to declining course and poor outcomes in psychosis. However, in vivo Magnetic Resonance Spectroscopy studies yield disparate results due to clinical stage, sample demographics, neuroanatomical focus, sample size, and acquisition method variations. We investigated glutathione in brain regions from participants with psychosis, and the relation of glutathione to clinical features and spectroscopy protocols. Meta-analysis comprised 21 studies. Glutathione levels did not differ between total psychosis patients (N = 639) and controls (N = 704) in the Medial Prefrontal region (k = 21, d = -0.09, CI = -0.28 to 0.10, p = 0.37). Patients with stable schizophrenia exhibited a small but significant glutathione reduction compared to controls (k = 14, d = -0.20, CI = -0.40 to -0.00, p = 0.05). Meta-regression showed older studies had greater glutathione reductions, possibly reflecting greater accuracy related to spectroscopy advancements in more recent studies. No significant effects of methodological variables, such as voxel size or echo time were found. Reduced glutathione in patients with stable established schizophrenia may provide novel targets for precision medicine. Standardizing MRS acquisition methods in future studies may help address discrepancies in glutathione levels.

Subjective experience and meaning of delusions in psychosis: a systematic review and qualitative evidence synthesis.

BACKGROUND: Delusions are a common transdiagnostic feature of psychotic disorders, and their treatment remains suboptimal. Despite the pressing need to better understand the nature, meaning, and course of these symptoms, research into the lived experience of delusional phenomena in psychosis is scarce. Thus, we aimed to explore the lived experience and subjective apprehension of delusions in help-seeking individuals with psychosis, regardless of diagnosis and thematic content of the delusion. METHODS: In our systematic review and qualitative evidence synthesis, we searched MEDLINE, Embase, PsycINFO, CINAHL, and Web of Science for qualitative studies published in English from database inception, with the last search on Sept 9, 2021. Grey literature search and hand-searching of relevant journals were also done. Studies were eligible if they provided an analysis of lived experience of delusions or predelusional phenomena presented from the perspective of individuals (age 14-65 years) who had developed a clinical high-risk stage of psychosis, or a diagnosable affective or non-affective psychotic disorder (as clinically defined, self-reported, or assessed within the primary study). Studies with only a subset of relevant participants were eligible only if data for the population of interest were reported separately. Studies that did not discriminate between the experience of delusion and other positive symptoms (eg, hallucinations) were included only if data for delusions were reported separately or could be extracted. First-person accounts (and author interpretations) discussing changes in the sense of self, lived world, and meaning in relation to delusions were extracted and synthesised using a novel thematic synthesis approach informed by a critical realist stance and a phenomenological theoretical framework. Analytic themes were developed into a new overarching framework for understanding the emergence of delusional phenomena. The study was registered with PROSPERO, CRD42020222104. FINDINGS: Of the 3265 records screened, 2115 were identified after duplicate removal. Of these, 1982 were excluded after title and abstract screening and 106 after full-text eligibility assessment. Of the 27 studies entering quality assessment, 24 eligible studies were included in the qualitative evidence synthesis, representing the perspectives of 373 help-seeking individuals with lived experience of delusions in the context of psychosis. Gender was reported as male (n=210), female (n=110), transgender (n=1), or not reported (n=52). Only 13 studies reported ethnicity, with White being predominant. The age of most participants ranged from 15 to 65 years. We found no eligible studies investigating subclinical or predelusional experiences in at-risk mental state populations through qualitative methods. Most studies were undertaken in western, educated, industrialised, rich, and democratic (WEIRD) societies, and most included participants had received or self-reported a diagnosis within the schizophrenia spectrum. Studies differed in relation to whether they focused on one kind or theme of delusion or delusional phenomena more generally as a unified category. Three superordinate themes relating to experiential changes and meanings in delusion were identified: (1) a radical rearrangement of the lived world dominated by intense emotions; (2) doubting, losing, and finding oneself again within delusional realities; and (3) searching for meaning, belonging, and coherence beyond mere dysfunction. Based on the review findings and thematic synthesis, we propose the Emergence Model of Delusion to advance understanding of delusional phenomena in psychosis. INTERPRETATION: Delusions are best understood as strongly individualised and inherently complex phenomena emerging from a dynamic interplay between interdependent subpersonal, personal, interpersonal, and sociocultural processes. Integrative approaches to research on delusion, which consider their potential adaptiveness and favour explanatory pluralism, might be advantageous. Effective clinical care for individuals with psychosis might need adapting to match more closely, and take account of, the subjective experience and meaning of delusions as they are lived through, which might also help redress power imbalances and enduring epistemic injustices in mental health. FUNDING: Priestley Scholars, Wellcome Trust.

Self-harm, suicidal ideation, and the positive symptoms of psychosis: Cross-sectional and prospective data from a national household survey.

BACKGROUND: Schizophrenia is associated with premature mortality, partly through increased suicide rates. AIMS: To examine (1) if persecutory ideas, auditory hallucinations, and probable cases of psychosis are associated with suicidal thoughts or attempts cross-sectionally and prospectively, and (2) if such links are mediated by specific affective factors (depression, impulsivity, mood instability). METHOD: We analysed the 2000, 2007, and 2014 British Adult Psychiatric Morbidity Surveys (APMS) separately. Measures of psychosis provided independent variables for multi-stage logistic regressions, with suicidal thoughts and attempts as dependent variables. We also conducted analyses to assess mediation by affective variables, and longitudinal analyses on a subset of the 2000 dataset. RESULTS: In every dataset, persecutory ideas, auditory hallucinations and probable psychosis were associated cross-sectionally with lifetime suicidal attempts and thoughts, even after controlling for confounders, with a single exception (persecutory ideation and suicide attempts were unconnected in APMS 2014). Cross-sectional associations between auditory hallucinations and suicidal phenomena were moderated by persecutory ideation. In the 2000 follow-up, initial persecutory ideas were associated with later suicidal thoughts (O.R. 1.77, p < 0.05); there were no other longitudinal associations. In the 2007 and 2014 datasets, mood instability mediated the effects of psychotic phenomena on suicidality more strongly than impulsivity; depression was also an important mediator. There were appreciable direct effects of positive symptoms on suicidal thoughts and behaviour. CONCLUSIONS: Improving psychotic symptoms and ameliorating co-morbid distress may in itself be effective in reducing suicidal risk in schizophrenia. Given their potential mediating role, mood instability and depression may also be targets for intervention.

The Sensory and Perceptual Scaffolding of Absorption, Inner Speech, and Self in Psychosis.

This study examines the interconnectedness between absorption, inner speech, self, and psychopathology. Absorption involves an intense focus and immersion in mental imagery, sensory/perceptual stimuli, or vivid imagination that involves decreased self-awareness and alterations in consciousness. In psychosis, the dissolution and permeability in the demarcation between self and one's sensory experiences and perceptions, and also between self-other and/or inter-object boundaries alter one's sense of self. Thus, as the individual integrates these changes new "meaning making" or understanding evolves as part of an ongoing inner dialogue and dialogue with others. This study consisted of 117 participants: 81 participants with psychosis and 36 controls. We first conducted a bivariate correlation to elucidate the relationship between absorption and inner speech. We next conducted hierarchical multiple regressions to examine the effect of absorption and inner speech to predict psychopathology. Lastly, we conducted a network analysis and applied extended Bayesian Information Criterion to select the best model. We showed that in both the control and psychosis group dialogic and emotional/motivational types of inner speech were strongly associated with absorption subscales, apart from the aesthetic subscale in the control group which was not significant, while in psychosis, condensed inner speech was uniquely associated with increased imaginative involvement. In psychosis, we also demonstrated that altered consciousness, dialogic, and emotional/motivational inner speech all predicted positive symptoms. In terms of network associations, imaginative involvement was the most central, influential, and most highly predictive node in the model from which all other nodes related to inner speech and psychopathology are connected. This study shows a strong interrelatedness between absorption, inner speech and psychosis thus identifying potentially fertile ground for future research and directions, particularly in the exploration into the underlying construct of imaginative involvement in psychotic symptoms.

Bipolar disorder: Prevalence, help-seeking and use of mental health care in England. Findings from the 2014 Adult Psychiatric Morbidity Survey.

BACKGROUND: To date, the lifetime prevalence of Bipolar Disorder (BD) and BD patients' access to mental health care in England has not been systematically studied. METHODS: We used data from the Adult Psychiatric Morbidity Survey 2014 (N = 7546). The Mood Disorders Questionnaire (MDQ) was used to screen for BD. Associations between sociodemographic and clinical variables and use of mental health services were investigated. Weighted regression modelling established factors associated with being in receipt of care for mental health problems over the last year. RESULTS: The lifetime prevalence of BD in the community in England was 1.7%. Approximately 40% had not received mental health care in the last year, and only 16.9% had received BD specific treatment. 14.6% had asked for a specific form of help but not received it. Psychopathology differed between individuals who successfully sought care and those who didn't. Obtaining care was independently associated with female sex (p<0.0001, odds ratio(OR):4.65 (Confidence Interval (CI):2.18-10.30), unemployment (p = 0.02, OR: 2.65 (C.I: 1.23-5.88) and suicidal ideation (p = 0.04, OR: 3.36, (C.I: 1.04-10.89). LIMITATIONS: The MDQ is less sensitive than some of the longer measures, especially in the general population. Some between-group comparisons may have suffered from limited power. CONCLUSIONS: The lifetime prevalence of BD in England was similar to rates worldwide. Most people with BD had not received any specific treatment for the condition in the last year, while 1 in 7 had requested specific help but did not receive it. Secondary mental health services in England for BD appear suboptimal.

Thinking, believing, and hallucinating self in schizophrenia.

In this Personal View, we discuss the history and concept of self-disturbance in relation to the pathophysiology and subjective experience of schizophrenia in terms of three approaches: the perceptual anomalies approach of the early Heidelberg School of Psychiatry, the ipseity model, and the predictive coding framework. Despite the importance of these approaches, there has been a notable absence of efforts to compare them and consider how they might be integrated. This Personal View compares the three approaches and offers suggestions as to how they might work together, which represents a novel position. We view self-disturbances as transformations of self that form the inseparable background against which psychotic symptoms emerge. Integrating computational psychiatric approaches with those used by phenomenologists in the first two listed approaches, we argue that delusions and hallucinations are inferences produced under extraordinary conditions and are both statistically and experientially as real for patients as other mental events. Such inferences still approximate Bayes-optimality, given the personal, neurobiological, and environmental circumstances, and might be the only ones available to minimise prediction error. The added contribution we hope to make focuses on how the dialogue between neuroscience and phenomenology might improve clinical practice. We hope this Personal View will act as a timely primer and bridging point for the different approaches of computational psychiatry and phenomenological psychopathology for interested clinicians.

From Computation to the First-Person: Auditory-Verbal Hallucinations and Delusions of Thought Interference in Schizophrenia-Spectrum Psychoses.

Schizophrenia-spectrum psychoses are highly complex and heterogeneous disorders that necessitate multiple lines of scientific inquiry and levels of explanation. In recent years, both computational and phenomenological approaches to the understanding of mental illness have received much interest, and significant progress has been made in both fields. However, there has been relatively little progress bridging investigations in these seemingly disparate fields. In this conceptual review and collaborative project from the 4th Meeting of the International Consortium on Hallucination Research, we aim to facilitate the beginning of such dialogue between fields and put forward the argument that computational psychiatry and phenomenology can in fact inform each other, rather than being viewed as isolated or even incompatible approaches. We begin with an overview of phenomenological observations on the interrelationships between auditory-verbal hallucinations (AVH) and delusional thoughts in general, before moving on to review several theoretical frameworks and empirical findings in the computational modeling of AVH. We then relate the computational models to the phenomenological accounts, with a special focus on AVH and delusions that involve the senses of agency and ownership of thought (delusions of thought interference). Finally, we offer some tentative directions for future research, emphasizing the importance of a mutual understanding between separate lines of inquiry.

The tangled roots of inner speech, voices and delusions.

The role of inner speech in the experience of auditory verbal hallucinations (AVH) and delusions remains unclear. This exploratory study tested for differences in inner speech (assessed via self-report questionnaire) between 89 participants with psychosis and 37 non-clinical controls. We also tested for associations of inner speech with, i) state/trait AVH, ii) AVH-severity; iii) patients' relations with their voices, and; iv) delusion-severity. Persons with psychosis had greater levels of dialogic inner speech, other people in inner speech, and evaluative/motivational inner speech than non-clinical controls. Those with state, but not trait AVH had greater levels of dialogic and evaluative/motivational inner speech than non-clinical controls. After controlling for delusions, there was a positive relation between AVH-severity and both evaluative/motivational inner speech and other people in inner speech. Participants with greater levels of dialogic inner speech reported better relations both with and between their voices. There was no association between delusion-severity and inner speech. These results highlight the importance of better understanding relations between inner speech and AVH, provide avenues for future research, and underscore the need for research into the interrelatedness of inner speech, voices and delusions, and the complexities involved in disentangling these experiences.

Evidence of absence: no relationship between behaviourally measured prediction error response and schizotypy.

INTRODUCTION: The predictive processing framework has attracted much interest in the field of schizophrenia research in recent years, with an increasing number of studies also carried out in healthy individuals with nonclinical psychosis-like experiences. The current research adopted a continuum approach to psychosis and aimed to investigate different types of prediction error responses in relation to psychometrically defined schizotypy. METHODS: One hundred and two healthy volunteers underwent a battery of behavioural tasks including (a) a force-matching task, (b) a Kamin blocking task, and (c) a reversal learning task together with three questionnaires measuring domains of schizotypy from different approaches. RESULTS: Neither frequentist nor Bayesian statistical methods supported the notion that alterations in prediction error responses were related to schizotypal traits in any of the three tasks. CONCLUSIONS: These null results suggest that deficits in predictive processing associated with clinical states of psychosis are not always present in healthy individuals with schizotypal traits.

Deficits in reality and internal source monitoring of actions are associated with the positive dimension of schizotypy.

People with schizophrenia have deficits in retrieving the source of memory information. Research has focused on two types of judgements: reality monitoring (discriminating internally-generated stimuli from external information) and internal source monitoring (distinguishing two different internal sources). The aim of the current study was to assess the relation between schizotypy and both types of source memory in healthy volunteers. One hundred and two participants completed two source memory tasks: one involved the completion of well-known word pairs (e.g. Fish and? ) and the other was an action based task (e.g. nod your head). At test participants needed to indicate whether the act had been performed or imagined by themselves, performed by the experimenter, or was new. The positive dimension of schizotypy was positively correlated with errors in internal source monitoring i.e. confusing participant performed and imagined acts. Furthermore, the same dimension of schizotypy was also positively associated with reality monitoring errors i.e. confusing participant performed/imagined with experimenter performed items. However, these relationships were not found in the word pair task. Our findings suggest that there might be overlap in the processes required to retrieve source information from memory, particularly for actions, and the occurrence of unusual experiences in healthy volunteers.

The relationship between different types of dissociation and psychosis-like experiences in a non-clinical sample.

This study investigated whether detachment-type dissociation, compartmentalisation-type dissociation or absorption was most strongly associated with psychosis-like experiences in the general population. Healthy participants (N=215) were tested with the Dissociative Experiences Scale (DES, for detachment-related dissociative experiences); the Harvard Group Scale of Hypnotic Susceptibility (HGSHS: A, for dissociative compartmentalisation); the Tellegen Absorption Scale (TAS, for non-clinical 'functional' dissociative experience); and two measures of psychotic-like experiences, the 21-item Peters et al. Delusions Inventory (PDI-21) and the Cardiff Anomalous Perceptions Scale (CAPS). In multiple regression analyses, DES and TAS but not HGSHS: A scores were found to be significantly associated with PDI-21 and CAPS overall scores. A post hoc hierarchical cluster analysis checking for cluster overlap between DES and CAPS items, and the TAS and CAPS items showed no overlap between items on the DES and CAPS and minimal overlap between TAS and CAPS items, suggesting the scales measure statistically distinct phenomena. These results show that detachment-type dissociation and absorption, but not compartmentalisation-type dissociation are significantly associated with psychosis-like experiences in a non-clinical population.

Investigating the roles of different monoamine transmitters and impulse control using the 5-choice serial reaction time task.

Previous studies have shown that drugs which block the reuptake of catecholamine neurotransmitters improve impulse control in diseases such as attention deficit hyperactivity disorder (ADHD). Serotonin-specific reuptake inhibitors (SSRI) lack efficacy in ADHD and have been linked to increased suicide risk. The present study investigated drugs with affinity for one or more of the monoamine reuptake transporters using the 5-choice serial reaction time task, a model of attention and impulsivity in rodents. We also tested the effects of the alpha(2)-adreoceptor antagonist, idazoxan and novel antidepressant, agomelatine, which both increase cortical noradrenaline concentrations through non-reuptake mechanisms. Improvements in impulse control were observed with venlafaxine, a serotonin and noradrenaline re-uptake inhibitor (SNRI) but not bupropion (dopamine and noradrenaline re-uptake inhibitor). Sibutramine (SNRI) reduced premature responses by ~50% at the highest dose tested but this was not significant. All three of the SSRIs tested reduced premature responding in a dose-dependent manner, although also slowed response and collection latencies. Neither idazoxan nor agomelatine significantly reduced premature responding, suggesting a lack of efficacy at the doses tested. None of the drugs tested improved attention in this task but sibutramine (SNRI), fluoxetine (SSRI) and paroxetine (SSRI) all increased omissions at the highest dose tested. These data suggest that the SNRIs and SSRIs reduce premature responding but tend to be less specific than noradrenaline specific reuptake inhibitors in this model. SSRIs did not induce any specific impairment in impulse control in this model.