Addressing the elephant in the screening room: an item response theory analysis of the Prodromal Questionnaire (PQ-16) for at-risk symptoms of psychosis.

OBJECTIVE: Within the context of patients at-risk of psychosis, where a variety of symptoms are present, identifying the most discriminative symptoms is essential for efficient detection and management. METHODS: This cross-sectional online study analyzed individuals from the general population in order to better assess their risk of presenting symptoms belonging to the clinical high risk (CHR) for psychosis, called "CHR-related symptoms". The Prodromal Questionnaire-16 (PQ-16) served as a self-report screening tool. Item response theory (IRT) with a graded response model was used to assess the discrimination and difficulty of its criteria. RESULTS: The analysis included 936 participants (mean age: 21.5 years; 28.1% male, 71.9% female). "Déjà vu" stood out for its high discriminative power, while "Voices or whispers" and "Seen things" demonstrated strong precision relatively to the other CHR-related symptoms. Conversely, "Smell or taste" and "Changing face" were associated with the most severe cases relatively to the other CHR-related symptoms. CONCLUSION: This study identified the most indicative CHR-related symptoms to emphasize their significance in accurately assessing severity and guiding targeted preventative interventions.

Impacts of risk thresholds and age on clinical high risk for psychosis: a comparative network analysis.

One of the main goals for supporting people with a psychotic disorder is early detection and intervention, and the detection of Clinical High Risk (CHR) is a major challenge in this respect. This study sought to compare core symptoms of CHR for psychosis networks based on two CHR self-assessment tools, across different risk thresholds and age groups. This cross-sectional online investigation analyzed 936 individuals for CHR, in France and the UK, with the Prodromal Questionnaire-16 (PQ-16) and the Perceptual and Cognitive Aberrations (PCA). Twelve different symptom networks were constructed, assessing relationships, compactness, centrality, predictability, and comparisons between them, based on different thresholds and age groups. In the above-threshold PQ-16 network, the most central symptom was "Voices or whispers"; in the PCA network, the most central symptom was "Non-relevant thoughts distract or bother". They presented low overall predictability. No significant difference was found between them. This study makes three key contributions. First, this cross-network analyses highlight the relative importance of some central symptoms. Secondly, comparisons between networks demonstrate the unity of the CHR construct across scales, thresholds, and ages, affirming its phenotypic homogeneity, an essential issue for patient care pathways. Thirdly, the low average network predictability suggests the existence of unconsidered symptoms within these CHR networks. These results shed light on the organization of CHR symptoms using routine clinical questionnaires, offering insights for preventive targets in a logic of precision semiology.

Effects of a novel, brief psychological therapy (Managing Unusual Sensory Experiences) for hallucinations in first episode psychosis (MUSE FEP): Findings from an exploratory randomised controlled trial.

Hallucinations are a common feature of psychosis, yet access to effective psychological treatment is limited. The Managing Unusual Sensory Experiences for First-Episode-Psychosis (MUSE-FEP) trial aimed to establish the feasibility and acceptability of a brief, hallucination-specific, digitally provided treatment, delivered by a non-specialist workforce for people with psychosis. MUSE uses psychoeducation about the causal mechanisms of hallucinations and tailored interventions to help a person understand and manage their experiences. We undertook a two-site, single-blind (rater) Randomised Controlled Trial and recruited 82 participants who were allocated 1:1 to MUSE and treatment as usual (TAU) (n = 40) or TAU alone (n = 42). Participants completed assessments before and after treatment (2 months), and at follow up (3-4 months). Information on recruitment rates, adherence, and completion of outcome assessments was collected. Analyses focussed on feasibility outcomes and initial estimates of intervention effects to inform a future trial. The trial is registered with the ISRCTN registry 16793301. Criteria for the feasibility of trial methodology and intervention delivery were met. The trial exceeded the recruitment target, had high retention rates (87.8%) at end of treatment, and at follow up (86.6%), with good acceptability of treatment. There were 3 serious adverse events in the therapy group, and 5 in the TAU group. Improvements were evident in both groups at the end of treatment and follow up, with a particular benefit in perceived recovery in the MUSE group. We showed it was feasible to increase access to psychological intervention but a definitive trial requires further changes to the trial design or treatment.

The experience of felt presence in a general population sample.

Felt presence is a widely occurring experience, but remains under-recognised in clinical and research practice. To contribute to a wider recognition of the phenomenon, we aimed to assess the presentation of felt presence in a large population sample (n = 10 447) and explore its relation to key risk factors for psychosis. In our sample 1.6% reported experiencing felt presence in the past month. Felt presence was associated with visual and tactile hallucinations and delusion-like thinking; it was also associated with past occurrence of adverse events, loneliness and poor sleep. The occurrence of felt presence may function as a marker for general hallucination proneness.

What can neurodiversity tell us about inner speech, and vice versa? A theoretical perspective.

Inner speech refers to the experience of talking to oneself in one's head. While notoriously challenging to investigate, it has also been central to a range of questions concerning mind, brain, and behaviour. Posited as a key component in executive function and self-regulation, inner speech has been claimed to be crucial in higher cognitive operations, self-knowledge and self-awareness. Such arguments have traditionally been supported with examples of atypical development. But variations in inner speech - and in some cases, significant diversity - in fact pose several key challenges to such claims, and raises many more questions for, language, thought and mental health more generally. In this review, we will summarise evidence on the experience and operation of inner speech in child and adult neurotypical populations, autistic people and other neurodivergent groups, and people with diverse experiences of linguistic and sensory development, including deafness. We will demonstrate that the relationship between inner speech and cognitive operations may be more complex than first assumed when explored through the lens of cognitive and neurological diversity, and the implications of that for understanding the developing brain in all populations. We discuss why and how the experience of inner speech in neurodivergent groups has often been assumed rather than investigated, making it an important opportunity for researchers to develop innovative future work that integrates participatory insights with cognitive methodology. Finally, we will outline why variations in inner speech - in neurotypical and neurodivergent populations alike - nevertheless have a range of important implications for mental health vulnerability and unmet need. In this sense, the example of inner speech offers us both a way of looking back at the logic of developmental psychology and neuropsychology, and a clue to its future in a neurodiverse world.

The felt-presence experience: from cognition to the clinic.

The felt presence experience is the basic feeling that someone else is present in the immediate environment, without clear sensory evidence. Ranging from benevolent to distressing, personified to ambiguous, felt presence has been observed in neurological case studies and within psychosis and paranoia, associated with sleep paralysis and anxiety, and recorded within endurance sports and spiritualist communities. In this Review, we summarise the philosophical, phenomenological, clinical, and non-clinical correlates of felt presence, as well as current approaches that use psychometric, cognitive, and neurophysiological methods. We present current mechanistic explanations for felt presence, suggest a unifying cognitive framework for the phenomenon, and discuss outstanding questions for the field. Felt presence offers a sublime opportunity to understand the cognitive neuroscience of own-body awareness and social agency detection, as an intuitive, but poorly understood, experience in health and disorder.

Learning to Discern the Voices of Gods, Spirits, Tulpas, and the Dead.

There are communities in which hearing voices frequently is common and expected, and in which participants are not expected to have a need for care. This paper compares the ideas and practices of these communities. We observe that these communities utilize cultural models to identify and to explain voice-like events-and that there are some common features to these models across communities. All communities teach participants to "discern," or identify accurately, the legitimate voice of the spirit or being who speaks. We also observe that there are roughly two methods taught to participants to enable them to experience spirits (or other invisible beings): trained attention to inner experience, and repeated speech to the invisible other. We also observe that all of these communities model a learning process in which the ability to hear spirit (or invisible others) becomes more skilled with practice, and in which what they hear becomes clearer over time. Practice-including the practice of discernment-is presumed to change experience. We also note that despite these shared cultural ideas and practices, there is considerable individual variation in experience-some of which may reflect psychotic process, and some perhaps not. We suggest that voice-like events in this context may be shaped by cognitive expectation and trained practice as well as an experiential pathway. We also suggest that researchers could explore these common features both as a way to help those struggling with psychosis, and to consider the possibility that expectations and practice may affect the voice-hearing experience.

Hallucinations as a risk marker for suicidal behaviour in individuals with a history of sexual assault: a general population study with instant replication.

BACKGROUND: Research has shown a strong relationship between hallucinations and suicidal behaviour in general population samples. Whether hallucinations also index suicidal behaviour risk in groups at elevated risk of suicidal behaviour, namely in individuals with a sexual assault history, remains to be seen. AIMS: We assessed whether hallucinations were markers of risk for suicidal behaviour among individuals with a sexual assault history. METHODS: Using the cross-sectional 2007 (N = 7403) and 2014 (N = 7546) Adult Psychiatric Morbidity Surveys, we assessed for an interaction between sexual assault and hallucinations in terms of the odds of suicide attempt, as well as directly comparing the prevalence of suicide attempt in individuals with a sexual assault history with v. without hallucinations. RESULTS: Individuals with a sexual assault history had increased odds of hallucinations and suicide attempt compared to individuals without a sexual assault history in both samples. There was a significant interaction between sexual assault and hallucinations in terms of the odds of suicide attempt. In total, 14-19% of individuals with a sexual assault history who did not report hallucinations had one or more suicide attempt. This increased to 33-52% of individuals with a sexual assault history who did report hallucinations (2007, aOR = 2.85, 1.71-4.75; 2014, aOR = 4.52, 2.78-7.35). CONCLUSIONS: Hallucinations are a risk marker for suicide attempt even among individuals with an elevated risk of suicidal behaviour, specifically individuals with a sexual assault history. This finding highlights the clinical significance of hallucinations with regard to suicidal behaviour risk, even among high-risk populations.

Varieties of felt presence? Three surveys of presence phenomena and their relations to psychopathology.

BACKGROUND: Experiences of felt presence (FP) are well documented in neurology, neuropsychology and bereavement research, but systematic research in relation to psychopathology is limited. FP is a feature of sensorimotor disruption in psychosis, hypnagogic experiences, solo pursuits and spiritual encounters, but research comparing these phenomena remains rare. A comparative approach to the phenomenology of FP has the potential to identify shared and unique processes underlying the experience across these contexts, with implications for clinical understanding and intervention. METHODS: We present a mixed-methods analysis from three online surveys comparing FP across three diverse contexts: a population sample which included people with experience of psychosis and voice-hearing (study 1, N = 75), people with spiritual and spiritualist beliefs (study 2, N = 47) and practitioners of endurance/solo pursuits (study 3, N = 84). Participants were asked to provide descriptions of their FP experiences and completed questionnaires on FP frequency, hallucinatory experiences, dissociation, paranoia, social inner speech and sleep. Data and code for the study are available via OSF. RESULTS: Hierarchical linear regression analysis indicated that FP frequency was predicted by a general tendency to experience hallucinations in all three studies, although paranoia and gender (female > male) were also significant predictors in sample 1. Qualitative analysis highlighted shared and diverging phenomenology of FP experiences across the three studies, including a role for immersive states in FP. CONCLUSIONS: These data combine to provide the first picture of the potential shared mechanisms underlying different accounts of FP, supporting a unitary model of the experience.

Prevalence and nature of multi-sensory and multi-modal hallucinations in people with first episode psychosis.

Hallucinations can occur in single or multiple sensory modalities. This study explored how common these experiences were in people with first episode of psychosis (n = 82). Particular attention was paid to the number of modalities reported and whether the experiences were seen to be linked temporally and thematically. It was predicted that those people reporting a greater number of hallucinations would report more delusional ideation, greater levels of distress generally and lower functioning. All participants reported hallucinations in the auditory domain, given the nature of the recruitment. The participants also reported a range of other unusual sensory experiences, with visual and tactile hallucinations being reported by over half. Moreover, single sensory experiences or unimodal hallucinations were less common than two or more hallucination modalities which was reported by 78% of the participants. The number of hallucinations was significantly associated with greater delusional ideation and higher levels of general distress, but not with reduced functioning. It is clear there is a need to refine psychological treatments so that they are better matched to the actual experiences reported by people with psychosis. Theoretical implications are also considered.

Continuities and Discontinuities in the Cognitive Mechanisms Associated With Clinical and Nonclinical Auditory Verbal Hallucinations.

Auditory verbal hallucinations (AVHs) are typically associated with schizophrenia but also occur in individuals without any need for care (nonclinical voice hearers [NCVHs]). Cognitive models of AVHs posit potential biases in source monitoring, top-down processes, or a failure to inhibit intrusive memories. However, research across clinical/nonclinical groups is limited, and the extent to which there may be continuity in cognitive mechanism across groups, as predicted by the psychosis-continuum hypothesis, is unclear. We report two studies in which voice hearers with psychosis (n = 31) and NCVH participants reporting regular spiritual voices (n = 26) completed a battery of cognitive tasks. Compared with non-voice-hearing groups (ns = 33 and 28), voice hearers with psychosis showed atypical performance on signal detection, dichotic listening, and memory-inhibition tasks but intact performance on the source-monitoring task. NCVH participants, however, showed only atypical signal detection, which suggests differences between clinical and nonclinical voice hearers potentially related to attentional control and inhibition. These findings suggest that at the level of cognition, continuum models of hallucinations may need to take into account continuity but also discontinuity between clinical and nonclinical groups.

Voice-Hearing Across The Continuum: A Phenomenology of Spiritual Voices.

BACKGROUND AND HYPOTHESIS: Voice-hearing in clinical and nonclinical groups has previously been compared using standardized assessments of psychotic experiences. Findings from several studies suggest that nonclinical voice-hearing is distinguished by reduced distress and increased control. However, symptom-rating scales developed for clinical populations may be limited in their ability to elucidate subtle aspects of nonclinical voices. Moreover, such experiences often occur within specific contexts and belief systems, such as spiritualism. We investigated similarities and differences in the phenomenology of clinical voice-hearing and nonclinical voice-hearer (NCVH). STUDY DESIGN: We conducted a comparative interdisciplinary study which administered a semi-structured interview to NCVH individuals (N = 26) and psychosis patients (N = 40). The nonclinical group was recruited from spiritualist communities. We used content analysis and inductive thematic analysis to create a coding frame which was used across both spiritual and patient groups to compare phenomenological features of voice-hearing. STUDY RESULTS: The findings were consistent with previous results regarding distress and control. Additionally, in the NCVH group, multiple modalities were often integrated into 1 entity, and there were high levels of associated visual imagery, and subtle differences in the location of voices relating to perceptual boundaries. Most NCVHs reported voices before encountering spiritualism, suggesting that their onset was not solely due to deliberate practice. CONCLUSIONS: Nonclinical spiritual voice-hearing has important similarities and differences to voices in psychosis. Future research should aim to understand how spiritual voice-hearers cultivate and control voice-hearing after its onset, which may inform interventions for people with psychosis with distressing voices.

Managing Unusual Sensory Experiences in People with First-Episode Psychosis (MUSE FEP): a study protocol for a single-blind parallel-group randomised controlled feasibility trial.

INTRODUCTION: Hallucinations (hearing or seeing things that others do not) are a common feature of psychosis, causing significant distress and disability. Existing treatments such as cognitive-behavioural therapy for psychosis (CBTp) have modest benefits, and there is a lack of CBTp-trained staff. Shorter, targeted treatments that focus on specific symptoms delivered by a non-specialist workforce could substantially increase access to treatment.Managing Unusual Sensory Experiences (MUSE) explains why people have hallucinations and helps the person to develop and use coping strategies to reduce distress. MUSE focuses only on hallucinations, and treatment is short (four to six, 1-hour sessions per week). It is a digital intervention, run on National Health Service (NHS) laptops, which provides information about hallucinations in an engaging way, using audio, video and animated content. Crucially, it is designed for use by non-specialist staff like community psychiatric nurses. METHODS AND ANALYSIS: The study is a two-arm feasibility randomised controlled trial comparing MUSE and treatment as usual (TAU) (n=40) to TAU alone (n=40), recruiting across two NHS Trusts, using 1:1 allocation and blind assessments before and after treatment (2 months) and at follow-up (3 months). Quantitative information on recruitment rates, adherence and completion of outcome assessments will be collected. Qualitative interviews will capture service users' experience of therapy and clinicians' experiences of the training and supervision in MUSE. Clinicians will also be asked about factors affecting uptake, adherence and facilitators/barriers to implementation. Analyses will focus on feasibility outcomes and provide initial estimates of intervention effects. Thematic analysis of the qualitative interviews will assess the acceptability of the training, intervention and trial procedures. ETHICS AND DISSEMINATION: The trial has received NHS Ethical and Health Research Authority approval. Findings will be disseminated directly to participants and services, as well as through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN16793301.

Susceptibility to auditory hallucinations is associated with spontaneous but not directed modulation of top-down expectations for speech.

Auditory verbal hallucinations (AVHs)-or hearing voices-occur in clinical and non-clinical populations, but their mechanisms remain unclear. Predictive processing models of psychosis have proposed that hallucinations arise from an over-weighting of prior expectations in perception. It is unknown, however, whether this reflects (i) a sensitivity to explicit modulation of prior knowledge or (ii) a pre-existing tendency to spontaneously use such knowledge in ambiguous contexts. Four experiments were conducted to examine this question in healthy participants listening to ambiguous speech stimuli. In experiments 1a (n = 60) and 1b (n = 60), participants discriminated intelligible and unintelligible sine-wave speech before and after exposure to the original language templates (i.e. a modulation of expectation). No relationship was observed between top-down modulation and two common measures of hallucination-proneness. Experiment 2 (n = 99) confirmed this pattern with a different stimulus-sine-vocoded speech (SVS)-that was designed to minimize ceiling effects in discrimination and more closely model previous top-down effects reported in psychosis. In Experiment 3 (n = 134), participants were exposed to SVS without prior knowledge that it contained speech (i.e. naïve listening). AVH-proneness significantly predicted both pre-exposure identification of speech and successful recall for words hidden in SVS, indicating that participants could actually decode the hidden signal spontaneously. Altogether, these findings support a pre-existing tendency to spontaneously draw upon prior knowledge in healthy people prone to AVH, rather than a sensitivity to temporary modulations of expectation. We propose a model of clinical and non-clinical hallucinations, across auditory and visual modalities, with testable predictions for future research.

"Figuring out how to be normal": Exploring how young people and parents make sense of voice-hearing in the family context.

OBJECTIVES: Making sense of voice-hearing-exploring the purpose, cause, and relationship with voices-is seen as therapeutically valuable for adults, but there is a paucity of research with adolescents. Family intervention is recommended for young people, yet little is known about families' perspectives on, or role in, a child's voice-hearing. This study therefore aimed to explore how both young people and parents had made sense of voice-hearing in the family context. METHOD: Semi-structured interviews were conducted with seven young people who hear voices (six females, one male, age M = 17 years) and six parents of young people who hear voices (five females, one male). Data were analysed using interpretative phenomenological analysis. RESULTS: The young people struggled to reconcile their voice-hearing experiences within themselves, wanted control, 'normality', and not to let their mental health hold them back. Parents saw the voices as separate to their child, who they were protective of, and came to an acceptance and hope for the future amidst continued uncertainty. Pragmatism, and shame, ran through parents' and young people's accounts. Tensions between them, such as autonomy versus involvement, were also apparent. CONCLUSIONS: Few participants had made sense of their experiences in any concrete form, yet hope, control, and getting on with their lives were not conditional on having done so. Young people valued the family as a safe, non-enquiring space to be 'normal' and not to talk about their experiences. While all had been challenged by their experiences, an energy and strength ran through their accounts.

Hearing spiritually significant voices: A phenomenological survey and taxonomy.

Whereas previous research in the medical humanities has tended to neglect theology and religious studies, these disciplines sometimes have a very important contribution to make. The hearing of spiritually significant voices provides a case in point. The context, content and identity of these voices, all of which have typically not been seen as important in the assessment of auditory-verbal hallucinations (AVHs) within psychiatry, are key to understanding their spiritual significance. A taxonomy of spiritually significant voices is proposed, which takes into account frequency, context, affect and identity of the voice. In a predominantly Christian sample of 58 people who reported having heard spiritually significant voices, most began in adult life and were infrequent experiences. Almost 90% reported that the voice was divine in identity and approximately one-third were heard in the context of prayer. The phenomenological characteristics of these voices were different from those in previous studies of voice hearing (AVHs). Most comprised a single voice; half were auditory; and a quarter were more thought-like (the rest being a mixture). Only half were characterful, and one-third included commands or prompts. The voices were experienced positively and as meaningful. The survey has implications for both clinical and pastoral work. The phenomenology of spiritually significant voices may be confused with that of psychopathology, thus potentially leading to misdiagnosis of normal religious experiences. The finding of meaning in content and context may be important in voice hearing more widely, and especially in coping with negative or distressing voices.

Measurement practices in hallucinations research.

Introduction: In several sub-fields of psychology, there has been a renewed focus on measurement practices. As far as we are aware, this has been absent in hallucinations research. Thus, we investigated (a) cross-study variation in how hallucinatory experiences are measured and (b) the reliability of measurements obtained using two tasks that are widely employed in hallucinations research.Method: In Study 1, we investigated to what extent there was variation in how the Launay-Slade Hallucination Scale (LSHS) has been used across 100 studies. In Study 2, we investigated the reliability of the measurements obtained through source monitoring and signal detection tasks, using data from four recent publications. Materials/data are available at doi: 10.17605/osf.io/d3gnk/.Results: In Study 1, we found substantial variation in how hallucinatory experiences were assessed using the LSHS and that descriptions of the LSHS were often incomplete in important ways. In Study 2, we reported a range of reliability estimates for the measurements obtained using source monitoring and signal discrimination tasks. Some measurements obtained using source monitoring tasks had unacceptably low levels of reliability.Conclusions: Our findings suggest that suboptimal measurement practices are common in hallucinations research and we suggest steps researchers could take to improve measurement practices.

Deep Learning for Protein-Protein Interaction Site Prediction.

Protein-protein interactions (PPIs) are central to cellular functions. Experimental methods for predicting PPIs are well developed but are time and resource expensive and suffer from high false-positive error rates at scale. Computational prediction of PPIs is highly desirable for a mechanistic understanding of cellular processes and offers the potential to identify highly selective drug targets. In this chapter, details of developing a deep learning approach to predicting which residues in a protein are involved in forming a PPI-a task known as PPI site prediction-are outlined. The key decisions to be made in defining a supervised machine learning project in this domain are here highlighted. Alternative training regimes for deep learning models to address shortcomings in existing approaches and provide starting points for further research are discussed. This chapter is written to serve as a companion to developing deep learning approaches to protein-protein interaction site prediction, and an introduction to developing geometric deep learning projects operating on protein structure graphs.

Utilizing graph machine learning within drug discovery and development.

Graph machine learning (GML) is receiving growing interest within the pharmaceutical and biotechnology industries for its ability to model biomolecular structures, the functional relationships between them, and integrate multi-omic datasets - amongst other data types. Herein, we present a multidisciplinary academic-industrial review of the topic within the context of drug discovery and development. After introducing key terms and modelling approaches, we move chronologically through the drug development pipeline to identify and summarize work incorporating: target identification, design of small molecules and biologics, and drug repurposing. Whilst the field is still emerging, key milestones including repurposed drugs entering in vivo studies, suggest GML will become a modelling framework of choice within biomedical machine learning.

Voice-Hearing and Personification: Characterizing Social Qualities of Auditory Verbal Hallucinations in Early Psychosis.

Recent therapeutic approaches to auditory verbal hallucinations (AVH) exploit the person-like qualities of voices. Little is known, however, about how, why, and when AVH become personified. We aimed to investigate personification in individuals' early voice-hearing experiences. We invited Early Intervention in Psychosis (EIP) service users aged 16-65 to participate in a semistructured interview on AVH phenomenology. Forty voice-hearers (M = 114.13 days in EIP) were recruited through 2 National Health Service trusts in northern England. We used content and thematic analysis to code the interviews and then statistically examined key associations with personification. Some participants had heard voices intermittently for multiple years prior to clinical involvement (M = 74.38 months), although distressing voice onset was typically more recent (median = 12 months). Participants reported a range of negative emotions (predominantly fear, 60%, 24/40, and anxiety, 62.5%, 26/40), visual hallucinations (75%, 30/40), bodily states (65%, 25/40), and "felt presences" (52.5%, 21/40) in relation to voices. Complex personification, reported by a sizeable minority (16/40, 40%), was associated with experiencing voices as conversational (odds ratio [OR] = 2.56) and companionable (OR = 3.19) but not as commanding or trauma-related. Neither age of AVH onset nor time since onset related to personification. Our findings highlight significant personification of AVH even at first clinical presentation. Personified voices appear to be distinguished less by their intrinsic properties, commanding qualities, or connection with trauma than by their affordances for conversation and companionship.