Barnaby Nelson

University of Melbourne | MSD · National Centre of Excellence in Youth Mental Health

Background and hypothesis Transition to psychosis rates within ultra-high risk (UHR) services have been declining. It may be possible to ‘enrich’ UHR cohorts based on the environmental characteristics seen more commonly in first-episode psychosis cohorts. This study aimed to determine whether transition rates varied according to the accumulated exp...

Many individuals with psychotic symptoms have less complex language than healthy individuals. Word etymology is a lexical feature that has not yet been studied in clinical populations, but among healthy individuals, words of Old French origin are chosen over Germanic-origin words to convey formality (e.g. “inquire” vs. “ask”). Differences in langua...

Several multivariate prognostic models have been published to predict outcomes in patients with first episode psychosis (FEP), but it remains unclear whether those predictions generalize to independent populations. Using a subset of demographic and clinical baseline predictors, we aimed to develop and externally validate different models predicting...

The concept of ultra-high risk for psychosis (UHR) has been at the forefront of psychiatric research for several decades, with the ultimate goal of preventing the onset of psychotic disorder in high-risk individuals. Orygen (Melbourne, Australia) has led a range of observational and intervention studies in this clinical population. These datasets h...

Background Since the late 1990s, there has been a worldwide surge of scientific interest in the pre-psychotic phase, resulting in the introduction of several clinical tools for early detection. The predictive accuracy of these tools has been limited, motivating the need for methodological and perspectival improvements. The EASE manual supports syst...

Background and Hypothesis Cognition has been associated with socio-occupational functioning in individuals at Clinical High Risk for Psychosis (CHR-P). The present study hypothesized that clustering CHR-P participants based on cognitive data could reveal clinically meaningful subtypes. Study Design A cohort of 291 CHR-P subjects was recruited thro...

Aims To map studies assessing both clinical high risk for psychosis (CHR-P) and borderline personality disorder (BPD) in clinical samples, focusing on clinical/research/preventive paradigms and proposing informed research recommendations. Methods We conducted a PRISMA-ScR/JBI-compliant scoping review (protocol: https://osf.io/8mz7a) of primary res...

Aim Lithium, even at low doses, appears to offer neuroprotection against a wide variety of insults. In this controlled pilot, we examined the safety (i.e., side-effect profile) of lithium in a sample of young people identified at ultra-high risk (UHR) for psychosis. The secondary aim was to explore whether lithium provided a signal of clinical effi...

Importance Psychiatric disorders may come and go with symptoms changing over a lifetime. This suggests the need for a paradigm shift in diagnosis and treatment. Here we present a fresh look inspired by dynamical systems theory. This theory is used widely to explain tipping points, cycles, and chaos in complex systems ranging from the climate to eco...

Importance Dynamical systems theory is widely used to explain tipping points, cycles, and chaos in complex systems ranging from the climate to ecosystems. It has been suggested that the same theory may be used to explain the nature and dynamics of psychiatric disorders, which may come and go with symptoms changing over a lifetime. Here we review ev...

Background Pre-diagnostic stages of psychotic illnesses, including ‘clinical high risk’ (CHR), are marked by sleep disturbances. These sleep disturbances appear to represent a key aspect in the etiology and maintenance of psychotic disorders. We aimed to examine the relationship between self-reported sleep dysfunction and attenuated psychotic sympt...

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of...

Background The majority of individuals at ultra-high risk (UHR) for psychosis do not transition to a full threshold psychotic disorder. It is therefore important to understand their longer-term clinical and functional outcomes, particularly given the high prevalence of comorbid mental disorders in this population at baseline. Aims This study inves...

Background. Mental illnesses mostly occur before 25 years of age when early identification and intervention could delay, ameliorate, or prevent lifelong disability. However, several challenges hinder optimal psychiatric care in youth due to the diversity of presentations, comorbidities, illness courses, and treatment responses. It is increasingly c...

Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accu...

This review describes the Hierarchical Taxonomy of Psychopathology (HiTOP) model of psychosis-related psychopathology, the psychosis superspectrum. The HiTOP psychosis superspectrum was developed to address shortcomings of traditional diagnoses for psychotic disorders and related conditions including low reliability, arbitrary boundaries between ps...

Background Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especia...

Introduction Schizotypal disorder is associated with a high level of disability at an individual level and high societal costs. However, clinical recommendations for the treatment of schizotypal disorder are scarce and based on limited evidence. This review aims to synthesise the current evidence on treatment for schizotypal disorder making recomm...

OBJECTIVE: Disruptions of axonal connectivity are thought to be a core pathophysiological feature of psychotic illness, but whether they are present early in the illness, prior to antipsychotic exposure, and whether they can predict clinical outcome remains unknown. METHODS: We acquired diffusion-weighted MRI to map axonal connectivity between each...

Importance The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective To quantify deviations from the normative ran...

Schizotypy has been approached in various ways – as a dimension of personality, a personality disorder, and as a disorder within the schizophrenia spectrum. Many conditions, both in general medicine and in psychiatry, are now defined according to clinical stages. However, the clinical staging approach has not yet been applied to schizotypy. In this...

Importance Psychotic illness is associated with anatomically distributed gray matter reductions that can worsen with illness progression, but the mechanisms underlying the specific spatial patterning of these changes is unknown. Objective To test the hypothesis that brain network architecture constrains cross-sectional and longitudinal gray matter...

Importance Predicting the onset of bipolar disorder (BD) could facilitate preventive treatments. Among risk measures, bipolar at-risk (BAR) criteria have shown promise in predicting onset of bipolar disorder in the first year in clinical cohorts; however, it is not known whether BAR criteria are associated with the onset of BD in the longer term....

Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). Methods: The initial workshop is described in the companion report from Addin...

Background and hypotheses: Sleep disturbances are increasingly recognized as cooccurring with psychotic symptoms. The potential importance of this relationship is complicated when considering the effects of anxiety and depressive symptoms which commonly present in early-stage illness states. This study aimed to investigate the relationship between...

Aim: Basic self disturbance is a putative core vulnerability marker of schizophrenia spectrum disorders. The primary aims of the Self, Neuroscience and Psychosis (SNAP) study are to: (1) empirically test a previously described neurophenomenological self-disturbance model of psychosis by examining the relationship between specific clinical, neuroco...

Background: Basic self disturbance, or anomalous self experiences (ASEs), is a core feature of the schizophrenia spectrum. We propose a novel method of natural language processing (NLP) to quantify ASE's in spoken language by direct comparison to an inventory of self-disturbance, the Inventory of Psychotic-Like Anomalous Self-Experiences (IPASE)....

Importance: Clinical trials have not established the optimal type, sequence, and duration of interventions for people at ultrahigh risk of psychosis. Objective: To determine the effectiveness of a sequential and adaptive intervention strategy for individuals at ultrahigh risk of psychosis. Design, setting, and participants: The Staged Treatmen...

The drivers of cognitive change following first-episode psychosis remain poorly understood. Evidence regarding the role of antipsychotic medication is primarily based on naturalistic studies or clinical trials without a placebo arm, making it difficult to disentangle illness from medication effects. A secondary analysis of a randomised, triple-blin...

Objectives: The field of early psychosis has undergone considerable expansion over the last few decades and has a strong evidence base of effectiveness. Like all areas of healthcare, however, early psychosis services need to more consistently deliver higher quality care to achieve better outcomes for patients and families. A national clinical rese...

Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). Methods: The initial workshop is described in the companion report from Addingto...

Aims: Evidence for case-control studies suggests that cannabis use is a risk factor for the development of psychosis. However, there have been limited prospective studies and the direction of this association remains controversial. The primary aim of the present study was to examine the association between cannabis use and the incidence of psychot...

Both psychotic illness and subclinical psychosis-like experiences (PLEs) have been associated with cortico-striatal dysfunction. This work has largely relied on a discrete parcellation of the striatum into distinct functional areas, but recent evidence suggests that the striatum comprises multiple overlapping and smoothly varying gradients (i.e., m...

Staging models with transdiagnostic validity across mood, psychotic, and anxiety disorders could advance early intervention efforts as well as our understanding of the common underpinnings of such psychopathology. However, there are few well-supported operationalisations for such transdiagnostic models, particularly in community-based samples. We a...

Introduction Basic self-disorders (SDs) and neurocognitive impairments are fundamental trait-like aspects of schizophrenia spectrum disorders. There has been little research on the association between SDs and neurocognitive impairments in schizophrenia, and no longitudinal studies have investigated if they are related. The aim of this study was to...

Background: It is unclear whether there is a specific association between stressful experiences and obsessive-compulsive symptoms or whether this relationship is due to stressful experiences increasing risk for psychopathology generally. Aims: The current study examined the association between stressful experiences and obsessive-compulsive sympt...

Background Adverse childhood experiences (ACE) can affect educational attainments, but little is known about their impact on educational achievements in people at clinical high risk of psychosis (CHR). Methods In total, 344 CHR individuals and 67 healthy controls (HC) were recruited as part of the European Community’s Seventh Framework Programme-f...

Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in the majority of individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective: To quantify deviations from...

Background and hypothesis Around 20% of people at clinical high risk (CHR) for psychosis later develop a psychotic disorder, but it is difficult to predict who this will be. We assessed the incidence of hearing speech (termed speech illusions [SIs]) in noise in CHR participants and examined whether this was associated with adverse clinical outcomes...

BACKGROUND Low engagement rates with digital mental health interventions are a major challenge in the field. Multicomponent digital interventions aim to improve engagement by adding components such as social networks. Although social networks may be engaging, they may not be sufficient to improve clinical outcomes or lead users to engage with key t...

Background Low engagement rates with digital mental health interventions are a major challenge in the field. Multicomponent digital interventions aim to improve engagement by adding components such as social networks. Although social networks may be engaging, they may not be sufficient to improve clinical outcomes or lead users to engage with key t...

Preliminary evidence indicates beneficial effects of omega-3 polyunsaturated fatty acids (PUFAs) in early psychosis. The present study investigates the molecular mechanism of omega-3 PUFA-associated therapeutic effects in clinical high-risk (CHR) participants. Plasma samples of 126 CHR psychosis participants at baseline and 6-months follow-up were...

Background: Cardiovascular and metabolic diseases are the leading contributors to the early mortality associated with psychotic disorders. To date, it has not been possible to disentangle the effect of medication and non-medication factors on the physical health of people with a first episode of psychosis (FEP). This study aimed to isolate the eff...

Cognitive impairment is a well-documented predictor of transition to a full-threshold psychotic disorder amongst individuals at ultra-high risk (UHR) for psychosis. However, less is known about whether change in cognitive functioning differs between those who do and do not transition. Studies to date have not examined trajectories in intelligence c...

Background: Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population. Aims: To investigate whether omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation improves cognitive fun...

Basic self-disturbance (BSD) has been proposed as a driver of symptom development in schizophrenia spectrum disorders (SSDs). In a one-year follow-up of 32 patients (15–30 years) at putative risk for psychosis, we investigated trajectories of BSD levels from baseline to follow-up, and associations between clinical characteristics at baseline and fo...

The hypothesis of the psychosis continuum enables to study the mechanisms of psychosis risk not only in clinical samples but in non-clinical as well. The aim of this longitudinal study was to investigate self-disturbances (SD), a risk factor that has attracted substantial interest over the last two decades, in combination with trauma, cognitive bia...

Objective People at ultra-high risk (UHR) for psychosis have a high prevalence of tobacco smoking, and rates are even higher among the subgroup that later develop a psychotic disorder. However, the longitudinal relationship between the course of tobacco smoking and clinical outcomes in UHR subjects is unknown. Methods We investigated associations...

Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface are...

Objective To examine the association between baseline alterations in grey matter volume (GMV) and clinical and functional outcomes in people at clinical high risk (CHR) for psychosis. Methods 265 CHR individuals and 92 healthy controls were recruited as part of a prospective multi-centre study. After a baseline assessment using magnetic resonance...

Cognitive impairments in psychosis negatively impact functional recovery and quality of life. Existing interventions for improving cognitive impairment in recent-onset psychosis show inconsistent treatment efficacy, small effects, suboptimal engagement and limited generalizability to daily life functioning. In this perspective we explore how digita...

Background Pineal volume reductions have been reported in schizophrenia and clinical high-risk states for the development of psychosis, supporting the role of melatonin dysregulation in the pathophysiology of psychosis. However, it remains unclear whether pineal volume is associated with the later onset of psychosis in individuals at clinical high-...

Background Schizophrenia is characterized by disturbances in sense of self (ipseity) and heightened awareness of experiences normally tacit or implicit (hyperreflexivity), typically measured using the Inventory of Psychotic-Like Anomalous Self-Experiences (IPASE) clinical rating scale. Natural language processing (NLP) analyses of spoken language m...

Background: There is a higher incidence of psychotic disorders in neighbourhoods of greater social deprivation. However, it is not known whether this represents a causal relationship, as the stage at which social deprivation exerts its influence on the development of psychotic disorders is yet to be elucidated. We aimed to investigate the associat...

Background: Patients with schizophrenia have been shown to present with cognitive and language disturbances prior to the first psychosis onset. Previous studies have shown high classification accuracy using neurocognitive pattern classification to identifying patients with schizophrenia (SCZ) and individuals at clinical high risk (CHR) for psychosi...

Background The clinical high-risk for psychosis (CHR-P) paradigm was introduced to detect individuals at risk of developing psychosis and to establish preventive strategies. While current prediction of outcomes in the CHR-P state is based mostly on the clinical assessment of presenting features, several emerging biomarkers have been investigated in...

Background Functional outcomes are important measures in the overall clinical course of psychosis and individuals at clinical high-risk (CHR), however, prediction of functional outcome remains difficult based on clinical information alone. In the first part of this study, we evaluated whether a combination of biological and clinical variables could...

Objective Cognitive impairment occurs in antipsychotic-naïve first-episode psychosis (FEP), but antipsychotics confound interpretation of the longitudinal course of cognition. The primary aim was to disentangle the effects of illness from antipsychotics on cognition over the first 6-months of FEP treatment. Methods Randomised, triple-blind placebo...

Introduction: Despite the established finding that migrants are at higher risk of developing a first-episode psychosis, they are under-represented in cohorts of young people identified as being at ultra-high risk for psychosis (UHR). Therefore, in order to determine the reasons for these conflicting findings, this study examined the pathways to ca...

Background Services for young people identified as having an ‘at-risk mental state’ (ARMS) aim to prevent transition to first-episode psychosis (FEP), in addition, early intervention services for other mental health disorders have also been developed. The aim of the current study was to determine the proportion of young people attending a specialis...

Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signaling or impaired top-down cortical regulation. We used spectral dynamic causal modelling of resting-state function...

Aim: Research has shown that preventative intervention in individuals at ultra-high risk of psychosis (UHR) improves symptomatic and functional outcomes. The staged treatment in early psychosis (STEP) trial aims to determine the most effective type, timing and sequence of interventions in the UHR population by sequentially studying the effectivene...

Understanding longitudinal cognitive performance in individuals at ultra-high risk for psychosis (UHR) is important for informing theoretical models and treatment. A vital step in this endeavor is to determine whether there are UHR subgroups that have similar patterns of cognitive change over time. The aims were to: i) identify latent class traject...

Increased severity of neurological soft signs (NSS) in schizophrenia have been associated with abnormal brain morphology in cerebello-thalamo-cortical structures, but it is unclear whether similar structures underlie NSS prior to the onset of psychosis. The present study investigated the relationship between severity of NSS and grey matter volume (...

Background Negative symptoms occur in individuals at ultrahigh risk (UHR) for psychosis. Although there is evidence that observer ratings of negative symptoms are associated with level of functioning, the predictive value of subjective experience in daily life for individuals at UHR has not been studied yet. Objective This study therefore aims to...

Background: Cognitive impairment is a well-documented predictor of transition to a full-threshold psychotic disorder amongst individuals at ultra-high risk (UHR) for psychosis. However, less is known about whether change in cognitive functioning differs between those who do and do not transition to a psychotic disorder. Studies to date have not exa...

Purpose Migrant and ethnic minority populations exhibit a higher incidence of psychotic disorders. The Ultra-High Risk for psychosis (UHR) paradigm provides an opportunity to explore the stage at which such factors influence the development of psychosis. In this systematic review, we collate and appraise the literature on the association between et...

Objective Language used in psychiatry is important because it provides an understandable and accurate way of describing clinical and theoretical concepts. The use of labels in psychiatry has often been associated with stigma and reduced engagement with clinical services. This studys aims were to generate new terms for the ‘at-risk mental state’ (AR...