Andrew Thompson

• MA (Oxon), MBBS, MMedSci, MD, FRANZCP, FRCPsych
• Professor at Orygen

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...

Background: Overweight and obesity are highly prevalent in people with severe mental illness (SMI). Antipsychotic-induced weight gain (AIWG) is one of the most commonly reported and distressing side effects of treatment and people living with SMI place a high value on the avoidance of this side effect. Metformin is the most effective pharmacologica...

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 In Australia, the first nationwide COVID-19 lockdown occurred in March 2020 bringing challenges for early intervention psychosis (EIP) services. Limited evidence exists on the impacts of the pandemic on treatment outcomes among EIP clients. Methods This prospective cohort study analysed routine data from 15 headspace Early Psychosis cen...

The Accelerating Medicines Partnership Schizophrenia (AMP® SCZ) program integrates lived experience into psychosis research, leveraging over three decades of foundational studies to improve research quality, promote community engagement, and ensure ethical implementation of precision psychiatry. Lived experience is embedded in the program’s governa...

Clinical ascertainment and clinical outcome are key features of any large multisite study. In the ProNET and PRESCIENT research networks, the Accelerating Medicines Partnership® Schizophrenia (AMP®SCZ) Clinical Ascertainment and Outcome Measures Team aimed to establish a harmonized clinical assessment protocol across these two research networks and...

Background Current treatments for schizophrenia and other psychotic disorders have limited efficacy, with high rates of nonresponse to “gold standard” treatments. New approaches are therefore urgently required. Objective The aims of this pilot study are to investigate the feasibility, acceptability, safety, and usability of Hybrid treatment (prima...

Cognitive impairment occurs at higher rates in individuals at clinical high risk (CHR) for psychosis relative to healthy peers, and it contributes unique variance to multivariate prediction models of transition to psychosis. Such impairment is considered a core biomarker of schizophrenia. Thus, cognition is a key domain measured in the Accelerating...

Background To improve early intervention and personalise treatment for individuals early on the psychosis continuum, a greater understanding of symptom dynamics is required. We address this by identifying and evaluating the movement between empirically derived attenuated psychotic symptomatic substates—clusters of symptoms that occur within individ...

Background Although cognitive remediation (CR) improves cognition and functioning, the key features that promote or inhibit its effectiveness, especially between cognitive domains, remain unknown. Discovering these key features will help to develop CR for more impact. AimTo identify interrelations between cognition, symptoms, and functioning, using...

Aim Accurate and appropriate cognitive screening can significantly enhance early psychosis care, yet no screening tools have been validated for the early psychosis population and little is known about current screening practices, experiences, or factors that may influence implementation. CogScreen is a hybrid type 1 study aiming to validate two pro...

Dysregulation of inflammatory mediators and complement cascade proteins has been implicated in psychosis. In the current study, we aimed to investigate the relationship between complement cascade proteins and inflammatory cytokines in blood from people at clinical high risk (CHR) for psychosis and at first episode of psychosis (FEP). Baseline blood...

Background Almost 40% of individuals at ultra-high risk (UHR) for psychosis experience persistent attenuated psychotic symptoms (APS) yet it is unclear (1) whether they share overlapping clinical and functional outcomes compared to individuals who transition to psychosis, (2) when symptom and functioning trajectories begin to diverge between UHR in...

BACKGROUND Third-wave psychological treatments, such as Acceptance and Commitment Therapy (ACT), can be effective for improving depression and anxiety in youth. However, third-wave therapeutic techniques such as cognitive defusion can be abstract, challenging to learn, and difficult to apply in real-world settings. Translating these techniques into...

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...

Background Suicide is the fourth leading cause of death among young people aged 15–29 worldwide. Young people often present to emergency departments (EDs) with self-harm and suicide-related behaviors. The period following discharge from the ED is recognized as one of elevated risk for both repeated self-harm and suicide. During this critical time,...

Aims Young people with first-episode psychosis (FEP) or at ultra-high risk (UHR) of psychosis often have lower vocational engagement than their peers. This study examines the effect of treatment in early intervention for psychosis services in Australia on engagement in education and employment. Methods This is a naturalistic sample of young people...

Objective: The current guidelines recommend continuation of antipsychotic medication for a minimum of at least 1 year following a first episode of psychosis (FEP). There have been several trials investigating whether early dose reduction or cessation leads to improved functional outcomes. The aim of this study was to explore the experience of conse...

BACKGROUND Current treatments for schizophrenia and other psychotic disorders have limited efficacy, with high rates of nonresponse to “gold standard” treatments. New approaches are therefore urgently required. OBJECTIVE The aims of this pilot study are to investigate the feasibility, acceptability, safety, and usability of Hybrid treatment (prima...

Aim Cognitive impairments are a core feature of first‐episode psychosis (FEP) and one of the strongest predictors of long‐term psychosocial functioning. Cognition should be assessed and treated as part of routine clinical care for FEP. Cognitive screening offers the opportunity to rapidly identify and triage those in most need of cognitive support....

Background Despite being the most effective antipsychotic medication for treatment-resistant psychosis, clozapine is often under-utilized with long delays to initiation. Aims This study aimed to determine whether the integration of a clozapine clinic within an early intervention for psychosis service resulted in a change in the rate and time to in...

Background: Suicide is the fourth leading cause of death among young people aged 15–29 worldwide. Young people often present to emergency departments (EDs) with self-harm and suicide related behaviors. The period following discharge from the ED is recognized as one of elevated risk for both repeated self-harm and suicide. During this critical time,...

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 Young people with mental ill-health experience higher rates of high-risk sexual behaviour, have poorer sexual health outcomes, and lower satisfaction with their sexual wellbeing compared to their peers. Ensuring good sexual health in this cohort is a public health concern, but best practice intervention in the area remains under-research...

Background To provide precision cognitive remediation therapy (CR) for schizophrenia, we need to understand whether the mechanism for improved functioning is via cognition improvements. This mechanism has not been rigorously tested for potential moderator effects. Study Design We used data (n = 377) from a randomized controlled trial using CIRCuiT...

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...

Cognitive Remediation (CR) improves cognition and functioning but is implemented in a variety of ways (independent, group and one-to-one). There is no information on whether service users find these implementation methods acceptable or if their satisfaction influences CR outcomes. We used mixed participatory methods, including focus groups, to co-d...

Aim: Vitamin D deficiency is prevalent in people with established psychotic disorders, but less is known about vitamin D levels in people with first-episode psychosis (FEP). This study aimed to determine the prevalence of vitamin D deficiency in people with FEP and identify the factors associated with vitamin D status. Methods: This was a prospe...

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...

Background Young people with mental ill-health have higher rates of high-risk sexual behaviour, poorer sexual health outcomes, and lower satisfaction with their sexual wellbeing compared to their peers. Ensuring good sexual health in this cohort is a public health concern, but best practice intervention in the area remains under-researched. The stu...

Objective: Early intervention for psychosis services result in superior outcomes in the domains of symptomatic and functional recovery, hospitalisation and employment compared to standard services; however, the optimal duration of care with these services is unknown. Knowledge on the discharge destinations, specifically the proportion discharged t...

Objective Integrating digital technologies with clinical practice promises to improve access and enhance care in the context of high service demand and constrained capacity. Method We outline the emerging research in the integration of digital tools in clinical care, known as blended care, and provide case examples of mental health technology plat...

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...

Background and Hypothesis Cognitive remediation (CR) benefits cognition and functioning in psychosis but we do not know the optimal level of therapist contact, so we evaluated the potential benefits of different CR modes. Study Design A multi-arm, multi-center, single-blinded, adaptive trial of therapist-supported CR. Participants from 11 NHS earl...

The COVID-19 pandemic has presented profound disruptions to young people at a critical period of psychosocial development. The current study aimed to explore the perceived negative and positive impacts of the COVID-19 pandemic on young people's mental health and wellbeing across a spectrum of clinical needs. A cross-sectional online survey includin...

Background Substance use remains a barrier to recovery for young people accessing early intervention services for psychosis. While correlates of use have been explored in populations experiencing a first episode of psychosis (FEP), sample sizes have been small and less research assesses cohorts at ultrahigh risk of psychosis (UHR). Methods This st...

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: Factors that contribute to the early mortality observed in psychotic disorders, specifically obesity, smoking and sedentary behaviour, occur early in the disorder. Aims: We aimed to determine whether the integration of a physical health nurse in the care of young people with first-episode psychosis could prevent clinically significan...

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...

Background: The role of antipsychotic medication in supporting young people in their recovery from early psychosis is complex and controversial. It is common for young people, often given antipsychotic medication for the first time, to express a choice to stop treatment, potentially increasing the risk of relapse and admission to hospital. Our sys...

Background Adolescent depression can place a young person at high risk of recurrence and a range of psychosocial and vocational impairments in adult life, highlighting the importance of early recognition and prevention. Parents/carers are well placed to notice changes in their child’s emotional wellbeing which may indicate risk, and there is increa...

Background: Substance use remains a barrier to recovery for young people accessing early intervention services for psychosis. While correlates of use have been explored in populations experiencing a First Episode of Psychosis (FEP), sample sizes have been small and less research assesses cohorts at Ultra-High Risk of psychosis (UHR). Methods: This...

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 Early warning signs monitoring by service users with schizophrenia has shown promise in preventing relapse but the quality of evidence is low. We aimed to establish the feasibility of undertaking a definitive randomised controlled trial to determine the effectiveness of a blended digital intervention for relapse prevention in schizophren...

Background Following the emergence of COVID-19 in the UK, on March 18 th 2020 the majority of schools in England closed and families and teachers were tasked with providing educational support for children and adolescents within the home environment. Little is known, however, regarding the impact of remote teaching and learning on the mental wellbe...

Psychopharmacology has long been considered central to prevention in mental health care, most often in relation to averting relapse. In recent decades, mental states that precede full-threshold disorders have been identified. These states, known as ‘at-risk’ states, commonly occur in young people from early teens to mid-20s. This has led to signifi...

Background Relapse is a major determinant of outcome for people with a diagnosis of schizophrenia. Early warning signs frequently precede relapse. A recent Cochrane Review found low-quality evidence to suggest a positive effect of early warning signs interventions on hospitalisation and relapse. Objective How feasible is a study to investigate the...

Background Adolescent depression can place a young person at high risk of recurrence and a range of psychosocial and vocational impairments in adult life, highlighting the importance of early recognition and prevention. Parents/carers are well placed to notice changes in their child’s emotional wellbeing which may indicate risk, and there is increa...

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...

Background Preventing psychotic disorders and effective treatment in first-episode psychosis are key priorities for the National Institute for Health and Care Excellence. This review assessed the evidence base for the cost-effectiveness of health and social care interventions for people at risk of psychosis and for first-episode psychosis. Methods...

Objective: Understanding the pathways to care for migrants experiencing a first episode of psychosis (FEP) is important, as they are more likely to experience longer delays to treatment and negative experiences, such as involuntary treatment. Despite the increased risk of developing a psychotic illness and barriers associated with pathways to care...

Aims: The COVID-19 pandemic forced the rapid move of mental health services to being delivered online. This included the delivery of a psychosocial recovery program (PRP) delivered in youth mental health services in Melbourne, Australia which consists of groups that address functional recovery. At the time, there was limited evidence about how thi...

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...

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...

Background Psychotic experiences emerge from abnormalities in perception and belief formation, and occur more commonly in those experiencing childhood trauma. Yet, which precise aspects of belief formation are atypical in psychosis is not well understood. We used a computational modelling approach to characterise belief-updating in young adults in...

Aims Services for individuals with a first episode of psychosis or at ultra-high risk of psychosis have become a treatment model of choice in mental health care. The longitudinal changes in clinical and functional outcomes as a result of real-world treatment remain under-reported. Methods We analysed data from first episode of psychosis and ultra-...

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...

Objective To present a practical, easy-to-implement clinical framework designed to support evidence-based quality prescribing for people with early psychosis. Method Identification and explanation of key principles relating to evidence-based pharmacotherapy for people with early psychosis. These were derived from the literature, practice guideline...

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...

Background Although studies suggest that concentrations of omega-3 and omega-6 fatty acids are lower in individuals with schizophrenia, evidence for beneficial effects of fatty acid supplementation is scarce. Therefore, in this study, we aimed to determine whether omega-3 and omega-6 fatty acid concentrations are causally related to schizophrenia....

The COVID-19 pandemic has had a profound effect on global mental health, with one-third of infected individuals developing a psychiatric or neurological disorder 6 months after infection. The risk of infection and the associated restrictions introduced to reduce the spread of the virus have also impacted help-seeking behaviours. Therefore, this stu...

Background Psychotic experiences are reported by 5–10% of young people, although only a minority persist and develop into psychotic disorders. It is unclear what characteristics differentiate those with transient psychotic experiences from those with persistent psychotic experiences that are more likely to be of clinical relevance. Aims To investi...

Background There is increasing evidence that dysregulation of polyunsaturated fatty acids (FAs) mediated membrane function plays a role in the pathophysiology of schizophrenia. Even though preclinical findings have supported the anti-inflammatory properties of omega-3 FAs on brain health, their biological roles as anti-inflammatory agents and their...

Causal interactions between specific psychiatric symptoms could contribute to the heterogenous clinical trajectories observed in early psychopathology. Current diagnostic approaches merge clinical manifestations that co-occur across subjects and could significantly hinder our understanding of clinical pathways connecting individual symptoms. Networ...

Aim The 0-19 model is an example of a service that has been retransformed in line with UK's recent policies. However, there is limited qualitative research exploring young people's experiences with the accessibility and acceptability of retransformed models through more participatory qualitative approaches. This study aimed to understand service us...

Background No biological treatment has been firmly established for the at-risk stage of psychotic disorder. In this study we aim to test if subthreshold psychotic symptoms can be effectively treated with cannabidiol (CBD), a non-psychoactive compound of the plant Cannabis sativa. The question has taken on increased importance in the wake of evidenc...

Background: Ultra high-risk (UHR) criteria were introduced to identify people at imminent risk of developing psychosis. To improve prognostic accuracy, additional clinical and biological risk factors have been researched. Associations between psychotic disorders and infections with Toxoplasma gondii and Herpesviridae have been found. It is unknown...

Sedentary behaviour is highly prevalent in people affected by severe and enduring mental health disorders, with affected individuals spending an average of over 8 h of their waking day sedentary (Vancampfort et al., 2017), much higher than their healthy peers. Individuals with a first episode of psychosis (FEP) are even more sedentary, with an aver...

PurposeMigrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder.Methods Hazard ratios for the risk of trans...

BACKGROUND There is currently an increased appetite and acceptance of technology-enabled mental health care. To adequately harness this opportunity, it is critical that the design and development of digital mental health technologies is informed by the needs and preferences of end-users. Despite young people and clinicians being predominant users o...

Background: There is currently an increased interest in and acceptance of technology-enabled mental health care. To adequately harness this opportunity, it is critical that the design and development of digital mental health technologies be informed by the needs and preferences of end users. Despite young people and clinicians being the predominant...

Whilst telehealth may overcome some traditional barriers to care, successful implementation into service settings is scarce, particularly within youth mental health care. This study aimed to leverage the rapid implementation of telehealth due to COVID-19 to understand the perspectives of young people and clinicians on how telehealth impacts service...

Objective: Although studies suggest that erythrocyte concentrations of omega-3 and omega-6 fatty acids are lower in individuals with schizophrenia, evidence of beneficial effects of omega-3 fatty acid supplementation is limited. This study therefore aimed to determine whether omega-3 and omega-6 fatty acid levels are causally related to schizophren...

Cognitive impairments are a core feature of first-episode psychosis (FEP), arising before illness onset and anti-psychotic exposure. Individuals with chronic psychosis experience poorer physical health while taking anti-psychotic medication, but health disparities may be evident at FEP onset, prior to antipsychotic exposure. Given the links between...

Aim: Investigating biological processes in at-risk individuals may help elucidate the aetiological mechanisms underlying psychosis development, refine prediction models and improve intervention strategies. This study examined the associations between sleep disturbances, chronotype, depressive and psychotic symptoms in individuals at ultra-high ris...

Aim Early psychosis delivery models have proliferated worldwide, but there is limited research into establishing model fidelity. In this context, this article aims to describe the development and implementation of a fidelity tool in a national network of early psychosis services across Australia—the headspace Early Psychosis program. Methods Follo...

Exposure to neurodevelopmental adversity and childhood trauma are both independently associated with psychosis. However, there is little research on the mechanism underlying their relationship with each other. The current study investigated both the independent and joint effects of neurodevelopmental adversity and childhood trauma to better underst...

Community-based mental health services for children and young people (CYP) can offer alternatives to inpatient settings and treat CYP in less restrictive environments. However, there has been limited implementation of such alternative models, and their efficacy is still inconclusive. Notably, little is known of the experiences of CYP and their pare...

Background Long chain polyunsaturated fatty acid (PUFA) levels have been implicated in the pathology of psychotic disorders. We investigated the relationship between childhood PUFA levels and later psychotic experiences (PE's) in a large birth cohort. Methods Plasma levels of Ω-3 and Ω-6 fatty acids (FA's) were assayed at ages 7 and 16 years. PE's...

Background Childhood trauma, particularly sexual abuse, has been associated with transition to psychosis in individuals at “ultra-high risk” (UHR). This study investigated whether the effects of various forms of childhood trauma on transition to psychosis are mediated by cortical thickness and surface area abnormalities. Methods This prospective s...

Background: Neurocognitive impairments are core early features of psychosis and are observed in those at ultra-high risk (UHR) for psychosis. The aim of the present study was to explore whether neurocognition is associated with polyunsaturated fatty acids (PUFAs), as has been observed in other clinical populations. Method: Erythrocyte levels of...

Objective: This paper provides the rationale for the development of sub-specialty training in youth psychiatry. Method: Training needs for youth psychiatry are discussed and the opportunities provided by sub-specialisation in youth psychiatry are presented. Results: The majority of mental disorders have their onset prior to 25 years. There has been...

Aims To synthesise and investigate how sleep disturbances relate to psychotic symptoms, functioning and Quality of Life (QoL) in At Risk Mental State (ARMS) youth. Method A comprehensive search of six databases (MEDLINE, PsycINFO, Embase, CINAHL, Web of Science and CENTRAL) was conducted. Eligible studies provided data on sleep disturbances or dis...

Virtual reality (VR) is a potentially powerful technology for enhancing assessment in mental health. At any time or place, individuals can be transported into immersive and interactive virtual worlds that are fully controlled by the researcher or clinician. This capability is central to recent interest in how VR might be harnessed in both treatment...