Alison R Yung

The University of Manchester · Institute of Brain, Behaviour and Mental Health

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...

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...

Background Mood disorders, including unipolar and bipolar depression, contribute significantly to the global burden of disease. Psychological therapy is considered a gold standard non-pharmacological treatment for managing these conditions; however, a growing body of evidence also supports the use of lifestyle therapies for these conditions. Despit...

Objectives This study aims to review studies developing or validating a prediction model for transition to psychosis in individuals meeting At Risk Mental State (ARMS) criteria focussing on predictors that can be obtained as part of standard clinical practice. Prediction of transition is crucial to facilitating identification of patients who would...

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 The prevalence of psychosis has been shown to be disproportionately high amongst sexual and gender minority individuals. However, there is currently little consideration of the unique needs of this population in mental health treatment, with LGBTQA+ individuals facing barriers in accessing timely and non-stigmatising support for psychoti...

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...

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: Preventing or delaying the onset of psychosis requires identification of those at risk for developing psychosis. For predictive purposes, the prodrome - a constellation of symptoms which may occur before the onset of psychosis - has been increasingly recognized as having utility. However, it is unclear what proportion of patients exper...

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...

Background: Multimodal modelling that combines biological and clinical data shows promise in predicting transition to psychosis in individuals at ultra high risk (UHR). Individuals who transition to psychosis are known to have deficits at baseline in cognitive function and reductions in grey matter volume in multiple brain regions identified by mag...

Novel approaches are required to find new treatments for schizophrenia and other neuropsychiatric disorders. This study utilised a combination of in vitro transcriptomics and in silico analysis with the BROAD Institute’s Connectivity Map to identify drugs that can be repurposed to treat psychiatric disorders. Human neuronal (NT2-N) cells were treat...

Background Bipolar disorders are serious mental illnesses, yet evidence suggests that the diagnosis and treatment of bipolar disorder can be delayed by around 6 years. Aim To identify signals of undiagnosed bipolar disorder using routinely collected electronic health records. Design and setting A nested case–control study conducted using the UK C...

Populations with common physical diseases – such as cardiovascular diseases, cancer and neurodegenerative disorders – experience substantially higher rates of major depressive disorder (MDD) than the general population. On the other hand, people living with MDD have a greater risk for many physical diseases. This high level of comorbidity is associ...

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...

Most mental disorders have a typical onset between 12 and 25 years of age, highlighting the importance of this period for the pathogenesis, diagnosis, and treatment of mental ill-health. This perspective addresses interactions between risk and protective factors and brain development as key pillars accounting for the emergence of psychopathology in...

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...

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)....

Background: Clinical trials suggest long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA; 'fish oil') may reduce depressive symptoms in adults with MDD. Hence, n-3 PUFA may be a potential treatment for depression in youth. Methods: Participants were aged 15-25 years with MDD who sought care in one of three government-funded mental health ser...

Objectives: Childhood trauma is common and associated with mental ill health. While high rates of trauma are observed across individual disorders, there is evidence that trauma is associated with an admixture of affective, anxiety and psychotic symptoms in adults. Given that early onset of mental disorder and trauma exposure herald poor outcomes,...

BACKGROUND: Preventing or delaying the onset of psychosis requires identification of those at risk for developing psychosis. For predictive purposes, the prodrome, a constellation of symptoms which may occur before the onset of psychosis, has been increasingly recognized as having utility. However, it is unclear what proportion of patients are expe...

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...

Objectives: Childhood trauma is common and associated with mental ill health. While high rates of trauma are observed across individual disorder groups, there is evidence that trauma is associated with an admixture of affective, anxiety, and psychotic symptoms in adults. Given that both early onset of mental disorder and trauma exposure herald poor...

The two most used semi‐structured psychometric instruments that define criteria for being at clinical high risk (CHR) for psychosis are the Comprehensive Assessment of At‐Risk Mental States (CAARMS) and the Structured Interview for Psychosis‐Risk Syndromes (SIPS). Although very similar there are important differences between these two measures. Dev...

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 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 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 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 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...

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...

Background: Young people with social disability and severe and complex mental health problems have poor outcomes, frequently struggling with treatment access and engagement. Outcomes may be improved by enhancing care and providing targeted psychological or psychosocial intervention. Aims: We aimed to test the hypothesis that adding social recove...

Objective Early intervention for psychosis services have been established worldwide and consist of specialist services for those with the At-Risk Mental State (ARMS) and a first episode of psychosis (FEP). This systematic review identified the literature on the outcomes of people who initially presented via an ARMS clinic and later transitioned to...

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: 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 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 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...

Background Schizophrenia is associated with a more than doubled risk of death from cardiovascular disease (CVD). Risk factors for CVD include low levels of physical activity, sedentary behaviour and sleep problems. These risk factors are not systematically assessed by health services. Aims Examine the feasibility, acceptability, validity and relia...

Intervention at the earliest illness stage, in ultra or clinical high-risk individuals, or indicated prevention, currently represents the most promising strategy to ameliorate, delay or prevent psychosis. We review the current state of evidence and conduct a broad-spectrum meta-analysis of various outcomes: transition to psychosis, attenuated posit...

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...

Over a quarter of a century ago, the formulation of the “at risk mental state” and operational criteria to prospectively identify individuals at “clinical” or “ultra-high risk” (UHR) for psychosis created a global wave of research momentum aimed at predicting and preventing first-episode psychosis. A substantial number of randomized controlled tria...

Objective To estimate prevalence of major cardiovascular events among people with schizophrenia who had experience of sleep disturbance, sedentary behavior or muscular weakness, and assess evidence for raised prevalence in these individuals compared to people with schizophrenia without these characteristics. Methods UK Biobank data on individuals...

Background There is now evolving data exploring the relationship between depression and various individual lifestyle factors such as diet, physical activity, sleep, alcohol intake, and tobacco smoking. While this data is compelling, there is a paucity of longitudinal research examining how multiple lifestyle factors relate to depressed mood, and ho...

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: The Multidimensional Adolescent Functioning Scale (MAFS) is a 23-item, self-report questionnaire assessing psychosocial functioning in adolescents aged 12-17 years. It captures three domains of functioning: 'general functioning', 'family-related functioning', and 'peer-related functioning'. The original English version has good psychom...

Background: People with schizophrenia have a higher premature mortality risk compared with the general population mainly due to cardiovascular disease (CVD). Despite this, people with schizophrenia are less likely to access physical health services or have their physical health investigated and monitored. Aims: To examine the beliefs and actions...

Recognizing that current frameworks for classification and treatment in psychiatry are inadequate, particularly for use in young people and early intervention services, transdiagnostic clinical staging models have gained prominence. These models aim to identify where individuals lie along a continuum of illness, to improve treatment selection and t...

Background The factors contributing to declining psychotic disorder transition rates in ultra-high-risk populations remain unclear. We examined the contribution of longitudinal changes in standard clinical treatment (‘treatment as usual’) to this decline. Method An audit was conducted on 105 clinical files of patients who received standard care at...

Experts discuss the potential of early intervention to transform outcomes for people with mental disorders. Mental illness represents one of the largest disease burdens worldwide, yet treatments have been largely ineffective in improving the quality of life for millions of affected individuals—in part because approaches taken have focused on late-s...

The prevalence and predictive power of schizotypal and borderline personality disorders in ultra high risk for psychosis patients (n=293) was assessed. While the prevalence of borderline personality disorder was higher than in the general population but that this was not the case for schizopytal personality disorder. However, schizotypal personalit...

This study examined whether distress in relation to attenuated psychotic symptoms (DAPS) is associated with clinical outcomes in an ultra-high-risk (UHR) for psychosis sample. We also investigated whether DAPS is associated with cognitive style (attributional style and cognitive biases) and whether amount of psychosocial treatment provided is assoc...

Aim: Over the past two decades, the youth mental health field has expanded and advanced considerably. Yet, mental disorders continue to disproportionately affect adolescents and young adults. Their prevalence and associated morbidity and mortality in young people have not substantially reduced, with high levels of unmet need and poor access to evi...

These updated guidelines from the British Association for Psychopharmacology replace the original version published in 2011. They address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting was held in 2017, involving experts in schizophrenia and its treatment. They were asked to review key areas and consider t...

There has been limited research into the predictive value of basic symptoms and their relationship with other psychopathology in patients identified using the 'ultra high risk' (UHR) for psychosis approach. The current study investigated whether basic symptoms, specifically cognitive disturbances (COGDIS), were associated with a greater risk of tra...

Aims: Current National Institute for Health and Care Excellence (NICE) guidelines for psychosis recommend psychological therapy with or without family intervention for individuals at-risk of developing psychosis. NICE guidelines have a specific research recommendation to investigate the clinical and cost effectiveness of combined individual and fa...

Objectives Emerging evidence suggests that handgrip strength (a proxy for muscular fitness) is associated with better cognitive performance in people with major depressive disorder (MDD). The underlying processes are unclear, although hippocampal volume (HCV) reductions and white matter hyperintensities (WMHs) have been implicated. Therefore, we in...

This study assessed the relationship between distress, severity and frequency of attenuated psychotic symptoms in individuals meeting Ultra High Risk (UHR) criteria, both at baseline and over time. It also assessed distress in relation to attenuated symptoms and whether cognitive behavioural therapy (CBT) reduced distress over time by symptom type....

Background In the 1990s criteria were developed to detect individuals at high and imminent risk of developing a psychotic disorder. These are known as the at risk mental state, ultra high risk or clinical high risk criteria. Individuals meeting these criteria are symptomatic and help-seeking. Services for such individuals are now found worldwide. R...

Background:Recent findings suggest that attenuated psychotic symptoms (APS) might serve as a risk factor for general mental health impairment in help-seeking youth. The current study was designed to test this possibility by examining the prognostic significance of APS in a large cohort of help-seeking youth not selected for psychosis risk. Method:...

Introduction Depression is highly prevalent and the leading contributor to the burden of disease in young people worldwide, making it an ongoing priority for early intervention. As the current evidence-based interventions of medication and psychological therapy are only modestly effective, there is an urgent need for additional treatment strategies...

Abstract: Background: NEURAPRO was a multicenter, double-blind, randomised, placebo-controlled trial RCT of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) ('fish oil') therapy provided for 6 months in individuals at ultra-high risk (UHR) for psychotic disorders, followed by an additional 6-month follow-up period. The study was conducted...

Omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) are necessary for optimum mental health, with recent studies showing low n-3 LCPUFA in people at ultra-high risk (UHR) of developing psychosis. Furthermore, people at UHR of psychosis had increased erythrocyte sphingomyelin (SM) and reduced phosphatidylethanolamine (PE) concentrations as w...

People with mental illness have an increased risk of physical disease, as well as reduced access to adequate health care. Physical-health disparities are observed across all mental illnesses in all countries. The high rate of physical comorbidity, which often has poor clinical management, reduces life expectancy for people with mental illness, and...

Background Adolescent-onset psychosis is associated with more severe symptoms and poorer outcomes than adult-onset psychosis. The National Institute for Clinical Excellence (NICE) recommend that adolescents with first episode psychosis (FEP) should be offered a combination of antipsychotic medication (APs), cognitive behavioural therapy (CBT) and f...

Background Persistent negative symptoms (PNS) defined as negative symptoms that persist for at least six months in the absence of high levels of positive, depressive and extrapyramidal symptoms, are evident early in the course of schizophrenia from the first episode of psychosis. However, their presence even earlier in the illness, in those at Ultr...