Rachel Upthegrove

Rachel Upthegrove
University of Birmingham · Institute for Mental Health

MBBS FRCPsych PhD

About

205
Publications
34,977
Reads
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3,831
Citations
Citations since 2017
160 Research Items
3402 Citations
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20172018201920202021202220230200400600800
20172018201920202021202220230200400600800
Additional affiliations
August 2012 - present
University of Birmingham
Position
  • Clinical Senior Lecturer
January 2006 - present
Birmingham and Solihull Mental Health NHS Foundation Trust
Position
  • Consultant Psychiatrist
Education
September 2006 - June 2010
University of Birmingham
Field of study
  • PhD
September 1988 - June 1993
Royal Free Hospital School of Medicine
Field of study

Publications

Publications (205)
Article
Full-text available
Objective: Auditory verbal hallucinations (AVHs) are core features of psychotic illness and remain significant in predicting poor outcome and risk. There has been a wide range of approaches to understanding these experiences. Method: A systematic literature review summarizing different methods of investigation and their results; phenomenology, d...
Article
Full-text available
Background There has been increasing interest in the association between childhood trauma and psychosis. Proposals for potential mechanisms involved include affective dysregulation and cognitive appraisals of threat. Aims To establish if, within bipolar disorder, childhood events show a significant association with psychosis, and in particular with...
Article
This systematic review sets out to give a comprehensive overview of the cytokine profile at the onset of psychosis un-confounded by medication. We aim to provide insight into the early pathophysiological process of psychosis and areas for future research of potential biomarkers able to chart the extent of illness or effectiveness of treatment. Foll...
Article
Full-text available
Introduction Evidence suggests a potentially causal role of interleukin 6 (IL-6), a pleiotropic cytokine that generally promotes inflammation, in the pathogenesis of psychosis. However, no interventional studies in patients with psychosis, stratified using inflammatory markers, have been conducted to assess the therapeutic potential of targeting IL...
Article
Full-text available
Background: Little is still known about the long-term impact of childhood and adolescent persistent depression and anxiety in adulthood. Aims: To investigate the impact of persistent anxiety, depression, and comorbid anxiety and depression across childhood and adolescence on the development of multiple adverse outcomes in young adulthood. Metho...
Article
Full-text available
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...
Article
Full-text available
Purpose Psychosis disproportionally affects ethnic minority groups in high-income countries, yet evidence of disparities in outcomes following intensive early intervention service (EIS) for First Episode Psychosis (FEP) is less conclusive. We investigated 5-year clinical and social outcomes of young people with FEP from different racial groups foll...
Article
Around a quarter of people who experience a first episode of psychosis (FEP) will develop treatment-resistant schizophrenia, but there are currently no established clinically useful methods to predict this from baseline. We aimed to explore the predictive potential for clozapine use as a proxy for treatment-resistant schizophrenia of routinely coll...
Article
Full-text available
Background: Several underlying mechanisms potentially account for the link between sleep and attention deficit and hyperactivity disorder (ADHD), including inflammation. However, studies so far have been cross sectional. We investigate (a) the association between early childhood sleep and probable ADHD diagnosis in childhood and (b) whether childh...
Article
Depression is common, costly, debilitating, and associated with increased risk of suicide. It is one of the leading global public health problems. Although existing available pharmacological treatments can be effective, their onset of action can take up to 6 weeks, side-effects are common, and recovery can require treatment with multiple different...
Chapter
It is well known that schizophrenia is associated with cognitive impairment, reduced cortical grey matter and increased circulating concentrations of inflammatory cytokines. However, the relationship between these findings is not clear. We outline the influential neuroinflammatory hypotheses that raised cytokines provoke a damaging immune response...
Article
Full-text available
Background Cardiometabolic dysfunction is common in young people with psychosis. Recently, the Psychosis Metabolic Risk Calculator (PsyMetRiC) was developed and externally validated in the UK, predicting up-to six-year risk of metabolic syndrome (MetS) from routinely collected data. The full-model includes age, sex, ethnicity, body-mass index, smok...
Article
Full-text available
Aberrant resting-state connectivity within and between the Default Mode Network, the Executive Control Network, and the Salience Network is well-established in schizophrenia. Meta-analyses have identified that bilateral lingual gyrus is as the only region showing hyperactivity in schizophrenia and there are reports of increased connectivity between...
Article
Full-text available
Background There is ongoing debate on the nosological position of bipolar disorder (BD) and borderline personality disorder (BPD). Identifying the unique and shared risks, developmental pathways, and symptoms in emerging BD and BPD could help the field refine aetiological hypotheses and improve the prediction of the onset of these disorders. This s...
Article
Full-text available
Introduction 23% of people experiencing a first episode of psychosis (FEP) develop treatment resistant schizophrenia (TRS). At present, there are no established methods to accurately identify who will develop TRS from baseline. Objectives In this study we used patient data from three UK early intervention services (EIS) to investigate the predicti...
Article
Full-text available
IntroductionThe comorbidity between cardiometabolic and psychotic disorders develops early. This is a crucial window of opportunity to reduce excess morbidity and mortality. Recently, a cardiometabolic risk prediction algorithm for young people with psychosis, the psychosis metabolic risk calculator (PsyMetRiC) was developed and externally validate...
Article
Full-text available
Importance: The behavioral and cognitive symptoms of severe psychotic disorders overlap with those seen in dementia. However, shared brain alterations remain disputed, and their relevance for patients in at-risk disease stages has not been explored so far. Objective: To use machine learning to compare the expression of structural magnetic resona...
Article
Full-text available
Subtle subjective visual dysfunctions (VisDys) are reported by about 50% of patients with schizophrenia and are suggested to predict psychosis states. Deeper insight into VisDys, particularly in early psychosis states, could foster the understanding of basic disease mechanisms mediating susceptibility to psychosis, and thereby inform preventive int...
Article
Full-text available
Functional impairment is a core feature of both autism and schizophrenia spectrum disorders. While diagnostically independent, they can co-occur in the same individual at both the trait and diagnostic levels. The effect of such co-occurrence is hypothesized to worsen functional impairment. The diametric model, however, suggests that the disorders a...
Article
Background Clozapine is the gold-standard medication for treatment-resistant schizophrenia (TRS) yet its initiation is often delayed. Objective To examine whether earlier initiation of clozapine in TRS is associated with lower Clinical Global Impression – Severity (CGI-S) scores at 2 years. Methods This was a retrospective cohort study from elect...
Preprint
Background Several underlying mechanisms potentially account for the link between sleep and attention deficit and hyperactivity disorder (ADHD), including inflammation. However, studies so far have been cross-sectional. We investigate (i) the association between early childhood sleep and probable ADHD diagnosis in childhood; and (ii) whether childh...
Preprint
Full-text available
Around a quarter of people who experience a first episode of psychosis (FEP) will develop treatment-resistant schizophrenia (TRS), but there are currently no established clinically useful methods to predict this from baseline. We aimed to explore the predictive potential for clozapine use as a proxy for TRS of routinely collected, objective biomedi...
Article
Importance: Approaches are needed to stratify individuals in early psychosis stages beyond positive symptom severity to investigate specificity related to affective and normative variation and to validate solutions with premorbid, longitudinal, and genetic risk measures. Objective: To use machine learning techniques to cluster, compare, and comb...
Article
Full-text available
Objective Social dysfunction is a major feature of clinical-high-risk states for psychosis (CHR-P). Prior research has identified a neuroanatomical pattern associated with impaired social function outcome in CHR-P. The aim of the current study was to test whether social dysfunction in CHR-P is neurobiologically distinct or in a continuum with the l...
Article
Full-text available
Background Formal thought disorder (FTD) has been associated with more severe illness courses and functional deficits in patients with psychotic disorders. However, it remains unclear whether the presence of FTD characterises a specific subgroup of patients showing more prominent illness severity, neurocognitive and functional impairments. This stu...
Article
Progress in developing personalised care for mental disorders is supported by numerous proof-of-concept machine learning studies in the area of risk assessment, diagnostics and precision prescribing. Most of these studies primarily use clinical data, but models might benefit from additional neuroimaging, blood and genetic data to improve accuracy....
Article
Full-text available
Background Identifying neurobiologically based transdiagnostic categories of depression and psychosis may elucidate heterogeneity, and provide better candidates for predictive modelling. We aimed to identify clusters across patients with recent onset depression (ROD) and recent onset psychosis (ROP) based on structural neuroimaging data. We hypothe...
Article
Full-text available
Importance: Previous in vitro and postmortem research suggests that inflammation may lead to structural brain changes via activation of microglia and/or astrocytic dysfunction in a range of neuropsychiatric disorders. Objective: To investigate the relationship between inflammation and changes in brain structures in vivo and to explore a transcri...
Article
Full-text available
Background Evidence suggests that cognitive subtypes exist in schizophrenia that may reflect different neurobiological trajectories. We aimed to identify whether IQ-derived cognitive subtypes are present in early-phase schizophrenia-spectrum disorder and examine their relationship with brain structure and markers of neuroinflammation. Method 161 p...
Article
Full-text available
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...
Article
Background Clinical high-risk states for psychosis (CHR) are associated with functional impairments and depressive disorders. A previous PRONIA study predicted social functioning in CHR and recent-onset depression (ROD) based on structural magnetic resonance imaging (sMRI) and clinical data. However, the combination of these domains did not lead to...
Article
Full-text available
Objective: To provide a comprehensive analysis of cytokine perturbations in antipsychotic-naïve first episode psychosis (FEP) populations and assess the relationship between inflammatory biomarkers and negative symptom severity. Methods: A systematic review and meta-analysis following PRISMA guidelines was conducted. A total of 1,042 records wer...
Article
Objective Psychotic disorders are frequently associated with decline in functioning and cognitive difficulties are observed in subjects at clinical high risk (CHR) for psychosis. In this work, we applied automatic approaches to neurocognitive and functioning measures, with the aim of investigating the link between global, social and occupational f...
Article
Full-text available
Background Schizophrenia commonly co-occurs with cardiometabolic and inflammation-related traits. It is unclear to what extent the comorbidity could be explained by shared genetic aetiology. Methods We used GWAS data to estimate shared genetic aetiology between schizophrenia, cardiometabolic, and inflammation-related traits: fasting insulin (FI),...
Article
Full-text available
Although the pathophysiology of auditory verbal hallucinations remains uncertain, the inner speech model remains a prominent theory. A systematic review and meta-analyses of both functional and structural neuroimaging studies were performed to investigate the inner speech model. Of the 417 papers retrieved, 26 met the inclusion criteria. Meta-analy...
Article
Full-text available
BACKGROUND Persistent anxiety in childhood and adolescents could represent a novel treatment target for psychosis, potentially targeting activation of stress pathways, and secondary non-resolving inflammatory response. Here, we examined the association between persistent anxiety through childhood and adolescence with individuals with psychotic expe...
Article
Full-text available
Early psychosis is characterised by heterogeneity in illness trajectories, where outcomes remain poor for many. Understanding psychosis symptoms and their relation to illness outcomes, from a novel network perspective, may help to delineate psychopathology within early psychosis and identify pivotal targets for intervention. Using network modelling...
Article
Personalised prediction of functional outcomes is a promising approach for targeted early intervention in psychiatry. However, generalisability and resource efficiency of such prognostic models represent challenges. In the PRONIA study (German Clinical Trials Register: DRKS00005042), we demonstrate excellent generalisability of prognostic models in...
Chapter
The rapidly growing field of immunopsychiatry combines expertise and insights from immunology, psychiatry and neuroscience to understand the role of inflammation and other immune processes in causing and treating mental illness. This represents a major shift in mental health science, traditionally focused on psychological and neuronal mechanisms of...
Article
Adult gyrification provides a window into coordinated early neurodevelopment when disruptions predispose individuals to psychiatric illness. We hypothesized that the echoes of such disruptions should be observed within structural gyrification networks in early psychiatric illness that would demonstrate associations with developmentally relevant var...
Article
Full-text available
Psychosis is a major mental illness with first onset in young adults. The prognosis is poor in around half of the people affected, and difficult to predict. The few tools available to predict prognosis have major weaknesses which limit their use in clinical practice. We aimed to develop and validate a risk prediction model of symptom non-remission...
Article
Background Psychosis expression in the general population may reflect a behavioral manifestation of the risk for psychotic disorder. It can be conceptualized as an interconnected system of psychotic and affective experiences; a so-called ‘symptom network’. Differences in demographics, as well as exposure to adversities and risk factors, may produce...
Article
Full-text available
Many studies have reported that patients with psychosis, even before drug treatment, have mildly raised levels of blood cytokines relative to healthy controls. In contrast, there is a remarkable scarcity of studies investigating the cellular basis of immune function and cytokine changes in psychosis. The few flow-cytometry studies have been limited...
Article
Full-text available
Background Auditory Verbal Hallucinations (AVH) are a hallmark of psychosis, but affect many other clinical populations. Patients’ understanding and self-management of AVH may differ between diagnostic groups, change over time, and influence clinical outcomes. This study aimed to explore patients’ understanding and self-management of AVH in a young...
Article
Full-text available
Many studies have reported that patients with psychosis, even before drug treatment, have mildly raised levels of blood cytokines relative to healthy controls. In contrast, there is a remarkable scarcity of studies investigating the cellular basis of immune function and cytokine changes in psychosis. The few flow-cytometry studies have been limited...
Article
Full-text available
Neuroimmunology in the broadest sense is the study of interactions between the nervous and the immune systems. These interactions play important roles in health from supporting neural development, homeostasis and plasticity to modifying behaviour. Neuroimmunology is increasingly recognised as a field with the potential to deliver a significant posi...
Article
Objectives Depression has long been considered a significant feature of schizophrenia and is associated with more frequent psychotic episodes, increased service utilisation, substance misuse, poor quality of life and completed suicide. However, there is a distinct lack of literature on this comorbidity from low- and middle-income countries or non-w...
Article
Background Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, an...
Article
Background Transition to psychosis is among the most adverse outcomes of the clinical high-risk (CHR) syndromes encompassing ultra-high-risk (UHR) and basic symptoms states. Clinical risk calculators may facilitate an early and individualized interception of psychosis, but their real-world implementation requires thorough validation across diverse...
Article
Full-text available
Background Schizophrenia, bipolar disorder and depression are associated with inflammation. However, it is unclear whether associations of immunological proteins/traits with these disorders are likely to be causal, or could be explained by reverse causality/residual confounding. Methods We used bi-directional two-sample Mendelian randomization (MR...
Article
Full-text available
Schizophrenia is associated with increased levels of oxidative stress, as reflected by an increase in the concentrations of damaging reactive species and a reduction in anti-oxidant defences to combat them. Evidence has suggested that whilst not the likely primary cause of schizophrenia, increased oxidative stress may contribute to declining course...
Article
Full-text available
Background Young people with psychosis are at high risk of developing cardiometabolic disorders; however, there is no suitable cardiometabolic risk prediction algorithm for this group. We aimed to develop and externally validate a cardiometabolic risk prediction algorithm for young people with psychosis. Methods We developed the Psychosis Metaboli...
Article
Full-text available
Aims Auditory Verbal Hallucinations (AVH) are a hallmark of psychosis, but affect many other clinical populations. Patients’ understanding and self-management of AVH may differ between diagnostic groups, change over time, and influence clinical outcomes. We aimed to explore patients’ understanding and self-management of AVH in a young adult clinica...
Article
Full-text available
Aims Psychosis is a major mental illness with first onset in young adults. The prognosis is poor in around half of the people affected, and difficult to predict. The few tools available to predict prognosis have major weaknesses which limit their use in clinical practice. We aimed to develop and validate a risk prediction model of symptom non-remis...
Article
Full-text available
Negative symptoms occur frequently in individuals at clinical high risk (CHR) for psychosis and contribute to functional impairments. The aim of this study was to predict negative symptom severity in CHR after 9 months. Predictive models either included baseline negative symptoms measured with the Structured Interview for Psychosis-Risk Syndromes (...
Preprint
Full-text available
Background: Psychosis expression in the general population, which may reflect a behavioral manifestation of risk for psychotic disorder, can be conceptualized as an interconnected system of psychotic and affective experiences; a so-called symptom network. Differences in demographics, as well as exposure to adversities and risk factors, may produce...
Article
Full-text available
Importance Cognitive deficits are core features of mental disorders and are important in predicting long-term prognosis. However, it is still unknown whether individual patterns of cognitive deficits predate specific mental disorders. Objective To investigate the specificity of the associations of attention, working memory, and inhibition in child...
Article
Full-text available
Introduction Approximately, 15- 26% of patients with first-episode psychosis, including schizophrenia, are likely to have attempted suicide by their first treatment contact. Studies of suicidal behavior outside of schizophrenia have indicated grey matter volume loss in the prefrontal and orbitofrontal cortex, and aberrant brain activity in relation...