Stephen James Wood

University of Birmingham · School of Psychology

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...

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (l...

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (l...

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: 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...

Glutamatergic dysfunction is implicated in the pathoaetiology of schizophrenia, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to cont...

Objective: To develop targeted treatment for young people experiencing mental illness , a better understanding of the biological, psychological, and social changes is required, particularly during the early stages of illness. To do this, large datasets need to be collected using standardized methods. A harmonized data collection protocol was tested...

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...

Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and brain diseases. The genetic underpinnings of these patterns remain largely unknown. We apply a stochastic multivariate factorization meth...

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...

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...

Autism spectrum disorder (ASD) is associated with high structural heterogeneity in magnetic resonance imaging (MRI). This work uncovers three neuroanatomical dimensions of ASD ( N =307) using machine learning methods and constructs their characteristic MRI signatures. The presence of these signatures, along with their clinical profiles and genetic...

Autism spectrum disorder (ASD) is associated with high structural heterogeneity in magnetic resonance imaging (MRI). This work uncovers three neuroanatomical dimensions of ASD ( N = 307) using machine learning methods and constructs their characteristic MRI signatures. The presence of these signatures, along with their clinical profiles and genetic...

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-...

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...

Objective: The prevalence and significance of schizophrenia-related phenotypes at the population level is debated in the literature. Here, the authors assessed whether two recently reported neuroanatomical signatures of schizophrenia-signature 1, with widespread reduction of gray matter volume, and signature 2, with increased striatal volume-could...

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...

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...

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...

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...

Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to structural covariance patterns across brain regions and individuals. We present a mega-analysis of structural covariance with magnetic resonance imaging of 50,699 healthy and diseased individuals (12 studies, 130 sites, and 12 countries)...

Continued cannabis use (CCu) is an important predictor for poor long-term outcomes in psychosis and clinically high-risk patients, but no generalizable model has hitherto been tested for its ability to predict CCu in these vulnerable patient groups. In the current study, we investigated how structured clinical and cognitive assessments and structur...

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 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...

The specific phenotype of depression in recent-onset schizophrenia spectrum disorders (SSD) and its relation to non-psychotic depression is unknown. Symptom profile and network analysis are complementary statistical techniques that may provide important insights into the presentation and relative importance of individual symptoms that give rise to...

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...

Objective Considering the peak age of onset for psychosis and bipolar disorder occurs in adulthood, we investigated the co-occurrence of these disorders in adults with autism. Methods We conducted a systematic review and meta-analysis (PROSPERO Registration Number: CRD42018104600) to (1) examine the prevalence of psychosis and bipolar disorder in...

Background: Different regions of the brain's grey matter are connected by a complex structural network of white matter fibres which are responsible for the propagation of action potentials and the transport of trophic and other molecules. In neurodegenerative disease, these connections constrain the way in which grey matter volume loss progresses....

The prevalence and significance of schizophrenia-related phenotypes at the population-level are debated in the literature. Here we assess whether two recently reported neuroanatomical signatures of schizophrenia, signature 1 with widespread reduction of gray matter volume and signature 2 with increased striatal volume, could be replicated in an ind...

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 (...

Aim Cognitive deficits are recognized features of depressive disorders in youth aged 12–25. These deficits are distressing, predict functional impairment and limit the effectiveness of psychological therapies. Cognitive enhancement using behavioural, biochemical or physical treatments may be useful in young people with depression, but studies have...

Disease heterogeneity is a significant obstacle to understanding pathological processes and delivering precision diagnostics and treatment. Clustering methods have gained popularity for stratifying patients into subpopulations (i.e., subtypes) of brain diseases using imaging data. However, unsupervised clustering approaches are often confounded by...

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...

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...

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...

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 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...

Importance Altered functional connectivity (FC) is a common finding in resting-state functional magnetic resonance imaging (rs-fMRI) studies of people with psychosis, yet how FC disturbances evolve in the early stages of illness, and how antipsychotic treatment influences these disturbances, remains unknown. Objective To investigate longitudinal F...

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...

Objective There is a need to better understand the interrelationships between positive and negative symptoms of recent-onset schizophrenia spectrum disorders (SSD) and co-occurrring depressive symptoms. Aims were to determine: (1) whether depressive symptoms are best conceptualised as distinct from, or intrinsic to, positive and negative symptoms;...

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...

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 (...

Importance: The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk. Objective: To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as betwee...

Background: Altered functional connectivity (FC) is a common finding in resting-state functional Magnetic Resonance Imaging (rs-fMRI) studies of people with psychosis, yet how FC disturbances evolve in the early stages of illness, and how antipsychotics may influence the temporal evolution of these disturbances, remains unclear. Here, we scanned fi...

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. Here, we used spectral dynamic causal modelling (DCM) of resting-st...

Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hit...

In schizophrenia, neurocognitive subtypes can be distinguished based on cognitive performance and they are associated with neuroanatomical alterations. We investigated the existence of cognitive subtypes in shortly medicated recent onset psychosis patients, their underlying gray matter volume patterns and clinical characteristics. We used a K-means...

Changes in brain volume are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis and numerous longitudinal studies suggest that volume deficits progress with illness duration. However, a major unresolved question concerns whether these changes are driven by the underlying illness or represent iatrogenic effects of a...

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...

Diagnostic heterogeneity within and across psychotic and affective disorders challenges accurate treatment selection, particularly in the early stages. Delineation of shared and distinct illness features at the phenotypic and brain levels may inform the development of more precise differential diagnostic tools. We aimed to identify prototypes of de...

Earlier recognition and accurate assessment of depressive symptoms is important to improving outcomes in individuals with recent-onset schizophrenia spectrum disorders (termed SSD hereafter)—regardless of whether positive psychotic symptoms are present or have resolved. The Montgomery–Åsberg Depression Rating Scale (MADRS) is frequently used to ass...

“Psychotic-Like Experiences” (PLEs) are common in the general population. While they are usually transient and resolve spontaneously, they can be distressing and signify increased risk for later psychosis or other psychopathology. It is important to investigate factors associated with PLEs which could be targeted to reduce their prevalence and impa...

A multitude of prediction models for a first psychotic episode in individuals at clinical high-risk (CHR) for psychosis have been proposed, but only rarely validated. We identified transition models based on clinical and neuropsychological data through a registered systematic literature search and evaluated their external validity in 173 CHRs from...

There is a need to develop and refine psychosocial interventions to improve functioning in First Episode Psychosis (FEP). Social cognition and neurocognition are closely linked to functioning in psychosis; examinations of cognition pre- and post- psychosocial intervention may provide insights into the mechanisms of these interventions, and identify...