Robin Murray

King's College London | KCL · Department of Psychosis Studies

Background: Extensive evidence indicates that rates of psychotic disorder are elevated in more urban compared with less urban areas, but this evidence largely originates from Northern Europe. It is unclear whether the same association holds globally. This study examined the association between urban residence and rates of psychotic disorder in cat...

Background and hypothesis: Risk for cannabis use and schizophrenia is influenced in part by genetic factors, and there is evidence that genetic risk for schizophrenia is associated with subclinical psychotic-like experiences (PLEs). Few studies to date have examined whether genetic risk for schizophrenia is associated with cannabis-related PLEs....

Background: The effects of cannabis are thought to be mediated by interactions between its constituents and the endocannabinoid system. Delta-9-tetrahydrocannabinol (THC) binds to central cannabinoid receptors, while cannabidiol (CBD) may influence endocannabinoid function without directly acting on cannabinoid receptors. We examined the effects of...

Glutamatergic and GABAergic dysfunction are implicated in the pathophysiology of schizophrenia. Previous work has shown relationships between glutamate, GABA, and brain activity in healthy volunteers. We conducted a systematic review to evaluate whether these relationships are disrupted in psychosis. Primary outcomes were the relationship between m...

Importance Less than 10% of research on psychotic disorders has been conducted in settings in the Global South, which refers broadly to the regions of Latin America, Asia, Africa, and Oceania. There is a lack of basic epidemiological data on the distribution of and risks for psychoses that can inform the development of services in many parts of the...

As countries adopt more permissive cannabis policies, it is increasingly important to identify strategies that can reduce the harmful effects of cannabis use. This study aimed to determine if increasing the CBD content of cannabis can reduce its harmful effects. Forty-six healthy, infrequent cannabis users participated in a double-blind, within-sub...

Background: Child maltreatment (CM) and migrant status are independently associated with psychosis. We examined prevalence of CM by migrant status and tested whether migrant status moderated the association between CM and first-episode psychosis (FEP). We further explored whether differences in CM exposure contributed to variations in the incidenc...

Studies conducted in psychotic disorders have shown that DNA-methylation (DNAm) is sensitive to the impact of Childhood Adversity (CA). However, whether it mediates the association between CA and psychosis is yet to be explored. Epigenome-wide association studies (EWAS) using the Illumina Infinium-Methylation EPIC array in peripheral blood tissue f...

Introduction: Our aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR. Methods: We combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised p...

Background: Given psychotic illnesses' high heritability and associations with brain structure, numerous neuroimaging-genetics findings have been reported in the last two decades. However, few findings have been replicated. In the present independent sample we aimed to replicate any psychosis-implicated SNPs (single nucleotide polymorphisms), whic...

Aims Gene x environment (G×E) interactions, i.e. genetic modulation of the sensitivity to environmental factors and/or environmental control of the gene expression, have not been reliably established regarding aetiology of psychotic disorders. Moreover, recent studies have shown associations between the polygenic risk scores for schizophrenia (PRS-...

Background: There is evidence of an association between life events and psychosis in Europe, North America and Australasia, but few studies have examined this association in the rest of the world. Aims: To test the association between exposure to life events and psychosis in catchment areas in India, Nigeria, and Trinidad and Tobago. Method: W...

Background Cognitive decline, including verbal memory and executive function, is among the most feared aspects of growing old, as it frequently heralds onset of dementia spectrum and other adverse health-related outcomes including mortality. Understanding the source of individual differences in withstanding the onslaught of cognitive ageing may hig...

Introduction: Glutamatergic dysfunction is implicated in the pathophysiology of schizophrenia. It is unclear whether glutamatergic dysfunction predicts response to treatment or if antipsychotic treatment influences glutamate levels. We investigated the effect of antipsychotic treatment on glutamatergic levels in the anterior cingulate cortex (ACC),...

Cluster studies identified a subgroup of patients with psychosis whose premorbid adjustment deteriorates before the onset, which may reflect variation in genetic influence. However, other studies reported a complex relationship between distinctive patterns of cannabis use and cognitive and premorbid impairment that is worthy of consideration. We ex...

Aims Transmission of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a global pandemic. Many studies are underway to ascertain the mental health impact of this seismic event, however no study has investigated its effect on psychosis incidence. We hypothesise that the overall crude incidence rates of first episode psychos...

RationaleMismatch negativity (MMN) is a candidate endophenotype for schizophrenia subserved by N-methyl-D-aspartate receptor (NMDAR) function and there is increasing evidence that prolonged cannabis use adversely affects MMN generation. Few human studies have investigated the acute effects of cannabinoids on brain-based biomarkers of NMDAR function...

The onset of schizophrenia is determined by biological and social risk factors operating predominantly during development. These result in subtle deviations in brain structure and cognitive function. Striatal dopamine dysregulation follows, causing abnormal salience and resultant psychotic symptoms. Most people diagnosed as having schizophrenia do...

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are exp...

Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are exp...

Gene x environment (GxE) interactions have not been reliably established regarding etiology of psychotic disorders, while genes-environment (G-E) associations have been displayed. We studied the role of GxE interaction between psychosocial stressors (childhood trauma, stressful life-events, self-reported discrimination experiences and low social ca...

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association...

Background and Hypothesis Facial Emotion Recognition is a key domain of social cognition associated with psychotic disorders as a candidate intermediate phenotype. In this study, we set out to investigate global and specific facial emotion recognition deficits in first-episode psychosis, and whether polygenic liability to psychotic disorders is ass...

BACKGROUND AND HYPOTHESIS: Facial Emotion Recognition is a key domain of social cognition associated with psychotic disorders as a candidate intermediate phenotype. In this study, we set out to investigate global and specific facial emotion recognition deficits in first-episode psychosis, and whether polygenic liability to psychotic disorders is as...

Objectives: The liberalisation of cannabis laws, the increasing availability and potency of cannabis has renewed concern about the risk of psychosis with cannabis. Methods: The objective of the WFSBP task force was to review the literature about this relationship. Results: Converging lines of evidence suggest that exposure to cannabis increase...

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, using MRI data from 5,08...

Background As an accelerated cognitive decline frequently heralds onset of severe neuropathological disorders, understanding the source of individual differences in withstanding the onslaught of cognitive ageing may highlight how best cognitive abilities may be retained into advanced age. Methods Using a population representative sample of 5088 ad...

Background and hypothesis Evidence suggests that childhood maltreatment (ie, childhood abuse and childhood neglect) affects educational attainment and cognition. However, the association between childhood maltreatment and Intelligence Quotient (IQ) seems stronger among controls compared to people with psychosis. We hypothesised that: the associatio...

Longitudinal MRI is used in clinical research studies to examine illness progression, neurodevelopment, and the effect of medical interventions. Such studies typically report changes in brain volume of less than 5%. However, there is a concern that these findings could be obscured or confounded by small changes in brain volume estimates caused by p...

Background: Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network...

Importance About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizo...

Objective Cannabis legalization in many jurisdictions worldwide has raised concerns that such legislation might increase the burden of transient and persistent psychotic illnesses in society. Our study aimed to address this issue. Methods Drawing upon emergency department (ED) presentations aggregated across Alberta and Ontario, Canada records (Ap...

Importance: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schiz...

Schoretsanitis et al conclude from their reanalysis of individual patient data that most people relapse when they stop antipsychotics but the risk of relapse is greater by about a factor of 4 in those who stop oral medication compared with those who stop depot medication.¹ It is perhaps no accident that depot antipsychotic concentrations slowly fal...

To characterise the trait-effects of increased genetic risk for schizophrenia, and highlight potential risk mediators, we test the association between schizophrenia polygenic risk scores (PRSs) and 529 behavioural traits (personality, psychological, lifestyle, nutritional) in the UK Biobank. Our primary analysis is performed on individuals aged 38–...

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating t...

Objective Low self-esteem has been suggested as a putative mechanism in the development and maintenance of psychosis. Uncertainty still exists about how unstable self-esteem relates to psychotic experiences. The present study examines the potential (temporal) associations between momentary self-esteem, fluctuations in self-esteem, and psychotic exp...

Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia. Of those affected, 70–84% are reported to be treatment resistant from the outset. This raises the possibility that the neurobiological mechanisms of treatment resistance emerge before the onset of psychosis and have a neurodevelopmental origin. Neuropsycholo...

Background 70%–84% of individuals with antipsychotic treatment resistance show non-response from the first episode. Emerging cross-sectional evidence comparing cognitive profiles in treatment resistant schizophrenia to treatment-responsive schizophrenia has indicated that verbal memory and language functions may be more impaired in treatment resist...

Premorbid functioning and cognitive measures may reflect gradients of developmental impairment across diagnostic categories in psychosis. In this study, we sought to examine the associations of current cognition and premorbid adjustment with symptom dimensions in a large first episode psychosis (FEP) sample. We used data from the international EU-G...

Background Patients with psychotic disorders show higher rates of the metabolic syndrome (MS) between the cluster of severe mental illnesses. Depressive symptoms can worsen outcomes of individuals with psychotic disorders. However, research on the association between MS and depression in psychotic disorders and their relevance to outcomes is lackin...

Background A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episod...

Methodological differences are a common justification for the replication crisis in scientific research. We have acknowledged in our paper¹ that the different scales used to measure early life complications (ELCs) between our study and Ursini et al² were a possible reason for the discrepancy in the findings. The McNeil–Sjöström scale is more detail...

Decades of research have revealed numerous risk factors for mental disorders beyond genetics, but their consistency and magnitude remain uncer­tain. We conducted a “meta-umbrella” systematic synthesis of umbrella reviews, which are systematic reviews of meta-analyses of individual studies, by searching international databases from inception to Janu...

Evidence suggests that people at Clinical High Risk for Psychosis (CHR) have a blunted cortisol response to stress and altered mediotemporal activation during fear processing, which may be neuroendocrine–neuronal signatures of maladaptive threat responses. However, whether these facets are associated with each other and how this relationship is aff...

The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. W...

Background Attention-deficit/hyperactivity disorder (ADHD) can be viewed as the extreme end of heritable traits distributed in the general population. Due to the focus on children in the literature on ADHD and data constraints, to-date, almost no research focused on the relationship between ADHD-related outcomes in older adults from the general pop...

Background In youth at clinical high-risk for psychosis, cortisol elevations predict transition to psychosis, but it is unclear whether cortisol alterations are evident at an earlier clinical stage. We investigated whether cortisol levels and stressors in childhood were associated with later attenuated psychotic (AP) symptoms. Methods A sample of...

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...

Background: People with psychosis experience cardiometabolic comorbidities, including metabolic syndrome, coronary heart disease and diabetes. These physical comorbidities have been linked to diet, inactivity and the effects of the illness itself, including disorganisation, impairments in global function and amotivation associated with negative sy...

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating t...

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, compr...

Background In youth at clinical high-risk for psychosis, elevated cortisol levels predict subsequent onset of psychotic disorder. However, it is unclear whether cortisol alterations are evident at an earlier clinical stage and promote progression of psychosis expression. The present study aimed to address this issue by investigating whether cortiso...

Background People with schizophrenia have shortened lives. This excess mortality seems to be related to physical health conditions that may be amenable to better primary and secondary prevention. Better continuity of care may enhance such interventions as well as help prevent death by self-injury. Aims We set out to examine the relationship betwee...