ORCID Profile
0000-0003-3051-0135
Current Organisations
University of Sussex
,
Brighton and Sussex Medical School
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Publisher: Springer Science and Business Media LLC
Date: 08-12-2011
DOI: 10.1038/NPP.2010.222
Publisher: Springer Science and Business Media LLC
Date: 19-05-2020
DOI: 10.1038/S41380-020-00899-W
Abstract: Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case–control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2% OR = 1.50 95% CI: 0.58–3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs ( p 0.001). Preliminary phenotypic analyses revealed that within the CHR s le, the NMDAR antibody seropositive subjects had higher levels of current depression, performed worse on the Rey Auditory Verbal Learning Task ( p 0.05), and had a markedly lower IQ ( p 0.01). NMDAR IgGs were not more frequent in subjects who later became psychotic than those who did not. NMDAR antibody serostatus and titre was associated with poorer levels of functioning at follow-up ( p 0.05) and the presence of a neuronal autoantibody was associated with larger amygdala volumes ( p 0.05). Altogether, these findings demonstrate that NMDAR autoantibodies are detectable in a subgroup of CHR subjects at equal rates to controls. In the CHR group, they are associated with affective psychopathology, impairments in verbal memory, and overall cognitive function: these findings are qualitatively and in idually similar to core features of autoimmune encephalitis and/or animal models of NMDAR antibody-mediated CNS disease. Overall the current work supports further evaluation of NMDAR autoantibodies as a possible prognostic biomarker and aetiological factor in a subset of people already meeting CHR criteria.
Publisher: American Medical Association (AMA)
Date: 06-2021
Publisher: Frontiers Media SA
Date: 10-05-2019
Publisher: Springer Science and Business Media LLC
Date: 18-11-2009
DOI: 10.1038/NPP.2009.184
Publisher: SAGE Publications
Date: 05-10-2012
Abstract: Community-based studies suggest that cannabis products that are high in Δ 9 -tetrahydrocannabinol (THC) but low in cannabidiol (CBD) are particularly hazardous for mental health. Laboratory-based studies are ideal for clarifying this issue because THC and CBD can be administered in pure form, under controlled conditions. In a between-subjects design, we tested the hypothesis that pre-treatment with CBD inhibited THC-elicited psychosis and cognitive impairment. Healthy participants were randomised to receive oral CBD 600mg ( n=22) or placebo ( n=26), 210 min ahead of intravenous (IV) THC (1.5 mg). Post-THC, there were lower PANSS positive scores in the CBD group, but this did not reach statistical significance. However, clinically significant positive psychotic symptoms (defined a priori as increases ≥3 points) were less likely in the CBD group compared with the placebo group, odds ratio (OR)=0.22 (χ 2 =4.74, p .05). In agreement, post-THC paranoia, as rated with the State Social Paranoia Scale (SSPS), was less in the CBD group compared with the placebo group ( t=2.28, p .05). Episodic memory, indexed by scores on the Hopkins Verbal Learning Task-revised (HVLT-R), was poorer, relative to baseline, in the placebo pre-treated group (-10.6±18.9%) compared with the CBD group (-0.4%±9.7 %) ( t=2.39, p .05). These findings support the idea that high-THC/low-CBD cannabis products are associated with increased risks for mental health.
Publisher: Elsevier BV
Date: 03-2014
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.BIOPSYCH.2010.08.033
Abstract: Both medial temporal cortical dysfunction and perturbed glutamatergic neurotransmission are regarded as fundamental pathophysiological features of psychosis. However, although animal models of psychosis suggest that these two abnormalities are interrelated, their relationship in humans has yet to be investigated. We used a combination of functional magnetic resonance imaging and magnetic resonance spectroscopy to investigate the relationship between medial temporal activation during an episodic memory task and local glutamate levels in 22 in iduals with an at-risk mental state for psychosis and 14 healthy volunteers. We observed a significant between-group difference in the coupling of medial temporal activation with local glutamate levels. In control subjects, medial temporal activation during episodic encoding was positively associated with medial temporal glutamate. However, in the clinical population, medial temporal activation was reduced, and the relationship with glutamate was absent. In in iduals at high risk of psychosis, medial temporal dysfunction seemed related to a loss of the normal relationship with local glutamate levels. This study provides the first evidence that links medial temporal dysfunction with the central glutamate system in humans and is consistent with evidence that drugs that modulate glutamatergic transmission might be useful in the treatment of psychosis.
Publisher: Elsevier BV
Date: 09-2009
Publisher: Springer Science and Business Media LLC
Date: 17-02-2023
DOI: 10.1038/S41380-023-01991-7
Abstract: Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-in idual 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 (log coefficient of variation ratio: CVR) (2) standardised mean differences (SMD) using Hedges g (3) modal distribution of in idual-level glutamate data (Hartigan’s unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on 8256 patients and 7532 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15, p 0.001 glutamine: CVR = 0.15, p = 0.003 Glx: CVR = 0.11, p = 0.002), dorsolateral prefrontal cortex (glutamine: CVR = 0.14, p = 0.05 Glx: CVR = 0.25, p 0.001) and thalamus (glutamate: CVR = 0.16, p = 0.008 Glx: CVR = 0.19, p = 0.008). Studies in younger, more symptomatic patients were associated with greater variability in the basal ganglia (BG glutamate with age: z = −0.03, p = 0.003, symptoms: z = 0.007, p = 0.02) and temporal lobe (glutamate with age: z = −0.03, p = 0.02), while studies with older, more symptomatic patients associated with greater variability in MFC (glutamate with age: z = 0.01, p = 0.02, glutamine with symptoms: z = 0.01, p = 0.02). For in idual patient data, most studies showed a unimodal distribution of glutamatergic metabolites. Meta-analysis of mean differences found lower MFC glutamate ( g = −0.15, p = 0.03), higher thalamic glutamine ( g = 0.53, p 0.001) and higher BG Glx in patients relative to controls ( g = 0.28, p 0.001). Proportion of males was negatively associated with MFC glutamate ( z = −0.02, p 0.001) and frontal white matter Glx ( z = −0.03, p = 0.02) in patients relative to controls. Patient PANSS total score was positively associated with glutamate SMD in BG ( z = 0.01, p = 0.01) and temporal lobe ( z = 0.05, p = 0.008). Further research into the mechanisms underlying greater glutamatergic metabolite variability in schizophrenia and their clinical consequences may inform the identification of patient subgroups for future treatment strategies.
Publisher: Springer Science and Business Media LLC
Date: 03-05-2016
DOI: 10.1038/TP.2016.68
Publisher: SAGE Publications
Date: 09-2022
DOI: 10.1177/02698811221099643
Abstract: Evidence from post-mortem studies and in vivo imaging studies suggests there may be reduced N-methyl-d-aspartate receptor (NMDAR) levels in the hippoc us in patients with schizophrenia. Other studies have reported increased glutamate in striatum in schizophrenia patients. It has been hypothesised that NMDAR hypofunction leads to the disinhibition of glutamatergic signalling however, this has not been tested in vivo. In this study, we investigated the relationship between hippoc al NMDAR and striatal glutamate using simultaneous positron emission tomography-magnetic resonance (PET-MR) imaging. We recruited 40 volunteers to this cross-sectional study 21 patients with schizophrenia, all in their first episode of illness, and 19 healthy controls. We measured hippoc al NMDAR availability using the PET ligand [ 18 F]GE179. This was indexed relative to whole brain as the distribution volume ratio (DVR). Striatal glutamatergic indices (glutamate and Glx) were acquired simultaneously, using combined PET-MR proton magnetic resonance spectroscopy ( 1 H-MRS). A total of 33 in iduals (15 healthy controls, 18 patients) were included in the analyses (mean (SD) age of controls, 27.31 (4.68) years mean (SD) age of patients, 24.75 (4.33), 27 male and 6 female). We found an inverse relationship between hippoc al DVR and striatal glutamate levels in people with first-episode psychosis (rho = −0.74, p 0.001) but not in healthy controls (rho = −0.22, p = 0.44). This study show that lower relative NMDAR availability in the hippoc us may drive increased striatal glutamate levels in patients with schizophrenia. Further work is required to determine whether these findings may yield new targets for drug development in schizophrenia.
Publisher: SAGE Publications
Date: 12-12-2019
Abstract: 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 the strength of the evidence on the risk-benefit balance of pharmacological interventions and the clinical implications, with an emphasis on meta-analyses, systematic reviews and randomised controlled trials where available, plus updates on current clinical practice. The guidelines cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. It is hoped that the practice recommendations presented will support clinical decision making for practitioners, serve as a source of information for patients and carers, and inform quality improvement.
Publisher: Cambridge University Press (CUP)
Date: 06-02-2014
Publisher: Cambridge University Press (CUP)
Date: 30-04-2014
Publisher: American Medical Association (AMA)
Date: 02-05-2011
DOI: 10.1001/ARCHGENPSYCHIATRY.2011.42
Abstract: People experiencing possible prodromal symptoms of psychosis have a very high risk of developing the disorder, but it is not possible to predict, on the basis of their presenting clinical features, which in iduals will subsequently become psychotic. Recent neuroimaging studies suggest that there are volumetric differences between in iduals at ultra-high risk (UHR) for psychosis who later develop psychotic disorder and those who do not. However, the s les examined to date have been small, and the findings have been inconsistent. To assess brain structure in in iduals at UHR for psychosis in a larger and more representative s le than in previous studies by combining magnetic resonance imaging data from 5 different scanning sites. Case-control study. Multisite. A total of 182 in iduals at UHR and 167 healthy controls. Participants were observed clinically for a mean of 2 years. Forty-eight in iduals (26.4%) in the UHR group developed psychosis and 134 did not. Magnetic resonance images were acquired from each participant. Group differences in gray matter volume were examined using optimized voxel-based morphometry. The UHR group as a whole had less gray matter volume than did controls in the frontal regions bilaterally. The UHR subgroup who later developed psychosis had less gray matter volume in the left parahippoc al cortex than did the UHR subgroup who did not. In iduals at high risk for psychosis show alterations in regional gray matter volume regardless of whether they subsequently develop the disorder. In the UHR population, reduced left parahippoc al volume was specifically associated with the later onset of psychosis. Alterations in this region may, thus, be crucial to the expression of illness. Identifying abnormalities that specifically predate the onset of psychosis informs the development of clinical investigations designed to predict which in iduals at high risk will subsequently develop the disorder.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for James Stone.