156 results on '"Sameer Jauhar"'
Search Results
2. The relationship between striatal dopamine and anterior cingulate glutamate in first episode psychosis changes with antipsychotic treatment
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Sameer Jauhar, Robert A. McCutcheon, Mattia Veronese, Faith Borgan, Matthew Nour, Maria Rogdaki, Fiona Pepper, James M. Stone, Alice Egerton, George Vamvakas, Federico Turkheimer, Philip K. McGuire, and Oliver D. Howes
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Abstract The neuromodulator dopamine and excitatory neurotransmitter glutamate have both been implicated in the pathogenesis of psychosis, and dopamine antagonists remain the predominant treatment for psychotic disorders. To date no study has measured the effect of antipsychotics on both of these indices together, in the same population of people with psychosis. Striatal dopamine synthesis capacity (Kicer) and anterior cingulate glutamate were measured using 18F-DOPA positron emission tomography and proton magnetic resonance spectroscopy respectively, before and after at least 5 weeks’ naturalistic antipsychotic treatment in people with first episode psychosis (n = 18) and matched healthy controls (n = 20). The relationship between both measures at baseline and follow-up, and the change in this relationship was analyzed using a mixed linear model. Neither anterior cingulate glutamate concentrations (p = 0.75) nor striatal Kicer (p = 0.79) showed significant change following antipsychotic treatment. The change in relationship between whole striatal Kicer and anterior cingulate glutamate, however, was statistically significant (p = 0.017). This was reflected in a significant difference in relationship between both measures for patients and controls at baseline (t = 2.1, p = 0.04), that was not present at follow-up (t = 0.06, p = 0.96). Although we did not find any effect of antipsychotic treatment on absolute measures of dopamine synthesis capacity and anterior cingulate glutamate, the relationship between anterior cingluate glutamate and striatal dopamine synthesis capacity did change, suggesting that antipsychotic treatment affects the relationship between glutamate and dopamine.
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- 2023
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3. A polygenic score indexing a DRD2-related co-expression network is associated with striatal dopamine function
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Enrico D’Ambrosio, Giulio Pergola, Antonio F. Pardiñas, Tarik Dahoun, Mattia Veronese, Leonardo Sportelli, Paolo Taurisano, Kira Griffiths, Sameer Jauhar, Maria Rogdaki, Michael A. P. Bloomfield, Sean Froudist-Walsh, Ilaria Bonoldi, James T. R. Walters, Giuseppe Blasi, Alessandro Bertolino, and Oliver D. Howes
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Medicine ,Science - Abstract
Abstract The D2 dopamine receptor (D2R) is the primary site of the therapeutic action of antipsychotics and is involved in essential brain functions relevant to schizophrenia, such as attention, memory, motivation, and emotion processing. Moreover, the gene coding for D2R (DRD2) has been associated with schizophrenia at a genome-wide level. Recent studies have shown that a polygenic co-expression index (PCI) predicting the brain-specific expression of a network of genes co-expressed with DRD2 was associated with response to antipsychotics, brain function during working memory in patients with schizophrenia, and with the modulation of prefrontal cortex activity after pharmacological stimulation of D2 receptors. We aimed to investigate the relationship between the DRD2 gene network and in vivo striatal dopaminergic function, which is a phenotype robustly associated with psychosis and schizophrenia. To this aim, a sample of 92 healthy subjects underwent 18F-DOPA PET and was genotyped for genetic variations indexing the co-expression of the DRD2-related genetic network in order to calculate the PCI for each subject. The PCI was significantly associated with whole striatal dopamine synthesis capacity (p = 0.038). Exploratory analyses on the striatal subdivisions revealed a numerically larger effect size of the PCI on dopamine function for the associative striatum, although this was not significantly different than effects in other sub-divisions. These results are in line with a possible relationship between the DRD2-related co-expression network and schizophrenia and extend it by identifying a potential mechanism involving the regulation of dopamine synthesis. Future studies are needed to clarify the molecular mechanisms implicated in this relationship.
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- 2022
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4. Parsing neurobiological heterogeneity of the clinical high-risk state for psychosis: A pseudo-continuous arterial spin labelling study
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Dominic Oliver, Cathy Davies, Fernando Zelaya, Pierluigi Selvaggi, Andrea De Micheli, Ana Catalan, Helen Baldwin, Maite Arribas, Gemma Modinos, Nicolas A. Crossley, Paul Allen, Alice Egerton, Sameer Jauhar, Oliver D. Howes, Philip McGuire, and Paolo Fusar-Poli
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clinical high risk for psychosis ,brief limited intermittent psychotic symptoms ,attenuated psychosis syndrome ,arterial spin labelling ,neuroimaging ,Psychiatry ,RC435-571 - Abstract
IntroductionThe impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subgroup stratification with information from candidate biomarkers based on neurobiological parameters, such as resting-state, regional cerebral blood flow (rCBF), may help refine risk estimates. Based on previous evidence, we hypothesized that individuals with BLIPS would exhibit increased rCBF compared to APS in key regions linked to dopaminergic pathways.MethodsData from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects (n = 30 healthy controls [HCs], n = 80 APS, n = 20 BLIPS and n = 20 FEP). Global gray matter (GM) rCBF was examined in addition to region-of-interest (ROI) analyses in bilateral/left/right frontal cortex, hippocampus and striatum. Group differences were assessed using general linear models: (i) alone; (ii) with global GM rCBF as a covariate; (iii) with global GM rCBF and smoking status as covariates. Significance was set at p 0.05). All results were robust to addition of covariates (p > 0.05). No significant clusters were identified in whole-brain voxel-wise analyses (p > 0.05FWE). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses.ConclusionOn this evidence, APS and BLIPS are unlikely to be neurobiologically distinct. Due to this and the weak-to-moderate evidence for the null hypothesis, future research should investigate larger samples of APS and BLIPS through collaboration across large-scale international consortia.
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- 2023
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5. Clozapine for treatment resistance in early psychosis: a survey of UK clinicians’ training, knowledge and confidence
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Ebenezer Oloyede, Bethany Mantell, Julie Williams, Serena Lai, Sameer Jauhar, David Taylor, James H. MacCabe, Robert Harland, Philip McGuire, and Graham Blackman
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Therapeutics. Pharmacology ,RM1-950 ,Psychiatry ,RC435-571 - Abstract
Background: Clozapine is the only medication licenced for patients with psychosis that is resistant to conventional antipsychotic treatment. However, despite its effectiveness, it remains widely underutilised. One contributory factor for this may be clinicians’ lack of confidence around the management of clozapine. Objective: We conducted a survey of clinicians working in Early Intervention in Psychosis (EIP) services to determine their training needs for clozapine management in EIP services. Methods: An electronic survey was made available to all clinicians working in EIP services in England. The survey assessed confidence and training needs regarding managing clozapine in patients with treatment-resistant psychosis. Quantitative data were analysed using total mean scores and the Mann–Whitney U test. Results: In all, 192 (27%) of approximately 700 clinicians from 35 EIP services completed the survey. Approximately half (54%) had not received training on treatment with clozapine. Experience of training was higher in prescribers than non-prescribers, and among medical than non-medical clinicians. Previous training was associated with significantly higher confidence in offering clozapine and managing treatment-resistant psychosis ( p
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- 2022
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6. N-methyl-D-aspartate receptor availability in first-episode psychosis: a PET-MR brain imaging study
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Katherine Beck, Atheeshaan Arumuham, Mattia Veronese, Barbara Santangelo, Colm J. McGinnity, Joel Dunn, Robert A. McCutcheon, Stephen J. Kaar, Nisha Singh, Toby Pillinger, Faith Borgan, James Stone, Sameer Jauhar, Teresa Sementa, Federico Turkheimer, Alexander Hammers, and Oliver D. Howes
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Abstract N-methyl-D-aspartate receptor (NMDAR) hypofunction is hypothesised to underlie psychosis but this has not been tested early in illness. To address this, we studied 40 volunteers (21 patients with first-episode psychosis and 19 matched healthy controls) using PET imaging with an NMDAR selective ligand, [18F]GE-179, that binds to the ketamine binding site to index its distribution volume ratio (DVR) and volume of distribution (V T). Hippocampal DVR, but not V T, was significantly lower in patients relative to controls (p = 0.02, Cohen’s d = 0.81; p = 0.15, Cohen’s d = 0.49), and negatively associated with total (rho = −0.47, p = 0.04), depressive (rho = −0.67, p = 0.002), and general symptom severity (rho = −0.74, p
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- 2021
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7. The effect of antipsychotics on glutamate levels in the anterior cingulate cortex and clinical response: A 1H-MRS study in first-episode psychosis patients
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Uzma Zahid, Robert A. McCutcheon, Faith Borgan, Sameer Jauhar, Fiona Pepper, Matthew M. Nour, Maria Rogdaki, Martin Osugo, Graham K. Murray, Pamela Hathway, Robin M. Murray, Alice Egerton, and Oliver D. Howes
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spectroscopy ,NMDA ,imaging and schizophrenia ,CSF-correction ,longitudinal ,glutamate ,Psychiatry ,RC435-571 - Abstract
IntroductionGlutamatergic 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), and whether there is a relationship between baseline glutamatergic levels and clinical response after antipsychotic treatment in people with first episode psychosis (FEP).Materials and methodsThe sample comprised 25 FEP patients; 22 completed magnetic resonance spectroscopy scans at both timepoints. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS).ResultsThere was no significant change in glutamate [baseline 13.23 ± 2.33; follow-up 13.89 ± 1.74; t(21) = −1.158, p = 0.260], or Glx levels [baseline 19.64 ± 3.26; follow-up 19.66 ± 2.65; t(21) = −0.034, p = 0.973]. There was no significant association between glutamate or Glx levels at baseline and the change in PANSS positive (Glu r = 0.061, p = 0.777, Glx r = −0.152, p = 0.477), negative (Glu r = 0.144, p = 0.502, Glx r = 0.052, p = 0.811), general (Glu r = 0.110, p = 0.607, Glx r = −0.212, p = 0.320), or total scores (Glu r = 0.078, p = 0.719 Glx r = −0.155, p = 0.470).ConclusionThese findings indicate that treatment response is unlikely to be associated with baseline glutamatergic metabolites prior to antipsychotic treatment, and there is no major effect of antipsychotic treatment on glutamatergic metabolites in the ACC.
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- 2022
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8. Controversies in bipolar disorder; role of second-generation antipsychotic for maintenance therapy
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Sameer Jauhar and Allan H. Young
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurophysiology and neuropsychology ,QP351-495 - Abstract
Abstract In this narrative review, we discuss use of second-generation antipsychotics (SGAs) in maintenance treatment of bipolar disorder. We compare their use to historically more established treatments (particularly lithium, the gold standard). To compare we review evidence on efficacy, effectiveness and tolerability across illness poles, possible mechanisms of treatment response, guidance given by guideline groups and pragmatic clinical considerations. We then illustrate the controversies in maintenance antipsychotic use, with the example of first episode mania and its treatment within first episode psychosis services. Finally, we make suggestions for future studies to unpick these differences.
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- 2019
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9. Early Intervention Services for First Episode of Psychosis in South London and the Maudsley (SLaM): 20 Years of Care and Research for Young People
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Paolo Fusar-Poli, Serena Lai, Marta Di Forti, Eduardo Iacoponi, Graham Thornicroft, Philip McGuire, and Sameer Jauhar
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psychosis ,schizophrenia ,early intervention ,SLaM ,implementation ,health service research ,Psychiatry ,RC435-571 - Abstract
Introduction: Early Intervention for a first episode of Psychosis (EI) is essential to improve outcomes. There is limited research describing real-world implementation of EI services.Method: Analysis of service characteristics, outcomes (described through a retrospective 2007–2017 Electronic Health Record (EHR) cohort study) and clinical research relating to the first 20 years of implementation of EI services in South London and Maudsley (SLaM) Trust.Results: SLaM EI are standalone services serving 443,050 young individuals in South-London, where (2017) incidence of psychosis (58.3–71.9 cases per 100,000 person-years) is greater than the national average. From 2007–2017 (when the EHR was established), 1,200 individuals (62.67% male, mean age 24.38 years, 88.17% single; two-thirds of non-white ethnicity) received NICE-compliant EI care. Pathways to EI services came mainly (75.26%) through inpatient (39.83%) or community (19.33%) mental health services or Accident and Emergency departments (A&E) (16%). At 6 year follow-up 34.92% of patients were still being prescribed antipsychotics. The 3 month and 6 year cumulative proportions of those receiving clozapine were 0.75 and 7.33%; those compulsorily admitted to psychiatric hospitals 26.92 and 57.25%; those admitted to physical health hospitals 6.83 and 31.17%, respectively. Average 3 months and 6 year days spent in hospital were 0.82 and 1.85, respectively; mean 6 year attendance at A&E was 3.01. SLaM EI clinical research attracted £58 million grant income and numerous high-impact scientific publications.Conclusions: SLaM EI services represent one of the largest, most established services of its kind, and are a leading model for development of similar services in the UK and worldwide.
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- 2020
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10. Methodological Biases in CBT Trial—Commentary: Modular Cognitive-Behavioral Therapy for Affective Symptoms in Young Individuals at Ultra-High Risk of First Episode of Psychosis: Randomized Controlled Trial
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Paolo Fusar-Poli, Joaquim Radua, Peter J. McKenna, Keith Laws, Cathy Davies, and Sameer Jauhar
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prevention ,psychosis ,clinical high risk (CHR) ,cognitive behavioural therapy (CBT) ,bias ,Psychiatry ,RC435-571 - Published
- 2020
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11. Cognitive Behavioural Therapy for schizophrenia - outcomes for functioning, distress and quality of life: a meta-analysis
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Keith R. Laws, Nicole Darlington, Tejinder K. Kondel, Peter J. McKenna, and Sameer Jauhar
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Schizophrenia ,Psychosis ,CBT ,CBTp ,Cognitive behavioural therapy ,Meta-analysis ,Psychology ,BF1-990 - Abstract
Abstract Background The effect of cognitive behavioural therapy for psychosis (CBTp) on the core symptoms of schizophrenia has proven contentious, with current meta-analyses finding at most only small effects. However, it has been suggested that the effects of CBTp in areas other than psychotic symptoms are at least as important and potentially benefit from the intervention. Method We meta-analysed RCTs investigating the effectiveness of CBTp for functioning, distress and quality of life in individuals diagnosed with schizophrenia and related disorders. Data from 36 randomised controlled trials (RCTs) met our inclusion criteria- 27 assessing functioning (1579 participants); 8 for distress (465 participants); and 10 for quality of life (592 participants). Results The pooled effect size for functioning was small but significant for the end-of-trial (0.25: 95% CI: 0.14 to 0.33); however, this became non-significant at follow-up (0.10 [95%CI -0.07 to 0.26]). Although a small benefit of CBT was evident for reducing distress (0.37: 95%CI 0.05 to 0.69), this became nonsignificant when adjusted for possible publication bias (0.18: 95%CI -0.12 to 0.48). Finally, CBTp showed no benefit for improving quality of life (0.04: 95% CI: -0.12 to 0.19). Conclusions CBTp has a small therapeutic effect on functioning at end-of-trial, although this benefit is not evident at follow-up. Although CBTp produced a small benefit on distress, this was subject to possible publication bias and became nonsignificant when adjusted. We found no evidence that CBTp increases quality of life post-intervention.
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- 2018
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12. Are we getting any better at staying better? The long view on relapse and recovery in first episode nonaffective psychosis and schizophrenia
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Mark Taylor and Sameer Jauhar
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Therapeutics. Pharmacology ,RM1-950 ,Psychiatry ,RC435-571 - Abstract
Relapse in, and recovery from, schizophrenia has been acknowledged since the disease was first described. In this review the authors summarize the long-term (>100 years) data on relapse and recovery in schizophrenia by reviewing the extant older and modern relevant literature. The authors systematically question the utility of pharmacological and nonpharmacological interventions, with an emphasis on first episode nonaffective psychosis. The method used is a narrative review of earlier meta-analytic and systematic reviews. Antipsychotic medication discontinuation studies suggest a role for prophylactic maintenance treatment in the majority of people with schizophrenia, despite recent debate on this subject. The authors conclude that long-term outcomes, including relapse and recovery rates, have improved in the last 100 years, though prospectively identifying those people who do not require long-term antipsychotic treatment has not yet been possible. Data also suggests that interventions and outcomes during the first 5 years of the disease can influence the long-term schizophrenia trajectory.
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- 2019
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13. The effect of perinatal brain injury on dopaminergic function and hippocampal volume in adult life
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Sean Froudist-Walsh, Michael AP Bloomfield, Mattia Veronese, Jasmin Kroll, Vyacheslav R Karolis, Sameer Jauhar, Ilaria Bonoldi, Philip K McGuire, Shitij Kapur, Robin M Murray, Chiara Nosarti, and Oliver Howes
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dopamine ,imaging ,preterm ,brain volume ,brain injury ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
Perinatal brain injuries, including hippocampal lesions, cause lasting changes in dopamine function in rodents, but it is not known if this occurs in humans. We compared adults who were born very preterm with perinatal brain injury to those born very preterm without perinatal brain injury, and age-matched controls born at full term using [18F]-DOPA PET and structural MRI. Dopamine synthesis capacity was reduced in the perinatal brain injury group relative to those without brain injury (Cohen’s d = 1.36, p=0.02) and the control group (Cohen’s d = 1.07, p=0.01). Hippocampal volume was reduced in the perinatal brain injury group relative to controls (Cohen’s d = 1.17, p=0.01) and was positively correlated with striatal dopamine synthesis capacity (r = 0.344, p=0.03). This is the first evidence in humans linking neonatal hippocampal injury to adult dopamine dysfunction, and provides a potential mechanism linking early life risk factors to adult mental illness.
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- 2017
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14. Muscarinic receptor agonists in animal models of psychosis: protocol for a systematic review and meta-analysis [version 1; peer review: awaiting peer review]
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Spyridon Siafis, Nobuyuki Nomura, Johannes Schneider-Thoma, Irene Bighelli, Alexandra Bannach-Brown, Fiona J. Ramage, Francesca Tinsdeall, Ioannis Mantas, Sameer Jauhar, Sridhar Natesan, Anthony C. Vernon, Andrea de Bartolomeis, Sabine M. Hölter, Natascha I. Drude, Ulf Tölch, Wulf-Peter Hansen, Virginia Chiocchia, Oliver D. Howes, Josef Priller, Malcolm R. Macleod, Georgia Salanti, and Stefan Leucht
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Study Protocol ,Articles ,antipsychotic ,schizophrenia ,psychosis ,muscarinic receptor ,acetylcholine ,meta-analysis - Abstract
Background Muscarinic receptor agonism is a promising mechanism of action for treating psychosis, not present in most D 2R-blocking antipsychotics. Xanomeline, an M1/M4-preferring agonist, has shown efficacy in late-stage clinical trials, with more compounds being investigated. Therefore, we aim to synthesize evidence on the preclinical efficacy of muscarinic receptor agonists in animal models of psychosis to provide unique insights and evidence-based information to guide drug development. Methods We plan a systematic review and meta-analysis of in vivo animal studies comparing muscarinic receptor agonists or positive allosteric modulators with control conditions and existing D2R-blocking antipsychotics in animals subjected to any method that induces behavioural changes of relevance for psychosis. We will identify eligible studies by searching multiple electronic databases. At least two independent reviewers will conduct the study selection and data extraction using prespecified forms and assess the risk of bias with the SYRCLE’s tool. Our primary outcomes include locomotor activity and prepulse inhibition measured with standardized mean differences. We will examine other behavioural readouts of relevance for psychosis as secondary outcomes, such as social interaction and cognitive function. We will synthesize the data using multi-level meta-analysis with a predefined random-effects structure, considering the non-independence of the data. In meta-regressions we will explore potential sources of heterogeneity from a predefined list of characteristics of the animal population, model, and intervention. We will assess the confidence in the evidence considering a self-developed instrument thatconsiders the internal and external validity of the evidence. Protocol registration PROSPERO-ID: CRD42024520914
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- 2024
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15. Reduced cortical cerebral blood flow in antipsychotic-free first-episode psychosis and relationship to treatment response
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Pierluigi Selvaggi, Sameer Jauhar, Vasileia Kotoula, Fiona Pepper, Mattia Veronese, Barbara Santangelo, Fernando Zelaya, Federico E. Turkheimer, Mitul A. Mehta, and Oliver D. Howes
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Psychiatry and Mental health ,Applied Psychology - Abstract
Background Altered cerebral blood flow (CBF) has been found in people at risk for psychosis, with first-episode psychosis (FEP) and with chronic schizophrenia (SCZ). Studies using arterial spin labelling (ASL) have shown reduction of cortical CBF and increased subcortical CBF in SCZ. Previous studies have investigated CBF using ASL in FEP, reporting increased CBF in striatum and reduced CBF in frontal cortex. However, as these people were taking antipsychotics, it is unclear whether these changes are related to the disorder or antipsychotic treatment and how they relate to treatment response. Methods We examined CBF in FEP free from antipsychotic medication (N = 21), compared to healthy controls (N = 22). Both absolute and relative-to-global CBF were assessed. We also investigated the association between baseline CBF and treatment response in a partially nested follow-up study (N = 14). Results There was significantly lower absolute CBF in frontal cortex (Cohen's d = 0.84, p = 0.009) and no differences in striatum or hippocampus. Whole brain voxel-wise analysis revealed widespread cortical reductions in absolute CBF in large cortical clusters that encompassed occipital, parietal and frontal cortices (Threshold-Free Cluster Enhancement (TFCE)-corrected r = 0.67, p = 0.008). Conclusions These results show lower cortical absolute perfusion in FEP prior to starting antipsychotic treatment and suggest relative-to-global frontal CBF as assessed with magnetic resonance imaging could potentially serve as a biomarker for antipsychotic response.
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- 2022
16. Off the RADAR; questions regarding the trial protocol of a randomised controlled trial of antipsychotic reduction and discontinuation
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Sameer Jauhar, Paolo Fusar-Poli, and David Foreman
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Pharmacology ,Psychiatry and Mental health ,Pharmacology (medical) - Abstract
The randomised controlled trial of antipsychotic reduction and discontinuation addresses essential questions with regard to continued use of antipsychotics in schizophrenia, pertaining to social functioning and continued antipsychotic use. However, significant methodological issues stated in the trial protocol have the potential to confound interpretation of any findings. These include use of a non-blinded outcome measure, treatment as usual comparator and possible sample size issues.
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- 2023
17. Fifty years on: serotonin and depression
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Sameer Jauhar, Philip J Cowen, and Michael Browning
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Pharmacology ,Psychiatry and Mental health ,Pharmacology (medical) - Abstract
It has been over 50 years since the original serotonin hypothesis was proposed by the British Psychiatrist Alec Coppen. Recently, some authors have questioned the validity of the hypothesis. In this narrative review, we summarise the evidence for the serotonin hypothesis of depression, focusing on psychopharmacology and molecular imaging, as well as systems-level neuroscience.
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- 2023
18. A systematic review and meta-analysis of treatments for rapid cycling bipolar disorder
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Rebecca Strawbridge, Suman Kurana, Jess Kerr‐Gaffney, Sameer Jauhar, Kenneth R. Kaufman, Nefize Yalin, and Allan H. Young
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Bipolar Disorder ,treatment ,Aripiprazole ,Venlafaxine Hydrochloride ,rapid cycling ,Citalopram ,Lamotrigine ,meta-analysis ,Psychiatry and Mental health ,Quetiapine Fumarate ,bipolar disorders ,systematic review ,Olanzapine ,Fluoxetine ,Humans - Abstract
Objectives: Rapid cycling is a common and disabling phenomenon in individuals with bipolar disorders. In the absence of a recent literature examination, this systematic review and meta-analysis aimed to synthesise the evidence of efficacy, acceptability and tolerability of treatments for individuals with rapid cycling bipolar disorder (RCBD). Method: A systematic search was conducted to identify randomised controlled trials assigning participants with RCBD to pharmacological and/or non-pharmacological interventions. Study inclusion and data extraction were undertaken by two reviewers independently. The primary outcome was continuous within-subject RCBD illness severity before and after treatment. Pre-post random effects meta-analyses were conducted for each outcome/intervention arm studied, generating a standardised effect size (hedge's g) and 95% confidence interval (CI). Results: A total of 34 articles describing 30 studies were included. A total of 16 separate pharmacological treatments were examined in contrast to 1 psychological therapy study. Only quetiapine and lamotrigine were assessed in >5 studies. By assessing 95% CI overlap of within-subject efficacy effects compared to placebo, the only interventions suggesting significant depression benefits (placebo g = 0.60) were olanzapine (with/without fluoxetine; g = 1.01), citalopram (g = 1.10) and venlafaxine (g = 2.48). For mania, benefits were indicated for quetiapine (g = 1.01), olanzapine (g = 1.19) and aripiprazole (g = 1.09), versus placebo (g = 0.33). Most of these effect sizes were from only one trial per treatment. Heterogeneity between studies was variable, and 20% were rated to have a high risk of bias. Conclusions: While many interventions appeared efficacious, there was a lack of robust evidence for most treatments. Given the limited and heterogeneous evidence base, the optimal treatment strategies for people with RCBD are yet to be established.
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- 2022
19. The association between
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Katherine, Beck, Atheeshaan, Arumuham, Stefan, Brugger, Robert A, McCutcheon, Mattia, Veronese, Barbara, Santangelo, Colm J, McGinnity, Joel, Dunn, Stephen, Kaar, Nisha, Singh, Toby, Pillinger, Faith, Borgan, Teresa, Sementa, Radhouene, Neji, Sameer, Jauhar, Franklin, Aigbirhio, Istvan, Boros, Federico, Turkheimer, Alexander, Hammers, David, Lythgoe, James, Stone, and Oliver D, Howes
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Adult ,Male ,Magnetic Resonance Spectroscopy ,Brain ,Glutamic Acid ,Neuroimaging ,Ligands ,Receptors, N-Methyl-D-Aspartate ,Young Adult ,Cross-Sectional Studies ,Psychotic Disorders ,Positron-Emission Tomography ,Humans ,Female - Abstract
Evidence from post-mortem studies and in vivo imaging studies suggests there may be reducedIn this study, we investigated the relationship between hippocampal 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 hippocampal NMDAR availability using the PET ligand [A total of 33 individuals (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 hippocampal DVR and striatal glutamate levels in people with first-episode psychosis (rho = -0.74,This study show that lower relative NMDAR availability in the hippocampus 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.
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- 2022
20. The association between N-methyl-d-aspartate receptor availability and glutamate levels:A multi-modal PET-MR brain imaging study in first-episode psychosis and healthy controls
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Katherine Beck, Atheeshaan Arumuham, Stefan Brugger, Robert A McCutcheon, Mattia Veronese, Barbara Santangelo, Colm J McGinnity, Joel Dunn, Stephen Kaar, Nisha Singh, Toby Pillinger, Faith Borgan, Teresa Sementa, Radhouene Neji, Sameer Jauhar, Franklin Aigbirhio, Istvan Boros, Federico Turkheimer, Alexander Hammers, David Lythgoe, James Stone, and Oliver D Howes
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Pharmacology ,Psychiatry and Mental health ,Pharmacology (medical) - Abstract
Background: Evidence from post-mortem studies and in vivo imaging studies suggests there may be reduced N-methyl-d-aspartate receptor (NMDAR) levels in the hippocampus 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. Methods: In this study, we investigated the relationship between hippocampal 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 hippocampal NMDAR availability using the PET ligand [18F]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 (1H-MRS). Results: A total of 33 individuals (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 hippocampal DVR and striatal glutamate levels in people with first-episode psychosis (rho = −0.74, p Conclusion: This study show that lower relative NMDAR availability in the hippocampus 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.
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- 2022
21. The effects of reserpine on depression: A systematic review
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Rebecca Strawbridge, Rahila R Javed, Jeremy Cave, Sameer Jauhar, and Allan H Young
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Pharmacology ,Psychiatry and Mental health ,Pharmacology (medical) - Abstract
Background: Reserpine is an effective antihypertensive drug, but its role in routine practice has declined such that it is rarely used. This is largely based on the assumption that reserpine causes depression. This assumption was a foundation for the original monoamine hypothesis of depression. However, there remains conflicting evidence as to whether reserpine causes depression, and no systematic review of available evidence. Aims: We systematically reviewed evidence on effects of reserpine on depressive and related symptoms (e.g. anxiety, suicidal ideation). Method: Electronic searches of MEDLINE, Embase and PsycINFO were conducted to identify studies up to 14 February 2021. Studies of any methodological design involving reserpine-treated and reserpine-untreated conditions, in any adult human population, were included and a narrative synthesis of findings was undertaken. Risk of bias (RoB) was examined using ROBINS-I. Results: Of the 35 studies meeting inclusion criteria, 9 were randomised controlled trials. Eleven studies reported some depressogenic effects, 13 reported no effect and 11 reported putative antidepressant effects. Studies identifying depressive effects were more likely to examine people without psychiatric disorders at baseline, while studies identifying a potential antidepressant effect tended to treat fewer participants for shorter durations, at higher doses. Around one-third of studies conducted in people with psychiatric disorders showed beneficial effects on depression symptoms. 30/35 studies were at high RoB. Conclusions: Associations between reserpine and depression are inconsistent and limited by a lack of high-quality evidence. Due to reserpine’s apparently complex effects, we urge nuance rather than simplicity surrounding the monoamine hypothesis of depression.
- Published
- 2022
22. Electroconvulsive therapy for depression: 80 years of progress
- Author
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Sameer Jauhar, Pascal Sienaert, Charles H. Kellner, Declan M. McLoughlin, and George Kirov
- Subjects
Psychotherapist ,Depression ,business.industry ,medicine.medical_treatment ,Evidence-based medicine ,Scientific literature ,030227 psychiatry ,Depressive Disorder, Treatment-Resistant ,03 medical and health sciences ,Psychiatry and Mental health ,Treatment Outcome ,0302 clinical medicine ,Electroconvulsive therapy ,Meta-analysis ,Humans ,Effective treatment ,Medicine ,Treatment resistance ,Electroconvulsive Therapy ,business ,030217 neurology & neurosurgery ,Depression (differential diagnoses) - Abstract
Electroconvulsive therapy is the most effective treatment for severe, psychotic or treatment-resistant depression. However, its effectiveness continues to be questioned, both in mainstream media and narratives within the scientific literature. In this analysis, we use an evidence-based approach to demonstrate the efficacy and safety of modern electroconvulsive therapy.
- Published
- 2021
23. A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse
- Author
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Sridhar Natesan, Robin M. Murray, David Taylor, Sameer Jauhar, and Mark Abie Horowitz
- Subjects
Male ,AcademicSubjects/MED00810 ,medicine.medical_treatment ,D2 occupancy ,dopaminergic hypersensitivity ,Tardive dyskinesia ,Risk Assessment ,Drug Administration Schedule ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,hyperbolic ,Randomized controlled trial ,law ,Recurrence ,Dopamine receptor D2 ,medicine ,Humans ,Antipsychotic ,business.industry ,withdrawal ,medicine.disease ,030227 psychiatry ,Blockade ,Discontinuation ,schizophrenia ,Psychiatry and Mental health ,Withholding Treatment ,Schizophrenia ,Anesthesia ,Female ,Animal studies ,business ,030217 neurology & neurosurgery ,Antipsychotic Agents ,Regular Articles ,discontinuation - Abstract
The process of stopping antipsychotics may be causally related to relapse, potentially linked to neuroadaptations that persist after cessation, including dopaminergic hypersensitivity. Therefore, the risk of relapse on cessation of antipsychotics may be minimized by more gradual tapering. There is converging evidence that suggests that adaptations to antipsychotic exposure can persist for months or years after stopping the medication—from animal studies, observation of tardive dyskinesia in patients, and the clustering of relapses in this time period after the cessation of antipsychotics. Furthermore, PET imaging demonstrates a hyperbolic relationship between doses of antipsychotic and D2 receptor blockade. We, therefore, suggest that when antipsychotics are reduced, it should be done gradually (over months or years) and in a hyperbolic manner (to reduce D2 blockade “evenly”): ie, reducing by one quarter (or one half) of the most recent dose of antipsychotic, equivalent approximately to a reduction of 5 (or 10) percentage points of its D2 blockade, sequentially (so that reductions become smaller and smaller in size as total dose decreases), at intervals of 3–6 months, titrated to individual tolerance. Some patients may prefer to taper at 10% or less of their most recent dose each month. This process might allow underlying adaptations time to resolve, possibly reducing the risk of relapse on discontinuation. Final doses before complete cessation may need to be as small as 1/40th a therapeutic dose to prevent a large decrease in D2 blockade when stopped. This proposal should be tested in randomized controlled trials.
- Published
- 2021
24. Antipsychotics, the heartland of clinical psychopharmacology?
- Author
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Sameer Jauhar and Allan H. Young
- Subjects
Pharmacology ,Psychiatry and Mental health ,medicine.medical_specialty ,Psychopharmacology ,business.industry ,Mental Disorders ,Humans ,Medicine ,Pharmacology (medical) ,business ,Psychiatry ,Antipsychotic Agents - Published
- 2021
25. Real-world clinical and cost-effectiveness of community clozapine initiation: mirror cohort study
- Author
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Emma Butler, Toby Pillinger, Kirsten Brown, Faith Borgan, Alice Bowen, Katherine Beck, Enrico D'Ambrosio, Lisa Donaldson, Sameer Jauhar, Stephen Kaar, Tiago Reis Marques, Robert A. McCutcheon, Maria Rogdaki, Fiona Gaughran, James MacCabe, Rosalind Ramsay, David Taylor, Paul McCrone, Alice Egerton, and Oliver D. Howes
- Subjects
Cohort Studies ,Psychiatry and Mental health ,Cost-Benefit Analysis ,Schizophrenia ,Humans ,Clozapine ,Antipsychotic Agents - Abstract
BackgroundClozapine is the only drug licensed for treatment-resistant schizophrenia (TRS) but the real-world clinical and cost-effectiveness of community initiation of clozapine is unclear.AimsThe aim was to assess the feasibility and cost-effectiveness of community initiation of clozapine.MethodThis was a naturalistic study of community patients recommended for clozapine treatment.ResultsOf 158 patients recommended for clozapine treatment, 88 (56%) patients agreed to clozapine initiation and, of these, 58 (66%) were successfully established on clozapine. The success rate for community initiation was 65.4%; which was not significantly different from that for in-patient initiation (58.82%, χ2(1,88) = 0.47, P = 0.49). Following clozapine initiation, there was a significant reduction in median out-patient visits over 1 year (from 24.00 (interquartile range (IQR) = 14.00–41.00) to 13.00 visits (IQR = 5.00–24.00), P < 0.001), and 2 years (from 47.50 visits (IQR = 24.75–71.00) to 22.00 (IQR = 11.00–42.00), P < 0.001), and a 74.71% decrease in psychiatric hospital bed days (z = −2.50, P = 0.01). Service-use costs decreased (1 year: –£963/patient (P < 0.001); 2 years: –£1598.10/patient (P < 0.001). Subanalyses for community-only initiation also showed significant cost reductions (1 year: –£827.40/patient (P < 0.001); 2 year: –£1668.50/patient (P < 0.001) relative to costs prior to starting clozapine. Relative to before initiation, symptom severity was improved in patients taking clozapine at discharge (median Positive and Negative Syndrome Scale total score: initial visit: 80 (IQR = 71.00–104.00); discharge visit 50.5 (IQR = 44.75–75.00), P < 0.001) and at 2 year follow-up (Health of Nation Outcome Scales total score median initial visit: 13.00 (IQR = 9.00–15.00); 2 year follow-up: 8.00 (IQR = 3.00–13.00), P = 0.023).ConclusionsThese findings indicate that community initiation of clozapine is feasible and is associated with significant reductions in costs, service use and symptom severity.
- Published
- 2022
26. Bench, bedside, and balance
- Author
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Allan Young and Sameer Jauhar
- Subjects
Pharmacology ,Psychiatry and Mental health ,Clinical Trials as Topic ,Drug Development ,Psychopharmacology ,Drug Evaluation, Preclinical ,Animals ,Humans ,Pharmacology (medical) - Published
- 2022
27. A potential biomarker for treatment stratification in psychosis: evaluation of an [18F] FDOPA PET imaging approach
- Author
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Jin Huajie, Hugh Salimbeni, Barbara Santangelo, Oliver D. Howes, Arsime Demjaha, Paul McCrone, Enrico D'Ambrosio, Federico Turkheimer, Sameer Jauhar, and Mattia Veronese
- Subjects
Oncology ,Psychosis ,medicine.medical_specialty ,Predictive markers ,Article ,Internal medicine ,Humans ,Medicine ,Pharmacology ,Reproducibility ,Receiver operating characteristic ,business.industry ,Area under the curve ,Reproducibility of Results ,Pet imaging ,medicine.disease ,Dihydroxyphenylalanine ,Psychiatry and Mental health ,Psychotic Disorders ,Sample size determination ,Schizophrenia ,Positron-Emission Tomography ,Biomarker (medicine) ,Radiopharmaceuticals ,business ,Biomarkers - Abstract
[18F]FDOPA PET imaging has shown dopaminergic function indexed asKicerdiffers between antipsychotic treatment responders and non-responders. However, the theragnostic potential of this biomarker to identify non-responders has yet to be evaluated. In view of this, we aimed to evaluate this as a theragnostic test using linear and non-linear machine-learning (i.e., Bernoulli, support vector, random forest and Gaussian processes) analyses and to develop and evaluate a simplified approach, standardised uptake value ratio (SUVRc). Both [18F]FDOPA PET approaches had good test-rest reproducibility across striatal regions (KicerICC: 0.68–0.94, SUVRc ICC: 0.76–0.91). Both our linear and non-linear classification models showed good predictive power to distinguish responders from non-responders (receiver operating curve area under the curve for region-of-interest approach:Kicer = 0.80, SUVRc = 0.79; for voxel-wise approach using a linear support vector machine: 0.88) and similar sensitivity for identifying treatment non-responders with 100% specificity (Kicer: ~50%, SUVRc: 40–60%). Although the findings were replicated in two independent datasets, given the total sample size (n = 84) and single setting, they warrant testing in other samples and settings. Preliminary economic analysis of [18F]FDOPA PET to fast-track treatment-resistant patients with schizophrenia to clozapine indicated a potential healthcare cost saving of ~£3400 (equivalent to $4232 USD) per patient. These findings indicate [18F]FDOPA PET dopamine imaging has potential as biomarker to guide treatment choice.
- Published
- 2020
28. One (effect) size does not fit at all: Interpreting clinical significance and effect sizes in depression treatment trials
- Author
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Allan H. Young, Fredrik Hieronymus, Sameer Jauhar, and Søren Dinesen Østergaard
- Subjects
Adult ,SEROTONIN REUPTAKE INHIBITORS ,efficacy ,03 medical and health sciences ,0302 clinical medicine ,MEDICATION ,Rating scale ,Outcome Assessment, Health Care ,Humans ,Medicine ,Pharmacology (medical) ,Clinical significance ,RATING-SCALE ,COGNITIVE-BEHAVIORAL THERAPY ,Depression (differential diagnoses) ,Psychiatric Status Rating Scales ,Pharmacology ,Depressive Disorder, Major ,clinical trials ,PLACEBO ,Depression ,business.industry ,REMISSION ,medicine.disease ,ANTIDEPRESSANTS ,Antidepressive Agents ,030227 psychiatry ,meta-analysis ,Clinical trial ,Psychiatry and Mental health ,Treatment Outcome ,Research Design ,antidepressants ,Meta-analysis ,Major depressive disorder ,HAMILTON DEPRESSION ,business ,030217 neurology & neurosurgery ,Perspectives ,Clinical psychology - Abstract
The efficacy of antidepressants in major depressive disorder has been continually questioned, mainly on the basis of studies using the sum-score of the Hamilton Depression Rating Scale as a primary outcome parameter. On this measure antidepressants show a standardised mean difference of around 0.3, which some authors suggested is below the cut-off for clinical significance. Prompted by a recent review that, using this argument, concluded antidepressants should not be used for adults with major depressive disorder, we (a) review the evidence in support of the cut-off for clinical significance espoused in that article (a Hamilton Depression Rating Scale standardised mean difference of 0.875); (b) discuss the limitations of average Hamilton Depression Rating Scale sum-score differences between groups as measure of clinical significance; (c) explore alternative measures of clinical importance; and (d) suggest future directions to help overcome disagreements on how to define clinical significance. We conclude that (a) the proposed Hamilton Depression Rating Scale cut-off of 0.875 has no scientific basis and is likely misleading; (b) there is no agreed upon way of delineating clinically significant from clinically insignificant; (c) evidence suggests the Hamilton Depression Rating Scale sum-score underestimates antidepressant efficacy; and (d) future clinical trials should consider including measures directly reflective of functioning and wellbeing, in addition to measures focused on depression psychopathology.
- Published
- 2020
29. The Topography of Striatal Dopamine and Symptoms in Psychosis: An Integrative Positron Emission Tomography and Magnetic Resonance Imaging Study
- Author
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Robert A. McCutcheon, Federico Turkheimer, Sameer Jauhar, Philip McGuire, Maria Rogdaki, Mattia Veronese, Alice Egerton, Mitul M. Mehta, Oliver D. Howes, Matthew M. Nour, and Fiona Pepper
- Subjects
Psychosis ,Cognitive Neuroscience ,Dopamine ,Striatum ,050105 experimental psychology ,03 medical and health sciences ,Functional connectivity ,0302 clinical medicine ,Medicine ,Humans ,0501 psychology and cognitive sciences ,Radiology, Nuclear Medicine and imaging ,Resting state ,Biological Psychiatry ,Default mode network ,Negative symptoms ,Positive symptoms ,Schizophrenia ,Resting state fMRI ,medicine.diagnostic_test ,business.industry ,05 social sciences ,Reproducibility of Results ,Magnetic resonance imaging ,medicine.disease ,Magnetic Resonance Imaging ,Corpus Striatum ,Archival Report ,Psychotic Disorders ,Positron emission tomography ,Positron-Emission Tomography ,Neurology (clinical) ,business ,Neuroscience ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background Striatal dopamine dysfunction is thought to underlie symptoms in psychosis, yet it remains unclear how a single neurotransmitter could cause the diverse presentations that are observed clinically. One hypothesis is that the consequences of aberrant dopamine signaling vary depending on where within the striatum the dysfunction occurs. Positron emission tomography allows for the quantification of dopamine function across the striatum. In the current study, we used a novel method to investigate the relationship between spatial variability in dopamine synthesis capacity and psychotic symptoms. Methods We used a multimodal imaging approach combining 18F-DOPA positron emission tomography and resting-state magnetic resonance imaging in 29 patients with first-episode psychosis and 21 healthy control subjects. In each participant, resting-state functional connectivity maps were used to quantify the functional connectivity of each striatal voxel to well-established cortical networks. Network-specific striatal dopamine synthesis capacity (Kicer) was then calculated for the resulting connectivity-defined parcellations. Results The connectivity-defined parcellations generated Kicer values with equivalent reliability, and significantly greater orthogonality compared with standard anatomical parcellation methods. As a result, dopamine-symptom associations were significantly different from one another for different subdivisions, whereas no unique subdivision relationships were found when using an anatomical parcellation. In particular, dopamine function within striatal areas connected to the default mode network was strongly associated with negative symptoms (p Conclusions These findings suggest that individual differences in the topography of dopamine dysfunction within the striatum contribute to shaping psychotic symptomatology. Further validation of the novel approach in future studies is necessary.
- Published
- 2020
30. What is the evidence for antipsychotic medication and alternative psychosocial interventions for people with acute, non-affective psychosis?
- Author
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Sameer Jauhar and Stephen M Lawrie
- Subjects
Psychotherapy ,Psychiatry and Mental health ,Cognitive Behavioral Therapy ,Psychotic Disorders ,antipsychotics, cognitive behavioural therapy ,Secondary Prevention ,Humans ,Psychosocial Intervention ,Biological Psychiatry ,Antipsychotic Agents - Abstract
In this Personal View, we critically appraise and summarise evidence for antipsychotic drugs and alternatives to drug treatment, with a focus on people in their first episode or acute relapses of schizophrenia and related conditions within the first 5–10 years of illness. There is a large body of generally moderate quality evidence from randomised controlled trials for antipsychotics in both treating acute psychosis and reducing relapse, in thousands of people in their first episode and in established illness. There is a much smaller evidence base, of generally low quality, in a few hundred people, for potential benefits of non-drug interventions, such as cognitive behavioural therapy, Open Dialogue, Soteria, and psychoanalytic psychotherapy.
- Published
- 2022
31. The relationship between glutamate, dopamine, and cortical gray matter: A simultaneous PET-MR study
- Author
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Antoine Rogeau, Giovanna Nordio, Mattia Veronese, Kirsten Brown, Matthew M. Nour, Martin Osugo, Sameer Jauhar, Oliver D. Howes, and Robert A. McCutcheon
- Subjects
Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Receptors, Dopamine D2 ,Dopamine ,Positron-Emission Tomography ,Humans ,Glutamic Acid ,Gray Matter ,Molecular Biology ,Magnetic Resonance Imaging ,Corpus Striatum - Abstract
Prefrontal cortex has been shown to regulate striatal dopaminergic function via glutamatergic mechanisms in preclinical studies. Concurrent disruption of these systems is also often seen in neuropsychiatric disease. The simultaneous measurement of striatal dopamine signaling, cortical gray matter, and glutamate levels is therefore of major interest, but has not been previously reported. In the current study, twenty-eight healthy subjects underwent 2 simultaneous [11C]-( + )-PHNO PET-MRI scans, once after placebo and once after amphetamine in a double-blind randomized cross-over design, to measure striatal dopamine release, striatal dopamine receptor (D2/3R) availability, anterior cingulate glutamate+glutamine (Glx) levels, and cortical gray matter volumes at the same time. Voxel-based morphometry was used to investigate associations between neurochemical measures and gray matter volumes. Whole striatum D2/3R availability was positively associated with prefrontal cortex gray matter volume (pFWE corrected = 0.048). This relationship was mainly driven by associative receptor availability (pFWE corrected = 0.023). In addition, an interaction effect was observed between sensorimotor striatum D2/3R availability and anterior cingulate Glx, such that in individuals with greater anterior cingulate Glx concentrations, D2/3R availability was negatively associated with right frontal cortex gray matter volumes, while a positive D2/3R-gray matter association was observed in individuals with lower anterior cingulate Glx levels (pFWE corrected = 0.047). These results are consistent with the hypothesis that the prefrontal cortex is involved in regulation of striatal dopamine function. Furthermore, the observed associations raise the possibility that this regulation may be modulated by anterior cingulate glutamate concentrations.
- Published
- 2022
32. The relationship between grey matter volume and striatal dopamine function in psychosis: a multi-modal 18F-DOPA PET and voxel-based morphometry study
- Author
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Seoyoung Kim, Sameer Jauhar, Oliver D. Howes, Fiona Pepper, Federico Turkheimer, Mattia Veronese, Enrico D'Ambrosio, Euitae Kim, Maria Rogdaki, Matthew J. Kempton, Jun Soo Kwon, Vasileia Kotoula, and Ilaria Bonoldi
- Subjects
0301 basic medicine ,Striatal dopamine ,Psychosis ,Dopamine ,neurochemistry ,Dihydroxyphenylalanine ,Gray Matter ,Humans ,Magnetic Resonance Imaging ,Positron-Emission Tomography ,Psychotic Disorders ,Grey matter ,Article ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,medicine ,Prefrontal cortex ,Molecular Biology ,business.industry ,Dopaminergic ,neurobiology ,treatment response ,imaging ,Voxel-based morphometry ,medicine.disease ,Pathophysiology ,schizophrenia ,Psychiatry and Mental health ,antipsychotics ,030104 developmental biology ,medicine.anatomical_structure ,resistant ,Schizophrenia ,biomarker ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
A leading hypothesis for schizophrenia and related psychotic disorders proposes that cortical brain disruption leads to subcortical dopaminergic dysfunction, which underlies psychosis in the majority of patients who respond to treatment. Although supported by preclinical findings that prefrontal cortical lesions lead to striatal dopamine dysregulation, the relationship between prefrontal structural volume and striatal dopamine function has not been tested in people with psychosis. We therefore investigated the in vivo relationship between striatal dopamine synthesis capacity and prefrontal grey matter volume in treatment-responsive patients with psychosis, and compared them to treatment non-responsive patients, where dopaminergic mechanisms are not thought to be central. Forty patients with psychosis across two independent cohorts underwent 18F-DOPA PET scans to measure dopamine synthesis capacity (indexed as the influx rate constant Kicer) and structural 3T MRI. The PET, but not MR, data have been reported previously. Structural images were processed using DARTEL-VBM. GLM analyses were performed in SPM12 to test the relationship between prefrontal grey matter volume and striatal Kicer. Treatment responders showed a negative correlation between prefrontal grey matter and striatal dopamine synthesis capacity, but this was not evident in treatment non-responders. Specifically, we found an interaction between treatment response, whole striatal dopamine synthesis capacity and grey matter volume in left (pFWE corr. = 0.017) and right (pFWE corr. = 0.042) prefrontal cortex. We replicated the finding in right prefrontal cortex in the independent sample (pFWE corr. = 0.031). The summary effect size was 0.82. Our findings are consistent with the long-standing hypothesis of dysregulation of the striatal dopaminergic system being related to prefrontal cortex pathology in schizophrenia, but critically also extend the hypothesis to indicate it can be applied to treatment-responsive schizophrenia only. This suggests that different mechanisms underlie the pathophysiology of treatment-responsive and treatment-resistant schizophrenia.
- Published
- 2019
33. Relapse prevention in schizophrenia
- Author
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Sameer Jauhar, Keith Laws, Paolo Fusar-Poli, and Peter McKenna
- Subjects
Psychiatry and Mental health ,Recurrence ,Schizophrenia ,Secondary Prevention ,Humans ,Biological Psychiatry ,Antipsychotic Agents - Published
- 2021
34. Overoptimistic Literature and Methodological Biases Favoring Cognitive Behavioral Therapy for the Prevention of Psychosis
- Author
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Joaquim Radua, Sameer Jauhar, Paolo Fusar-Poli, and Cathy Davies
- Subjects
Psychosis ,Psychotherapist ,Cognitive Behavioral Therapy ,business.industry ,medicine.medical_treatment ,medicine.disease ,Cognitive behavioral therapy ,Psychiatry and Mental health ,Bias ,Psychotic Disorders ,medicine ,Humans ,business ,Regular Articles - Abstract
OBJECTIVE: This study aimed to provide insight into the efficacy of cognitive-behavioral therapy for psychosis (CBTp) in patients with “clinical high risk of psychosis (CHR-P)”. METHODS: Major scientific databases were searched up to April 17, 2020. Randomized controlled trials in CHR-P individuals, comparing CBTp with needs-based interventions (NBI, including treatment as usual or nonspecific control treatment) were included, following PRISMA guidelines. The primary outcome (efficacy) was transition to psychosis by 6 months, 12 months, 24 months, and over 24 months. Secondary outcomes were change in attenuated psychotic symptoms, depression, distress, improvements in functioning, and quality of life. RESULTS: Ten randomized controlled studies met inclusion criteria. The comparisons included 1128 participants. CBTp was significantly more efficacious in reducing rate of transition to psychosis by 6 months (after post-hoc sensitivity analysis) (relative risk [RR] = 0.44, 95% confidence interval [CI]: 0.26, 0.73), 12 months (RR = 0.44, 95% CI: 0.30, 0.64), 12 months (RR = 0.46, 95%CI: 0.30, 0.69), and over 24 months (RR = 0.58, 95% CI: 0.35, 0.95) after treatment, compared with those receiving NBI. CBTp was also associated with more reduced attenuated psychotic symptoms by 12 months (SMD = −0.17, 95% CI: −0.33, −0.02) and by 24 months (SMD = −0.24, 95% CI: −0.43, −0.06). No beneficial effects on functioning, depression, quality of life, or distress were observed favoring CBTp. CONCLUSIONS: CBTp is effective in reducing both psychosis transition rates and attenuated psychotic symptoms for the prodromal stage of psychosis. It is a promising intervention at the preventative stage.
- Published
- 2021
35. Lack of robust meta-analytic evidence to favour cognitive behavioural therapy for prevention of psychosis
- Author
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Joaquim Radua, Sameer Jauhar, and Paolo Fusar-Poli
- Subjects
Psychiatry and Mental health ,medicine.medical_specialty ,Psychosis ,business.industry ,medicine ,MEDLINE ,Cognition ,Pshychiatric Mental Health ,Psychiatry ,business ,medicine.disease ,Letters to the Editor - Published
- 2021
36. Mindfulness‐based cognitive therapy and depression relapse—evaluating evidence through a meta‐analytic lens may indicate myopia
- Author
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Sameer Jauhar, Allan H. Young, and Keith R. Laws
- Subjects
Mindfulness ,Psychotherapist ,Cognitive Behavioral Therapy ,Depression ,business.industry ,medicine.medical_treatment ,Network Meta-Analysis ,MEDLINE ,Lens (geology) ,Cognitive behavioral therapy ,Psychiatry and Mental health ,Recurrence ,Myopia ,medicine ,Humans ,business ,Depression (differential diagnoses) ,Mindfulness-based cognitive therapy - Published
- 2021
37. 'Melancholy can be overwhelmed only by melancholy.' Robert Burton, Anatomy of Melancholy
- Author
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Allan H. Young and Sameer Jauhar
- Subjects
Psychiatry and Mental health ,Depressive Disorder, Major ,Psychoanalysis ,Depression (economics) ,Depression ,media_common.quotation_subject ,medicine ,Humans ,Pessimism ,Psychology ,Melancholic depression ,medicine.disease ,media_common - Abstract
Whilst the above 17th Century view of what we would now term melancholic depression may be pessimistic, it does remind us of how the concept and treatments for depression have changed over time.The...
- Published
- 2021
38. Schizophrenia
- Author
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Sameer Jauhar, Mandy Johnstone, and Peter J McKenna
- Subjects
Male ,Dopamine Antagonists/therapeutic use ,Cognitive Behavioral Therapy ,Marijuana Smoking/adverse effects ,Adverse Childhood Experiences/psychology ,Marijuana Smoking ,General Medicine ,Sex Factors ,Adverse Childhood Experiences ,Risk Factors ,Schizophrenia/diagnosis ,Schizophrenia ,Dopamine Antagonists ,Humans ,Female ,Schizophrenic Psychology - Abstract
Schizophrenia, characterised by psychotic symptoms and in many cases social and occupational decline, remains an aetiological and therapeutic challenge. Contrary to popular belief, the disorder is modestly more common in men than in women. Nor is the outcome uniformly poor. A division of symptoms into positive, negative, and disorganisation syndromes is supported by factor analysis. Catatonic symptoms are not specific to schizophrenia and so-called first rank symptoms are no longer considered diagnostically important. Cognitive impairment is now recognised as a further clinical feature of the disorder. Lateral ventricular enlargement and brain volume reductions of around 2% are established findings. Brain functional changes occur in different subregions of the frontal cortex and might ultimately be understandable in terms of disturbed interaction among large-scale brain networks. Neurochemical disturbance, involving dopamine function and glutamatergic N-methyl-D-aspartate receptor function, is supported by indirect and direct evidence. The genetic contribution to schizophrenia is now recognised to be largely polygenic. Birth and early life factors also have an important aetiological role. The mainstay of treatment remains dopamine receptor-blocking drugs; a psychological intervention, cognitive behavioural therapy, has relatively small effects on symptoms. The idea that schizophrenia is better regarded as the extreme end of a continuum of psychotic symptoms is currently influential. Other areas of debate include cannabis and childhood adversity as causative factors, whether there is progressive brain change after onset, and the long-term success of early intervention initiatives.
- Published
- 2021
39. Correction: Striatal dopaminergic alterations in individuals with copy number variants at the 22q11.2 genetic locus and their implications for psychosis risk: a [18F]-DOPA PET study
- Author
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Maria Rogdaki, Céline Devroye, Mariasole Ciampoli, Mattia Veronese, Abhishekh H. Ashok, Robert A. McCutcheon, Sameer Jauhar, Ilaria Bonoldi, Maria Gudbrandsen, Eileen Daly, Therese van Amelsvoort, Marianne Van Den Bree, Michael J. Owen, Federico Turkheimer, Francesco Papaleo, and Oliver D. Howes
- Subjects
Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Molecular Biology - Published
- 2021
40. N-methyl-D-aspartate receptor availability in first-episode psychosis: a PET-MR brain imaging study
- Author
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Toby Pillinger, Stephen J. Kaar, Robert A. McCutcheon, Barbara Santangelo, Federico Turkheimer, Sameer Jauhar, Faith Borgan, Atheeshaan Arumuham, Oliver D. Howes, Katherine Beck, Teresa Sementa, James M. Stone, Colm J. McGinnity, Joel Dunn, Nisha Singh, Alexander Hammers, and Mattia Veronese
- Subjects
medicine.medical_specialty ,Psychosis ,Thalamus ,Hippocampus ,Neurosciences. Biological psychiatry. Neuropsychiatry ,Neuroimaging ,Striatum ,Hippocampal formation ,Molecular neuroscience ,Receptors, N-Methyl-D-Aspartate ,Article ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Biological Psychiatry ,Anterior cingulate cortex ,030304 developmental biology ,Temporal cortex ,0303 health sciences ,business.industry ,Brain ,medicine.disease ,Psychiatry and Mental health ,medicine.anatomical_structure ,Endocrinology ,nervous system ,Psychotic Disorders ,Positron-Emission Tomography ,Schizophrenia ,NMDA receptor ,business ,030217 neurology & neurosurgery ,RC321-571 - Abstract
N-methyl-D-aspartate receptor (NMDAR) hypofunction is hypothesised to underlie psychosis but this has not been tested early in illness. To address this, we studied 40 volunteers (21 patients with first-episode psychosis and 19 matched healthy controls) using PET imaging with an NMDAR selective ligand, [18F]GE-179, that binds to the ketamine binding site to index its distribution volume ratio (DVR) and volume of distribution (VT). Hippocampal DVR, but not VT, was significantly lower in patients relative to controls (p = 0.02, Cohen’s d = 0.81; p = 0.15, Cohen’s d = 0.49), and negatively associated with total (rho = −0.47, p = 0.04), depressive (rho = −0.67, p = 0.002), and general symptom severity (rho = −0.74, p
- Published
- 2021
41. Striatal dopaminergic alterations in individuals with copy number variants at the 22q11.2 genetic locus and their implications for psychosis risk: a [18F]-DOPA PET study
- Author
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Robert A. McCutcheon, Sameer Jauhar, Abhishekh Hulegar Ashok, Oliver D. Howes, Francesco Papaleo, Federico Turkheimer, Ilaria Bonoldi, Mariasole Ciampoli, Mattia Veronese, Eileen Daly, Marianne Bernadette van den Bree, Céline Devroye, Therese van Amelsvoort, Maria Rogdaki, Michael John Owen, Maria Gudbrandsen, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, and MUMC+: MA Med Staf Spec Psychiatrie (9)
- Subjects
Psychosis ,medicine.medical_specialty ,TRANSMISSION ,Locus (genetics) ,MECHANISMS ,Prodrome ,SYNTHESIS CAPACITY ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Internal medicine ,Gene duplication ,medicine ,Copy-number variation ,SCHIZOPHRENIC-PATIENTS ,BRAIN ,Molecular Biology ,business.industry ,Dopaminergic ,DELETION SYNDROME ,PSYCHIATRIC-DISORDERS ,medicine.disease ,DUPLICATION ,DYSFUNCTION ,030227 psychiatry ,EMISSION-TOMOGRAPHY ,Psychiatry and Mental health ,Endocrinology ,Schizophrenia ,Anxiety ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Dopaminergic dysregulation is one of the leading hypotheses for the pathoetiology underlying psychotic disorders such as schizophrenia. Molecular imaging studies have shown increased striatal dopamine synthesis capacity (DSC) in schizophrenia and people in the prodrome of psychosis. However, it is unclear if genetic risk for psychosis is associated with altered DSC. To investigate this, we recruited healthy controls and two antipsychotic naive groups of individuals with copy number variants, one with a genetic deletion at chromosome 22q11.2, and the other with a duplication at the same locus, who are at increased and decreased risk for psychosis, respectively. Fifty-nine individuals (21 with 22q11.2 deletion, 12 with the reciprocal duplication and 26 healthy controls) received clinical measures and [18F]-DOPA PET imaging to index striatal Kicer. There was an inverse linear effect of copy number variant number on striatal Kicer value (B = −1.2 × 10−3, SE = 2 × 10−4, p cer was significantly higher in the 22q11.2 deletion group compared to the healthy control (p d = 1.44) and 22q11.2 duplication (p d = 2) groups. Moreover, Kicer was positively correlated with the severity of psychosis-risk symptoms (B = 730.5, SE = 310.2, p
- Published
- 2021
42. Psychosocial interventions versus antipsychotics for early-onset psychosis: can we fill the evidence gap?
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Sameer Jauhar
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Cognitive behavioral therapy ,Psychiatry and Mental health ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Early onset psychosis ,medicine ,Psychological intervention ,MEDLINE ,Psychiatry ,business ,Psychosocial ,Biological Psychiatry - Published
- 2020
43. The war on antidepressants: What we can, and can't conclude, from the systematic review of antidepressant withdrawal effects by Davies and Read
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Sameer Jauhar and Joseph Hayes
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medicine.medical_specialty ,business.industry ,Incidence ,Incidence (epidemiology) ,MEDLINE ,Medicine (miscellaneous) ,Toxicology ,Antidepressive Agents ,Article ,Psychiatry and Mental health ,Clinical Psychology ,medicine ,Humans ,Antidepressant ,Psychiatry ,business - Published
- 2019
44. The case for improved care and provision of treatment for people with first-episode mania
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Phillip McGuire, Allan H. Young, Sameer Jauhar, Aswin Ratheesh, Christopher G. Davey, Patrick D. McGorry, Lakshmi N. Yatham, and Michael Berk
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medicine.medical_specialty ,Bipolar Disorder ,Bipolar I disorder ,medicine.medical_treatment ,Psychological intervention ,Guidelines as Topic ,Context (language use) ,behavioral disciplines and activities ,03 medical and health sciences ,0302 clinical medicine ,mental disorders ,Humans ,Medicine ,030212 general & internal medicine ,Bipolar disorder ,Psychiatry ,Biological Psychiatry ,First episode ,business.industry ,medicine.disease ,Quality Improvement ,Mental health ,030227 psychiatry ,Cognitive behavioral therapy ,Psychiatry and Mental health ,medicine.symptom ,business ,Mania - Abstract
The care of people with first-episode mania has been overlooked in comparison with the care of patients with other non-affective psychoses, despite evidence suggesting targeted treatments might be of benefit for this patient group. In this Personal View, we outline the general epidemiology of first-episode mania in the context of bipolar disorder, the natural history of mania (with an emphasis on its recurrent nature), current evidence for pharmacological, psychological, and service-level interventions, current guidelines for the treatment of first-episode mania, and provide a patient's point of view of the care pathway (appendix). We note the paucity of high-quality evidence for interventions in first-episode mania and the lack of agreement among treatment guidelines in relation to treatment, especially maintenance treatment. We suggest that, based on high morbidity and clinical need, research evidence to inform guideline development is necessary, and in the interim, clearer guidance on treatment and diagnosis should be given; specifically, we have suggested that patients should be cared for within a first-episode psychosis service, when such a service exists.
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- 2019
45. Early intervention for bipolar disorder – Do current treatment guidelines provide recommendations for the early stages of the disorder?
- Author
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Mark Phelan, Steven Marwaha, Michael Berk, Sameer Jauhar, Patrick D. McGorry, Christopher G. Davey, Kate Filia, Sue M. Cotton, Ming Fang Chia, Aswin Ratheesh, and Philippe Conus
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Adult ,Male ,medicine.medical_specialty ,Bipolar Disorder ,Adolescent ,Population ,Psychological intervention ,Young Adult ,Early Medical Intervention ,Intervention (counseling) ,medicine ,Humans ,Bipolar disorder ,Young adult ,Psychiatry ,education ,Depression (differential diagnoses) ,First episode ,education.field_of_study ,business.industry ,medicine.disease ,Psychiatry and Mental health ,Clinical Psychology ,Practice Guidelines as Topic ,Female ,medicine.symptom ,business ,Mania ,Antipsychotic Agents - Abstract
Background Interventions early in the course of bipolar disorder (BD) may have the potential to limit its functional and symptomatic impact. However, the implementation of specific early interventions for BD has been limited which may at least partly be due to the lack of guidelines focused on the early illness stages. We therefore aimed to review the current recommendations for early stage BD from clinical practice guidelines. Methods We searched PubMED and PsychINFO for clinical guidelines for BD published in the ten years prior to 1 November 2018. Recommendations from identified guidelines that addressed early stage BD or first episode mania were consolidated and compared. We also reviewed the guidelines relating to adolescents with BD to complement the guidelines related to those in the early illness course. Results We identified fourteen international and national guidelines on BD or affective psychoses. Most guidelines contained a separate section on adolescents, but only a few referred specifically to early stage BD. There were no consistent recommendations for early stage disorder, except with respect to the indications for maintenance medication treatments. For adolescents, there was a consistent recommendation for the use of second generation antipsychotics for treating acute mania. Limitation The main limitation is that the identified guidelines did not include primary data that clearly separated illness and developmental stages. Conclusions There is a lack of emphasis on early BD among widely-respected current clinical guidelines, likely reflecting the dearth of primary data. Future evidence or consensus-based recommendations could significantly inform clinical practice for this population.
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- 2019
46. Antidepressants, withdrawal, and addiction; where are we now?
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David S. Baldwin, Sameer Jauhar, Guy M. Goodwin, Joseph Hayes, David J. Nutt, and Philip J. Cowen
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Conduct Disorder ,Pharmacology ,medicine.medical_specialty ,Addiction ,media_common.quotation_subject ,Article ,Antidepressive Agents ,Substance Withdrawal Syndrome ,030227 psychiatry ,Behavior, Addictive ,Benzodiazepines ,03 medical and health sciences ,Psychiatry and Mental health ,0302 clinical medicine ,medicine ,Humans ,Pharmacology (medical) ,Psychiatry ,Serotonin Uptake Inhibitors ,Psychology ,030217 neurology & neurosurgery ,media_common - Abstract
Controversy continues with regard to antidepressants and withdrawal. Recent debates have focused on the prevalence and length of withdrawal, and some continue to state that withdrawal from these compounds constitutes ‘addiction’. In this editorial we examine the evidence underlying these recent debates. We acknowledge gaps in knowledge, and make suggestions for how the field can progress.
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- 2019
47. Unbalanced appraisal of psychosocial versus antipsychotic literature – Authors’ reply
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Sameer Jauhar and Stephen M Lawrie
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Psychiatry and Mental health ,Biological Psychiatry - Published
- 2022
48. Is there a symptomatic distinction between the affective psychoses and schizophrenia? A machine learning approach
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Sameer Jauhar, Stephen M. Lawrie, Matthew M. Nour, Eve C. Johnstone, David G. Cunningham-Owens, and Rajeev Krishnadas
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Adult ,Affective Disorders, Psychotic ,Male ,Nosology ,First rank symptoms ,Psychosis ,Adolescent ,Bipolar disorder ,Logistic regression ,Machine learning ,computer.software_genre ,Cohort Studies ,Machine Learning ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,mental disorders ,medicine ,Humans ,Diagnosis, Computer-Assisted ,Biological Psychiatry ,Aged ,Psychopathology ,business.industry ,Middle Aged ,Classification ,medicine.disease ,030227 psychiatry ,Psychiatry and Mental health ,ROC Curve ,Schizophrenia ,Unsupervised learning ,Female ,Schizophrenic Psychology ,Artificial intelligence ,medicine.symptom ,Psychology ,business ,Mania ,computer ,030217 neurology & neurosurgery - Abstract
Dubiety exists over whether clinical symptoms of schizophrenia can be distinguished from affective psychosis, the assumption being that absence of a “point of rarity” indicates lack of nosological distinction, based on prior group-level analyses. Advanced machine learning techniques, using unsupervised (hierarchical clustering) and supervised (regularized logistic regression algorithm and nested-cross-validation) were applied to a dataset of 202 patients with functional psychosis (schizophrenia n = 120, affective psychosis, n = 82). Patients were initially assessed with the Present State Examination (PSE), and followed up 2.5 years later, when DSM III diagnoses were applied (independent of initial PSE). Based on PSE syndromes, unsupervised learning discriminated depressive (approximately unbiased probability, AUP = 0.92) and mania/psychosis (AUP = 0.94) clusters. The mania/psychosis cluster further split into two groups - a mania (AUP = 0.84) and a psychosis cluster (AUP = 0.88). Supervised machine learning classified schizophrenia or affective psychosis with 83.66% (95% CI = 77.83% to 88.48%) accuracy. Area under the ROC curve (AUROC) was 89.14%. True positive rate for schizophrenia was 88.24% (95%CI = 81.05–93.42%) and affective psychosis 77.11% (95%CI = 66.58–85.62). Classification accuracy and AUROC remained high when PSE syndromes corresponding to affective symptoms (those that corresponded to the depressive and mania clusters) were removed. PSE syndromes, based on clinical symptoms, therefore discriminated between schizophrenia and affective psychosis, suggesting validity to these diagnostic constructs.
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- 2018
49. Association of Age, Antipsychotic Medication, and Symptom Severity in Schizophrenia With Proton Magnetic Resonance Spectroscopy Brain Glutamate Level: A Mega-analysis of Individual Participant-Level Data
- Author
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John Lauriello, Akira Sawa, Elias Mouchlianitis, Lawrence S. Kegeles, Edith J. Liemburg, Lijing Xin, Oswald J.N. Bloemen, Jürgen R. Reichenbach, Fei Du, Charles Gasparovic, Cedric E. Ginestet, Eric Plitman, Oliver D. Howes, Sotirios Posporelis, Stephen J. Wood, Peter Jeon, Jeffrey A. Stanley, Arsime Demjaha, Jürgen Gallinat, Agata Szulc, Alice Egerton, Peter C. Williamson, Aristides A. Capizzano, Dost Öngür, Jennifer M. Coughlin, Christos Pantelis, Matcheri S. Keshavan, Scot E. Purdon, H-Mrs in Schizophrenia Investigators, Ariel Graff-Guerrero, Jean Théberge, Lena Palaniyappan, Reggie Taylor, Therese van Amelsvoort, Faith Borgan, Igor Nenadic, Sameer Jauhar, Sang-Young Kim, Camilo de la Fuente-Sandoval, Beata Galińska-Skok, Philip McGuire, Meghan E. McIlwain, Charles A. Kaufmann, Jun Nakamura, Beng Choon Ho, André Aleman, Philip G. Tibbo, James M. Stone, Jerzy Walecki, Kate Merritt, Tadafumi Kato, Hiroshi Kunugi, Kim Q. Do, Bruce R. Russell, Wolfgang Block, Kara Dempster, Martin Schaefer, Peter Falkai, Dikoma C. Shungu, Miho Ota, Gemma Modinos, Naoki Goto, Hidenori Yamasue, Juan R. Bustillo, Perry F. Renshaw, Stefan Smesny, Katy Thakkar, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), RS: MHeNs - R2 - Mental Health, Clinical Cognitive Neuropsychiatry Research Program (CCNP), and Clinical Neuropsychology
- Subjects
Male ,medicine.medical_treatment ,Glutamine ,Proton Magnetic Resonance Spectroscopy ,PREFRONTAL CORTEX ,Biomarkers/metabolism ,chemistry.chemical_compound ,0302 clinical medicine ,IN-VIVO ,1ST EPISODE PSYCHOSIS ,Original Investigation ,Age Factors ,Brain ,METABOLIC-CHANGES ,Antipsychotic Agents/pharmacology ,Psychiatry and Mental health ,Frontal lobe ,Schizophrenia ,Female ,WHITE-MATTER ,ULTRA-HIGH-RISK ,Comments ,Antipsychotic Agents ,Adult ,medicine.medical_specialty ,Psychosis ,Glutamic Acid ,Creatine ,Glutamic Acid/drug effects ,behavioral disciplines and activities ,Phosphocreatine ,Prodrome ,03 medical and health sciences ,Schizophrenia/drug therapy ,Young Adult ,N-ACETYL-ASPARTATE ,Internal medicine ,Severity of illness ,medicine ,Humans ,Online First ,1ST-EPISODE PSYCHOSIS ,Antipsychotic ,GAMMA-AMINOBUTYRIC-ACID ,business.industry ,Glutamine/drug effects ,Research ,Patient Acuity ,medicine.disease ,Brain/diagnostic imaging ,030227 psychiatry ,Featured ,chemistry ,ANTERIOR CINGULATE ,business ,030217 neurology & neurosurgery ,Biomarkers - Abstract
Key Points Question Are clinical and demographic factors associated with brain glutamate or glutamate plus glutamine (Glx) levels in schizophrenia? Findings In this mega-analysis of 1251 patients with schizophrenia and 1197 healthy volunteers, medial frontal cortex glutamatergic metabolite levels were lower in patients and negatively associated with the dose of antipsychotic medication, although a reduction in glutamate levels with age was not accelerated in patients with schizophrenia compared with healthy individuals. Higher medial frontal cortex and medial temporal lobe glutamate levels were associated with more severe symptoms in patients with schizophrenia. Meaning Lower brain glutamate levels may be associated with antipsychotic exposure rather than with greater age-related decline, whereas higher glutamate levels may serve as a biomarker of illness severity in patients with schizophrenia., Importance Proton magnetic resonance spectroscopy (1H-MRS) studies indicate that altered brain glutamatergic function may be associated with the pathophysiology of schizophrenia and the response to antipsychotic treatment. However, the association of altered glutamatergic function with clinical and demographic factors is unclear. Objective To assess the associations of age, symptom severity, level of functioning, and antipsychotic treatment with brain glutamatergic metabolites. Data Sources The MEDLINE database was searched to identify journal articles published between January 1, 1980, and June 3, 2020, using the following search terms: MRS or magnetic resonance spectroscopy and (1) schizophrenia or (2) psychosis or (3) UHR or (4) ARMS or (5) ultra-high risk or (6) clinical high risk or (7) genetic high risk or (8) prodrome* or (9) schizoaffective. Authors of 114 1H-MRS studies measuring glutamate (Glu) levels in patients with schizophrenia were contacted between January 2014 and June 2020 and asked to provide individual participant data. Study Selection In total, 45 1H-MRS studies contributed data. Data Extraction and Synthesis Associations of Glu, Glu plus glutamine (Glx), or total creatine plus phosphocreatine levels with age, antipsychotic medication dose, symptom severity, and functioning were assessed using linear mixed models, with study as a random factor. Main Outcomes and Measures Glu, Glx, and Cr values in the medial frontal cortex (MFC) and medial temporal lobe (MTL). Results In total, 42 studies were included, with data for 1251 patients with schizophrenia (mean [SD] age, 30.3 [10.4] years) and 1197 healthy volunteers (mean [SD] age, 27.5 [8.8] years). The MFC Glu (F1,1211.9 = 4.311, P = .04) and Glx (F1,1079.2 = 5.287, P = .02) levels were lower in patients than in healthy volunteers, and although creatine levels appeared lower in patients, the difference was not significant (F1,1395.9 = 3.622, P = .06). In both patients and volunteers, the MFC Glu level was negatively associated with age (Glu to Cr ratio, F1,1522.4 = 47.533, P, This mega-analysis assesses whether age, symptom severity, level of functioning, and antipsychotic treatment are associated with glutamate or glutamatergic metabolite levels measured with proton magnetic resonance spectroscopy in the medial frontal cortex or medial temporal lobe of patients with schizophrenia.
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- 2021
50. Morbidity and mortality associated with electroconvulsive therapy: can we control for confounding?
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Sameer Jauhar and Allan H. Young
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medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Confounding ,MEDLINE ,Psychiatry and Mental health ,Electroconvulsive therapy ,Text mining ,Humans ,Medicine ,Morbidity ,Electroconvulsive Therapy ,business ,Intensive care medicine ,Biological Psychiatry - Published
- 2021
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