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Shitij kapur

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, Oliver Howes
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...
November 28, 2017: ELife
Judit García-González, Katherine E Tansey, Joanna Hauser, Neven Henigsberg, Wolfgang Maier, Ole Mors, Anna Placentino, Marcella Rietschel, Daniel Souery, Tina Žagar, Piotr M Czerski, Borut Jerman, Henriette N Buttenschøn, Thomas G Schulze, Astrid Zobel, Anne Farmer, Katherine J Aitchison, Ian Craig, Peter McGuffin, Michel Giupponi, Nader Perroud, Guido Bondolfi, David Evans, Michael O'Donovan, Tim J Peters, Jens R Wendland, Glyn Lewis, Shitij Kapur, Roy Perlis, Volker Arolt, Katharina Domschke, Gerome Breen, Charles Curtis, Lee Sang-Hyuk, Carol Kan, Stephen Newhouse, Hamel Patel, Bernhard T Baune, Rudolf Uher, Cathryn M Lewis, Chiara Fabbri
BACKGROUND: Major depressive disorder (MDD) has a high personal and socio-economic burden and >60% of patients fail to achieve remission with the first antidepressant. The biological mechanisms behind antidepressant response are only partially known but genetic factors play a relevant role. A combined predictor across genetic variants may be useful to investigate this complex trait. METHODS: Polygenic risk scores (PRS) were used to estimate multi-allelic contribution to: 1) antidepressant efficacy; 2) its overlap with MDD and schizophrenia...
April 3, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
Nicolas A Crossley, Tiago Reis Marques, Heather Taylor, Chris Chaddock, Flavio Dell'Acqua, Antje A T S Reinders, Valeria Mondelli, Marta DiForti, Andrew Simmons, Anthony S David, Shitij Kapur, Carmine M Pariante, Robin M Murray, Paola Dazzan
Connectomic approaches using diffusion tensor imaging have contributed to our understanding of brain changes in psychosis, and could provide further insights into the neural mechanisms underlying response to antipsychotic treatment. We here studied the brain network organization in patients at their first episode of psychosis, evaluating whether connectome-based descriptions of brain networks predict response to treatment, and whether they change after treatment. Seventy-six patients with a first episode of psychosis and 74 healthy controls were included...
February 2017: Brain: a Journal of Neurology
Dragana Bugarski-Kirola, Nakao Iwata, Snjezana Sameljak, Carol Reid, Thomas Blaettler, Laurie Millar, Tiago Reis Marques, George Garibaldi, Shitij Kapur
BACKGROUND: Many patients with schizophrenia require high doses of medication for their ongoing psychotic symptoms. Glutamate theories and findings from studies showing efficacy of sarcosine, an endogenous, non-selective glycine-reuptake inhibitor mediated by GlyT1, offer an alternative approach. We undertook the SearchLyte trial programme to examine the efficacy of bitopertin, a selective GlyT1-mediated glycine-reuptake inhibitor, as an adjunctive treatment to ongoing antipsychotic treatment...
December 2016: Lancet Psychiatry
Hitoshi Sakurai, Takefumi Suzuki, Robert R Bies, Bruce G Pollock, Masaru Mimura, Shitij Kapur, Hiroyuki Uchida
OBJECTIVE: While doctors often increase the dose of an antipsychotic when there is insufficient response, there is limited evidence that this intervention is any better than waiting longer on the lower dose. We put the proposition to test. METHOD: In this 4-week, double-blind, randomized controlled trial conducted in psychiatric care from September 2012 to March 2015, 103 patients with schizophrenia (ICD-10) who did not respond to olanzapine 10 mg/d or risperidone 3 mg/d were randomly allocated to a dose-increment or -continuation group...
October 2016: Journal of Clinical Psychiatry
Gerome Breen, Qingqin Li, Bryan L Roth, Patricio O'Donnell, Michael Didriksen, Ricardo Dolmetsch, Paul F O'Reilly, Héléna A Gaspar, Husseini Manji, Christopher Huebel, John R Kelsoe, Dheeraj Malhotra, Alessandro Bertolino, Danielle Posthuma, Pamela Sklar, Shitij Kapur, Patrick F Sullivan, David A Collier, Howard J Edenberg
Genome-wide association studies (GWAS) in psychiatry, once they reach sufficient sample size and power, have been enormously successful. The Psychiatric Genomics Consortium (PGC) aims for mega-analyses with sample sizes that will grow to >1 million individuals in the next 5 years. This should lead to hundreds of new findings for common genetic variants across nine psychiatric disorders studied by the PGC. The new targets discovered by GWAS have the potential to restart largely stalled psychiatric drug development pipelines, and the translation of GWAS findings into the clinic is a key aim of the recently funded phase 3 of the PGC...
October 26, 2016: Nature Neuroscience
Heather Wilson, Flavia Niccolini, Salman Haider, Tiago Reis Marques, Gennaro Pagano, Christopher Coello, Sridhar Natesan, Shitij Kapur, Eugenii A Rabiner, Roger N Gunn, Sarah J Tabrizi, Marios Politis
Huntington's disease (HD) is a monogenic neurodegenerative disorder with an underlying pathology involving the toxic effect of mutant huntingtin protein primarily in striatal and cortical neurons. Phosphodiesterase 10A (PDE10A) regulates intracellular signalling cascades, thus having a key role in promoting neuronal survival. Using positron emission tomography (PET) with [(11)C]IMA107, we investigated the in vivo extra-striatal expression of PDE10A in 12 early premanifest HD gene carriers. Image processing and kinetic modelling was performed using MIAKAT™...
September 15, 2016: Journal of the Neurological Sciences
Jonathan Rabinowitz, Nomi Werbeloff, Francine S Mandel, François Menard, Lauren Marangell, Shitij Kapur
Several often-cited meta-analyses have reported that the efficacy of antidepressant medications depends on the severity of depression. They found that drug-placebo differences increased as a function of initial severity, which was attributed to decreased responsiveness to placebo among patients with severe depression rather than to increased responsiveness to medication. We retested this using patient-level data and also undertaking a meta-analysis of trial-level data from 34 randomised placebo controlled trials (n = 10 737) from the NEWMEDS registry...
November 2016: British Journal of Psychiatry: the Journal of Mental Science
Tiago Reis Marques, Sridhar Natesan, Flavia Niccolini, Marios Politis, Roger N Gunn, Graham E Searle, Oliver Howes, Eugenii A Rabiner, Shitij Kapur
OBJECTIVE: Phosphodiesterase 10A (PDE10A) is an enzyme present in striatal medium spiny neurons that degrades the intracellular second messengers triggered by dopamine signaling. The pharmaceutical industry has considerable interest in PDE10A inhibitors because they have been shown to have an antipsychotic-like effect in animal models. However, the status of PDE10A in schizophrenia is unknown. Using a newly developed and validated radioligand, [(11)C]IMA107, the authors report the first in vivo assessment of PDE10A brain expression in patients with schizophrenia...
July 1, 2016: American Journal of Psychiatry
Shitij Kapur, Tiago Reis Marques
No abstract text is available yet for this article.
February 2016: JAMA Psychiatry
Ingeborg Bolstad, Ole A Andreassen, Inge Groote, Andres Server, Ivar Sjaastad, Shitij Kapur, Jimmy Jensen
The atypical antipsychotic drug aripiprazole is a partial dopamine (DA) D2 receptor agonist, which differentiates it from most other antipsychotics. This study compares the brain activation characteristic produced by aripiprazole with that of haloperidol, a typical D2 receptor antagonist. Healthy participants received an acute oral dose of haloperidol, aripiprazole or placebo, and then performed an active aversive conditioning task with aversive and neutral events presented as sounds, while blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was carried out...
December 2015: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Anthony C Vernon, Po-Wah So, David J Lythgoe, Winfred Chege, Jonathan D Cooper, Steven C R Williams, Shitij Kapur
Proton magnetic resonance spectroscopy ((1)H MRS) studies in schizophrenia patients generally report decreased levels of N-acetyl-aspartate (NAA), glutamate and glutathione, particularly in frontal cortex. However, these data are inconsistent in part due to confounds associated with clinical samples. The lack of validated diagnostic biomarkers also hampers analysis of the neurodevelopmental trajectory of neurochemical abnormalities. Rodent models are powerful tools to address these issues, particularly when combined with (1)H MRS (clinically comparable technology)...
December 2015: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Tine Bryan Stensbøl, Shitij Kapur
No abstract text is available yet for this article.
November 2015: Psychopharmacology
Marie-Caroline Cotel, Ewelina M Lenartowicz, Sridhar Natesan, Michel M Modo, Jonathan D Cooper, Steven C R Williams, Shitij Kapur, Anthony C Vernon
Neuroinflammation is increasingly implicated in the pathogenesis of Schizophrenia (SCZ). In addition, there is increasing evidence for a relationship between the dose and duration of antipsychotic drug (APD) treatment and reductions in grey matter volume. The potential contribution of microglia to these phenomena is however not yet defined. Adult rats were treated with a common vehicle, haloperidol (HAL, 2 mg/kg/day) or olanzapine (OLZ, 10 mg/kg/day) for 8 weeks via an osmotic mini-pump implanted subcutaneously...
November 2015: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Pauline Whelan, Matthew Machin, Shôn Lewis, Iain Buchan, Caroline Sanders, Eve Applegate, Charlotte Stockton, Sally Preston, Robert Andrew Bowen, Zhimin Ze, Chris Roberts, Linda Davies, Til Wykes, Nicholas Tarrier, Shitij Kapur, John Ainsworth
Current approaches to the management of severe mental illness have four major limitations: 1) symptom reporting is intermittent and subject to problems with reliability; 2) service users report feelings of disengagement from their care planning; 3) late detection of symptoms delay interventions and increase the risk of relapse; and 4) care systems are held back by the costs of unscheduled hospital admissions that could have been avoided with earlier detection and intervention. The ClinTouch system was developed to close the loop between service users and health professionals...
2015: Studies in Health Technology and Informatics
Flavia Niccolini, Thomas Foltynie, Tiago Reis Marques, Nils Muhlert, Andri C Tziortzi, Graham E Searle, Sridhar Natesan, Shitij Kapur, Eugenii A Rabiner, Roger N Gunn, Paola Piccini, Marios Politis
The mechanisms underlying neurodegeneration and loss of dopaminergic signalling in Parkinson's disease are still only partially understood. Phosphodiesterase 10A (PDE10A) is a basal ganglia expressed dual substrate enzyme, which regulates cAMP and cGMP signalling cascades, thus having a key role in the regulation of dopaminergic signalling in striatal pathways, and in promoting neuronal survival. This study aimed to assess in vivo the availability of PDE10A in patients with Parkinson's disease using positron emission tomography molecular imaging with (11)C-IMA107, a highly selective PDE10A radioligand...
October 2015: Brain: a Journal of Neurology
Steven Wooding, Thed N Van Leeuwen, Sarah Parks, Shitij Kapur, Jonathan Grant
BACKGROUND: The UK, like some other countries, carries out a periodic review of research quality in universities and the most recent Research Excellence Framework (REF) reported a doubling (103% increase) in its "world leading" or so-called "4*" research outputs in the areas of life sciences and medicine between 2008 and 2014. This is a remarkable improvement in six years and if validated internationally could have profound implications for health sciences. METHODS: We compared the reported changes in 4* quality to bibliometric measures of quality for the 56,639 articles submitted to the RAE 2008 and the 50,044 articles submitted to the REF 2014 to Panel A, which assesses the life sciences, including medicine...
2015: PloS One
Flavia Niccolini, Salman Haider, Tiago Reis Marques, Nils Muhlert, Andri C Tziortzi, Graham E Searle, Sridhar Natesan, Paola Piccini, Shitij Kapur, Eugenii A Rabiner, Roger N Gunn, Sarah J Tabrizi, Marios Politis
There is an urgent need for early biomarkers and novel disease-modifying therapies in Huntington's disease. Huntington's disease pathology involves the toxic effect of mutant huntingtin primarily in striatal medium spiny neurons, which highly express phosphodiesterase 10A (PDE10A). PDE10A hydrolyses cAMP/cGMP signalling cascades, thus having a key role in the regulation of striatal output, and in promoting neuronal survival. PDE10A could be a key therapeutic target in Huntington's disease. Here, we used combined positron emission tomography (PET) and multimodal magnetic resonance imaging to assess PDE10A expression in vivo in a unique cohort of 12 early premanifest Huntington's disease gene carriers with a mean estimated 90% probability of 25 years before the predicted onset of clinical symptoms...
October 2015: Brain: a Journal of Neurology
Suzanne H So, Emmanuelle R Peters, Shitij Kapur, Philippa A Garety
Delusional experiences can be considered on a range of dimensions including conviction, distress, preoccupation, and disruption, which have been shown to be related to depression and anxiety. This study aimed to test the hypotheses that delusional conviction is less responsive to antipsychotic treatment than delusional distress and preoccupation, and that depression and anxiety reduce alongside improvements in delusional dimensions. Forty acutely ill inpatients with delusions were assessed during their early stage of antipsychotic treatment...
August 30, 2015: Psychiatry Research
Stephen Z Levine, Jonathan Rabinowitz, Rudolf Uher, Shitij Kapur
Emerging data from on imaging and genetic studies have generated interest in "clinically significant" biomarkers to predict response and prognosis. What constitutes "clinical significance" and how a biomarker would reach that threshold are unclear. To develop a benchmark we reviewed different approaches for defining "clinical significance" applied in schizophrenia research and identified that an improvement of 15 points on the PANSS Total is considered meaningful in clinical settings. Using this benchmark and we simulated thousands of schizophrenia trials, using characteristics derived from the NEWMEDS database with over 8000 patients with schizophrenia, to the kind of imaging, genetic, and other biomarkers that could attain clinical significance...
October 2015: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
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