Imperial College London

DrOliverHowes

Faculty of MedicineInstitute of Clinical Sciences

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 3313 4318oliver.howes Website

 
 
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Location

 

Steiner MRI UnitHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

124 results found

Rizzo G, Veronese M, Tonietto M, Bodini B, Stankoff B, Wimberley C, Lavisse S, Bottlaender M, Bloomfield PS, Howes O, Zanotti-Fregonara P, Turkheimer FE, Bertoldo Aet al., 2019, Generalization of endothelial modelling of TSPO PET imaging: Considerations on tracer affinities., J Cereb Blood Flow Metab, Vol: 39, Pages: 874-885

The 18 kDa translocator protein (TSPO) is a marker of microglia activation and the main target of positron emission tomography (PET) ligands for neuroinflammation. Previous works showed that accounting for TSPO endothelial binding improves PET quantification for [11C]PBR28, [18F]DPA714 and [11C]-R-PK11195. It is still unclear, however, whether the vascular signal is tracer-dependent. This work aims to explore the relationship between the TSPO vascular and tissue components for PET tracers with varying affinity, also assessing the impact of affinity towards the differentiability amongst kinetics and the ensuing ligand amenability to cluster analysis for the extraction of a reference region. First, we applied the compartmental model accounting for vascular binding to [11C]-R-PK11195 data from six healthy subjects. Then, we compared the [11C]-R-PK11195 vascular binding estimates with previously published values for [18F]DPA714 and [11C]PBR28. Finally, we determined the suitability for reference region extraction by calculating the angle between grey and white matter kinetics. Our results showed that endothelial binding is common to all TSPO tracers and proportional to their affinity. By consequence, grey and white matter kinetics were most similar for the radioligand with the highest affinity (i.e. [11C]PBR28), hence poorly suited for the extraction of a reference region using supervised clustering.

JOURNAL ARTICLE

Osimo EF, Beck K, Marques TR, Howes ODet al., 2019, Synaptic loss in schizophrenia: a meta-analysis and systematic review of synaptic protein and mRNA measures, MOLECULAR PSYCHIATRY, Vol: 24, Pages: 549-561, ISSN: 1359-4184

JOURNAL ARTICLE

Lally J, Ajnakina O, Singh N, Gardner-Sood P, Stubbs B, Stringer D, Di Forti M, David AS, Smith S, Murray RM, Howes OD, Gaughran Fet al., 2019, Vitamin D and clinical symptoms in First Episode Psychosis (FEP): A prospective cohort study, SCHIZOPHRENIA RESEARCH, Vol: 204, Pages: 381-388, ISSN: 0920-9964

JOURNAL ARTICLE

Bloomfield PS, Bonsall D, Wells L, Dormann D, Howes O, De Paola Vet al., 2018, The effects of haloperidol on microglial morphology and translocator protein levels: An in vivo study in rats using an automated cell evaluation pipeline, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 32, Pages: 1264-1272, ISSN: 0269-8811

JOURNAL ARTICLE

Marques TR, Ashok AH, Pillinger T, Veronese M, Turkheimer FE, Dazzan P, Sommer IEC, Howes ODet al., 2018, Neuroinflammation in schizophrenia: meta-analysis of in vivo microglial imaging studies., Psychol Med, Pages: 1-11

BACKGROUND: Converging lines of evidence implicate an important role for the immune system in schizophrenia. Microglia are the resident immune cells of the central nervous system and have many functions including neuroinflammation, axonal guidance and neurotrophic support. We aimed to provide a quantitative review of in vivo PET imaging studies of microglia activation in patients with schizophrenia compared with healthy controls. METHODS: Demographic, clinical and imaging measures were extracted from each study and meta-analysis was conducted using a random-effects model (Hedge's g). The difference in 18-kDa translocator protein (TSPO) binding between patients with schizophrenia and healthy controls, as quantified by either binding potential (BP) or volume of distribution (VT), was used as the main outcome. Sub-analysis and sensitivity analysis were carried out to investigate the effects of genotype, ligand and illness stage. RESULTS: In total, 12 studies comprising 190 patients with schizophrenia and 200 healthy controls met inclusion criteria. There was a significant elevation in tracer binding in schizophrenia patients relative to controls when BP was used as an outcome measure, (Hedge's g = 0.31; p = 0.03) but no significant differences when VT was used (Hedge's g = -0.22; p = 0.29). CONCLUSIONS: In conclusion, there is evidence for moderate elevations in TSPO tracer binding in grey matter relative to other brain tissue in schizophrenia when using BP as an outcome measure, but no difference when VT is the outcome measure. We discuss the relevance of these findings as well as the methodological issues that may underlie the contrasting difference between these outcomes.

JOURNAL ARTICLE

Nour MM, Dahoun T, Schwartenbeck P, Adams RA, FitzGerald THB, Coello C, Wall MB, Dolan RJ, Howes ODet al., 2018, Dopaminergic basis for signaling belief updates, but not surprise, and the link to paranoia, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 115, Pages: E10167-E10176, ISSN: 0027-8424

JOURNAL ARTICLE

Allen P, Azis M, Modinos G, Bossong MG, Bonoldi I, Samson C, Quinn B, Kempton MJ, Howes OD, Stone JM, Calem M, Perez J, Bhattacharayya S, Broome MR, Grace AA, Zelaya F, McGuire Pet al., 2018, Increased Resting Hippocampal and Basal Ganglia Perfusion in People at Ultra High Risk for Psychosis: Replication in a Second Cohort, Schizophrenia Bulletin, Vol: 44, Pages: 1323-1331, ISSN: 0586-7614

JOURNAL ARTICLE

Horder J, Andersson M, Mendez MA, Singh N, Tangen A, Lundberg J, Gee A, Halldin C, Veronese M, Bolte S, Farde L, Sementa T, Cash D, Higgins K, Spain D, Turkheimer F, Mick I, Selvaraj S, Nutt DJ, Lingford-Hughes A, Howes OD, Murphy DG, Borg Jet al., 2018, GABA(A) receptor availability is not altered in adults with autism spectrum disorder or in mouse models, SCIENCE TRANSLATIONAL MEDICINE, Vol: 10, ISSN: 1946-6234

JOURNAL ARTICLE

Plaven-Sigray P, Matheson GJ, Collste K, Ashok AH, Coughlin JM, Howes OD, Mizrahi R, Pomper MG, Rusjan P, Veronese M, Wang Y, Cervenka Set al., 2018, Positron Emission Tomography Studies of the Glial Cell Marker Translocator Protein in Patients With Psychosis: A Meta-analysis Using Individual Participant Data, BIOLOGICAL PSYCHIATRY, Vol: 84, Pages: 433-442, ISSN: 0006-3223

JOURNAL ARTICLE

Winton-Brown T, Schmidt A, Roiser JP, Howes OD, Egerton A, Fusar-Poli P, Bunzeck N, Grace AA, Duzel E, Kapur S, McGuire Pet al., 2018, Altered activation and connectivity in a hippocampal-basal ganglia-midbrain circuit during salience processing in subjects at ultra high risk for psychosis (vol 7, e1245, 2017), TRANSLATIONAL PSYCHIATRY, Vol: 8, ISSN: 2158-3188

JOURNAL ARTICLE

Veronese M, Marques TR, Bloomfield PS, Rizzo G, Singh N, Jones D, Agushi E, Mosses D, Bertoldo A, Howes O, Roncaroli F, Turkheimer FEet al., 2018, Kinetic modelling of [C-11]PBR28 for 18kDa translocator protein PET data: A validation study of vascular modelling in the brain using XBD173 and tissue analysis, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, Vol: 38, Pages: 1227-1242, ISSN: 0271-678X

JOURNAL ARTICLE

Selvaraj S, Bloomfield PS, Cao B, Veronese M, Turkheimer F, Howes ODet al., 2018, Brain TSPO imaging and gray matter volume in schizophrenia patients and in people at ultra high risk of psychosis: An [11C]PBR28 study., Schizophr Res, Vol: 195, Pages: 206-214

Patients with schizophrenia show whole brain and cortical gray matter (GM) volume reductions which are progressive early in their illness. Microglia, the resident immune cells in the CNS, phagocytose neurons and synapses. Some post mortem and in vivo studies in schizophrenia show evidence for elevated microglial activation compared to matched controls. However, it is currently unclear how these results relate to changes in cortical structure. METHODS: Fourteen patients with schizophrenia and 14 ultra high risk for psychosis (UHR) subjects alongside two groups of age and genotype matched healthy controls received [11C]PBR28 PET scans to index TSPO expression, a marker of microglial activation and a 3T MRI scan. We investigated the relationship between the volume changes of cortical regions and microglial activation in cortical GM (as indexed by [11C]PBR28 distribution volume ratio (DVR). RESULTS: The total cortical GM volume was significantly lower in SCZ than the controls [mean (SD)/cm3: SCZ=448.83 (39.2) and controls=499.6 (59.2) (p=0.02) but not in UHR (mean (SD)=503.06 (57.9) and controls=524.46 (45.3) p=0.3). Regression model fitted the total cortical GM DVR values with the cortical regional volumes in SCZ (r=0.81; p<0.001) and in UHR (r=0.63; p=0.02). We found a significant negative correlation between the TSPO signal and total cortical GM volume in SCZ with the highest absolute correlation coefficient in the right superior-parietal cortex (r=-0.72; p=0.006). CONCLUSIONS: These findings suggest that microglial activity is related to the altered cortical volume seen in schizophrenia. Longitudinal investigations are required to determine whether microglial activation leads to cortical gray matter loss.

JOURNAL ARTICLE

Nour M, Dahoun T, Schwartenbeck P, Adams R, Coello C, Wall M, FitzGerald T, Dolan R, Howes Oet al., 2018, Dopamine modulates belief updating but not surprise in the midbrain and ventral striatum, European-College-of-Neuropsychopharmacology Workshop for Junior Scientists in Europe, Publisher: ELSEVIER SCIENCE BV, Pages: S26-S27, ISSN: 0924-977X

CONFERENCE PAPER

Sandhu EC, Fernando ABP, Irvine EE, Tossell K, Kokkinou M, Glegola J, Smith MA, Howes OD, Withers DJ, Ungless MAet al., 2018, Phasic Stimulation of Midbrain Dopamine Neuron Activity Reduces Salt Consumption, ENEURO, Vol: 5, ISSN: 2373-2822

JOURNAL ARTICLE

Scott G, Zetterberg H, Jolly A, Cole JH, De Simoni S, Jenkins PO, Feeney C, Owen DR, Lingford-Hughes A, Howes O, Patel MC, Goldstone AP, Gunn RN, Blennow K, Matthews PM, Sharp DJet al., 2018, Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration, BRAIN, Vol: 141, Pages: 459-471, ISSN: 0006-8950

JOURNAL ARTICLE

McCutcheon R, Beck K, D'Ambrosio E, Donocik J, Gobjila C, Jauhar S, Kaar S, Pillinger T, Marques TR, Rogdaki M, Howes ODet al., 2018, Antipsychotic plasma levels in the assessment of poor treatment response in schizophrenia, ACTA PSYCHIATRICA SCANDINAVICA, Vol: 137, Pages: 39-46, ISSN: 0001-690X

JOURNAL ARTICLE

Kokkinou M, Ashok AH, Howes OD, 2018, The effects of ketamine on dopaminergic function: meta-analysis and review of the implications for neuropsychiatric disorders, MOLECULAR PSYCHIATRY, Vol: 23, Pages: 59-69, ISSN: 1359-4184

JOURNAL ARTICLE

Howes OD, Rogdaki M, Findon JL, Wichers RH, Charman T, King BH, Loth E, McAlonan GM, McCracken JT, Parr JR, Povey C, Santosh P, Wallace S, Simonoff E, Murphy DGet al., 2018, Autism spectrum disorder: Consensus guidelines on assessment, treatment and research from the British Association for Psychopharmacology, Journal of Psychopharmacology, Vol: 32, Pages: 3-29, ISSN: 0269-8811

JOURNAL ARTICLE

Jauhar S, Nour MM, Veronese M, Rogdaki M, Bonoldi I, Azis M, Turkheimer F, McGuire P, Young AH, Howes ODet al., 2017, A Test of the Transdiagnostic Dopamine Hypothesis of Psychosis Using Positron Emission Tomographic Imaging in Bipolar Affective Disorder and Schizophrenia, JAMA PSYCHIATRY, Vol: 74, Pages: 1206-1213, ISSN: 2168-622X

JOURNAL ARTICLE

Bonsall DR, Kokkinou M, Veronese M, Coello C, Wells LA, Howes ODet al., 2017, Single cocaine exposure does not alter striatal pre-synaptic dopamine function in mice: an [18 F]-FDOPA PET study., J Neurochem, Vol: 143, Pages: 551-560

Cocaine is a recreational drug of abuse that binds to the dopamine transporter, preventing reuptake of dopamine into pre-synaptic terminals. The increased presence of synaptic dopamine results in stimulation of both pre- and post-synaptic dopamine receptors, considered an important mechanism by which cocaine elicits its reinforcing properties. However, the effects of acute cocaine administration on pre-synaptic dopamine function remain unclear. Non-invasive imaging techniques such as positron emission tomography have revealed impaired pre-synaptic dopamine function in chronic cocaine users. Similar impairments have been seen in animal studies, with microdialysis experiments indicating decreased basal dopamine release. Here we use micro positron emission tomography imaging techniques in mice to measure dopamine synthesis capacity and determine the effect of acute cocaine administration of pre-synaptic dopamine function. We show that a dose of 20 mg/kg cocaine is sufficient to elicit hyperlocomotor activity, peaking 15-20 min post treatment (p < 0.001). However, dopamine synthesis capacity in the striatum was not significantly altered by acute cocaine treatment (KiCer: 0.0097 per min vs. 0.0112 per min in vehicle controls, p > 0.05). Furthermore, expression levels of two key enzymes related to dopamine synthesis, tyrosine hydroxylase and aromatic l-amino acid decarboxylase, within the striatum of scanned mice were not significantly affected by acute cocaine pre-treatment (p > 0.05). Our findings suggest that while the regulation of dopamine synthesis and release in the striatum have been shown to change with chronic cocaine use, leading to a reduced basal tone, these adaptations to pre-synaptic dopaminergic neurons are not initiated following a single exposure to the drug.

JOURNAL ARTICLE

Bhattacharyya S, Egerton A, Kim E, Rosso L, Barros DR, Hammers A, Brammer M, Turkheimer FE, Howes OD, McGuire Pet al., 2017, Acute induction of anxiety in humans by delta-9-tetrahydrocannabinol related to amygdalar cannabinoid-1 (CB1) receptors, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322

JOURNAL ARTICLE

Winton-Brown T, Schmidt A, Roiser JP, Howes OD, Egerton A, Fusar-Poli P, Bunzeck N, Grace AA, Duzel E, Kapur S, McGuire Pet al., 2017, Altered activation and connectivity in a hippocampal-basal ganglia-midbrain circuit during salience processing in subjects at ultra high risk for psychosis, TRANSLATIONAL PSYCHIATRY, Vol: 7, ISSN: 2158-3188

JOURNAL ARTICLE

Kokkinou M, Irvine EE, Bonsall DR, Ungless MA, Withers DJ, Howes ODet al., 2017, Modulation of sub-chronic ketamine-induced locomotor sensitisation by midbrain dopamine neuron firing, 30th Congress of the European-College-of-Neuropsychopharmacology (ECNP), Publisher: ELSEVIER SCIENCE BV, Pages: S925-S926, ISSN: 0924-977X

CONFERENCE PAPER

Demjaha A, Lappin JM, Stahl D, Patel MX, MacCabe JH, Howes OD, Heslin M, Reininghaus UA, Donoghue K, Lomas B, Charalambides M, Onyejiaka A, Fearon P, Jones P, Doody G, Morgan C, Dazzan P, Murray RMet al., 2017, Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors, PSYCHOLOGICAL MEDICINE, Vol: 47, Pages: 1981-1989, ISSN: 0033-2917

JOURNAL ARTICLE

Ashok AH, Marques TR, Jauhar S, Nour MM, Goodwin GM, Young AH, Howes ODet al., 2017, The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment, MOLECULAR PSYCHIATRY, Vol: 22, Pages: 666-679, ISSN: 1359-4184

JOURNAL ARTICLE

Ashok AH, Mizuno Y, Volkow ND, Howes ODet al., 2017, Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine A Systematic Review and Meta-analysis, JAMA PSYCHIATRY, Vol: 74, Pages: 511-519, ISSN: 2168-622X

JOURNAL ARTICLE

Lapa CDO, Rocha GP, Marques TR, Howes O, Smith S, Monteiro RT, Zorzetti R, Spanemberg Let al., 2017, Translation and cross-cultural adaptation of the Sexual Function Questionnaire (SFQ) into Brazilian Portuguese., Trends Psychiatry Psychother, Vol: 39, Pages: 110-115

Introduction: Sexual dysfunction is common in patients with psychotic illness. This article describes the translation and cross-cultural adaptation of the Sexual Function Questionnaire (SFQ) into Brazilian Portuguese. Methods: The translation and cross-cultural adaptation followed the guidelines for adapting self-report instruments proposed by the Task Force of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Briefly, ISPOR steps include: preparation, forward translation, reconciliation, back-translation, back-translation review, harmonization, cognitive debriefing, review of cognitive debriefing and finalization, before proofreading and final version. The original authors authorized the translation and participated in the study. Results: There was good agreement between translations and between the back-translation and the original English version of the SFQ. The final version was prepared with certificated evaluators in the original language and in Portuguese. Few changes were necessary to the new version in Portuguese. Conclusion: The translated and adapted Brazilian Portuguese version of the SFQ is reliable and semantically equivalent to the original version. Studies on psychotropic-related sexual dysfunction may now test the validity of the instrument and can investigate sexual dysfunction in Portuguese-speaking patients.

JOURNAL ARTICLE

Howes OD, McCutcheon R, Agid O, de Bartolomeis A, van Beveren NJM, Birnbaum ML, Bloomfield MAP, Bressan RA, Buchanan RW, Carpenter WT, Castle DJ, Citrome L, Daskalakis ZJ, Davidson M, Drake RJ, Dursun S, Ebdrup BH, Elkis H, Falkai P, Fleischacker WW, Gadelha A, Gaughran F, Glenthoj BY, Graff-Guerrero A, Hallak JEC, Honer WG, Kennedy J, Kinon BJ, Lawrie SM, Lee J, Leweke FM, MacCabe JH, McNabb CB, Meltzer H, Moeller H-J, Nakajima S, Pantelis C, Marques TR, Remington G, Rossell SL, Russell BR, Siu CO, Suzuki T, Sommer IE, Taylor D, Thomas N, Ucok A, Umbricht D, Walters JTR, Kane J, Correll CUet al., 2017, Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology, AMERICAN JOURNAL OF PSYCHIATRY, Vol: 174, Pages: 216-229, ISSN: 0002-953X

JOURNAL ARTICLE

Jauhar S, Veronese M, Rogdaki M, Bloomfield M, Natesan S, Turkheimer F, Kapur S, Howes ODet al., 2017, Regulation of dopaminergic function: an [F-18]-DOPA PET apomorphine challenge study in humans, TRANSLATIONAL PSYCHIATRY, Vol: 7, ISSN: 2158-3188

JOURNAL ARTICLE

Dahoun T, Trossbach SV, Brandon NJ, Korth C, Howes ODet al., 2017, The impact of Disrupted-in-Schizophrenia 1 (DISC1) on the dopaminergic system: a systematic review, TRANSLATIONAL PSYCHIATRY, Vol: 7, ISSN: 2158-3188

JOURNAL ARTICLE

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