We use translational approaches in patients and preclinical models to understand the regulation of brain systems. Our studies use innovative in vivo imaging with PET, MRI and other techniques to quantify molecular and brain system interactions.
There are three converging themes. The first theme centres around the genetic and molecular control of the dopaminergic system in the brain and how dysregulation of this leads to symptoms. The second theme investigates the molecular mechanisms underlying therapeutic response. The third theme focuses on the regulation of synaptic function. Finally, the group also investigates the mechanisms underlying cardiometabolic dysfunction in schizophrenia.
Studies generally involve healthy volunteer and patients, as well as back translation into preclinical models.
Selected media links to articles and programmes about our work:
Regions of elevated dopamine synthesis capacity in red in the brains of people developing psychosis (A). A loss of normal brain connectivity (B) as people develop psychosis (C), particularly in the anterior cingulate cortex, highlighted with yellow arrows.
Nour MM, Dahoun T, Schwartenbeck P, Adams RA, FitzGerald THB, Coello C, Wall MB, DOlan RJ, Howes OD. (2018). Dopaminergic basis for signaling belief updates, but not surprise, and the link to paranoia. Proceeding of the National Academy of Science of the United States of America, 115(43), 10167-10176.
Bloomfield MA, Ashok AH, Volkow ND, Howes OD. (2016). The effects of Δ9-tetrahydrocannabinol on the dopamine system. Nature 17, 539(7629), 369-377.
Howes OD, Murray RM. (2014). Schizophrenia: an integrated sociodevelopmental-cognitive model. Lancet 383(9929), 1677–1687.
Borgan F, O’Daly O, Hoang K, Veronese M, Withers D, Batterham R, Howes O. (2019). Neural Responsivity to Food Cues in Patients With Unmedicated First-Episode Psychosis. JAMA Netw Open, DOI: 10.1001/jamanetworkopen.2018.6893.
Bloomfield PS, Bonsall D, Wells L, Dormann D, Howes O, De Paola V. (2018). The effects of haloperidol on microglial morphology and translocator protein levels: An in vivo study in rats using an automated cell evaluation pipeline. J Psychopharmacol. 32(11):1264-1272.
Dahoun T, Pardiñas AF, Veronese M, Bloomfield MAP, Jauhar S, Bonoldi I, Froudist-Walsh S, Nosarti C, Korth C, Hennah W, Walters J, Prata D, Howes OD. (2018). The effect of the DISC1 Ser704Cys polymorphism on striatal dopamine synthesis capacity: an [18F]-DOPA PET study. Hum Mol Genet, 27(20):3498-3506.
Selvaraj S, Walker C, Arnone D, Cao B, Faulkner P, Cowen PJ, Roiser JP, Howes OD (2018). Effect of Citalopram on Emotion Processing in Humans: A Combined 5-HT1A [11C]CUMI-101 PET and Functional MRI Study. Neuropsychopharmacology doi: 10.1038/npp.2017.166.
Pillinger T, Beck K, Gobjila C, Donocik JG, Jauhar S, Howes OD. (2017). Impaired Glucose Homeostasis in First-Episode Schizophrenia: A Systematic Review and Meta-analysis. JAMA Psychiatry, 74(2):261-269.
Jauhar S, Nour MM, Veronese M, Rogdaki M, Bonoldi I, Azis M, Turkheimer F, McGuire P, Young AH, Howes OD. (2017). A Test of the Transdiagnostic Dopamine Hypothesis of Psychosis Using Positron Emission Tomographic Imaging in Bipolar Affective Disorder and Schizophrenia. JAMA Psychiatry 74(12), 1206-1213.
Jauhar S, Veronese M, Rogdaki M, Bloomfield M, Natesan S, Turkheimer F, Kapur S, Howes OD. (2017). Regulation of dopaminergic function: an [18F]-DOPA PET apomorphine challenge study in humans. Transl Psychiatry 7(2):e1027.
Howes OD, McCutcheon R, Owen MJ, Murray RM. (2017). The Role of Genes, Stress, and Dopamine in the Development of Schizophrenia. Biol Psychiatry 81(1), 9-20.
Bloomfield PS, Selvaraj S, Veronese M, Rizzo G, Bertoldo A, Owen DR, Bloomfield MA, Bonoldi I, Kalk N, Turkheimer F, McGuire P, de Paola V, Howes OD. (2016). Microglial Activity in People at Ultra High Risk of Psychosis and in Schizophrenia: An [(11)C]PBR28 PET Brain Imaging Study. Am J Psychiatry 173(1), 44-52.
Selvaraj S, Mouchlianitis E, Faulkner P, Turkheimer F, Cowen PJ, Roiser JP, Howes O. (2015). Presynaptic Serotoninergic Regulation of Emotional Processing: A Multimodal Brain Imaging Study. Biol Psychiatry, 78(8):563-571.
Stokes PR, Shotbolt P, Mehta MA, Turkheimer E, Benecke A, Copeland C, Turkheimer FE, Lingford-Hughes AR, Howes OD. (2013). Nature or nurture? determining the heritability of human striatal dopamine function: an [18F]-DOPA PET study. Neuropsychopharmacology 38(3), 485–491.
Selvaraj S, Turkheimer F, Rosso L, Faulkner P, Mouchlianitis E, Roiser JP, McGuire P, Cowen PJ, Howes O. (2012). Measuring endogenous changes in serotonergic neurotransmission in humans: a [11C]CUMI-101 PET challenge study. Molecular Psychiatry 17(12), 1254–1260.