We aim to understand the biological and cognitive mechanisms underlying symptoms and response to treatment. Our studies use an integrative approach to investigate the brain systems involved, using in vivo imaging and other techniques. There are three converging themes. The first theme centres around the role of dopamine in psychotic disorders. The second theme investigates the regulation of dopamine by glutamate, GABA and other mechanisms. The third theme integrates data across measures to investigate the neural networks involved in these disorders.
We study high risk groups, the link to positive and negative symptoms, and developing new potential treatments and treatment predictors.
Studies generally involve healthy volunteer and patients using imaging and other biological and cognitive measures, as well as back translation into preclinical models.
Selected media links:
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.
Selvaraj S, Walker C, Arnone D, Cao B, Faulkner P, Cowen PJ, Roiser JP, Howes O. (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.
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 MA, Ashok AH, Volkow ND, Howes OD. (2016) The effects of Δ9-tetrahydrocannabinol on the dopamine system. Nature. 17;539(7629):369-377
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.
Howes, O. D., & Murray, R. M. (2014). Schizophrenia: an integrated sociodevelopmental-cognitive model. Lancet, 383(9929), 1677–1687.
Selvaraj, S., Mouchlianitis, E., Faulkner, P., Turkheimer, F., Cowen, P. J., Roiser, J. P., & Howes, O. (2014). Presynaptic serotoninergic regulation of emotional processing: A multimodal brain imaging study. Biological Psychiatry.
Stokes, P. R., Shotbolt, P., Mehta, M. A., Turkheimer, E., Benecke, A., Copeland, C., Turkheimer, F. E., Lingford-Hughes, A. R., & Howes, O. D. (2013). Nature or nurture? determining the heritability of human striatal dopamine function: an [18F]-DOPA PET study. Neuropsychopharmacology, 38(3), 485–491.
Demjaha, A., Murray, R. M., McGuire, P. K., Kapur, S., & Howes, O. D. (2012). Dopamine synthesis capacity in patients with treatment-resistant schizophrenia. The American Journal of Psychiatry, 169(11), 1203–1210.
Selvaraj, S., Turkheimer, F., Rosso, L., Faulkner, P., Mouchlianitis, E., Roiser, J. P., McGuire, P., Cowen, P. J., & Howes, O. (2012). Measuring endogenous changes in serotonergic neurotransmission in humans: a [11C]CUMI-101 PET challenge study. Molecular Psychiatry, 17(12), 1254–1260.
Howes, O., Bose, S., Turkheimer, F., Valli, I., Egerton, A., Stahl, D., Valmaggia, L., Allen, P., Murray, R., & McGuire, P. (2011). Progressive increase in striatal dopamine synthesis capacity as patients develop psychosis: a PET study. Molecular Psychiatry, 16(9), 885–886.