“Our research focuses on understanding the causes of mental illnesses to improve their treatment. We primarily use functional imaging and experimental models in patients and controls”

Mental illness is a major cause of ill health and premature death. It accounts for four of the six leading causes of adult disability in the world and one in every ten hospital beds in the UK is allocated for the treatment of psychotic disorders such as schizophrenia.

We investigate the brain changes that underlie the onset of psychosis and response to treatment. There are two converging themes. The first theme centres around dopamine dysfunction in the development of psychotic disorders. This includes studying high risk groups, and the impact of risk factors for schizophrenia on dopaminergic function. The second theme investigates the role of dopamine and glutamate in treatment response. Studies are predominantly in patients or subjects at clinical risk of psychosis and use positron emission tomography to index neurochemical function in vivo. A key component of the Group’s approach involves integrating complex datasets from clinical, PET and related measures to probe the neural systems underlying psychosis.

Psychiatric Imaging

Left: Shows regions of elevated dopamine synthesis capacity in red in the brains of people developing psychosis. Right: There is a loss of normal brain connectivity (top right) as people develop psychosis (bottom right), particularly in the anterior cingulate cortex (arrow).

The research team has developed software called a CellProfiler pipeline to identify and analyse microglial cells to provide cell density, size and process coverage. Find out more and download the CellProfiler pipeline here.

Selected Publications

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.

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.

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.

Howes, O. D., Kambeitz, J., Kim, E., Stahl, D., Slifstein, M., Abi-Dargham, A., & Kapur, S. (2012). The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Archives of General Psychiatry, 69(8), 776–786.

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.

Howes, O. D., Montgomery, A. J., Asselin, M.-C. C., Murray, R. M., Valli, I., Tabraham, P., Bramon-Bosch, E., Valmaggia, L., Johns, L., Broome, M., McGuire, P. K., & Grasby, P. M. (2009). Elevated striatal dopamine function linked to prodromal signs of schizophrenia. Archives of General Psychiatry, 66(1), 13–20.

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. Microglial Activity in People at Ultra High Risk of Psychosis and in Schizophrenia: An [(11)C]PBR28 PET Brain Imaging Study. Am J Psychiatry. 2016 Jan;173(1):44-52.

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