All Group Leaders 

Psychosis

Philip  McGuire

Philip McGuire

Professor of Psychiatry and Cognitive Neuroscience

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Overview

The IOPPN hosts one of the world’s largest groups conducting research on psychosis. Our work is focused on understanding the neurobiological mechanisms underlying psychosis, particularly those related to the onset of psychotic disorders. We have particular strengths in neuroimaging, -omic, cognitive, and psychopharmacological studies in the early phases of psychosis. These often involve people who are at ‘ultra high risk’ for psychosis (but have not yet developed a psychotic disorder), and patients with first episode psychosis (who have just become psychotic for the first time). Research in this field is facilitated by an international network of early detection and intervention centres that provides a unique platform for recruiting and following up these subjects. We also have excellent partnerships with the pharmaceutical industry and with SMEs with expertise in developing clinical tools. Our findings in clinical subjects are broadly consistent with data from animal models of psychosis, and we are very keen on work that integrates human and basic science research in this field.

The long term ambition is to use our research findings to provide a scientific rationale for the development of: a) tools that use biomarkers to predict key clinical outcomes, such as the onset of psychosis, or the response to treatment in psychosis; and b) new forms of treatment that can be used to prevent the onset of psychosis and to improve outcomes in patients who have a psychotic disorder.

Selected publications

Colizzi M, Weltens N, McGuire P, Lythgoe D, Williams S, Van Oudenhove L, Bhattacharyya S (2019) Delta-9-tetrahydrocannabinol increases striatal glutamate levels in healthy individuals: implications for psychosis. Mol Psychiatry

Minichino A, Rutigliano G, Merlino S, Davies C, Oliver D, De Micheli A, Patel R, McGuire P, Fusar-Poli P (2019) Unmet needs in patients with brief psychotic disorders: Too ill for clinical high risk services and not ill enough for first episode services. Eur Psychiatry 57: 26-32

Modinos G, ?im?ek F, Azis M, Bossong M, Bonoldi I, Samson C, Quinn B, Perez J, Broome MR, Zelaya F, Lythgoe DJ, Howes OD, Stone JM, Grace AA, Allen P, McGuire P (2018) Correction: Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis. Neuropsychopharmacology 43: 2660
Kravariti E, Reeve-Mates C, Da Gama Pires R, Tsakanikos E, Hayes D, Renshaw S, McAllister S, Bhavsar V, Patterson P, Daley E, Stewart J, Pritchard M, Shetty H, Ramsay R, Perez-Iglesias R, McGuire P (2018) Effectiveness of automated appointment reminders in Psychosis Community Services: A randomised controlled trial - CORRIGENDUM. BJPsych Open 4: 419
Sato JR, Biazoli CE, Salum GA, Gadelha A, Crossley N, Vieira G, Zugman A, Picon FA, Pan PM, Hoexter MQ, Amaro E, Anés M, Moura LM, Del'Aquilla MAG, Mcguire P, Rohde LA, Miguel EC, Bressan RA, Jackowski AP (2018) Associations between children's family environment, spontaneous brain oscillations, and emotional and behavioral problems. Eur Child Adolesc Psychiatry
Bossong MG, Antoniades M, Azis M, Samson C, Quinn B, Bonoldi I, Modinos G, Perez J, Howes OD, Stone JM, Allen P, McGuire P (2018) Association of Hippocampal Glutamate Levels With Adverse Outcomes in Individuals at Clinical High Risk for Psychosis. JAMA Psychiatry
Pollak TA, Rogers JP, Nagele RG, Peakman M, Stone JM, David AS, McGuire P (2018) Antibodies in the Diagnosis, Prognosis, and Prediction of Psychotic Disorders. Schizophr Bull
Orlov ND, Giampietro V, O'Daly O, Lam SL, Barker GJ, Rubia K, McGuire P, Shergill SS, Allen P (2018) Real-time fMRI neurofeedback to down-regulate superior temporal gyrus activity in patients with schizophrenia and auditory hallucinations: a proof-of-concept study. Transl Psychiatry 8: 46
Bossong MG, Wilson R, Appiah-Kusi E, McGuire P, Bhattacharyya S (2018) Human striatal response to reward anticipation linked to hippocampal glutamate levels. Int J Neuropsychopharmacol
Oliver D, Kotlicka-Antczak M, Minichino A, Spada G, McGuire P, Fusar-Poli P (2018) Meta-analytical prognostic accuracy of the Comprehensive Assessment of at Risk Mental States (CAARMS): The need for refined prediction. Eur Psychiatry 49: 62-68
Modinos G, ?im?ek F, Azis M, Bossong M, Bonoldi I, Samson C, Quinn B, Perez J, Broome MR, Zelaya F, Lythgoe DJ, Howes OD, Stone JM, Grace AA, Allen P, McGuire P (2018) Prefrontal GABA levels, hippocampal resting perfusion and the risk of psychosis. Neuropsychopharmacology
McGuire P, Robson P, Cubala WJ, Vasile D, Morrison PD, Barron R, Taylor A, Wright S (2017) Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial. Am J Psychiatry : appiajp201717030325
Froudist-Walsh S, Bloomfield MA, Veronese M, Kroll J, Karolis VR, Jauhar S, Bonoldi I, McGuire PK, Kapur S, Murray RM, Nosarti C, Howes O (2017) The effect of perinatal brain injury on dopaminergic function and hippocampal volume in adult life. Elife 6

Shakoor S, McGuire P, Cardno AG, Freeman D, Ronald A (2017) A twin study exploring the association between childhood emotional and behaviour problems and specific psychotic experiences in a community sample of adolescents. J Child Psychol Psychiatry

Bhattacharyya S, Egerton A, Kim E, Rosso L, Riano Barros D, Hammers A, Brammer M, Turkheimer FE, Howes OD, McGuire P (2017) Acute induction of anxiety in humans by delta-9-tetrahydrocannabinol related to amygdalar cannabinoid-1 (CB1) receptors. Sci Rep 7: 15025

Patel R, Chesney E, Taylor M, Taylor D, McGuire P (2017) Is paliperidone palmitate more effective than other long-acting injectable antipsychotics? Psychol Med : 1-10

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: 1206-1213

Modinos G, Allen P, Grace AA, McGuire P (2015) Translating the MAM model of psychosis to humans. Trends Neurosci 38: 129-38
Demjaha A, Egerton A, Murray RM, Kapur S, Howes OD, Stone JM, McGuire PK (2014) Antipsychotic treatment resistance in schizophrenia associated with elevated glutamate levels but normal dopamine function. Biol Psychiatry 75: e11-3
Crossley NA, Mechelli A, Vértes PE, Winton-Brown TT, Patel AX, Ginestet CE, McGuire P, Bullmore ET (2013) Cognitive relevance of the community structure of the human brain functional coactivation network. Proc Natl Acad Sci U S A 110: 11583-8
Fusar-Poli P, Bonoldi I, Yung AR, Borgwardt S, Kempton MJ, Valmaggia L, Barale F, Caverzasi E, McGuire P (2012) Predicting psychosis: meta-analysis of transition outcomes in individuals at high clinical risk. Arch Gen Psychiatry 69: 220-9
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. Mol Psychiatry 16: 885-6
Benetti S, Mechelli A, Picchioni M, Broome M, Williams S, McGuire P (2009) Functional integration between the posterior hippocampus and prefrontal cortex is impaired in both first episode schizophrenia and the at risk mental state. Brain 132: 2426-36
Howes OD, Montgomery AJ, Asselin MC, Murray RM, Valli I, Tabraham P, Bramon-Bosch E, Valmaggia L, Johns L, Broome M, McGuire PK, Grasby PM (2009) Elevated striatal dopamine function linked to prodromal signs of schizophrenia. Arch Gen Psychiatry 66: 13-20
Shergill SS, Kanaan RA, Chitnis XA, O'Daly O, Jones DK, Frangou S, Williams SC, Howard RJ, Barker GJ, Murray RM, McGuire P (2007) A diffusion tensor imaging study of fasciculi in schizophrenia. Am J Psychiatry 164: 467-73
Pantelis C, Velakoulis D, McGorry PD, Wood SJ, Suckling J, Phillips LJ, Yung AR, Bullmore ET, Brewer W, Soulsby B, Desmond P, McGuire PK (2003) Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet 361: 281-8
Shergill SS, Brammer MJ, Williams SC, Murray RM, McGuire PK (2000) Mapping auditory hallucinations in schizophrenia using functional magnetic resonance imaging. Arch Gen Psychiatry 57: 1033-8
McGuire PK, Silbersweig DA, Wright I, Murray RM, David AS, Frackowiak RS, Frith CD (1995) Abnormal monitoring of inner speech: a physiological basis for auditory hallucinations. Lancet 346: 596-600
McGuire PK, Shah GM, Murray RM (1993) Increased blood flow in Broca's area during auditory hallucinations in schizophrenia. Lancet 342: 703-6