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Failure to deactivate medial prefrontal cortex in people at high risk for psychosis

Published online by Cambridge University Press:  15 April 2020

I. Falkenberg ,
C. Chaddock ,
R.M. Murray ,
C. McDonald ,
G. Modinos ,
E. Bramon ,
M. Walshe ,
M. Broome ,
P. McGuire  and
P. Allen
I. Falkenberg*
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom Department of Psychiatry and Psychotherapy, Philipps-University of Marburg, Marburg, Germany
C. Chaddock
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom
R.M. Murray
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom
C. McDonald
Affiliation:
Department of Psychiatry, Clinical Science Institute, National University of Ireland, Galway, Galway, Ireland
G. Modinos
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom
E. Bramon
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom Department of Clinical Neuroscience, Institute of Psychiatry, King's College London, London, United Kingdom
M. Walshe
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom
M. Broome
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom Division of Mental Health and Wellbeing, Warwick Medical School, University of Warwick, Gibbet Hill, Coventry, CV4 7AL, United Kingdom
P. McGuire
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom
P. Allen
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, United Kingdom
*
⁎Corresponding author. Department of Psychosis Studies (PO67), Institute of Psychiatry, King's College London, 16, De Crespigny Park, London SE5 8AF, United Kingdom. Tel.: +44 20 7848 0801; fax: +44 20 7848 0976. E-mail address:[email protected] (I. Falkenberg).
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Abstract

Impaired working memory is a core feature of schizophrenia and is linked with altered engagement the lateral prefrontal cortex. Although altered PFC activation has been reported in people with increased risk of psychosis, at present it is not clear if this neurofunctional alteration differs between familial and clinical risk states and/or increases in line with the level of psychosis risk. We addressed this issue by using functional MRI and a working memory paradigm to study familial and clinical high-risk groups. We recruited 17 subjects at ultra-high-risk (UHR) for psychosis, 10 non-affected siblings of patients with schizophrenia (familial high risk [FHR]) and 15 healthy controls. Subjects were scanned while performing the N-back working memory task. There was a relationship between the level of task-related deactivation in the medial PFC and precuneus and the level of psychosis risk, with deactivation weakest in the UHR group, greatest in healthy controls, and at an intermediate level in the FHR group. In the high-risk groups, activation in the precuneus was associated with the level of negative symptoms. These data suggest that increased vulnerability to psychosis is associated with a failure to deactivate in the medial PFC and precuneus during a working memory task, and appears to be most evident in subjects at clinical, as opposed to familial high risk.

Keywords

PsychosisWorking memoryCognitionUHRDefault mode networkfMRI
Type
Original article
Information
European Psychiatry , Volume 30 , Issue 5 , July 2015 , pp. 633 - 640
Copyright
Copyright © Elsevier Masson SAS 2015

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