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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
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
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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.

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Original article
Copyright
Copyright © Elsevier Masson SAS 2015

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References

Allen, P., Luigjes, J., Howes, O.D., Egerton, A., Hirao, K., Valli, I., et al.Transition to psychosis associated with prefrontal and subcortical dysfunction in ultra-high-risk individuals. Schizophr Bull 2012 [Internet; refd 2012 May 9] http://www.ncbi.nlm.nih.gov/pubmed/22290265.CrossRefGoogle ScholarPubMed
Barkus, E.J., Stirling, J., Hopkins, R.S., Lewis, S.. Cannabis-induced psychosis-like experiences are associated with high schizotypy. Psychopathology 2006;39(4):175178.CrossRefGoogle ScholarPubMed
Broome, M.R., Woolley, J.B., Johns, L.C., Valmaggia, L.R., Tabraham, P., Gafoor, R., et al.Outreach and support in south London (OASIS): implementation of a clinical service for prodromal psychosis and the at risk mental state. Eur Psychiatry 2005;20(5–6):372378.CrossRefGoogle ScholarPubMed
Broome, M.R., Matthiasson, P., Fusar-Poli, P., Woolley, J.B., Johns, L.C., Tabraham, P., et al.Neural correlates of executive function and working memory in the “at-risk mental state”. Br J Psychiatry 2009;194(1):2533.CrossRefGoogle Scholar
Buckner, R.L., Andrews-Hanna, J.R., Schacter, D.L.. The brain's default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci 2008;1124:138.CrossRefGoogle ScholarPubMed
Choi, J.-S., Park, J.-Y., Jung, M.H., Jang, J.H., Kang, D.-H., Jung, W.H., et al.Phase-specific brain change of spatial working memory processing in genetic and ultra-high-risk groups of schizophrenia. Schizophr Bull 2011 [Internet] http://www.ncbi.nlm.nih.gov/pubmed/21518920.Google ScholarPubMed
Coren, S.. Measurement of handedness via self-report: the relationship between brief and extended inventories. Percept Mot Skills 1993;76(3 Pt 1):10351042.CrossRefGoogle ScholarPubMed
Cornblatt, B.A., Carrión, R.E., Addington, J., Seidman, L., Walker, E.F., Cannon, T.D., et al.Risk factors for psychosis: impaired social and role functioning. Schizophr Bull 2012;38(6):12471257.CrossRefGoogle ScholarPubMed
Egan, M.F., Goldberg, T.E., Gscheidle, T., Weirich, M., Rawlings, R., Hyde, T.M., et al.Relative risk for cognitive impairments in siblings of patients with schizophrenia. Biol Psychiatry 2001;50(2):98107.CrossRefGoogle ScholarPubMed
Frommann, I., Pukrop, R., Brinkmeyer, J., Bechdolf, A., Ruhrmann, S., Berning, J., et al.Neuropsychological profiles in different at-risk states of psychosis: executive control impairment in the early – and additional memory dysfunction in the late – prodromal state. Schizophr Bull 2011;37(4):861873.CrossRefGoogle ScholarPubMed
Fusar-Poli, P., Broome, M.R., Woolley, J.B., Johns, L.C., Tabraham, P., Bramon, E., et al.Altered brain function directly related to structural abnormalities in people at ultra-high-risk of psychosis: longitudinal VBM-fMRI study. J Psychiatr Res 2011;45(2):190198.CrossRefGoogle ScholarPubMed
Fusar-Poli, P., Borgwardt, S., Crescini, A., Deste, G., Kempton, M.J., Lawrie, S., et al.Neuroanatomy of vulnerability to psychosis: a voxel-based meta-analysis. Neurosci Biobehav Rev 2011;35(5):11751185.CrossRefGoogle ScholarPubMed
Fusar-Poli, P., Bonoldi, I., Yung, A.R., Borgwardt, S., Kempton, M.J., Valmaggia, L., et al.Predicting psychosis: meta-analysis of transition outcomes in individuals at high clinical risk. Arch Gen Psychiatry 2012;69(3):220229.CrossRefGoogle ScholarPubMed
Fusar-Poli, P., Deste, G., Smieskova, R., Barlati, S., Yung, A.R., Howes, O., et al.Cognitive functioning in prodromal psychosis: a meta-analysis. Arch Gen Psychiatry 2012;69(6):562571.CrossRefGoogle ScholarPubMed
Glahn, D.C., Ragland, J.D., Abramoff, A., Barrett, J., Laird, A.R., Bearden, C.E., et al.Beyond hypofrontality: a quantitative meta-analysis of functional neuroimaging studies of working memory in schizophrenia. Hum Brain Mapp 2005;25(1):6069.CrossRefGoogle Scholar
Gottesman, I.L., Wolfgram, D.L.Schizophrenia genesis: the origins of madness. New York: W H Freeman & Co; 1990 [296 p.].Google Scholar
Guerrero-Pedraza, A., McKenna, P.J., Gomar, J.J., Sarró, S., Salvador, R., Amann, B., et al.First-episode psychosis is characterized by failure of deactivation but not by hypo- or hyperfrontality. Psychol Med 2012;42(1):7384.CrossRefGoogle ScholarPubMed
Häfner, H., Maurer, K., Löffler, W., Fätkenheuer, B., an der Heiden, W., Riecher-Rössler, A., et al.The epidemiology of early schizophrenia. Influence of age and gender on onset and early course. Br J Psychiatry Suppl 1994;(23):2938.CrossRefGoogle ScholarPubMed
Hall, R.C.W.. Global assessment of functioning: a modified scale. Psychosomatics 1995;36(3):267275.CrossRefGoogle ScholarPubMed
Jang, J.H., Jung, W.H., Choi, J.-S., Choi, C.-H., Kang, D.-H., Shin, N.Y., et al.Reduced prefrontal functional connectivity in the default mode network is related to greater psychopathology in subjects with high genetic loading for schizophrenia. Schizophr Res 2011;127(1–3):5865.CrossRefGoogle Scholar
Kay, S.R., Fiszbein, A., Opler, L.A.. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13(2):261.CrossRefGoogle Scholar
Lin, A., Wood, S.J., Nelson, B., Brewer, W.J., Spiliotacopoulos, D., Bruxner, A., et al.Neurocognitive predictors of functional outcome two to 13 years after identification as ultra-high-risk for psychosis. Schizophr Res 2011;132(1):17.CrossRefGoogle ScholarPubMed
McDonald, C., Bullmore, E.T., Sham, P.C., Chitnis, X., Wickham, H., Bramon, E., et al.Association of genetic risks for schizophrenia and bipolar disorder with specific and generic brain structural endophenotypes. Arch Gen Psychiatry 2004;61(10):974984.CrossRefGoogle ScholarPubMed
Mechelli, A., Henson, R.N.A., Price, C.J., Friston, K.J.. Comparing event-related and epoch analysis in blocked design fMRI. Neuroimage 2003;18(3):806810.CrossRefGoogle ScholarPubMed
Meda, S.A., Gill, A., Stevens, M.C., Lorenzoni, R.P., Glahn, D.C., Calhoun, V.D., et al.Differences in resting-state functional magnetic resonance imaging functional network connectivity between schizophrenia and psychotic bipolar probands and their unaffected first-degree relatives. Biol Psychiatry 2012;71(10):881889.CrossRefGoogle ScholarPubMed
Mingoia, G., Wagner, G., Langbein, K., Maitra, R., Smesny, S., Dietzek, M., et al.Default mode network activity in schizophrenia studied at resting state using probabilistic ICA. Schizophr Res 2012;138(2–3):143149.CrossRefGoogle ScholarPubMed
Minzenberg, M.J., Laird, A.R., Thelen, S., Carter, C.S., Glahn, D.C.. Meta-analysis of 41 functional neuroimaging studies of executive function in schizophrenia. Arch Gen Psychiatry 2009;66(8):811822.CrossRefGoogle Scholar
Morey, R.A., Inan, S., Mitchell, T.V., Perkins, D.O., Lieberman, J.A., Belger, A.. Imaging frontostriatal function in ultra-high-risk, early, and chronic schizophrenia during executive processing. Arch Gen Psychiatry 2005;62(3):254262.CrossRefGoogle ScholarPubMed
Mortensen, P.B., Pedersen, M.G., Pedersen, C.B.. Psychiatric family history and schizophrenia risk in Denmark: which mental disorders are relevant?. Psychol Med 2010;40(2):201210.CrossRefGoogle ScholarPubMed
Nelson, H., Willison, J.National adult reading test (NART): test manual. Windsor: NFER-Nelson; 1982.Google Scholar
Nenadic, I., Dietzek, M., Schönfeld, N., Lorenz, C., Gussew, A., Reichenbach, J.R., et al.Brain structure in people at ultra-high-risk of psychosis, patients with first-episode schizophrenia, and healthy controls: a VBM study. Schizophr Res 2015;161(2–3):169176.CrossRefGoogle ScholarPubMed
Raichle, M.E., MacLeod, A.M., Snyder, A.Z., Powers, W.J., Gusnard, D.A., Shulman, G.L.A default mode of brain function. Proc Natl Acad Sci U S A 2001;98(2):676682.CrossRefGoogle ScholarPubMed
Rasetti, R., Mattay, V.S., Wiedholz, L.M., Kolachana, B.S., Hariri, A.R., Callicott, J.H., et al.Evidence that altered amygdala activity in schizophrenia is related to clinical state and not genetic risk. Am J Psychiatry 2009;166(2):216225.CrossRefGoogle Scholar
Resnick, S.M.Matching for education in studies of schizophrenia. Arch Gen Psychiatry 1992;49(3):246.CrossRefGoogle ScholarPubMed
Shim, G., Oh, J.S., Jung, W.H., Jang, J.H., Choi, C.-H., Kim, E., et al.Altered resting-state connectivity in subjects at ultra-high-risk for psychosis: an fMRI study. Behav Brain Funct 2010;6:58.CrossRefGoogle Scholar
Smieskova, R., Allen, P., Simon, A., Aston, J., Bendfeldt, K., Drewe, J., et al.Different duration of at-risk mental state associated with neurofunctional abnormalities. A multimodal imaging study. Hum Brain Mapp 2011 [Internet] http://www.ncbi.nlm.nih.gov/pubmed/21922599.Google ScholarPubMed
Wager, T.D., Smith, E.E.Neuroimaging studies of working memory: a meta-analysis. Cogn Affect Behav Neurosci 2003;3(4):255274.CrossRefGoogle ScholarPubMed
Weissman, D.H., Roberts, K.C., Visscher, K.M., Woldorff, M.G.The neural bases of momentary lapses in attention. Nat Neurosci 2006;9(7):971978.CrossRefGoogle ScholarPubMed
Whitfield-Gabrieli, S., Thermenos, H.W., Milanovic, S., Tsuang, M.T., Faraone, S.V., McCarley, R.W., et al.Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia. Proc Natl Acad Sci U S A 2009;106(4):12791284.CrossRefGoogle ScholarPubMed
Wood, S.J., Yücel, M., Velakoulis, D., Phillips, L.J., Yung, A.R., Brewer, W., et al.Hippocampal and anterior cingulate morphology in subjects at ultra-high-risk for psychosis: the role of family history of psychotic illness. Schizophr Res 2005;75(2–3):295301.CrossRefGoogle ScholarPubMed
World Medical Association World Medical Association declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013;310(20):21912194.CrossRefGoogle Scholar
Yung, A.R., Phillips, L.J., McGorry, P.D., McFarlane, C.A., Francey, S., Harrigan, S., et al.Prediction of psychosis. A step towards indicated prevention of schizophrenia. Br J Psychiatry Suppl 1998;172(33):1420.CrossRefGoogle ScholarPubMed
Yung, A.R., Yuen, H.P., McGorry, P.D., Phillips, L.J., Kelly, D., Dell’Olio, M., et al.Mapping the onset of psychosis: the Comprehensive Assessment of At-Risk Mental States. Aust N Z J Psychiatry 2005;39(11–12):964971.CrossRefGoogle ScholarPubMed
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