Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-27T07:17:39.623Z Has data issue: false hasContentIssue false
  • English
  • Français

First-episode psychosis is characterized by failure of deactivation but not by hypo- or hyperfrontality

Published online by Cambridge University Press:  07 July 2011

A. Guerrero-Pedraza ,
P. J. McKenna ,
J. J. Gomar ,
S. Sarró ,
R. Salvador ,
B. Amann ,
M. I. Carrión ,
R. Landin-Romero ,
J. Blanch  and
E. Pomarol-Clotet
A. Guerrero-Pedraza
Affiliation:
Benito Menni CASM, Barcelona, Spain Psychiatry and Clinical Psychology Programme, Universitat Autònoma de Barcelona, Spain
P. J. McKenna
Affiliation:
Benito Menni CASM, Barcelona, Spain FIDMAG, Germanes Hospitàries and CIBERSAM, Spain
J. J. Gomar
Affiliation:
Psychiatry and Clinical Psychology Programme, Universitat Autònoma de Barcelona, Spain FIDMAG, Germanes Hospitàries and CIBERSAM, Spain
S. Sarró
Affiliation:
Psychiatry and Clinical Psychology Programme, Universitat Autònoma de Barcelona, Spain FIDMAG, Germanes Hospitàries and CIBERSAM, Spain
R. Salvador
Affiliation:
FIDMAG, Germanes Hospitàries and CIBERSAM, Spain
B. Amann
Affiliation:
Benito Menni CASM, Barcelona, Spain FIDMAG, Germanes Hospitàries and CIBERSAM, Spain
M. I. Carrión
Affiliation:
Hospital Sant Rafael, Barcelona, Spain
R. Landin-Romero
Affiliation:
FIDMAG, Germanes Hospitàries and CIBERSAM, Spain
J. Blanch
Affiliation:
Hospital Sant Joan de Déu infantil, Barcelona, Spain
E. Pomarol-Clotet*
Affiliation:
FIDMAG, Germanes Hospitàries and CIBERSAM, Spain
*
*Address for correspondence: Dr E. Pomarol-Clotet, Benito Menni CASM, Germanes Hospitalàries del Sagrat Cor de Jesús, C/ Dr Antoni Pujadas 38-C, 08830 Sant Boi de Llobregat, Barcelona, Spain. (Email: edith.pomarol@gmail.com)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

It is not known whether first-episode psychosis is characterized by the same prefrontal cortex functional imaging abnormalities as chronic schizophrenia.

Method

Thirty patients with a first episode of non-affective functional psychosis and 28 healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back working memory task. Voxel-based analyses of brain activations and deactivations were carried out and compared between groups. The connectivity of regions of significant difference between the patients and controls was also examined.

Results

The first-episode patients did not show significant prefrontal hypo- or hyperactivation compared to controls. However, they showed failure of deactivation in the medial frontal cortex. This area showed high levels of connectivity with the posterior cingulate gyrus/precuneus and parts of the parietal cortex bilaterally. Failure of deactivation was significantly greater in first-episode patients who had or went on to acquire a DSM-IV diagnosis of schizophrenia than in those who did not, and in those who met RDC criteria for schizophrenia compared to those who did not.

Conclusions

First-episode psychosis is not characterized by hypo- or hyperfrontality but instead by a failure of deactivation in the medial frontal cortex. The location and connectivity of this area suggest that it is part of the default mode network. The failure of deactivation seems to be particularly marked in first-episode patients who have, or progress to, schizophrenia.

Keywords

Default mode networkfirst-episode psychosisfunctional imagingschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 42 , Issue 1 , January 2012 , pp. 73 - 84
Copyright
Copyright © Cambridge University Press 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Barch, DM, Carter, CS, Braver, TS, Sabb, FW, MacDonald, A 3rd, Noll, DC, Cohen, JD (2001). Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia. Archives of General Psychiatry 58, 280–288.CrossRefGoogle ScholarPubMed
Beckmann, CF, Jenkinson, M, Woolrich, MW, Behrens, TE, Flitney, DE, Devlin, JT, Smith, SM (2006). Applying FSL to the FIAC data: model-based and model-free analysis of voice and sentence repetition priming. Human Brain Mapping 27, 380–391.CrossRefGoogle Scholar
Bluhm, RL, Miller, J, Lanius, RA, Osuch, EA, Boksman, K, Neufeld, RW, Theberge, J, Schaefer, B, Williamson, P (2007). Spontaneous low-frequency fluctuations in the BOLD signal in schizophrenic patients: anomalies in the default network. Schizophrenia Bulletin 33, 1004–1012.CrossRefGoogle ScholarPubMed
Boksman, K, Theberge, J, Williamson, P, Drost, DJ, Malla, A, Densmore, M, Takhar, J, Pavlosky, W, Menon, RS, Neufeld, RW (2005). A 4.0-T fMRI study of brain connectivity during word fluency in first-episode schizophrenia. Schizophrenia Research 75, 247–263.CrossRefGoogle Scholar
Brillinger, DR (1981). Time Series. Data Analysis and Theory. Holden Day: San Francisco.Google Scholar
Broome, MR, Matthiasson, P, Fusar-Poli, P, Woolley, JB, Johns, LC, Tabraham, P, Bramon, E, Valmaggia, L, Williams, SC, Brammer, MJ, Chitnis, X, McGuire, PK (2009). Neural correlates of executive function and working memory in the ‘at-risk mental state’. British Journal of Psychiatry 194, 25–33.CrossRefGoogle ScholarPubMed
Broyd, SJ, Demanuele, C, Debener, S, Helps, SK, James, CJ, Sonuga-Barke, EJ (2009). Default-mode brain dysfunction in mental disorders: a systematic review. Neuroscience and Biobehavioral Reviews 33, 279–296.CrossRefGoogle ScholarPubMed
Buckner, RL, Andrews-Hanna, JR, Schacter, DL (2008). The brain's default network: anatomy, function, and relevance to disease. Annals of the New York Academy of Sciences 1124, 1–38.CrossRefGoogle ScholarPubMed
Calhoun, VD, Maciejewski, PK, Pearlson, GD, Kiehl, KA (2008). Temporal lobe and ‘default’ hemodynamic brain modes discriminate between schizophrenia and bipolar disorder. Human Brain Mapping 29, 1265–1275.CrossRefGoogle ScholarPubMed
Callicott, JH, Bertolino, A, Mattay, VS, Langheim, FJ, Duyn, J, Coppola, R, Goldberg, TE, Weinberger, DR (2000). Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cerebral Cortex 10, 1078–1092.CrossRefGoogle ScholarPubMed
Callicott, JH, Mattay, VS, Verchinski, BA, Marenco, S, Egan, MF, Weinberger, DR (2003). Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down. American Journal of Psychiatry 160, 2209–2215.CrossRefGoogle ScholarPubMed
Camchong, J, MacDonald, AW III, Bell, C, Mueller, BA, Lim, KO (2010). Altered functional and anatomical connectivity in schizophrenia. Schizophrenia Bulletin 37, 640–650.CrossRefGoogle Scholar
Del Ser, T, Gonzalez-Montalvo, JI, Martinez-Espinosa, S, Delgado-Villapalos, C, Bermejo, F (1997). Estimation of premorbid intelligence in Spanish people with the Word Accentuation Test and its application to the diagnosis of dementia. Brain and Cognition 33, 343–356.CrossRefGoogle Scholar
Garrity, AG, Pearlson, GD, McKiernan, K, Lloyd, D, Kiehl, KA, Calhoun, VD (2007). Aberrant ‘default mode’ functional connectivity in schizophrenia. American Journal of Psychiatry 164, 450–457.CrossRefGoogle ScholarPubMed
Gevins, A, Cutillo, B (1993). Spatiotemporal dynamics of component processes in human working memory. Electroencephalography and Clinical Neurophysiology 87, 128–143.CrossRefGoogle ScholarPubMed
Glahn, DC, Ragland, JD, Abramoff, A, Barrett, J, Laird, AR, Bearden, CE, Velligan, DI (2005). Beyond hypofrontality: a quantitative meta-analysis of functional neuroimaging studies of working memory in schizophrenia. Human Brain Mapping 25, 60–69.CrossRefGoogle ScholarPubMed
Green, DM, Swets, JA (1966). Signal Detection Theory and Psychophysics. Krieger: New York.Google Scholar
Gusnard, DA, Raichle, ME (2001). Searching for a baseline: functional imaging and the resting human brain. Nature Reviews. Neuroscience 2, 685–694.CrossRefGoogle ScholarPubMed
Harrison, BJ, Yucel, M, Pujol, J, Pantelis, C (2007). Task-induced deactivation of midline cortical regions in schizophrenia assessed with fMRI. Schizophrenia Research 91, 82–86.CrossRefGoogle ScholarPubMed
Hill, K, Mann, L, Laws, KR, Stephenson, CM, Nimmo-Smith, I, McKenna, PJ (2004). Hypofrontality in schizophrenia: a meta-analysis of functional imaging studies. Acta Psychiatrica Scandinavica 110, 243–256.CrossRefGoogle ScholarPubMed
John, JP, Halahalli, HN, Vasudev, MK, Jayakumar, PN, Jain, S (2011). Regional brain activation/deactivation during word generation in schizophrenia: fMRI study. British Journal of Psychiatry 198, 213–222.CrossRefGoogle ScholarPubMed
Johnson, MR, Morris, NA, Astur, RS, Calhoun, VD, Mathalon, DH, Kiehl, KA, Pearlson, GD (2006). A functional magnetic resonance imaging study of working memory abnormalities in schizophrenia. Biological Psychiatry 60, 11–21.CrossRefGoogle ScholarPubMed
Liang, M, Zhou, Y, Jiang, T, Liu, Z, Tian, L, Liu, H, Hao, Y (2006). Widespread functional disconnectivity in schizophrenia with resting-state functional magnetic resonance imaging. Neuroreport 17, 209–213.CrossRefGoogle ScholarPubMed
Liu, H, Kaneko, Y, Ouyang, X, Li, L, Hao, Y, Chen, EY, Jiang, T, Zhou, Y, Liu, Z (2010). Schizophrenic patients and their unaffected siblings share increased resting-state connectivity in the task-negative network but not its anticorrelated task-positive network. Schizophrenia Bulletin. Published online: 30 June 2010. doi:10.1093/schbul/sbq074.Google Scholar
Manoach, DS, Press, DZ, Thangaraj, V, Searl, MM, Goff, DC, Halpern, E, Saper, CB, Warach, S (1999). Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task, as measured by fMRI. Biological Psychiatry 45, 1128–1137.CrossRefGoogle ScholarPubMed
Mendrek, A, Laurens, KR, Kiehl, KA, Ngan, ET, Stip, E, Liddle, PF (2004). Changes in distributed neural circuitry function in patients with first-episode schizophrenia. British Journal of Psychiatry 185, 205–214.CrossRefGoogle ScholarPubMed
Milanovic, SM, Thermenos, HW, Goldstein, JM, Brown, A, Gabrieli, SW, Makris, N, Tsuang, MT, Buka, SL, Seidman, LJ (2011). Medial prefrontal cortical activation during working memory differentiates schizophrenia and bipolar psychotic patients: a pilot FMRI study. Schizophrenia Research. Published online: 24 March 2011. doi:10.1016/j.schres.2011.02.025.CrossRefGoogle ScholarPubMed
Minzenberg, MJ, Laird, AR, Thelen, S, Carter, CS, Glahn, DC (2009). Meta-analysis of 41 functional neuroimaging studies of executive function in schizophrenia. Archives of General Psychiatry 66, 811–822.CrossRefGoogle ScholarPubMed
Nejad, AB, Ebdrup, BH, Siebner, HR, Rasmussen, H, Aggernaes, B, Glenthoj, BY, Baare, WF (2011). Impaired temporoparietal deactivation with working memory load in antipsychotic-naive patients with first-episode schizophrenia. World Journal of Biological Psychiatry 12, 271–281.CrossRefGoogle ScholarPubMed
Ongur, D, Lundy, M, Greenhouse, I, Shinn, AK, Menon, V, Cohen, BM, Renshaw, PF (2010). Default mode network abnormalities in bipolar disorder and schizophrenia. Psychiatry Research 183, 59–68.CrossRefGoogle Scholar
Pomarol-Clotet, E, Salvador, R, Sarro, S, Gomar, J, Vila, F, Martinez, A, Guerrero, A, Ortiz-Gil, J, Sans-Sansa, B, Capdevila, A, Cebamanos, JM, McKenna, PJ (2008). Failure to deactivate in the prefrontal cortex in schizophrenia: dysfunction of the default mode network? Psychological Medicine 38, 1185–1193.CrossRefGoogle ScholarPubMed
Rasser, PE, Johnston, P, Lagopoulos, J, Ward, PB, Schall, U, Thienel, R, Bender, S, Toga, AW, Thompson, PM (2005). Functional MRI BOLD response to Tower of London performance of first-episode schizophrenia patients using cortical pattern matching. NeuroImage 26, 941–951.CrossRefGoogle Scholar
Salgado-Pineda, P, Fakra, E, Delaveau, P, McKenna, PJ, Pomarol-Clotet, E, Blin, O (2011). Correlated structural and functional brain abnormalities in the default mode network in schizophrenia patients. Schizophrenia Research 125, 101–109.CrossRefGoogle ScholarPubMed
Salvador, R, Martinez, A, Pomarol-Clotet, E, Gomar, J, Vila, F, Sarro, S, Capdevila, A, Bullmore, E (2008). A simple view of the brain through a frequency-specific functional connectivity measure. NeuroImage 39, 279–289.CrossRefGoogle ScholarPubMed
Salvador, R, Martinez, A, Pomarol-Clotet, E, Sarro, S, Suckling, J, Bullmore, E (2007). Frequency based mutual information measures between clusters of brain regions in functional magnetic resonance imaging. NeuroImage 35, 83–88.CrossRefGoogle ScholarPubMed
Salvador, R, Sarro, S, Gomar, JJ, Ortiz-Gil, J, Vila, F, Capdevila, A, Bullmore, E, McKenna, PJ, Pomarol-Clotet, E (2010). Overall brain connectivity maps show cortico-subcortical abnormalities in schizophrenia. Human Brain Mapping 31, 2003–2014.CrossRefGoogle ScholarPubMed
Scheuerecker, J, Ufer, S, Zipse, M, Frodl, T, Koutsouleris, N, Zetzsche, T, Wiesmann, M, Albrecht, J, Bruckmann, H, Schmitt, G, Moller, HJ, Meisenzahl, EM (2008). Cerebral changes and cognitive dysfunctions in medication-free schizophrenia – an fMRI study. Journal of Psychiatric Research 42, 469–476.CrossRefGoogle ScholarPubMed
Schneider, F, Habel, U, Reske, M, Kellermann, T, Stocker, T, Shah, NJ, Zilles, K, Braus, DF, Schmitt, A, Schlosser, R, Wagner, M, Frommann, I, Kircher, T, Rapp, A, Meisenzahl, E, Ufer, S, Ruhrmann, S, Thienel, R, Sauer, H, Henn, FA, Gaebel, W (2007). Neural correlates of working memory dysfunction in first-episode schizophrenia patients: an fMRI multi-center study. Schizophrenia Research 89, 198–210.CrossRefGoogle ScholarPubMed
Schneider, FC, Royer, A, Grosselin, A, Pellet, J, Barral, FG, Laurent, B, Brouillet, D, Lang, F (2011). Modulation of the default mode network is task-dependant in chronic schizophrenia patients. Schizophrenia Research 125, 110–117.CrossRefGoogle ScholarPubMed
Smith, SM, Jenkinson, M, Woolrich, MW, Beckmann, CF, Behrens, TE, Johansen-Berg, H, Bannister, PR, De Luca, M, Drobnjak, I, Flitney, DE, Niazy, RK, Saunders, J, Vickers, J, Zhang, Y, De Stefano, N, Brady, JM, Matthews, PM (2004). Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage 23 (Suppl. 1), S208–219.CrossRefGoogle ScholarPubMed
Snitz, BE, MacDonald, A 3rd, Cohen, JD, Cho, RY, Becker, T, Carter, CS (2005). Lateral and medial hypofrontality in first-episode schizophrenia: functional activity in a medication-naive state and effects of short-term atypical antipsychotic treatment. American Journal of Psychiatry 162, 2322–2329.CrossRefGoogle Scholar
Tan, HY, Callicott, JH, Weinberger, DR (2007). Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis of schizophrenia. Cerebral Cortex 17 (Suppl. 1), i171–i181.CrossRefGoogle ScholarPubMed
Tan, HY, Choo, WC, Fones, CS, Chee, MW (2005). fMRI study of maintenance and manipulation processes within working memory in first-episode schizophrenia. American Journal of Psychiatry 162, 1849–1858.CrossRefGoogle ScholarPubMed
Tan, HY, Sust, S, Buckholtz, JW, Mattay, VS, Meyer-Lindenberg, A, Egan, MF, Weinberger, DR, Callicott, JH (2006). Dysfunctional prefrontal regional specialization and compensation in schizophrenia. American Journal of Psychiatry 163, 1969–1977.CrossRefGoogle ScholarPubMed
Van Snellenberg, JX, Torres, IJ, Thornton, AE (2006). Functional neuroimaging of working memory in schizophrenia: task performance as a moderating variable. Neuropsychology 20, 497–510.CrossRefGoogle ScholarPubMed
van Veelen, NM, Vink, M, Ramsey, NF, Kahn, RS (2010). Left dorsolateral prefrontal cortex dysfunction in medication-naive schizophrenia. Schizophrenia Research 123, 22–29.CrossRefGoogle ScholarPubMed
Wechsler, D (1997). Wechsler Memory Scale – Third Edition (WMS-III). The Psychological Corporation: San Antonio, TX.Google Scholar
Weinberger, DR, Egan, MF, Bertolino, A, Callicott, JH, Mattay, VS, Lipska, BK, Berman, KF, Goldberg, TE (2001). Prefrontal neurons and the genetics of schizophrenia. Biological Psychiatry 50, 825–844.CrossRefGoogle ScholarPubMed
Whitfield-Gabrieli, S, Thermenos, HW, Milanovic, S, Tsuang, MT, Faraone, SV, McCarley, RW, Shenton, ME, Green, AI, Nieto-Castanon, A, LaViolette, P, Wojcik, J, Gabrieli, JD, Seidman, LJ (2009). Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia. Proceedings of the National Academy of Sciences USA 106, 1279–1284.CrossRefGoogle ScholarPubMed
Wilson, BA, Burgess, PW, Emslie, H, Evans, JJ (1996). Behavioural Assessment of the Dysexecutive Syndrome (BADS). Thames Valley Test Company: Reading, UK.Google Scholar
Woodward, ND, Waldie, B, Rogers, B, Tibbo, P, Seres, P, Purdon, SE (2009). Abnormal prefrontal cortical activity and connectivity during response selection in first episode psychosis, chronic schizophrenia, and unaffected siblings of individuals with schizophrenia. Schizophrenia Research 109, 182–190.CrossRefGoogle ScholarPubMed
Zhou, Y, Liang, M, Tian, L, Wang, K, Hao, Y, Liu, H, Liu, Z, Jiang, T (2007). Functional disintegration in paranoid schizophrenia using resting-state fMRI. Schizophrenia Research 97, 194–205.CrossRefGoogle ScholarPubMed