Abnormal effective connectivity and psychopathological symptoms in the psychosis high-risk state

Abnormal effective connectivity and psychopathological symptoms in the psychosis high-risk state

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J Psychiatry Neurosci 2014;39(4):239-48

André Schmidt, PhD; Renata Smieskova, PhD; Andor Simon, MD; Paul Allen, PhD; Paolo Fusar-Poli, MD, PhD; Philip K. McGuire, MD, PhD; Kerstin Bendfeldt, PhD; Jacqueline Aston, MD; Undine E. Lang, MD, PhD; Marc Walter, MD, PhD; Ernst-Wilhelm Radue, MD, PhD; Anita Riecher-Rössler, MD, PhD; Stefan J. Borgwardt, MD, PhD

Schmidt, Smieskova, Simon, Aston, Lang, Walter, Riecher-Rössler, Borgwardt — Department of Psychiatry (UPK), University of Basel, Petersgraben, Basel, Switzerland; Schmidt, Smieskova, Bendfeldt, Radue, Borgwardt — Medical Image Analysis Centre, University Hospital Basel, Schanzenstrasse, Basel, Switzerland; Allen, Fusar-Poli, McGuire, Borgwardt — Department of Psychosis Studies, Institute of Psychiatry, King’s College London, London, United Kingdom

Abstract

Background: Recent evidence has revealed abnormal functional connectivity between the frontal and parietal brain regions during working memory processing in patients with schizophrenia and first-episode psychosis. However, it still remains unclear whether abnormal frontoparietal connectivity during working memory processing is already evident in the psychosis high-risk state and whether the connection strengths are related to psychopathological outcomes.

Methods: Healthy controls and antipsychotic-naive individuals with an at-risk mental state (ARMS) performed an n-back working memory task while undergoing functional magnetic resonance imaging. Effective connectivity between frontal and parietal brain regions during working memory processing were characterized using dynamic causal modelling.

Results: Our study included 19 controls and 27 individuals with an ARMS. In individuals with an ARMS, we found significantly lower task performances and reduced activity in the right superior parietal lobule and middle frontal gyrus than in controls. Furthermore, the working memory–induced modulation of the connectivity from the right middle frontal gyrus to the right superior parietal lobule was significantly reduced in individuals with an ARMS, while the extent of this connectivity was negatively related to the Brief Psychiatric Rating Scale total score.

Limitations: The modest sample size precludes a meaningful subgroup analysis for participants with a later transition to psychosis.

Conclusion: This study demonstrates that abnormal frontoparietal connectivity during working memory processing is already evident in individuals with an ARMS and is related to psychiatric symptoms. Thus, our results provide further insight into the pathophysiological mechanisms of the psychosis high-risk state by linking functional brain imaging, computational modelling and psychopathology.


Submitted May 31, 2013; Revised Aug. 21, Nov. 26, 2013; Accepted Nov. 27, 2013.

Acknowledgements: We acknowledge the contribution of the individuals who took part in this study and we thank the FEPSY study group for recruitment and management of participants. This work was supported by the Swiss National Science Foundation (No. 3232BO_119382; R.S., S.J.B.).

Competing interests: E.W. Radue has received honoraria for serving as speaker at scientific meetings and consultant for Novartis, Biogen Idec, Merck Serono, and Bayer Schering. He has received financial support for research activities from Actelion, Bsilea Pharmaceuticals Ltd, Biogen Idec, Merck Serono and Novartis. No other competing interests declared.

Contributors: P.K. McGuire, U.E. Lang, E.W. Radue, A. Riecher- Rössler and S.J. Borgwardt designed the study. R. Smieskova, A. Simon, J. Aston, M. Walter and S.J. Borgwardt acquired the data, which A. Schmidt, R. Smieskova, P. Allen, P. Fusar-Poli, P.K. McGuire and K. Bendfeldt analyzed. A. Schmidt and R. Smieskova wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.130102

Correspondence to: A. Schmidt, University of Basel, University Hospital of Basel, Department of Psychiatry, Medical Image Analysis Centre, Petersgraben 4, 4031 Basel, Switzerland; andre.schmidt@unibas.ch