Dysfunctional insular connectivity during reward prediction in patients with first-episode psychosis

Dysfunctional insular connectivity during reward prediction in patients with first-episode psychosis

PDF | Appendix

J Psychiatry Neurosci 2016;41(6):367-376

André Schmidt, PhD; Lena Palaniyappan, MBBS, MMedSci; Renata Smieskova, PhD; Andor Simon, MD; Anita Riecher-Rössler, MD, PhD; Undine E. Lang, MD, PhD; Paolo Fusar-Poli, MD, PhD; Philip McGuire, MD, PhD; Stefan J. Borgwardt, MD, PhD


Background: Increasing evidence indicates that psychosis is associated with abnormal reward processing. Imaging studies in patients with first-episode psychosis (FEP) have revealed reduced activity in diverse brain regions, including the ventral striatum, insula and anterior cingulate cortex (ACC), during reward prediction. However, whether these reductions in local brain activity are due to altered connectivity has rarely been explored.

Methods: We applied dynamic causal modelling and Bayesian model selection to fMRI data during the Salience Attribution Task to investigate whether patients with FEP showed abnormal modulation of connectivity between the ventral striatum, insula and ACC induced by rewarding cues and whether these changes were related to positive psychotic symptoms and atypical antipsychotic medication.

Results: The model including reward-induced modulation of insula–ACC connectivity was the best fitting model in each group. Compared with healthy controls (n = 19), patients with FEP (n = 29) revealed reduced right insula–ACC connectivity. After subdividing patients according to current antipsychotic medication, we found that the reduced insula–ACC connectivity relative to healthy controls was observed only in untreated patients (n = 17), not in patients treated with antipsychotics (n = 12), and that it correlated negatively with unusual thought content in untreated patients with FEP.

Limitations: The modest sample size of untreated patients with FEP was a limitation of our study.

Conclusion: This study indicates that insula–ACC connectivity during reward prediction is reduced in untreated patients with FEP and related to the formation of positive psychotic symptoms. Our study further suggests that atypical antipsychotics may reverse connectivity between the insula and the ACC during reward prediction.

Submitted July 1, 2015; Revised Sept. 9, 2015; Accepted Sept. 14, 2015; Early-released Feb. 9, 2016

Acknowledgements: This work was supported by the Swiss National Science Foundation (grant number P2ZHP3_155184 awarded to A. Schmidt; grant number 3232BO_119382 awarded to R. Smieskova and S.J. Borgwardt). The authors thank Jon Roiser for providing the SAT task.

Affiliations: From the Department of Psychiatry (UPK), University of Basel, Switzerland (Schmidt, Smieskova, Simon, Rössler, Lang, Borgwardt); the Institute of Psychiatry, Department of Psychosis Studies, King’s College London, UK (Schmidt, Fusar-Poli, McGuire, Borgwardt); the Medical Image Analysis Center (MIAC), University Hospital Basel, Switzerland (Schmidt, Smieskova, Borgwardt); the Departments of Psychiatry and Medical Biophysics, Western Univeristy, London, Ont., Canada (Palaniyappan); and the Division of Psychiatry, University of Nottingham, UK (Palaniyappan).

Competing interests: L. Palaniyappan declares royalties from Oxford University Press for books published for MRCPsych revision, fees for preparing MRCPsych teaching materials, travel support from Magstim Limited, and grants unrelated to the present work from the Medical Research Council UK and EU CASCADE Programme. He also declares that his spouse’s pension fund holds shares in GlaxoSmith-Kline. No other competing interests declared.

Contributors: R. Smieskova, A. Riecher-Rössler, P. McGuire and S. Borgwardt designed the study. R. Smieskova, A. Simon and A. Riecher-Rössler acquired the data, which A. Schmidt, L. Palaniyappan, U. Lang, P. Fusar-Poli and P. McGuire analyzed. A. Schmidt, L. Palaniyappan and R. Smieskova wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.150234

Correspondence to: A. Schmidt, University of Basel, Department of Psychiatry (UPK), Wilhelm Klein Strasse 27, 4012 Basel, Switzerland; andre.schmidt@unibas.ch