Reduced activation in the ventral striatum during probabilistic decision-making in patients in an at-risk mental state

Reduced activation in the ventral striatum during probabilistic decision-making in patients in an at-risk mental state

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J Psychiatry Neurosci 2015;40(3):163-173

Franziska Rausch, PhD; Daniela Mier, PhD; Sarah Eifler, MSc; Sabrina Fenske, MSc; Frederike Schirmbeck, PhD; Susanne Englisch, PhD; Claudia Schilling, PhD; Andreas Meyer-Lindenberg, PhD; Peter Kirsch, PhD; Mathias Zink, PhD

Abstract

Background: Patients with schizophrenia display metacognitive impairments, such as hasty decision-making during probabilistic reasoning — the “jumping to conclusion” bias (JTC). Our recent fMRI study revealed reduced activations in the right ventral striatum (VS) and the ventral tegmental area (VTA) to be associated with decision-making in patients with schizophrenia. It is unclear whether these functional alterations occur in the at-risk mental state (ARMS).

Methods: We administered the classical beads task and fMRI among ARMS patients and healthy controls matched for age, sex, education and premorbid verbal intelligence. None of the ARMS patients was treated with antipsychotics. Both tasks request probabilistic decisions after a variable amount of stimuli. We evaluated activation during decision-making under certainty versus uncertainty and the process of final decision-making.

Results: We included 24 AMRS patients and 24 controls in our study. Compared with controls, ARMS patients tended to draw fewer beads and showed significantly more JTC bias in the classical beads task, mirroring findings in patients with schizophrenia. During fMRI, ARMS patients did not demonstrate JTC bias on the behavioural level, but showed a significant hypoactivation in the right VS during the decision stage.

Limitations: Owing to the cross-sectional design of the study, results are constrained to a better insight into the neurobiology of risk constellations, but not prepsychotic stages. Nine of the ARMS patients were treated with antidepressants and/or lorazepam.

Conclusion: As in patients with schizophrenia, a striatal hypoactivation was found in ARMS patients. Confounding effects of antipsychotic medication can be excluded. Our findings indicate that error prediction signalling and reward anticipation may be linked to striatal dysfunction during prodromal stages and should be examined for their utility in predicting transition risk.


Submitted July 10, 2014; Revised Sept. 12, 2014; Revised Oct. 10, 2014; Accepted Oct. 15, 2014; Early-released Jan. 27, 2015

Acknowledgements: The authors are grateful to all participants, to Dagmar Gass for assistance with data acquisition and to Dr. Steffen Moritz (UKE Hamburg, Germany) for helpful discussion.

Affiliations: From the Department of Psychiatry and Psychotherapy (Rausch, Eifler, Englisch, Schilling, Meyer-Lindenberg, Zink) and the Department of Clinical Psychology (Mier, Fenske, Kirsch), Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany; and the Academic Medical Centre, Amsterdam University, Netherlands (Schirmbeck).

Funding: A. Meyer-Lindenberg, P. Kirsch and M. Zink, are funded by the Deutsche Forschungsgesellschaft (DFG, www.dfg.de, projects ZI1253/3-1, ZI1253/3-2, KI 576/14-2, ME 1591/6-2). S. Englisch is funded by the LGFG (Landesgraduiertenförderungsgesetz), C. Schilling and D. Mier by the Olympia-Morata Program and F. Schirmbeck by the Evangelisches Studienwerk. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Competing interests: None declared for F. Rausch, D. Mier, S. Eifler, S. Fenske, C. Schilling and P. Kirsch. S. Englisch has received travel expenses and consultant fees from AstraZeneca, Bristol-Myers Squibb GmbH & CoKGaA, Eli-Lilly, Janssen Cilag, Otsuka, Pfizer and Servier. A. Meyer-Lindenberg receives consultant fees and travel expenses from AstraZeneca, Hoffmann-La Roche and Lundbeck Foundation and speaker fees from Pfizer, Lilly Deutschland, GlaxoSmithKline, Janssen Cilag, Bristol-Myers Squibb, Lundbeck, Servier and AstraZeneca. M. Zink declares unrestricted scientific grants of the European Research Advisory Board (ERAB), German Research Foundation (DFG), Pfizer Pharma GmbH, Servier and Bristol Myers Squibb and speaker and travel grants from AstraZeneca, Lilly, Pfizer Pharma GmbH, Bristol Myers Squibb Pharmaceuticals, Otsuka, Servier, Lundbeck, Janssen Cilag, Roche and Trommsdorff.

Contributors: A. Meyer-Lindenberg, P. Kirsch and M. Zink designed the study. F. Rausch, D. Mier, S. Eifler, S. Fenske, F. Shirmbeck, S. English and C. Schilling acquired the data, which F. Rausch and D. Mier analyzed. F. Rausch and D. Mier wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.140191

Correspondence to: F. Rausch, Central Institute of Mental Health, Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim/ Heidelberg University J5D-68159, Mannheim, Germany; franziska.rausch@zi-mannheim.de