Ventral striatal hypoactivation is associated with apathy but not diminished expression in patients with schizophrenia

Ventral striatal hypoactivation is associated with apathy but not diminished expression in patients with schizophrenia

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J Psychiatry Neurosci 2016;41(3):152-161

Matthias Kirschner, MD; Oliver M. Hager, MSc; Martin Bischof, MD; Matthias N. Hartmann, PhD; Agne Kluge, MSc; Erich Seifritz, MD; Philippe N. Tobler, PhD; Stefan Kaiser, MD

Abstract

Background: Negative symptoms of schizophrenia can be grouped in 2 dimensions: apathy and diminished expression. Increasing evidence suggests that negative symptoms are associated with altered neural activity of subcortical and cortical regions in the brain reward system. However, the neurobiological basis of the distinct symptom dimensions within negative symptoms is still poorly understood. The primary aim of our study was to examine the neural correlates of the negative symptom dimensions apathy and diminished expression during a reward processing task.

Methods: Patients with schizophrenia and healthy controls underwent event-related fMRI while performing a variant of the Monetary Incentive Delay Task. We assessed negative symptom dimensions using the Brief Negative Symptom Scale.

Results: We included 27 patients and 25 controls in our study. Both groups showed neural activation indicated by blood oxygen–level dependent signal in the ventral striatum during reward anticipation. Ventral striatal activation during reward anticipation showed a strong negative correlation with apathy. Importantly, this effect was not driven by cognitive ability, medication, depressive or positive symptoms. In contrast, no significant correlation with the diminished expression dimension was observed.

Limitations: Although the results remain significant when controlling for chlorpromazine equivalents, we cannot fully exclude potential confounding effects of medication with atypical antipsychotics.

Conclusion: The specific correlation of ventral striatal hypoactivation during reward anticipation with apathy demonstrates a differentiation of apathy and diminished expression on a neurobiological level and provides strong evidence for different pathophysiological mechanisms underlying these 2 negative symptom dimensions. Our findings contribute to a multilevel framework in which apathy and motivational impairment in patients with schizophrenia can be described on psychopathological, behavioural and neural levels.


Submitted Dec. 26, 2014; Revised Apr. 27, 2015; Accepted May 6, 2015; Early-released Sept. 22, 2015

Acknowledgments: This study was supported by the Swiss National Science Foundation (Grant No. 105314_140351 to S. Kaiser). P.N. Tobler was supported by the Swiss National Science Foundation (PP00P1_128574, PP00P1_150739, and CRSII3_141965). The authors thank Dr. Philipp Staempfli and Dr. Benedikt Habermeyer for their excellent support, and all patients and healthy volunteers for their participation.

Affiliations: From the Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, (Kirschner, Hager, Bischof, Hartmann, Kluge, Seifritz, Kaiser); and the Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich (Hager, Hartmann, Tobler), Zurich, Switzerland.

Competing interests: E. Seifritz has received grant support from Lundbeck and has served as a consultant and/or speaker for Astra- Zeneca, Otsuka, Eli Lilly, Janssen, Lundbeck, Novartis, Pfizer, Roche, and Servier. S. Kaiser has received speaker honoraria from Roche, Lundbeck, Janssen and Takeda. He receives royalties from Schuhfried for cognitive test and training software. None of these activities is related to the present study. None declared by any other authors.

Contributors: M. Kirschner, O.M. Hager, E. Seifritz, P.N. Tobler and S. Kaiser designed the study. M. Kirschner, O.M. Hager, M. Bischof, M.N. Hartmann and A. Kluge acquired the data, which M. Kirschner, O.M. Hager, M.N. Hartmann, P.N. Tobler and S. Kaiser analyzed. M. Kirschner and S. Kaiser wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.140383

Correspondence to: M. Kirschner, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Lenggstrasse 31, 8032 Zurich, Switzerland; matthias.kirschner@puk.zh.ch