Cerebral blood flow in striatal regions is associated with apathy in patients with schizophrenia

Cerebral blood flow in striatal regions is associated with apathy in patients with schizophrenia

J Psychiatry Neurosci 2019;44(2):102-110 | PDF

Karoline Schneider, MD*; Lars Michels, PhD*; Matthias N. Hartmann-Riemer, PhD; Achim Burrer, MD; Philippe N. Tobler, PhD; Philipp Stämpfli, PhD; Matthias Kirschner, MD; Erich Seifritz, MD; Stefan Kaiser, MD

Abstract

Background: Striatal dysfunction has been proposed as a pathomechanism for negative symptoms in schizophrenia. There is consensus that negative symptoms can be grouped into 2 dimensions: apathy and diminished expression. Recent studies suggest that different neural mechanisms underlie these dimensions, but the relationship between regional resting-state cerebral blood flow (rCBF) and negative symptom dimensions has not been investigated.

Methods: This study included 29 patients with schizophrenia and 20 healthy controls. We measured rCBF in the striatum using arterial spin labelling (ASL) MRI. We assessed negative symptoms using the Brief Negative Symptom Scale.

Results: In the ventral and dorsal striatum, rCBF was not different between patients with schizophrenia and controls. However, we did find a positive association between the severity of apathy and increased rCBF in the ventral and dorsal striatum in patients with schizophrenia. This effect was not present for diminished expression.

Limitations: All patients were taking atypical antipsychotics, so an effect of antipsychotic medication on rCBF could not be excluded, although we did not find a significant association between rCBF and chlorpromazine equivalents.

Conclusion: The main finding of this study was a specific association between increased striatal rCBF and the negative symptom dimension of apathy. Our results further support the separate assessment of apathy and diminished expression when investigating the neural basis of negative symptoms. The ASL technique can provide a direct and quantitative approach to investigating the role of rCBF changes in the pathophysiology of negative symptoms.


*These authors contributed equally to the work.

Submitted Aug. 6, 2017; Revised Nov. 30, 2017; Accepted Mar. 15, 2018; Published online Sept. 7, 2018

Acknowledgements: 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, CRSII3_141965 and 00014_165884). The authors thank M. Bischof for his support in data acquisition, A. Manoliu for his support with layout of the figures, and all patients and healthy volunteers for their participation.

Affiliations: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich (Schneider, Hartmann-Riemer, Burrer, Stämpfli, Kirschner, Seifritz); Institute of Neuroradiology, University Hospital Zurich (Michels); Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich (Hartmann-Riemer, Tobler); MR Center of the Psychiatric University Hospital and the Department of Child and Adolescent Psychiatry, University of Zurich (Stämpfli); and the Adult Psychiatry Division, Department of Mental Health and Psychiatry, Geneva University Hospitals (Kaiser).

Competing interests: P. Tobler has received grant support from Pfizer. E. Seifritz has received grant support from H. Lundbeck and has served as a consultant and/or speaker for AstraZeneca, Otsuka, Takeda, Eli Lilly, Janssen, Lundbeck, Novartis, Pfizer, Roche and Servier. S. Kaiser has received speaker honoraria from Roche, Lundbeck, Janssen and Takeda. He receives royalties for cognitive test and training software from Schuhfried. None of these activities is related to the present study. All other authors declare no biomedical financial interest or potential conflicts of interest.

Contributors: M. Kirschner, M.N. Hartmann-Riemer, E. Seifritz, P. Stämpfli, P.N. Tobler and S. Kaiser designed the study. M. Kirschner and M.N. Hartmann-Riemer acquired the data, which K. Schneider, L. Michels, M. Kirschner, A. Burrer and S. Kaiser analyzed. K. Schneider, L. Michels, E. Seifritz and S. Kaiser wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

DOI: 10.1503/jpn.170150

Correspondence to: K. Schneider, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Lenggstrasse 31 8032 Zurich, Switzerland; karoline.schneider@puk.zh.ch