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Psychopharmacology

, Volume 196, Issue 4, pp 673–684 | Cite as

Reward system activation in schizophrenic patients switched from typical neuroleptics to olanzapine

  • Florian Schlagenhauf
  • Georg Juckel
  • Michael Koslowski
  • Thorsten Kahnt
  • Brian Knutson
  • Theresa Dembler
  • Thorsten Kienast
  • Jürgen Gallinat
  • Jana Wrase
  • Andreas HeinzEmail author
Original Investigation

Abstract

Rationale

High blockade of dopamine D2 receptors in the ventral striatum including the nucleus accumbens may interfere with reward anticipation and cause secondary negative symptoms such as apathy or anhedonia. This may not be the case with newer neuroleptics such as olanzapine, which show less dopamine D2 receptor blockade and a faster off-rate from the receptor.

Objectives

We used functional magnetic resonance imaging to assess the blood oxygenation level dependent response in the ventral striatum of schizophrenics medicated with typical neuroleptics (T1) and after switching them to olanzapine (T2) and of healthy control subjects at corresponding time points during reward anticipation.

Materials and methods

Ten schizophrenics, while medicated with typical neuroleptics (T1) and after having been switched to olanzapine (T2), and ten matched healthy volunteers participated in a monetary incentive delay task, in which visual cues predicted that a rapid response to a subsequent target stimulus would either result in monetary gain or have no consequence.

Results

During reward anticipation, healthy volunteers showed significantly higher ventral striatal activation compared to schizophrenic patients treated with typical neuroleptics but not olanzapine, which was reflected in a significant interaction between group and session. In patients treated with typical neuroleptics, but not with olanzapine, decreased left ventral striatal activation was correlated with negative symptoms.

Conclusions

Failure to activate the ventral striatum during reward anticipation was pharmacologically state-dependent and observed only in patients treated with typical neuroleptics but not with olanzapine, which may indicate that this drug did not induce secondary negative symptoms via interference with reward anticipation.

Keywords

Accumbens Basal ganglia Reward Schizophrenia Motivation Functional magnetic resonance imaging Antipsychotic agents 

Notes

Acknowledgments

This study was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft; HE 2597/4-2) and by investigator-initiated trails funded by Lilly Germany and by the Bernstein Center for Computational Neuroscience Berlin (BMBF grant 01GQ0411).

Financial Disclosures

Dr. Schlagenhauf, Mr. Koslowski, Mr. Kahnt, Mrs. Dembler, Dr. Knutson, Dr. Kienast and Dr. Wrase reported no biomedical financial interests or potential conflicts of interest. Dr. Juckel reports having received research funding from Lilly (IIT) and consultant fees from Janssen-Cilag, AstraZenics, Lilly, GSK and Bristol Myers Squibb. Dr. Gallinat disclosed research support from AstraZeneca and fees as consultant from Bristol Myers Squibb. Dr. Heinz has received research funding from the German Research Foundation and the Bernstein Center for Computational Neuroscience Berlin (German Federal Ministry of Education and Research), Eli Lilly & Company, Janssen-Cilag, and Bristol-Myers Squibb. Dr. Heinz has received Speaker Honoraria from Janssen-Cilag, Johnson & Johnson, Lilly, Pfizer, and Servier.

Supplementary material

213_2007_1016_MOESM1_ESM.doc (97 kb)
ESM Table 1 Activation during anticipation of monetary loss compared to the neutral condition in the healthy controls at two time points (T1 and T2) and in schizophrenic patients while treated with typical neuroleptics and after switching to olanzapine. Displayed are the corrected p values, the cluster size, the t values, uncorrected p values, and coordinates in MNI space of the peak voxels (DOC 97.0 kb).

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Florian Schlagenhauf
    • 1
  • Georg Juckel
    • 1
    • 2
  • Michael Koslowski
    • 1
  • Thorsten Kahnt
    • 1
  • Brian Knutson
    • 3
  • Theresa Dembler
    • 1
  • Thorsten Kienast
    • 1
  • Jürgen Gallinat
    • 1
  • Jana Wrase
    • 1
  • Andreas Heinz
    • 1
    Email author
  1. 1.Department of Psychiatry and PsychotherapyCharité University Medical Center, Campus Charité Mitte (CCM)BerlinGermany
  2. 2.Department of PsychiatryRuhr-University BochumBochumGermany
  3. 3.Department of PsychologyStanford UniversityStanfordUSA

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