Altered reward functions in patients on atypical antipsychotic medication in line with the revised dopamine hypothesis of schizophrenia

Psychopharmacology (Berl). 2009 Sep;206(1):121-32. doi: 10.1007/s00213-009-1586-4. Epub 2009 Jun 12.


Objective: To study the mesolimbic dopamine system during expectation and receipt or omission of rewards in partially remitted patients with schizophrenia treated with the atypical antipsychotic olanzapine.

Methods: We studied 16 patients with a current episode of schizophrenia, all treated with the atypical drug olanzapine, and 16 healthy subjects using functional magnetic resonance imaging. Subjects performed a delayed incentive paradigm with monetary rewards.

Results: During reward expectation, both, patients with schizophrenia and healthy control subjects, showed activation of the ventral striatum and midbrain in the vicinity of the ventral tegmental area. Significant categorical group differences emerged in the anterior cingulate cortex with only healthy controls showing increasing activation with increasing reward. In the patients, activation of this region was inversely correlated with positive symptoms. During outcome, both, patients with schizophrenia and healthy controls, showed activation of the ventral striatum and the mesial prefrontal cortex. Significant categorical group differences emerged in the right ventrolateral prefrontal cortex for the salience contrast with healthy controls showing a U-shaped activation curve, i.e., higher activation for either omission or receipt of reward compared to no reward.

Conclusions: Our findings partially support the current concept of dopaminergic dysfunction in schizophrenia, suggesting a rather hyperactive mesolimbic dopamine system and reduced prefrontal activation, at least in partially remitted patients treated with atypical antipsychotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use
  • Basal Ganglia / physiopathology
  • Benzodiazepines / pharmacology*
  • Benzodiazepines / therapeutic use
  • Dopamine / metabolism*
  • Female
  • Gyrus Cinguli / physiopathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Olanzapine
  • Prefrontal Cortex / physiopathology
  • Psychomotor Performance / drug effects
  • Reward*
  • Schizophrenia / drug therapy
  • Schizophrenia / physiopathology*
  • Schizophrenic Psychology*


  • Antipsychotic Agents
  • Benzodiazepines
  • Olanzapine
  • Dopamine