Dysfunction of ventral striatal reward prediction in schizophrenic patients treated with typical, not atypical, neuroleptics

Psychopharmacology (Berl). 2006 Aug;187(2):222-8. doi: 10.1007/s00213-006-0405-4. Epub 2006 May 24.


Rationale: Clinical studies in patients with schizophrenia suggest that atypical neuroleptics are more effective than typical neuroleptics in reducing negative symptoms including apathy and anhedonia. Dysfunction of the dopaminergic reward system may contribute to negative symptoms in schizophrenia.

Objective: We used functional magnetic resonance imaging to assess the blood oxygen level dependency response in the ventral striatum of medicated schizophrenics and healthy control subjects during reward anticipation.

Methods: Twenty schizophrenics [ten medicated with typical (e.g., haloperidol) and ten with atypical (e.g., olanzapine and risperidone) neuroleptics] and ten age-matched healthy volunteers participated in an incentive monetary delay task in which visual cues predicted that a rapid response to a subsequent target stimulus would result either in monetary gain or no consequence.

Results: Healthy volunteers and schizophrenics treated with atypical neuroleptics showed ventral striatal activation in response to reward-indicating cues, but schizophrenics treated with typical neuroleptics did not. In patients treated with typical neuroleptics, decrease in activation of the left ventral striatum was correlated with the severity of negative symptoms.

Conclusions: Failure to activate the ventral striatum during reward anticipation was previously associated with the severity of negative symptoms in schizophrenia and was also found in schizophrenics treated with typical neuroleptics in this study. Significant blunting of ventral striatal activation was not observed in patients treated with atypical neuroleptics, which may reflect the improved efficacy of these drugs in treating negative symptoms.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affect / drug effects
  • Affect / physiology
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Arousal / drug effects
  • Arousal / physiology
  • Basal Ganglia / drug effects*
  • Basal Ganglia / physiopathology
  • Benzodiazepines / adverse effects
  • Benzodiazepines / therapeutic use
  • Cues
  • Dominance, Cerebral / drug effects
  • Dominance, Cerebral / physiology
  • Female
  • Humans
  • Image Enhancement*
  • Image Processing, Computer-Assisted*
  • Magnetic Resonance Imaging*
  • Male
  • Motivation
  • Olanzapine
  • Oxygen / blood*
  • Reference Values
  • Reward*
  • Risperidone / adverse effects
  • Risperidone / therapeutic use*
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology*
  • Schizophrenic Psychology*
  • Treatment Outcome


  • Antipsychotic Agents
  • Benzodiazepines
  • Risperidone
  • Olanzapine
  • Oxygen