Modulation of limbic circuitry predicts treatment response to antipsychotic medication: a functional imaging study in schizophrenia

Neuropsychopharmacology. 2009 Dec;34(13):2675-90. doi: 10.1038/npp.2009.94. Epub 2009 Aug 12.


The regional neuronal changes taking place in the early and late stages of antipsychotic treatment are still not well characterized in humans. In addition, it is not known whether these regional changes are predictive of or are correlated with treatment response. Using PET with 15O, we evaluated the time course of regional cerebral blood flow (rCBF) patterns generated by a first (haloperidol) and a second (olanzapine) generation antipsychotic drug in patients with schizophrenia during a 6-week treatment trial. Patients were initially scanned after withdrawal of all psychotropic medication (2 weeks), and then blindly randomized to treatment with haloperidol (n=12) or olanzapine (n=17) for a period of 6 weeks. Patients were scanned again after 1 and 6 weeks of treatment. All assessments, including scanning sessions, were obtained in a double-blind manner. As hypothesized, we observed rCBF changes that were common to both the drugs, implicating cortico-subcortical and limbic neuronal networks in antipsychotic action. In addition, in these regions, some patterns seen at weeks 1 and 6 were distinctive, indexing neuronal changes related to an early (ventral striatum, hippocampus) and consolidated (anterior cingulate/medial frontal cortex) stage of drug response. Finally, both after 1 and 6 weeks of treatment, we observed differential patterns of rCBF activation between good and poor responders. After 1 week of treatment, greater rCBF increase in the ventral striatum and greater decrease in the hippocampus were associated with good response.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines / therapeutic use*
  • Brain / blood supply
  • Brain / diagnostic imaging
  • Brain / physiopathology*
  • Cerebrovascular Circulation / physiology
  • Female
  • Haloperidol / therapeutic use*
  • Humans
  • Limbic System / blood supply
  • Limbic System / diagnostic imaging
  • Limbic System / physiopathology*
  • Magnetic Resonance Imaging
  • Male
  • Olanzapine
  • Psychiatric Status Rating Scales
  • Radionuclide Imaging
  • Regional Blood Flow / physiology
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / drug therapy
  • Schizophrenia / physiopathology*
  • Treatment Outcome


  • Antipsychotic Agents
  • Benzodiazepines
  • Haloperidol
  • Olanzapine