Ventral tegmental area/midbrain functional connectivity and response to antipsychotic medication in schizophrenia

Neuropsychopharmacology. 2014 Mar;39(4):1020-30. doi: 10.1038/npp.2013.305. Epub 2013 Oct 29.


Medication management in schizophrenia is a lengthy process, as the lack of clinical response can only be confirmed after at least 4 weeks of antipsychotic treatment at a therapeutic dose. Thus, there is a clear need for the discovery of biomarkers that have the potential to accelerate the management of treatment. Using resting-state functional MRI, we examined the functional connectivity of the ventral tegmental area (VTA), the origin of the mesocorticolimbic dopamine projections, in 21 healthy controls and 21 unmedicated patients with schizophrenia at baseline (pre-treatment) and after 1 week of treatment with the antipsychotic drug risperidone (1-week post-treatment). Group-level functional connectivity maps were obtained and group differences in connectivity were assessed on the groups' participant-level functional connectivity maps. We also examined the relationship between pre-treatment/1-week post-treatment functional connectivity and treatment response. Compared with controls, patients exhibited significantly reduced pre-treatment VTA/midbrain connectivity to multiple cortical and subcortical regions, including the dorsal anterior cingulate cortex (dACC) and thalamus. After 1 week of treatment, VTA/midbrain connectivity to bilateral regions of the thalamus was re-established. Pre-treatment VTA/midbrain connectivity strength to dACC was positively correlated with good response to a 6-week course of risperidone, whereas pre-treatment VTA/midbrain connectivity strength to the default mode network was negatively correlated. Our findings suggest that VTA/midbrain resting-state connectivity may be a useful biomarker for the prediction of treatment response.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Antipsychotic Agents / therapeutic use*
  • Brain Mapping*
  • Female
  • Follow-Up Studies
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neural Pathways / blood supply
  • Neural Pathways / drug effects*
  • Oxygen / blood
  • Psychiatric Status Rating Scales
  • Risperidone / therapeutic use*
  • Schizophrenia / drug therapy*
  • Schizophrenia / pathology
  • Severity of Illness Index
  • Ventral Tegmental Area / blood supply
  • Ventral Tegmental Area / drug effects*
  • Young Adult


  • Antipsychotic Agents
  • Risperidone
  • Oxygen