title: Model-based parametric study of frontostriatal abnormalities in schizophrenia patients.
abstract: BACKGROUND
  Several studies have suggested that the activity of the prefrontal cortex (PFC) and the dopamine (DA) release in the striatum has an inverse relationship. One would attribute this relationship primarily to the circuitry comprised of the glutamatergic projection from the PFC to the striatum and the GABAergic projection from the striatum to the midbrain DA nucleus. However, this circuitry has not characterized satisfactorily yet, so that no quantitative analysis has ever been made on the activities of the PFC and the striatum and also the DA release in the striatum.
  
  
  METHODS
  In this study, a system dynamics model of the corticostriatal system with dopaminergic innervations is constructed to describe the relationships between the activities of the PFC and the striatum and the DA release in the striatum. By taking published receptor imaging data from schizophrenia patients and healthy subjects into this model, this article analyzes the effects of striatal D2 receptor activation on the balance of the activity and neurotransmission in the frontostriatal system of schizophrenic patients in comparison with healthy controls.
  
  
  RESULTS
  The model predicts that the suppressive effect by D2 receptors at the terminals of the glutamatergic afferents to the striatum from the PFC enhances the hypofrontality-induced elevation of striatal DA release by at most 83%. The occupancy-based estimation of the 'optimum' D2 receptor occupancy by antipsychotic drugs is 52%. This study further predicts that patients with lower PFC activity tend to have greater improvement of positive symptoms following antipsychotic medication.
  
  
  CONCLUSIONS
  This model-based parametric study would be useful for system-level analysis of the brains with psychiatric diseases. It will be able to make reliable prediction of clinical outcome when sufficient data will be available.
authors.affiliation: Department of Information and Communication Sciences, Sophia University, Tokyo 102-8554, Japan. tanaka-s@sophia.ac.jp
authors.forename: Shoji
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D000465:Algorithms; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019295:Computational Biology / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006801:Humans; D008959:Models, Neurological; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D012107:Research Design; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism*; D012720:Severity of Illness Index; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D005680:gamma-Aminobutyric Acid; D004298:Dopamine