title: Increased caudate dopamine D2 receptor availability as a genetic marker for schizophrenia.
abstract: BACKGROUND
  Schizophrenia has a heritability of about 80%, but the detailed molecular genetic basis of the disorder has remained elusive. Relative hyperfunction of the subcortical dopamine system has been previously suggested to be one of the key pathophysiologic mechanisms in schizophrenic psychosis.
  
  
  OBJECTIVE
  To examine the contributions of genetic vulnerability for schizophrenia to the dopamine system in the human brain.
  
  
  METHODS
  Population-based twin cohort study.
  
  
  METHODS
  Finland.
  
  
  METHODS
  Six monozygotic and 5 dizygotic unaffected co-twins of patients with schizophrenia were ascertained, along with 4 monozygotic and 3 dizygotic healthy control twins with no family history of psychotic disorders.
  
  
  METHODS
  Striatal dopamine D(2) receptor availability estimated with positron emission tomographic imaging and carbon 11 ((11)C)-labeled raclopride, and performance on neuropsychological tests sensitive to frontal lobe functioning and to schizophrenia vulnerability.
  
  
  RESULTS
  Unaffected monozygotic co-twins had increased caudate D(2) density compared with unaffected dizygotic co-twins and healthy control twins. Higher D(2) receptor binding in caudate was associated with a poor performance on cognitive tasks related to schizophrenia vulnerability in the whole sample.
  
  
  CONCLUSIONS
  The caudate dopamine D(2) receptor up-regulation is related to genetic risk for schizophrenia. Higher dopamine D(2) receptor density in caudate is also associated with poorer performance on cognitive tasks involving corticostriatal pathways. This finding suggests that caudate dopamine dysregulation is also a trait phenomenon related to psychosis vulnerability. This pattern of results provides a theoretical rationale for early pharmacologic intervention approaches using dopamine D(2) receptor blocking drugs.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, and Turku PET Centre, University of Turku, Kiinamyllynkatu, Turku 20520, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Theo G M
authors.initials: TG
authors.lastname: van Erp
authors.forename: Jukka
authors.initials: J
authors.lastname: Huttunen
authors.forename: Sargo
authors.initials: S
authors.lastname: Aalto
authors.forename: Kjell
authors.initials: K
authors.lastname: Någren
authors.forename: Matti
authors.initials: M
authors.lastname: Huttunen
authors.forename: Jouko
authors.initials: J
authors.lastname: Lönnqvist
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.forename: Jarmo
authors.initials: J
authors.lastname: Hietala
authors.forename: Tyrone D
authors.initials: TD
authors.lastname: Cannon
mesh_terms: D002250:Carbon Radioisotopes; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism*; D003072:Cognition Disorders / Q000175:diagnosis / Q000378:metabolism; D015331:Cohort Studies; D004200:Diseases in Twins / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D004298:Dopamine / Q000235:genetics / Q000378:metabolism; D005260:Female; D005387:Finland; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic
chemical_list: D002250:Carbon Radioisotopes; D005819:Genetic Markers; D017448:Receptors, Dopamine D2; D020891:Raclopride; D004298:Dopamine