title: Brain dopamine d1 receptors in twins discordant for schizophrenia.
abstract: OBJECTIVE
  It has been suggested that deficits in higher-order cognitive functions serve as intermediate phenotypic indicators of genetic vulnerability to schizophrenia. The dopamine hypothesis of schizophrenia postulates that insufficiency of dopamine transmission in the prefrontal cortex contributes to the cognitive deficits observed in patients with the disease, and there is robust empirical evidence for a central role of prefrontal cortex dopamine D(1) receptors in working memory functions.
  
  
  METHODS
  The authors examined the genetic and nongenetic effects on D(1) receptor binding in schizophrenia by studying monozygotic and dizygotic twin pairs discordant for schizophrenia as well as healthy comparison twins using positron emission tomography (PET) and the D(1) receptor antagonist ligand [(11)C]SCH 23390. Performance on neuropsychological tests sensitive to frontal lobe functioning was evaluated.
  
  
  RESULTS
  High D(1) receptor density in the medial prefrontal cortex, superior temporal gyrus, and heteromodal association cortex (angular gyrus) was associated with increasing genetic risk for schizophrenia (comparison twins < unaffected dizygotic co-twins < unaffected monozygotic co-twins). Medicated schizophrenia patients demonstrated a widespread reduction in D(1) receptor binding when compared with the unaffected co-twin, and higher doses of antipsychotics were associated with lower D(1) receptor binding in the frontotemporal regions.
  
  
  CONCLUSIONS
  This study demonstrated an association between genetic risk for schizophrenia and alterations in cortical D(1) receptor binding, an observation that has implications for future studies of the molecular genetics of schizophrenia. In addition, the data indicate a widespread reduction of D(1) receptor binding in medicated schizophrenia patients, supporting a link between antipsychotic drug action and dopamine D(1) receptor down-regulation.
authors.affiliation: Department of Psychiatry, University of Turku, Kunnallissairaalantie 20, Bldg. 9, 20700 Turku, 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: Tyrone D
authors.initials: TD
authors.lastname: Cannon
authors.forename: Jarmo
authors.initials: J
authors.lastname: Hietala
mesh_terms: D001552:Benzazepines / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D004200:Diseases in Twins / Q000235:genetics*; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: D001552:Benzazepines; D017447:Receptors, Dopamine D1