Striatal dopamine D1 and D2 receptor balance in twins at increased genetic risk for schizophrenia.
The dopamine hypothesis of schizophrenia postulates that a dysfunctional dopaminergic system is a major pathophysiological mechanism in the disease. Most studies have focused on striatal dopamine D2 receptors, but a disturbed link between dopamine D1 and D2 receptors has also been proposed. Schizophrenia is highly heritable, and recent evidence suggests that alterations in the dopaminergic system confer susceptibility for schizophrenia instead of being solely related to the to overt expression of the disease. To explore the impact of genetic vulnerability for schizophrenia on the balance of striatal dopamine D1 and D2 receptors, we studied monozygotic (MZ) and dizygotic (DZ) unaffected co-twins from twin pairs discordant for schizophrenia as well as healthy control twins using positron emission tomography (PET). Both [(11)C]SCH 23390 and [(11)C]raclopride were used to quantitate D1 and D2 receptor binding, respectively, in the same individuals during the same day. The association between D1 and D2 receptor binding was analyzed using conventional region of interests as well as voxel-wise D1/D2 ratio maps. All levels of analyses failed to show any differences in D1/D2 ratio between the unaffected MZ or DZ co-twins and control twins. We noted rostrocaudally declining and dorsoventrally increasing gradients in D1/D2 ratio in the striatum, with no differences between groups in these gradients. In this sample, we did not find evidence for an association between increased genetic risk for schizophrenia and altered D1/D2 receptor balance in the striatum.
Hirvonen
Jussi
J
Department of Psychiatry, University of Turku, 20520, Finland. jueshi@utu.fi
van Erp
Theo G M
TG
Huttunen
Jukka
J
Någren
Kjell
K
Huttunen
Matti
M
Aalto
Sargo
S
Lönnqvist
Jouko
J
Kaprio
Jaakko
J
Cannon
Tyrone D
TD
Hietala
Jarmo
J
D000328:Adult; D015331:Cohort Studies; D003342:Corpus Striatum / Q000378:metabolism* / Q000503:physiopathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D017447:Receptors, Dopamine D1 / Q000235:genetics* / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism*; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*; D014427:Twins / Q000235:genetics*
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2