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Schizophrenia is associated with abnormal striatal dopamine signalling, and all antipsychotic drugs block striatal dopamine 2\/3 receptors (D<jats:sub>2\/3<\/jats:sub>Rs). Importantly, the DISC1 protein directly interacts and forms a protein complex with the dopamine D<jats:sub>2<\/jats:sub> receptor (D<jats:sub>2<\/jats:sub>R) that inhibits agonist\u2010induced D<jats:sub>2<\/jats:sub>R internalisation. Moreover, animal studies have found large striatal increases in the proportion of D<jats:sub>2<\/jats:sub>R receptors in a high affinity state (D<jats:sub>2<\/jats:sub><jats:sup>high<\/jats:sup>R) in DISC1 rodent models. Here, we investigated the relationship between the three most common polymorphisms altering the amino\u2010acid sequence of the DISC1 protein (Ser704Cys (rs821616), Leu607Phe (rs6675281) and Arg264Gln (rs3738401)) and striatal D<jats:sub>2\/3<\/jats:sub>R availability in 41 healthy human volunteers, using [<jats:sup>11<\/jats:sup>C]\u2010(+)\u2010PHNO positron emission tomography. We found no association between DISC1 polymorphisms and D<jats:sub>2\/3<\/jats:sub>R availability in the striatum and D<jats:sub>2<\/jats:sub>R availability in the caudate and putamen. Therefore, despite a direct interaction between DISC1 and the D<jats:sub>2<\/jats:sub>R, none of its main functional polymorphisms impact striatal D<jats:sub>2\/3<\/jats:sub>R binding potential, suggesting DISC1 variants act through other mechanisms.<\/jats:p>","DOI":"10.1111\/gbb.12596","type":"journal-article","created":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T08:39:00Z","timestamp":1562056740000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Disrupted\u2010in\u2010schizophrenia 1 functional polymorphisms and D<sub>2<\/sub>\/D<sub>3<\/sub> receptor availability: A [<sup>11<\/sup>C]\u2010(+)\u2010PHNO imaging study"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9831-4926","authenticated-orcid":false,"given":"Tarik","family":"Dahoun","sequence":"first","affiliation":[{"name":"Psychiatric Imaging Group, Robert Steiner MRI Unit MRC London Institute of Medical 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