Disrupted-in-schizophrenia 1 functional polymorphisms and D2/D3 receptor availability: A [11C]-(+)-PHNO imaging study

Tarik Dahoun, Matthew M. Nour, Rick A. Adams, Svenja Trossbach, Sang H. Lee, Hamel Patel, Charles Curtis, Carsten Korth, Oliver D. Howes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


The disrupted-in-schizophrenia 1 (DISC1) protein has been implicated in a range of biological mechanisms underlying chronic mental disorders such as schizophrenia. Schizophrenia is associated with abnormal striatal dopamine signalling, and all antipsychotic drugs block striatal dopamine 2/3 receptors (D2/3Rs). Importantly, the DISC1 protein directly interacts and forms a protein complex with the dopamine D2 receptor (D2R) that inhibits agonist-induced D2R internalisation. Moreover, animal studies have found large striatal increases in the proportion of D2R receptors in a high affinity state (D2highR) in DISC1 rodent models. Here, we investigated the relationship between the three most common polymorphisms altering the amino-acid sequence of the DISC1 protein (Ser704Cys (rs821616), Leu607Phe (rs6675281) and Arg264Gln (rs3738401)) and striatal D2/3R availability in 41 healthy human volunteers, using [11C]-(+)-PHNO positron emission tomography. We found no association between DISC1 polymorphisms and D2/3R availability in the striatum and D2R availability in the caudate and putamen. Therefore, despite a direct interaction between DISC1 and the D2R, none of its main functional polymorphisms impact striatal D2/3R binding potential, suggesting DISC1 variants act through other mechanisms.

Original languageEnglish
Article numbere12596
JournalGenes, Brain and Behavior
Issue number8
Early online date2 Jun 2019
Publication statusPublished - 1 Nov 2019


  • Arg264Gln
  • DISC1
  • dopamine
  • Leu607Phe
  • PET
  • PHNO
  • polymorphism
  • psychosis
  • receptor
  • Ser704Cys


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