title: Prefronto-striatal physiology is associated with schizotypy and is modulated by a functional variant of DRD2.
abstract: "Schizotypy" is a latent organization of personality related to the genetic risk for schizophrenia. Some evidence suggests that schizophrenia and schizotypy share some biological features, including a link to dopaminergic D2 receptor signaling. A polymorphism in the D2 gene (DRD2 rs1076560, guanine > thymine (G > T)) has been associated with the D2 short/long isoform expression ratio, as well as striatal dopamine signaling and prefrontal cortical activity during different cognitive operations, which are measures that are altered in patients with schizophrenia. Our aim is to determine the association of schizotypy scores with the DRD2 rs1076560 genotype in healthy individuals and their interaction with prefrontal activity during attention and D2 striatal signaling. A total of 83 healthy subjects were genotyped for DRD2 rs1076560 and completed the Schizotypal Personality Questionnaire (SPQ). Twenty-six participants underwent SPECT with [(123)I]IBZM D2 receptor radiotracer, while 68 performed an attentional control task during fMRI. We found that rs1076560 GT subjects had greater SPQ scores than GG individuals. Moreover, the interaction between schizotypy and the GT genotype predicted prefrontal activity and related attentional behavior, as well as striatal binding of IBZM. No interaction was found in GG individuals. These results suggest that rs1076560 GT healthy individuals are prone to higher levels of schizotypy, and that the interaction between rs1076560 and schizotypy scores modulates phenotypes related to the pathophysiology of schizophrenia, such as prefrontal activity and striatal dopamine signaling. These results provide systems-level qualitative evidence for mapping the construct of schizotypy in healthy individuals onto the schizophrenia continuum.
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy ; IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo Foggia, Italy.
authors: Paolo
authors: P
authors: Taurisano
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy.
authors: Raffaella
authors: R
authors: Romano
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy.
authors: Marina
authors: M
authors: Mancini
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy ; IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo Foggia, Italy.
authors: Annabella Di
authors: AD
authors: Giorgio
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy.
authors: Linda A
authors: LA
authors: Antonucci
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy ; IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo Foggia, Italy.
authors: Leonardo
authors: L
authors: Fazio
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy.
authors: Antonio
authors: A
authors: Rampino
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy ; Department of Behavioural Sciences, Cognitive Brain Research Unit, University of Helsinki Helsinki, Finland.
authors: Tiziana
authors: T
authors: Quarto
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy.
authors: Barbara
authors: B
authors: Gelao
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy.
authors: Annamaria
authors: A
authors: Porcelli
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy.
authors: Apostolos
authors: A
authors: Papazacharias
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy ; Lieber Institute for Brain Development, Johns Hopkins University Medical Campus Baltimore, MD, USA.
authors: Gianluca
authors: G
authors: Ursini
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy.
authors: Grazia
authors: G
authors: Caforio
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy.
authors: Rita
authors: R
authors: Masellis
authors: Department of Internal Medicine and of Public Medicine, Nuclear Medicine Unit, University of Bari Aldo Moro Bari, Italy.
authors: Artor
authors: A
authors: Niccoli-Asabella
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy.
authors: Orlando
authors: O
authors: Todarello
authors: IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo Foggia, Italy.
authors: Teresa
authors: T
authors: Popolizio
authors: Department of Internal Medicine and of Public Medicine, Nuclear Medicine Unit, University of Bari Aldo Moro Bari, Italy.
authors: Giuseppe
authors: G
authors: Rubini
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy.
authors: Giuseppe
authors: G
authors: Blasi
authors: Department of Basic Medical Science, Psychiatric Neuroscience Group, Neuroscience and Sense Organs, University of Bari Aldo Moro Bari, Italy ; IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo Foggia, Italy ; pRED, NORD DTA, Hoffmann-La Roche, Ltd. Basel, Switzerland.
authors: Alessandro
authors: A
authors: Bertolino
keywords: DRD2; SPECT; dopamine; fMRI; schizotypy