title: DRD2 genotype-based variation of default mode network activity and of its relationship with striatal DAT binding.
abstract: The default mode network (DMN) comprises a set of brain regions with "increased" activity during rest relative to cognitive processing. Activity in the DMN is associated with functional connections with the striatum and dopamine (DA) levels in this brain region. A functional single-nucleotide polymorphism within the dopamine D2 receptor gene (DRD2, rs1076560 G > T) shifts splicing of the 2 D2 isoforms, D2 short and D2 long, and has been associated with striatal DA signaling as well as with cognitive processing. However, the effects of this polymorphism on DMN have not been explored. The aim of this study was to evaluate the effects of rs1076560 on DMN and striatal connectivity and on their relationship with striatal DA signaling. Twenty-eight subjects genotyped for rs1076560 underwent functional magnetic resonance imaging during a working memory task and 123 55 I-Fluoropropyl-2-beta-carbomethoxy-3-beta(4-iodophenyl) nortropan Single Photon Emission Computed Tomography ([(123)I]-FP-CIT SPECT) imaging (a measure of dopamine transporter [DAT] binding). Spatial group-independent component (IC) analysis was used to identify DMN and striatal ICs. Within the anterior DMN IC, GG subjects had relatively greater connectivity in medial prefrontal cortex (MPFC), which was directly correlated with striatal DAT binding. Within the posterior DMN IC, GG subjects had reduced connectivity in posterior cingulate relative to T carriers. Additionally, rs1076560 genotype predicted connectivity differences within a striatal network, and these changes were correlated with connectivity in MPFC and posterior cingulate within the DMN. These results suggest that genetically determined D2 receptor signaling is associated with DMN connectivity and that these changes are correlated with striatal function and presynaptic DA signaling.
authors: Brain Center for Motor and Social Cognition, Istituto Italiano di Tecnologia@UniPr, Parma, Italy.
authors: Fabio
authors: F
authors: Sambataro
authors: Leonardo
authors: L
authors: Fazio
authors: Paolo
authors: P
authors: Taurisano
authors: Barbara
authors: B
authors: Gelao
authors: Annamaria
authors: A
authors: Porcelli
authors: Marina
authors: M
authors: Mancini
authors: Lorenzo
authors: L
authors: Sinibaldi
authors: Gianluca
authors: G
authors: Ursini
authors: Rita
authors: R
authors: Masellis
authors: Grazia
authors: G
authors: Caforio
authors: Annabella
authors: A
authors: Di Giorgio
authors: Artor
authors: A
authors: Niccoli-Asabella
authors: Teresa
authors: T
authors: Popolizio
authors: Giuseppe
authors: G
authors: Blasi
authors: Alessandro
authors: A
authors: Bertolino
mesh_terms: D000328:Adult; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods; D008297:Male; D009415:Nerve Net / Q000378:metabolism / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D011485:Protein Binding / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D015899:Tomography, Emission-Computed, Single-Photon / Q000295:instrumentation / Q000379:methods*; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2