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DRD2 Genotype-Based Variation of Default Mode Network Activity and of Its Relationship With Striatal DAT Binding

Fabio Sambataro, Leonardo Fazio, Paolo Taurisano, Barbara Gelao, Annamaria Porcelli, Marina Mancini, Lorenzo Sinibaldi, Gianluca Ursini, Rita Masellis, Grazia Caforio, Annabella di Giorgio, Artor Niccoli Asabella, Teresa Popolizio, Giuseppe Blasi, Alessandro Bertolino

Schizophrenia Bulletin October 5, 2011 DOI: 10.1093/schbul/sbr128 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Peer reviewed
Sample size 28
Population Human subjects genotyped for DRD2 rs1076560
Measures functional magnetic resonance imaging (fMRI), [(123)I]-FP-CIT SPECT, spatial group-independent component (IC) analysis
Topics Default mode network
Citations 59
Key findings The DRD2 rs1076560 polymorphism was associated with differences in default mode network connectivity: GG carriers showed greater medial prefrontal cortex connectivity within the anterior DMN, correlated with striatal dopamine transporter binding, but reduced posterior cingulate connectivity within the posterior DMN relative to T carriers. Genotype also predicted striatal network connectivity differences correlated with DMN regions. The authors suggest these findings indicate that genetically determined D2 receptor signaling is associated with DMN connectivity and striatal function.

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.

Comparable studies

Other observational and cohort studies on default mode network, most cited first.

Study Year Design Participants
A default mode of brain function Normal adult human brain 2001 Observational study
Resting-State Functional Connectivity Reflects Structural Connectivity in the Default Mode Network Healthy subjects 2008 Observational cohort
Meditation experience is associated with increased cortical thickness Participants with extensive Insight meditation experience and matched controls 2005 Observational cohort n = 20
Meditation experience is associated with differences in default mode network activity and connectivity Experienced meditators and matched meditation-naive controls 2011 Observational cohort
The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: Evidence from a partial correlation network analysis Healthy subjects 2008 Observational study

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Default mode network