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- Title
Functional Connectivity in Healthy Subjects Is Nonlinearly Modulated by the COMT and DRD2 Polymorphisms in a Functional System-Dependent Manner.
- Authors
Tian, Tian; Wen Qin; Bing Liu; Tianzi Jiang; Chunshui Yu
- Abstract
The dopamine system is known to modulate brain function in an inverted U-shaped manner. Recently, the functional networks of the brain were categorized into two systems, a "control system" and a "processing system." However, it remains unclear whether the inverted U-shaped model of dopaminergic modulation could be applied to both of these functional systems. The catechol-O-methyltransferase (COMT) and dopamine D2 receptor (DRD2) were genotyped in 258 healthy young human subjects. The local and long-range functional connectivity densities (FCDs) of each voxel were calculated and compared in a voxel-wise manner using a two-way (COMT and DRD2 genotypes) analysis of covariance. The resting-state functional connectivity analysis was performed to determine the functional networks to which brain regions with significant FCD differences belonged. Significant COMT ✕ DRD2 interaction effects were found in the local FCDs of the superior portion of the right temporal pole (sTP) and left lingual gyrus (LG) and in the long-range FCDs of the right putamen and left medial prefrontal cortex (MPFC). Post hoc tests showed nonlinear relationships between the genotypic subgroups and FCD. In the control system, the sTP and putamen, components of the salience network, showed a U-shaped modulation by dopamine signaling. In the processing system, however, the MPFC of the default-mode network and the LG of the visual network showed an inverted U-shaped modulation by the dopamine system. Our findings suggest an interaction between COMT and DRD2 genotypes and show a functional system-dependent modulation of dopamine signaling.
- Subjects
BRAIN function localization; GENETIC polymorphisms; DOPAMINE receptors; NEURAL circuitry; CATECHOL-O-methyltransferase; CELLULAR signal transduction
- Publication
Journal of Neuroscience, 2013, Vol 33, Issue 44, p17519
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.2163-13.2013