Network-dependent Modulation Of COMT And DRD2 Polymorphisms In Healthy Young Adults

Objective: In this study, we used the ICA approach to explore the specific modulation of the dopamine(DA) signaling on the intra-network connectivity in the resting-state networks(RSNs) in healthy young adults by analyzing the interaction effects between the COMT rs4680 and DRD2 rs1076560.Subjects and Methods: A total of 250 healthy right-handed subjects(mean age: 22.7 ± 2.4 years; 115 males) were selected from 323 Chinese Han subjects who participated in this study. Then they finished the behavioral assessments.1. Genotyping Genomic DNA was extracted from 3000 ?l of whole blood using the EZgene TM Blood g DNA Miniprep Kit(Biomiga). We determined the genotypes for COMT rs4680 and DRD2 rs1076560 of the subject using the PCR and ligation detection reaction(LDR) method.2. Data acquisition and fMRI data preprocessing MRI data were acquired using a 3.0-Tesla MR system(Discovery MR750, General Electric, Milwaukee, WI, USA). Tight but comfortable foam padding was used to minimize head motion, and earplugs were used to reduce scanner noise. The fMRI data were preprocessed using the Statistical Parametric Mapping(SPM8, http://www.fil.ion.ucl.ac.uk/spm) and Data Processing Assistant for Resting-State fMRI(DPARSF).3. Identification of RSNs We used group ICA(GICA) to decompose all the data into independent components(ICs) using the GIFT software(http://icatb.sourceforge.net/, version 1.3 h), acquiring eleven meaningful RSNs.4. Intra-network connectivity analysis A two-way analysis of covariance(ANCOVA) was used to investigate the interaction effects between the COMT and DRD2 on intra-network connectivity in each RSN mask with gender, age and years of education as nuisance covariates.Result: 1. Eleven meaningful components were identified by visual inspection, including anterior(a DMN) and posterior(p DMN) default mode networks, salience network(SN), left(l DAN) and right(r DAN) dorsal attention networks, ventral(v SMN) and dorsal(d SMN) sensorimotor networks, left(l FPN) and right(r FPN) frontoparietal networks, visual network(VN), and auditory network(AN).2. The COMT × DRD2 interaction effects on intra-network connectivity was found in the left medial prefrontal cortex(MPFC) of the a DMN, in the left dorsal anterior cingulate cortex(d ACC) of the SN, and in the right dorsolateral frontal cortex of the r DAN.3. Post hoc tests revealed that the DA-related genetic variations COMT and DRD2 exhibited different nonlinear modulation patterns on intra-network connectivity in different RSNs.Conclusion: 1. The interaction effects of DA-related genetic variations COMT and DRD2 was found in a DMN, SN and DAN, with a nonlinear modulation way.2. The nonlinear modulation of the dopamine-related genes on functionality of the brain is network-dependent.