Interactions of genetic variants reveal inverse modulation patterns of dopamine system on brain gray matter volume and resting-state functional connectivity in healthy young adults.
Different genotypic combinations of COMT and DRD2 can generate multiple subgroups with different levels of dopamine signaling. Its modulations on brain properties can be investigated by analyzing the combined gene effects of COMT and DRD2. However, the inherent association between modulation patterns of the dopamine system on structural and functional properties of the brain remains unknown. In 294 healthy young adults, we investigated both additive and non-additive interactions of COMT and DRD2 on gray matter volume (GMV) and resting-state functional connectivity (rsFC) using a voxel-based analysis. We found a significant non-additive COMT × DRD2 interaction in the right dorsal anterior cingulate cortex (dACC), exhibiting an inverted U-shape modulation by dopamine signaling. We also found a significant non-additive COMT × DRD2 interaction in the rsFC between the right dACC and precuneus, displaying a U-shape modulation by dopamine signaling. Moreover, this rsFC was negatively correlated with the GMV of the right dACC. Although the additive interaction did not pass corrections for multiple comparisons, we also found a trend towards an inverse modulation pattern and a negative correlation between the GMV and rsFC of the right inferior frontal gyrus. No genotypic differences were detected in any assessments of the cognition, mood and personality. These findings suggest that healthy young adults without optimal dopamine signaling may maintain their normal behavioral performance via a functional compensatory mechanism in response to structural deficit due to genetic variation.
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
Jiayuan
J
Xu
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
Wen
W
Qin
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.|National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.
Bing
B
Liu
Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.|National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.
Tianzi
T
Jiang
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China. chunshuiyu@tijmu.edu.cn.
Chunshui
C
Yu
D000328:Adult; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004298:Dopamine / Q000502:physiology*; D005260:Female; D005838:Genotype; D066128:Gray Matter / Q000502:physiology*; D006179:Gyrus Cinguli / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D010296:Parietal Lobe / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D055815:Young Adult
C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D004298:Dopamine
Catechol-O-methyltransferase; Dopamine D2 receptor; Functional magnetic resonance imaging; Gray matter volume; Resting-state functional connectivity