COMT Val158Met Polymorphism Influences the Cerebral Blood Flow Changes Related to Psychomotor Retardation in Major Depressive Disorder

Abstract

Background

Previous studies revealed different cerebral blood flow (CBF) changes of major depressive disorder (MDD) patients with psychomotor retardation (PMR). These different changes might result from the modulation of other factors, such as genes. This study aimed to investigate the influence of COMT Val158Met polymorphism on the CBF alterations in MDD patients with PMR.

Methods

COMT Val158Met genotypes and arterial spin labeling-magnetic resonance imaging (ASL-MRI) data of 103 Chinese Han participants (63 MDD, 40 NCs) were collected in this study. MDD patients were divided into PMR group (N = 23) and NPMR group (N = 40) according to the Salpetriere Retardation Rating Scale score. PMR, NPMR and NCs groups were further divided into two subgroups, respectively, based on the COMT Val158Met genotype. CBF throughout the whole brain was calculated based on the ASL-MRI data. A two-way factorial analysis of covariance was used to investigate the main effects of PMR, COMT Met allele, as well as the interactions between COMT genotype and PMR on the CBF in a voxel-wise manner. Partial correlation analyses were also applied to evaluate the association between the CBF of significant brain regions and the PMR severity.

Results

Main effect of PMR mainly influenced the CBF of the prefrontal cortex (PFC). Main effect of COMT Met allele mainly influenced the CBF of the thalamus. The interaction between PMR and COMT Met allele primarily influenced the CBF of left precuneus and right caudate. The CBF of PFC was positively correlated with the PMR severity.

Conclusion

Our findings indicate that the COMT Met allele could modulate the CBF changes of the left precuneus and right caudate in MDD patients with PMR, providing additional layer of information regarding earlier reports for different CBF changes of MDD patients with psychomotor retardation in the literature, which were assessed irrespective of polymorphisms among patients.

Keywords:

• major depressive disorder
• psychomotor retardation
• ASL
• cerebral blood flow
• COMT Val158Met polymorphism

Ethics Approval and Consent to Participate

The study protocol was approved by the medical ethics committee for clinical research of ZhongDa Hospital affiliated to Southeast University. The methods were performed in accordance with approved guidelines. Written informed consent was available for all participants.

Acknowledgments

We wish to thank all the participants in this study as well as all those who provided financial support.

Disclosure

The authors declare that they have no competing interests in this work.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81971277, Y. Yuan; 81801349, Y. Yin) and the Program for one thousand Zhongyuan Talents (204200510020, H.X. Zhang) for data collection, the Natural Science Foundation of Jiangsu Province (BK20180373, Y. Yin) for the analysis and interpretation of data, and Jiangsu Provincial Key Research and Development Program (BE2019748, Y. Yuan) for the paper’s publication. The funding program provides capital for the researchers to do the data collection, analysis, interpretation, and the publication of the paper.