The Dopaminergic Polymorphisms in Psychomotor Retardation of Depression: A Pathway-based Imaging Genetics Association Study

Abstract

IntroductionSeveral lines of evidence implicate dopamine is involved in the psychomotor retardation (PMR) in major depressive disorder (MDD). Besides, abnormal cerebral blood flow (CBF) of PMR was also found in the cortico-basal ganglia-thalamo-cortical (CBTC) circuitry. We hypothesize that the polymorphisms of the dopaminergic pathway should be associated the abnormal CBF in the CBTC circuitry.ObjectiveTo investigate the association of the polymorphisms throughout the dopaminergic pathway with the cerebral blood flow (CBF) of PMR in MDD.MethodsThe blood sample of 63 patients (23 PMR, 40 NPMR) were collected for genotyping the dopaminergic polymorphisms (92 SNPs from10 genes). After quality controlling, 15 SNPs in 8 candidate genes were entered into the mass univariate modeling analysis. For the statistical analysis, patients with unqualified fMRI image and unmatched demographic data were ruled out. Consequently 56 patients (23 PMR, 33 NPMR) were taken into the statistical analysis.ResultsGenotype-by PMR associations with the CBF differences predominately distributed in bilateral prefrontal cortex (PFC), temporal cortex, and striatum, the left thalamus, the right primary motor cortex, insular cortex, fusiform gyri, and lingual gyri. There were significant negative correlation between the CBF of the PFC and the PMR severity. However, the CBF of the striatum and the thalamus were positively correlated with the PMR severity.ConclusionsThe polymorphisms of dopaminergic pathway are associated with not only CSTC circuitry, but also some other brain regions involving in cognition and emotion controlling. While the increased CBF of PFC might suppress PMR, the increased CBF of striatum and thalamus adversely aggravate PMR.