Dopamine Multilocus Genetic Profile, Spontaneous Activity of Left Superior Temporal Gyrus, and Early Therapeutic Effect in Major Depressive Disorder

Abstract

Objectives: This study aimed to examine the interactive effects of dopamine (DA) pathway gene and disease on spontaneous brain activity and further to explore the relationship between spontaneous brain activity and the early antidepressant therapeutic effect in patients with major depressive disorder (MDD). Methods: A total of 104 patients with MDD and 64 healthy controls (HCs) were recruited. The Hamilton Depression Scale-24 (HAMD-24) was used to measure the depression severity. Both groups were given resting-state functional magnetic resonance imaging (rs-fMRI) scan. The amplitude of low-frequency fluctuation (ALFF) was calculated to reflect the spontaneous brain activity based on the rs-fMRI data. After treatment for 2 weeks, depression severity was evaluated again, and HAMD-24 reductive rate was used to measure the therapeutic effect of antidepressants. Multilocus genetic profile scores (MGPS) were used to assess the multi-site cumulative effect of DA pathway gene. The interactive effects of MDD and DA pathway gene on the ALFF of regional brain areas were measured by the multivariate linear regression analysis. Finally, partial correlation analysis (age, sex, education, and illness durations as covariates) was performed to identify the relationship between regional ALFF and therapeutic effect. Results: MDD and DA-MGPS had interactive effects on the left fusiform gyrus (FG_L), right calcarine sulcus (CS_R), left superior temporal gyrus (STG_L), bilateral cerebellum posterior lobe (CPL), bilateral inferior frontal gyrus (IFG), and bilateral superior frontal gyrus (SFG). Partial correlation analysis revealed that the ALFF of STG_L had a significant negative correlation with 2-week HAMD-24 reductive rate (r = -0.211, P = 0.035). Conclusions: The spontaneous activity of STG_L may be a potential biomarker of antidepressant-related early therapeutic effect underlying the influence of DA pathway genes in MDD.

Keywords: amplitude of low-frequency fluctuation; dopamine; early therapeutic effect; major depressive disorder; multilocus genetic profile scores.

Figure 1

The interactive brain areas of DA pathway gene and major depressive disorder. The colored bar indicated the display window for the threshold t-value maps. Hot color represented a higher ALFF value, while blue represented a lower ALFF value. FG_L, left fusiform gyrus; CPL_R, right cerebellum posterior lobe; STG_L, left superior temporal gyrus; CPL_L, left cerebellum posterior lobe; IFG_R, right inferior frontal gyrus; IFG_L, left inferior frontal gyrus; CS_R, right calcarine sulcus; SFG_L, left superior frontal gyrus; SFG_R, right superior frontal gyrus.

Figure 2

The STG_L ALFF had a negative correlation with 2-week HAMD reductive rate (r = −0.211, P = 0.035). ALFF_STG_L, the amplitude of low-frequency fluctuation of left superior temporal gyrus.