Clinical characteristics
67 patients with PD were preliminarily enrolled in this study, 5 of which were removed for incompletion of follow-up period, and 2 were removed for unqualified blood samples. Then, a cohort of 60 patients was resulted in for analysis (mean age: 35.13±9.838 years; mean age of onset: 34.20±10.133 years; male/female=24/36).
After the 6-week treatment, 28 patients have reached clinical remission while the other 32 patients reached clinical response. The total score of HAMA at baseline was 25±7.606, and 8.53±4.734 after treatment (t = 7.118, p < 0.001). The total score of PDSS at baseline was 15.20±4.523, and 4.93±3.826 after treatment (t = 6.712, p < 0.001)
Detection of differential miRNAs
Of the 752 human plasma miRNAs, 147 and 37 miRNAs were significantly up- and down- regulated after sertraline treatment, in comparison with those before treatment (p 0.05, fold change>2). Furthermore, 5 up-regulated miRNAs (miR-451a, miR-144-5p, miR-409-3p, miR-25-3p, miR-660-5p) and 3 down-regulated miRNAs (miR-1, miR-99b-3p, miR-148b-5p) were selected as differentially expressed miRNA, in consideration of the significance of change and the potential biological activity reported previously (Table 1).
The 8 differentially expressed miRNAs were validated by real-time RT-PCR in the total 60 pairs of samples. Of the 5 up-regulated miRNAs, 4 were found to be significantly up-regulated in RT-PCR (miR-451a, miR-144-5p, miR-25-3p, miR-660-5p). Of the 3 down-regulated miRNAs, 2 were found to be significantly down-regulated in RT-PCR (miR-1, miR-148-5p) (Table 2). The regulation patterns were consistent in 6 of the 8 miRNAs, achieving a consistency percentage of 75%.
The relationship between miRNAs and the clinical characteristics before and after treatment
To clarify the potential relationship between the miRNAs and the changes of clinical characteristics along with sertraline treatment, we used Pearson correlation analysis to explore the relationship of the changes between miRNAs and scores of total/factor HAMA/PDSS scales (Table 3 and Table 4).
The change of miR-25-3p before and after treatment (△miR-25-3p) was positively related with both the changes of PDSS3 (the severity of expected anxiety) scores before and after treatment (△PDSS3) and PDSS7 (the impairment of social function) scores before and after treatment (△PDSS7) (r = 0.603, p = 0.017 for the former, and r = 0.609, p = 0.016 for the latter). When the △miR-25-3p increased, the △PDSS3 and △PDSS7 both increased accordingly.
The △miR-660-5p was positively related with both the △HAMA5 (memory and attention disorders) and △PDSS7 (r = 0.559, p = 0.030 for the former, and r = 0.554, p = 0.032 for the latter). When the △miR-660-5p increased, the △HAMA5 and △PDSS7 both increased accordingly.
The △miR-148-5p was positively related with the △ PDSS4 (scene scared and/or avoidance) (r = 0.521, p = 0.046), but negatively related with the △HAMA13 (autonomic nerve symptoms) (r = -0.679, p = 0.005). When the △miR-148-5p increased, the △PDSS4 increased accordingly, but the △HAMA13 decreased.
The △miR-144-5p was negatively related with the △HAMA9 (symptoms of cardiovascular system) (r = -0.554, p = 0.032). When the △miR-144-5p increased, the △HAMA9 decreased.