Serum sortilin-derived propeptides concentrations are decreased in major depressive disorder patients

Background: Despite intense research on mechanisms underlying the depressive pathophysiology, reliable biomarkers to assess antidepressant treatment response are still lacking. Since the sortilin-derived propeptide (PE) displays potent antidepressant activities and can be measured in the blood of rodents, we wondered whether in human its seric level can vary between patients affected by major depressive disorder (MDD) and healthy controls and after antidepressant treatment. Methods: By using a specific dosing method, characterized by structure-recognition analysis with various synthesized PE analogues, we conducted a translational study to test whether blood levels of PE are under pathophysiological regulation and could serve as biomarkers of the depression state. Results: The serum concentration of PE, a peptide displaying potent antidepressant activities in rodents, is decreased in patients affected by major depressive disorder (MDD) when compared to healthy non-psychiatric controls cohort (p=0.035). Interestingly, pharmacological antidepressant treatments restore normal PE levels. Limitations: The limitation of the study concerns the relatively small patient samples that could negatively affect the likelihood that a nominally statistically significant finding actually reflects a true effect. Conclusions: The longitudinal quantification of the serum PE concentration could assist psychiatrists in the diagnosis of antidepressant response efficacy, and the need to modify the therapeutic strategy.