We previously discovered that spadin, a short analogue of the propeptide (PE) released from the maturation of sortilin, displays potent antidepressant properties. Since the PE level can be measured in the blood, we aimed to investigate how the PE serum concentration is regulated in mice. We wondered whether the PE serum levels vary between healthy subjects and patients with major depressive disorder (MDD).

We developped a dosing method based on the AlphaScreen™ technology (Perkin) which allow to selectively detect both PE, spadin and metabolic products from these peptides with a detection range of 1 ng/mL.

We found that insulin significantly up-regulated serum PE concentration from 26.15 ± 2.63 to 41.43 ± 6.27 nM (P = 0.0318). Analysis during circadian cycle in mice revealed that the amount of PE and its derivatives significantly varied during the cycle being higher during the period of maximal activity (dark period). We also measured serum insulin concentration between 1 and 7 pm and observed a significant rise confirming the relationships between insulin and PE concentration. We showed that the serum level of PE is lower in depressive patients than in healthy non-psychiatric. We observed that the weaker level of PE in depressive patients can recover the level of healthy subjects after a chronic antidepressant treatment.

Dosing the serum level of PE could be a promising approach for the diagnosis of depression and to determine the remission of the disease.

The authors have not supplied their declaration of competing interest.