Platelet serotonin and serotonin transporter as peripheral surrogates in depression and anxiety patients

Eur J Pharmacol. 2018 Sep 5:834:213-220. doi: 10.1016/j.ejphar.2018.07.033. Epub 2018 Jul 20.

Abstract

Previous studies suggested that serotonergic neurons and platelets share similarities in serotonin (5-HT) uptake by serotonin transporter (SERT), storage, metabolism and release mechanisms, indicating that platelets may be used as a reliable peripheral surrogate to measure central SERT activity in neuropsychiatric research. In this study, platelet 5-HT content and 5-HT uptake capacity of SERT in depression and anxiety patients were measured by ELISA and flow cytometry with IDT307 at baseline and after serotonin reuptake inhibitors (SSRIs) treatment for 4 weeks. Healthy persons matched with age and gender were used as reference. The clinical presentations of the patients were assessed with Hamilton Depression (HAMD) and Anxiety Rating Scales (HAMA) at the same time points. Compared to healthy subjects, anxiety and depression patients showed higher levels of platelet 5-HT and IDT307 fluorescence intensity, but the values were comparable between the patient groups. SSRIs administration for 4 weeks significantly decreased scores of HAMD (29 vs 14) and HAMA (22 vs 14) in depression and anxiety patients, respectively; while it decreased platelet 5-HT content, but did not change the IDT307 fluorescence intensity of platelets. After incubation with fluoxetine in vitro, the IDT307 fluorescence intensity of isolated platelets from both healthy subjects and patients decreased in a dose-dependent manner. These results provide further evidence supporting the employment of platelet 5-HT content and SERT as peripheral surrogates in depression and anxiety patients, and are of help in understanding the several weeks' delay from the initiation of antidepressant medication to their full therapeutic effects in the patients.

Keywords: IDT307; Platelets; Selective serotonin reuptake inhibitors; Serotonin; Serotonin transporters.

MeSH terms

  • Adult
  • Anxiety / blood*
  • Anxiety / drug therapy
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Depression / blood*
  • Depression / drug therapy
  • Dose-Response Relationship, Drug
  • Female
  • Fluoxetine / pharmacology
  • Humans
  • Male
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Serotonin / blood*
  • Serotonin Plasma Membrane Transport Proteins / blood*

Substances

  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Serotonin