Electroconvulsive therapy modulates plasma pigment epithelium-derived factor in depression: a proteomics study

Abstract

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, yet its mechanism of action is not fully understood. Peripheral blood proteomic analyses may offer insights into the molecular mechanisms of ECT. Patients with a major depressive episode were recruited as part of the EFFECT-Dep trial (enhancing the effectiveness of electroconvulsive therapy in severe depression; ISRCTN23577151) along with healthy controls. As a discovery-phase study, patient plasma pre-/post-ECT (n=30) was analyzed using 2-dimensional difference in gel electrophoresis and mass spectrometry. Identified proteins were selected for confirmation studies using immunodetection methods. Samples from a separate group of patients (pre-/post-ECT; n=57) and matched healthy controls (n=43) were then used to validate confirmed changes. Target protein mRNA levels were also assessed in rat brain and blood following electroconvulsive stimulation (ECS), the animal model of ECT. We found that ECT significantly altered 121 protein spots with 36 proteins identified by mass spectrometry. Confirmation studies identified a post-ECT increase (P<0.01) in the antiangiogenic and neuroprotective mediator pigment epithelium-derived factor (PEDF). Validation work showed an increase (P<0.001) in plasma PEDF in depressed patients compared with the controls that was further increased post-ECT (P=0.03). PEDF levels were not associated with mood scores. Chronic, but not acute, ECS increased PEDF mRNA in rat hippocampus (P=0.02) and dentate gyrus (P=0.03). This study identified alterations in blood levels of PEDF in depressed patients and further alterations following ECT, as well as in an animal model of ECT. These findings implicate PEDF in the biological response to ECT for depression.

Peripheral blood microRNA and VEGFAmRNA changes following electroconvulsive therapy: implications for psychotic depression

“…Studies measuring serum VEGF‐A protein levels have shown more variation, but two meta‐analyses have now concluded that peripheral blood VEGF‐A levels are significantly higher in depressed subjects compared to controls . Similar findings have been found with pigment epithelium‐derived factor (PEDF) . We are not aware of any previously published reports that provide data on VEGFA /VEGF‐A levels in psychotic depression.…”

Quantitative Proteomic Approach for Discriminating Major Depressive Disorder and Bipolar Disorder by Multiple Reaction Monitoring-Mass Spectrometry

“…Patients who were on anti-inflammatory analgesics and steroids were excluded because immune and inflammatory pathways are linked to mood disorders, , and those who were undergoing intensive psychotherapy were excluded to confine treatment influences to psychotropic medications. Most of the other exclusion criteria were based on previous studies of certain diseases and conditions and their association with altered protein expression. − …”

Peroxisome proliferator-activated receptor gamma co-activator-1 alpha in depression and the response to electroconvulsive therapy

“…Moreover, we and others have shown that VEGFA, another shared target of these microRNAs, is altered in depression (Carvalho et al ., 2015; Kolshus et al ., 2017) and PGC-1 α has previously been implicated in VEGFA regulation (Arany et al ., 2008). Of note, we have shown that protein levels of the neurotrophin pigment epithelium-derived neurotrophic factor (PEDF), which can also regulate VEGFA, are increased in patients with depression and levels are augmented by treatment with ECT (Ryan et al ., 2017).…”