title: 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.
authors.affiliation: Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.|Department of Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, Dublin, Ireland.
authors.forename: K M
authors.initials: KM
authors.lastname: Ryan
authors.affiliation: Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Glaviano
authors.affiliation: Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: S M
authors.initials: SM
authors.lastname: O'Donovan
authors.affiliation: Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.|Department of Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, Dublin, Ireland.
authors.forename: E
authors.identifier: 0000-0002-1565-570X
authors.initials: E
authors.lastname: Kolshus
authors.affiliation: Department of Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, Dublin, Ireland.
authors.forename: R
authors.initials: R
authors.lastname: Dunne
authors.affiliation: Department of Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, Dublin, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Kavanagh
authors.affiliation: Department of Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, Dublin, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Jelovac
authors.affiliation: Department of Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, Dublin, Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Noone
authors.affiliation: Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: G M
authors.initials: GM
authors.lastname: Tucker
authors.affiliation: Conway Institute of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.
authors.forename: M J
authors.initials: MJ
authors.lastname: Dunn
authors.affiliation: Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.|Department of Psychiatry, Trinity College Dublin, St. Patrick's University Hospital, Dublin, Ireland.
authors.forename: D M
authors.initials: DM
authors.lastname: McLoughlin
mesh_terms: D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000097:blood / Q000628:therapy*; D004565:Electroconvulsive Therapy; D015180:Electrophoresis, Gel, Two-Dimensional; D004597:Electroshock; D005136:Eye Proteins / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood* / Q000235:genetics; D040901:Proteomics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015843:Serpins / Q000097:blood* / Q000235:genetics; D016896:Treatment Outcome; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor