{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T21:03:33Z","timestamp":1774559013577,"version":"3.50.1"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T00:00:00Z","timestamp":1490659200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T00:00:00Z","timestamp":1490659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 (<jats:italic>n<\/jats:italic>=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; <jats:italic>n<\/jats:italic>=57) and matched healthy controls (<jats:italic>n=<\/jats:italic>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 (<jats:italic>P<\/jats:italic>&lt;0.01) in the antiangiogenic and neuroprotective mediator pigment epithelium-derived factor (PEDF). Validation work showed an increase (<jats:italic>P<\/jats:italic>&lt;0.001) in plasma PEDF in depressed patients compared with the controls that was further increased post-ECT (<jats:italic>P<\/jats:italic>=0.03). PEDF levels were not associated with mood scores. Chronic, but not acute, ECS increased PEDF mRNA in rat hippocampus (<jats:italic>P<\/jats:italic>=0.02) and dentate gyrus (<jats:italic>P<\/jats:italic>=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.<\/jats:p>","DOI":"10.1038\/tp.2017.51","type":"journal-article","created":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T15:43:18Z","timestamp":1490715798000},"page":"e1073-e1073","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Electroconvulsive therapy modulates plasma pigment epithelium-derived factor in depression: a proteomics study"],"prefix":"10.1038","volume":"7","author":[{"given":"K M","family":"Ryan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Glaviano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S M","family":"O'Donovan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1565-570X","authenticated-orcid":false,"given":"E","family":"Kolshus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Dunne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Kavanagh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Jelovac","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Noone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G M","family":"Tucker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M J","family":"Dunn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D M","family":"McLoughlin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,3,28]]},"reference":[{"key":"BFtp201751_CR1","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1002\/da.22060","volume":"30","author":"MT Berlim","year":"2013","unstructured":"Berlim MT, Van den Eynde F, Daskalakis ZJ . Efficacy and acceptability of high frequency repetitive transcranial magnetic stimulation (rTMS) versus electroconvulsive therapy (ECT) for major depression: a systematic review and meta-analysis of randomized trials. Depress Anxiety 2013; 30: 614\u2013623.","journal-title":"Depress Anxiety"},{"key":"BFtp201751_CR2","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/S0140-6736(03)12705-5","volume":"361","author":"UK ECT Review Group","year":"2003","unstructured":"UK ECT Review Group. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet 2003; 361: 799\u2013808.","journal-title":"Lancet"},{"key":"BFtp201751_CR3","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.expneurol.2009.04.027","volume":"219","author":"A Merkl","year":"2009","unstructured":"Merkl A, Heuser I, Bajbouj M . Antidepressant electroconvulsive therapy: mechanism of action, recent advances and limitations. Exp Neurol 2009; 219: 20\u201326.","journal-title":"Exp Neurol"},{"key":"BFtp201751_CR4","doi-asserted-by":"publisher","first-page":"e609","DOI":"10.1038\/tp.2015.100","volume":"5","author":"EM van Buel","year":"2015","unstructured":"van Buel EM, Patas K, Peters M, Bosker FJ, Eisel UL, Klein HC . Immune and neurotrophin stimulation by electroconvulsive therapy: is some inflammation needed after all? Transl Psychiatry 2015; 5: e609.","journal-title":"Transl Psychiatry"},{"key":"BFtp201751_CR5","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.neures.2009.01.014","volume":"64","author":"N Kato","year":"2009","unstructured":"Kato N . Neurophysiological mechanisms of electroconvulsive therapy for depression. Neurosci Res 2009; 64: 3\u201311.","journal-title":"Neurosci Res"},{"key":"BFtp201751_CR6","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1097\/00124509-199809000-00004","volume":"14","author":"RS Duman","year":"1998","unstructured":"Duman RS, Vaidya VA . Molecular and cellular actions of chronic electroconvulsive seizures. J ECT 1998; 14: 181\u2013193.","journal-title":"J ECT"},{"key":"BFtp201751_CR7","doi-asserted-by":"publisher","first-page":"4894","DOI":"10.1523\/JNEUROSCI.0237-07.2007","volume":"27","author":"TD Perera","year":"2007","unstructured":"Perera TD, Coplan JD, Lisanby SH, Lipira CM, Arif M, Carpio C et al. Antidepressant-induced neurogenesis in the hippocampus of adult nonhuman primates. J Neurosci 2007; 27: 4894\u20134901.","journal-title":"J Neurosci"},{"key":"BFtp201751_CR8","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1017\/S1461145710000738","volume":"14","author":"AB Klein","year":"2011","unstructured":"Klein AB, Williamson R, Santini MA, Clemmensen C, Ettrup A, Rios M et al. Blood BDNF concentrations reflect brain-tissue BDNF levels across species. Int J Neuropsychopharmacol 2011; 14: 347\u2013353.","journal-title":"Int J Neuropsychopharmacol"},{"key":"BFtp201751_CR9","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.conb.2016.04.016","volume":"39","author":"EM Kramer-Albers","year":"2016","unstructured":"Kramer-Albers EM, Hill AF . Extracellular vesicles: interneural shuttles of complex messages. Curr Opin Neurobiol 2016; 39: 101\u2013107.","journal-title":"Curr Opin Neurobiol"},{"key":"BFtp201751_CR10","first-page":"61","volume":"14","author":"MR Wilkins","year":"1996","unstructured":"Wilkins MR, Pasquali C, Appel RD, Ou K, Golaz O, Sanchez JC et al. From proteins to proteomes: large scale protein identification by two-dimensional electrophoresis and amino acid analysis. Biotechnology 1996; 14: 61\u201365.","journal-title":"Biotechnology"},{"key":"BFtp201751_CR11","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1177\/0269881114552742","volume":"28","author":"A Glaviano","year":"2014","unstructured":"Glaviano A, O'Donovan SM, Ryan K, O'Mara S, Dunn MJ, McLoughlin DM . Acute phase plasma proteins are altered by electroconvulsive stimulation. J Psychopharmacol 2014; 28: 1125\u20131134.","journal-title":"J Psychopharmacol"},{"key":"BFtp201751_CR12","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.brainres.2014.10.020","volume":"1593","author":"SM O'Donovan","year":"2014","unstructured":"O'Donovan SM, O'Mara S, Dunn MJ, McLoughlin DM . The persisting effects of electroconvulsive stimulation on the hippocampal proteome. Brain Res 2014; 1593: 106\u2013116.","journal-title":"Brain Res"},{"key":"BFtp201751_CR13","doi-asserted-by":"publisher","first-page":"132","DOI":"10.3346\/jkms.2009.24.1.132","volume":"24","author":"CS Lee","year":"2009","unstructured":"Lee CS, Kang KR, Lee JY, Park CS, Hahn KH, Sohn JW et al. Proteomic analysis of rat brains following exposure to electroconvulsive therapy. J Korean Med Sci 2009; 24: 132\u2013137.","journal-title":"J Korean Med Sci"},{"key":"BFtp201751_CR14","doi-asserted-by":"publisher","first-page":"227","DOI":"10.2174\/157016461204160119155351","volume":"12","author":"SM O'Donovan","year":"2015","unstructured":"O'Donovan SM, Dalton VS, Dunn MJ, McLoughlin DM . The effects of chronic electroconvulsive stimulation on the rodent hippocampal proteome. Curr Proteomics 2015; 12: 227\u2013235.","journal-title":"Curr Proteomics"},{"key":"BFtp201751_CR15","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1016\/j.euroneuro.2012.10.012","volume":"23","author":"V Stelzhammer","year":"2013","unstructured":"Stelzhammer V, Guest PC, Rothermundt M, Sondermann C, Michael N, Schwarz E et al. Electroconvulsive therapy exerts mainly acute molecular changes in serum of major depressive disorder patients. Eur Neuropsychopharmacol 2013; 23: 1199\u20131207.","journal-title":"Eur Neuropsychopharmacol"},{"key":"BFtp201751_CR16","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1176\/appi.ajp.2015.15030372","volume":"173","author":"M Semkovska","year":"2016","unstructured":"Semkovska M, Landau S, Dunne R, Kolshus E, Kavanagh A, Jelovac A et al. Bitemporal versus high-dose unilateral twice-weekly electroconvulsive therapy for depression (EFFECT-Dep): a pragmatic, randomized, non-inferiority trial. Am J Psychiatry 2016; 173: 408\u2013417.","journal-title":"Am J Psychiatry"},{"key":"BFtp201751_CR17","volume-title":"Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV)","author":"M First","year":"1996","unstructured":"First M, Spitzer R, Gibbon M, Williams J . Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV). American Psychiatric Press: Washington DC, USA, 1996."},{"key":"BFtp201751_CR18","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1136\/jnnp.23.1.56","volume":"23","author":"M Hamilton","year":"1960","unstructured":"Hamilton M . A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23: 56\u201362.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"BFtp201751_CR19","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1176\/ajp.2007.164.1.73","volume":"164","author":"S Eranti","year":"2007","unstructured":"Eranti S, Mogg A, Pluck G, Landau S, Purvis R, Brown RG et al. A randomized, controlled trial with 6-month follow-up of repetitive transcranial magnetic stimulation and electroconvulsive therapy for severe depression. Am J Psychiatry 2007; 164: 73\u201381.","journal-title":"Am J Psychiatry"},{"key":"BFtp201751_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/nar\/gkn923","volume":"37","author":"Huang","year":"2009","unstructured":"Huang, da W, Sherman BT, Lempicki RA . Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009; 37: 1\u201313.","journal-title":"Nucleic Acids Res"},{"key":"BFtp201751_CR21","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","volume":"4","author":"Huang","year":"2009","unstructured":"Huang, da W, Sherman BT, Lempicki RA . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4: 44\u201357.","journal-title":"Nat Protoc"},{"key":"BFtp201751_CR22","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1038\/npp.2011.285","volume":"37","author":"C Ditzen","year":"2012","unstructured":"Ditzen C, Tang N, Jastorff AM, Teplytska L, Yassouridis A, Maccarrone G et al. Cerebrospinal fluid biomarkers for major depression confirm relevance of associated pathophysiology. Neuropsychopharmacology 2012; 37: 1013\u20131025.","journal-title":"Neuropsychopharmacology"},{"key":"BFtp201751_CR23","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1017\/S1461145714000819","volume":"17","author":"V Stelzhammer","year":"2014","unstructured":"Stelzhammer V, Haenisch F, Chan MK, Cooper JD, Steiner J, Steeb H et al. Proteomic changes in serum of first onset, antidepressant drug-naive major depression patients. Int J Neuropsychopharmacol 2014; 17: 1599\u20131608.","journal-title":"Int J Neuropsychopharmacol"},{"key":"BFtp201751_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0165-1781(96)02915-0","volume":"66","author":"M Maes","year":"1997","unstructured":"Maes M, Delange J, Ranjan R, Meltzer HY, Desnyder R, Cooremans W et al. Acute phase proteins in schizophrenia, mania and major depression: modulation by psychotropic drugs. Psychiatry Res 1997; 66: 1\u201311.","journal-title":"Psychiatry Res"},{"key":"BFtp201751_CR25","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1038\/sj.npp.1301497","volume":"33","author":"BH Miller","year":"2008","unstructured":"Miller BH, Schultz LE, Gulati A, Cameron MD, Pletcher MT . Genetic regulation of behavioral and neuronal responses to fluoxetine. Neuropsychopharmacology 2008; 33: 1312\u20131322.","journal-title":"Neuropsychopharmacology"},{"key":"BFtp201751_CR26","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.neulet.2013.05.035","volume":"549","author":"KM Ryan","year":"2013","unstructured":"Ryan KM, O'Donovan SM, McLoughlin DM . Electroconvulsive stimulation alters levels of BDNF-associated microRNAs. Neurosci Lett 2013; 549: 125\u2013129.","journal-title":"Neurosci Lett"},{"key":"BFtp201751_CR27","doi-asserted-by":"publisher","first-page":"E2114","DOI":"10.1210\/jc.2012-1894","volume":"97","author":"KL Sunderland","year":"2012","unstructured":"Sunderland KL, Tryggestad JB, Wang JJ, Teague AM, Pratt LV, Zhang SX et al. Pigment epithelium-derived factor (PEDF) varies with body composition and insulin resistance in healthy young people. J Clin Endocrinol Metab 2012; 97: E2114\u2013E2118.","journal-title":"J Clin Endocrinol Metab"},{"key":"BFtp201751_CR28","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1111\/j.1530-0277.2010.01336.x","volume":"35","author":"K Sogawa","year":"2011","unstructured":"Sogawa K, Kodera Y, Satoh M, Kawashima Y, Umemura H, Maruyama K et al. Increased serum levels of pigment epithelium-derived factor by excessive alcohol consumption-detection and identification by a three-step serum proteome analysis. Alcohol Clin Exp Res 2011; 35: 211\u2013217.","journal-title":"Alcohol Clin Exp Res"},{"key":"BFtp201751_CR29","doi-asserted-by":"publisher","first-page":"e16722","DOI":"10.1371\/journal.pone.0016722","volume":"6","author":"M Pons","year":"2011","unstructured":"Pons M, Marin-Castano ME . Cigarette smoke-related hydroquinone dysregulates MCP-1, VEGF and PEDF expression in retinal pigment epithelium in vitro and in vivo. PLoS ONE 2011; 6: e16722.","journal-title":"PLoS ONE"},{"key":"BFtp201751_CR30","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/2001-1326-3-7","volume":"3","author":"M Frantzi","year":"2014","unstructured":"Frantzi M, Bhat A, Latosinska A . Clinical proteomic biomarkers: relevant issues on study design & technical considerations in biomarker development. Clin Transl Med 2014; 3: 7.","journal-title":"Clin Transl Med"},{"key":"BFtp201751_CR31","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/nrc3484","volume":"13","author":"SP Becerra","year":"2013","unstructured":"Becerra SP, Notario V . The effects of PEDF on cancer biology: mechanisms of action and therapeutic potential. Nat Rev Cancer 2013; 13: 258\u2013271.","journal-title":"Nat Rev Cancer"},{"key":"BFtp201751_CR32","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1007\/s00406-009-0093-2","volume":"260","author":"D Martins-de-Souza","year":"2010","unstructured":"Martins-de-Souza D, Harris LW, Guest PC, Turck CW, Bahn S . The role of proteomics in depression research. Eur Arch Psychiatry Clin Neurosci 2010; 260: 499\u2013506.","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"BFtp201751_CR33","doi-asserted-by":"publisher","first-page":"e0141564","DOI":"10.1371\/journal.pone.0141564","volume":"10","author":"M Polyakova","year":"2015","unstructured":"Polyakova M, Schroeter ML, Elzinga BM, Holiga S, Schoenknecht P, de Kloet ER et al. Brain-derived neurotrophic factor and antidepressive effect of electroconvulsive therapy: systematic review and meta-analyses of the preclinical and clinical literature. PLoS ONE 2015; 10: e0141564.","journal-title":"PLoS ONE"},{"key":"BFtp201751_CR34","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1038\/mp.2013.105","volume":"19","author":"ML Molendijk","year":"2014","unstructured":"Molendijk ML, Spinhoven P, Polak M, Bus BA, Penninx BW, Elzinga BM . Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N=9484). Mol Psychiatry 2014; 19: 791\u2013800.","journal-title":"Mol Psychiatry"},{"key":"BFtp201751_CR35","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/0014-4835(91)90248-D","volume":"53","author":"J Tombran-Tink","year":"1991","unstructured":"Tombran-Tink J, Chader GG, Johnson LV . PEDF: a pigment epithelium-derived factor with potent neuronal differentiative activity. Exp Eye Res 1991; 53: 411\u2013414.","journal-title":"Exp Eye Res"},{"key":"BFtp201751_CR36","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1042\/bj20030313","volume":"374","author":"SV Petersen","year":"2003","unstructured":"Petersen SV, Valnickova Z, Enghild JJ . Pigment-epithelium-derived factor (PEDF) occurs at a physiologically relevant concentration in human blood: purification and characterization. Biochem J 2003; 374: 199\u2013206.","journal-title":"Biochem J"},{"key":"BFtp201751_CR37","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1046\/j.1471-4159.2002.00813.x","volume":"81","author":"RW Kuncl","year":"2002","unstructured":"Kuncl RW, Bilak MM, Bilak SR, Corse AM, Royal W, Becerra SP . Pigment epithelium-derived factor is elevated in CSF of patients with amyotrophic lateral sclerosis. J Neurochem 2002; 81: 178\u2013184.","journal-title":"J Neurochem"},{"key":"BFtp201751_CR38","first-page":"2759","volume":"37","author":"J Ortego","year":"1996","unstructured":"Ortego J, Escribano J, Becerra SP, Coca-Prados M . Gene expression of the neurotrophic pigment epithelium-derived factor in the human ciliary epithelium. Synthesis and secretion into the aqueous humor. Invest Ophthalmol Vis Sci 1996; 37: 2759\u20132767.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"BFtp201751_CR39","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1038\/nrn1176","volume":"4","author":"J Tombran-Tink","year":"2003","unstructured":"Tombran-Tink J, Barnstable CJ . PEDF: a multifaceted neurotrophic factor. Nature Rev Neurosci 2003; 4: 628\u2013636.","journal-title":"Nature Rev Neurosci"},{"key":"BFtp201751_CR40","doi-asserted-by":"publisher","first-page":"38022","DOI":"10.1074\/jbc.M600353200","volume":"281","author":"L Notari","year":"2006","unstructured":"Notari L, Baladron V, Aroca-Aguilar JD, Balko N, Heredia R, Meyer C et al. Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor. J Biol Chem 2006; 281: 38022\u201338037.","journal-title":"J Biol Chem"},{"key":"BFtp201751_CR41","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1515\/hsz-2012-0192","volume":"393","author":"B Radovic","year":"2012","unstructured":"Radovic B, Aflaki E, Kratky D . Adipose triglyceride lipase in immune response, inflammation, and atherosclerosis. Biol Chem 2012; 393: 1005\u20131011.","journal-title":"Biol Chem"},{"key":"BFtp201751_CR42","doi-asserted-by":"publisher","first-page":"2471","DOI":"10.1194\/jlr.M048553","volume":"55","author":"A Dichlberger","year":"2014","unstructured":"Dichlberger A, Schlager S, Maaninka K, Schneider WJ, Kovanen PT . Adipose triglyceride lipase regulates eicosanoid production in activated human mast cells. J Lipid Res 2014; 55: 2471\u20132478.","journal-title":"J Lipid Res"},{"key":"BFtp201751_CR43","doi-asserted-by":"publisher","first-page":"1940","DOI":"10.1194\/jlr.M600185-JLR200","volume":"47","author":"PA Wilson","year":"2006","unstructured":"Wilson PA, Gardner SD, Lambie NM, Commans SA, Crowther DJ . Characterization of the human patatin-like phospholipase family. J Lipid Res 2006; 47: 1940\u20131949.","journal-title":"J Lipid Res"},{"key":"BFtp201751_CR44","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.exer.2014.08.004","volume":"127","author":"JD Unterlauft","year":"2014","unstructured":"Unterlauft JD, Claudepierre T, Schmidt M, Muller K, Yafai Y, Wiedemann P et al. Enhanced survival of retinal ganglion cells is mediated by Muller glial cell-derived PEDF. Exp Eye Res 2014; 127: 206\u2013214.","journal-title":"Exp Eye Res"},{"key":"BFtp201751_CR45","doi-asserted-by":"publisher","first-page":"12152","DOI":"10.1523\/JNEUROSCI.0628-12.2012","volume":"32","author":"J Sohn","year":"2012","unstructured":"Sohn J, Selvaraj V, Wakayama K, Orosco L, Lee E, Crawford SE et al. PEDF is a novel oligodendrogenic morphogen acting on the adult SVZ and corpus callosum. J Neurosci 2012; 32: 12152\u201312164.","journal-title":"J Neurosci"},{"key":"BFtp201751_CR46","doi-asserted-by":"publisher","first-page":"280","DOI":"10.3109\/08977191003604513","volume":"28","author":"ML Broadhead","year":"2010","unstructured":"Broadhead ML, Becerra SP, Choong PF, Dass CR . The applied biochemistry of PEDF and implications for tissue homeostasis. Growth Factors 2010; 28: 280\u2013285.","journal-title":"Growth Factors"},{"key":"BFtp201751_CR47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1677\/jme.1.02008","volume":"37","author":"SX Zhang","year":"2006","unstructured":"Zhang SX, Wang JJ, Gao G, Parke K, Ma JX . Pigment epithelium-derived factor downregulates vascular endothelial growth factor (VEGF) expression and inhibits VEGF-VEGF receptor 2 binding in diabetic retinopathy. J Mol Endocrinol 2006; 37: 1\u201312.","journal-title":"J Mol Endocrinol"},{"key":"BFtp201751_CR48","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.psyneuen.2015.07.002","volume":"62","author":"AF Carvalho","year":"2015","unstructured":"Carvalho AF, Kohler CA, McIntyre RS, Knochel C, Brunoni AR, Thase ME et al. Peripheral vascular endothelial growth factor as a novel depression biomarker: A meta-analysis. Psychoneuroendocrinology 2015; 62: 18\u201326.","journal-title":"Psychoneuroendocrinology"},{"key":"BFtp201751_CR49","doi-asserted-by":"publisher","first-page":"2667","DOI":"10.1523\/JNEUROSCI.5377-03.2004","volume":"24","author":"CA Altar","year":"2004","unstructured":"Altar CA, Laeng P, Jurata LW, Brockman JA, Lemire A, Bullard J et al. Electroconvulsive seizures regulate gene expression of distinct neurotrophic signaling pathways. J Neurosci 2004; 24: 2667\u20132677.","journal-title":"J Neurosci"},{"key":"BFtp201751_CR50","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1016\/j.euroneuro.2006.04.010","volume":"16","author":"L Bocchio-Chiavetto","year":"2006","unstructured":"Bocchio-Chiavetto L, Zanardini R, Bortolomasi M, Abate M, Segala M, Giacopuzzi M et al. Electroconvulsive therapy (ECT) increases serum brain derived neurotrophic factor (BDNF) in drug resistant depressed patients. Eur Neuropsychopharmacol 2006; 16: 620\u2013624.","journal-title":"Eur Neuropsychopharmacol"},{"key":"BFtp201751_CR51","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1016\/j.biopsych.2006.02.013","volume":"59","author":"RS Duman","year":"2006","unstructured":"Duman RS, Monteggia LM . A neurotrophic model for stress-related mood disorders. Biol Psychiatry 2006; 59: 1116\u20131127.","journal-title":"Biol Psychiatry"},{"key":"BFtp201751_CR52","doi-asserted-by":"publisher","first-page":"9378","DOI":"10.1523\/JNEUROSCI.22-21-09378.2002","volume":"22","author":"MM Bilak","year":"2002","unstructured":"Bilak MM, Becerra SP, Vincent AM, Moss BH, Aymerich MS, Kuncl RW . Identification of the neuroprotective molecular region of pigment epithelium-derived factor and its binding sites on motor neurons. J Neurosci 2002; 22: 9378\u20139386.","journal-title":"J Neurosci"},{"key":"BFtp201751_CR53","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1073\/pnas.90.4.1526","volume":"90","author":"FR Steele","year":"1993","unstructured":"Steele FR, Chader GJ, Johnson LV, Tombran-Tink J . Pigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family. Proc Natl Acad Sci USA 1993; 90: 1526\u20131530.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFtp201751_CR54","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1002\/(SICI)1096-9861(19990927)412:3<506::AID-CNE9>3.0.CO;2-E","volume":"412","author":"LJ Houenou","year":"1999","unstructured":"Houenou LJ, D'Costa AP, Li L, Turgeon VL, Enyadike C, Alberdi E et al. Pigment epithelium-derived factor promotes the survival and differentiation of developing spinal motor neurons. J Comp Neurol 1999; 412: 506\u2013514.","journal-title":"J Comp Neurol"},{"key":"BFtp201751_CR55","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.neulet.2005.01.035","volume":"380","author":"T Sanagi","year":"2005","unstructured":"Sanagi T, Yabe T, Yamada H . The regulation of pro-inflammatory gene expression induced by pigment epithelium-derived factor in rat cultured microglial cells. Neurosci Lett 2005; 380: 105\u2013110.","journal-title":"Neurosci Lett"},{"key":"BFtp201751_CR56","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1002\/glia.20203","volume":"51","author":"A Takanohashi","year":"2005","unstructured":"Takanohashi A, Yabe T, Schwartz JP . Pigment epithelium-derived factor induces the production of chemokines by rat microglia. Glia 2005; 51: 266\u2013278.","journal-title":"Glia"},{"key":"BFtp201751_CR57","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1002\/glia.20171","volume":"50","author":"T Yabe","year":"2005","unstructured":"Yabe T, Sanagi T, Schwartz JP, Yamada H . Pigment epithelium-derived factor induces pro-inflammatory genes in neonatal astrocytes through activation of NF-kappa B and CREB. Glia 2005; 50: 223\u2013234.","journal-title":"Glia"},{"key":"BFtp201751_CR58","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1016\/S0140-6736(11)60602-8","volume":"379","author":"DJ Kupfer","year":"2012","unstructured":"Kupfer DJ, Frank E, Phillips ML . Major depressive disorder: new clinical, neurobiological, and treatment perspectives. Lancet 2012; 379: 1045\u20131055.","journal-title":"Lancet"},{"key":"BFtp201751_CR59","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/s10456-007-9074-0","volume":"10","author":"C Costa","year":"2007","unstructured":"Costa C, Incio J, Soares R . Angiogenesis and chronic inflammation: cause or consequence? Angiogenesis 2007; 10: 149\u2013166.","journal-title":"Angiogenesis"},{"key":"BFtp201751_CR60","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1007\/s00401-007-0228-3","volume":"113","author":"S Raab","year":"2007","unstructured":"Raab S, Plate KH . Different networks, common growth factors: shared growth factors and receptors of the vascular and the nervous system. Acta Neuropathol 2007; 113: 607\u2013626.","journal-title":"Acta Neuropathol"},{"key":"BFtp201751_CR61","doi-asserted-by":"publisher","first-page":"28058","DOI":"10.1074\/jbc.M113.470765","volume":"288","author":"AR Hajrasouliha","year":"2013","unstructured":"Hajrasouliha AR, Jiang G, Lu Q, Lu H, Kaplan HJ, Zhang HG et al. Exosomes from retinal astrocytes contain antiangiogenic components that inhibit laser-induced choroidal neovascularization. J Biol Chem 2013; 288: 28058\u201328067.","journal-title":"J Biol Chem"},{"key":"BFtp201751_CR62","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1182\/blood-2004-04-1569","volume":"105","author":"G Maik-Rachline","year":"2005","unstructured":"Maik-Rachline G, Shaltiel S, Seger R . Extracellular phosphorylation converts pigment epithelium-derived factor from a neurotrophic to an antiangiogenic factor. Blood 2005; 105: 670\u2013678.","journal-title":"Blood"},{"key":"BFtp201751_CR63","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/s00406-014-0543-3","volume":"265","author":"JM Bumb","year":"2015","unstructured":"Bumb JM, Aksay SS, Janke C, Kranaster L, Geisel O, Gass P et al. Focus on ECT seizure quality: serum BDNF as a peripheral biomarker in depressed patients. Eur Arch Psychiatry Clin Neurosci 2015; 265: 227\u2013232.","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"BFtp201751_CR64","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1055\/s-0029-1224162","volume":"42","author":"A Sartorius","year":"2009","unstructured":"Sartorius A, Hellweg R, Litzke J, Vogt M, Dormann C, Vollmayr B et al. Correlations and discrepancies between serum and brain tissue levels of neurotrophins after electroconvulsive treatment in rats. Pharmacopsychiatry 2009; 42: 270\u2013276.","journal-title":"Pharmacopsychiatry"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/tp201751.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/tp201751","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/tp.2017.51","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/www.nature.com\/articles\/tp201751.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T16:49:27Z","timestamp":1671727767000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/tp201751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,28]]},"references-count":64,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,3]]}},"alternative-id":["BFtp201751"],"URL":"https:\/\/doi.org\/10.1038\/tp.2017.51","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,28]]},"assertion":[{"value":"24 October 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2017","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 February 2017","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2017","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}