P11 promoter methylation predicts the antidepressant effect of electroconvulsive therapy

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dc.contributor.author Neyazi, Alexandra
dc.contributor.author Theilmann, Wiebke
dc.contributor.author Brandt, C
dc.contributor.author Rantamäki, Tomi Pentti Johannes
dc.contributor.author Matsui, Nobuaki
dc.contributor.author Rhein, M
dc.contributor.author Kornhuber, J
dc.contributor.author Bajbouj, M
dc.contributor.author Sperling, W
dc.contributor.author Bleich, S
dc.contributor.author Frieling, H
dc.contributor.author Löscher, W
dc.date.accessioned 2018-03-22T10:51:01Z
dc.date.available 2018-03-22T10:51:01Z
dc.date.issued 2018-01-22
dc.identifier.citation Neyazi , A , Theilmann , W , Brandt , C , Rantamäki , T P J , Matsui , N , Rhein , M , Kornhuber , J , Bajbouj , M , Sperling , W , Bleich , S , Frieling , H & Löscher , W 2018 , ' P11 promoter methylation predicts the antidepressant effect of electroconvulsive therapy ' , Translational Psychiatry , vol. 8 , no. 25 , 25 . https://doi.org/10.1038/s41398-017-0077-3
dc.identifier.other PURE: 95008087
dc.identifier.other PURE UUID: 3d0d5634-28b9-4f6c-924a-ce40589bd493
dc.identifier.other Scopus: 85040865360
dc.identifier.other WOS: 000424024400005
dc.identifier.other ORCID: /0000-0002-0052-1434/work/43226448
dc.identifier.uri http://hdl.handle.net/10138/233655
dc.description.abstract Although electroconvulsive therapy (ECT) is among the most effective treatment options for pharmacoresistant major depressive disorder (MDD), some patients still remain refractory to standard ECT practise. Thus, there is a need for markers reliably predicting ECT non/response. In our study, we have taken a novel translational approach for discovering potential biomarkers for the prediction of ECT response. Our hypothesis was that the promoter methylation of p11, a multifunctional protein involved in both depressive-like states and antidepressant treatment responses, is differently regulated in ECT responders vs. nonresponders and thus be a putative biomarker of ECT response. The chronic mild stress model of MDD was adapted with the aim to obtain rats that are resistant to conventional antidepressant drugs (citalopram). Subsequently, electroconvulsive stimulation (ECS) was used to select responders and nonresponders, and compare p11 expression and promoter methylation. In the rat experiments we found that the gene promoter methylation and expression of p11 significantly correlate with the antidepressant effect of ECS. Next, we investigated the predictive properties of p11 promoter methylation in two clinical cohorts of patients with pharmacoresistant MDD. In a proof-of-concept clinical trial in 11 patients with refractory MDD, higher p11 promoter methylation was found in responders to ECT. This finding was replicated in an independent sample of 65 patients with pharmacoresistant MDD. This translational study successfully validated the first biomarker reliably predicting the responsiveness to ECT. Prescreening of this biomarker could help to identify patients eligible for first-line ECT treatment and also help to develop novel antidepressant treatment procedures for depressed patients resistant to all currently approved antidepressant treatments. en
dc.format.extent 13
dc.language.iso eng
dc.relation.ispartof Translational Psychiatry
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject 3112 Neurosciences
dc.subject 3124 Neurology and psychiatry
dc.subject CHRONIC MILD STRESS
dc.subject EPIGENETIC REGULATION
dc.subject TREATMENT RESISTANCE
dc.subject UNIPOLAR DEPRESSION
dc.subject NEUROTROPHIC FACTOR
dc.subject INDUCED ANHEDONIA
dc.subject MAJOR DEPRESSION
dc.subject RAT MODEL
dc.subject RESILIENCE
dc.subject BDNF
dc.title P11 promoter methylation predicts the antidepressant effect of electroconvulsive therapy en
dc.type Article
dc.contributor.organization Biosciences
dc.contributor.organization Laboratory of Neurotherapeutics
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1038/s41398-017-0077-3
dc.relation.issn 2158-3188
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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