P11 promoter methylation predicts the antidepressant effect of electroconvulsive therapy

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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

Title: P11 promoter methylation predicts the antidepressant effect of electroconvulsive therapy
Author: Neyazi, Alexandra; Theilmann, Wiebke; Brandt, C; Rantamäki, Tomi Pentti Johannes; Matsui, Nobuaki; Rhein, M; Kornhuber, J; Bajbouj, M; Sperling, W; Bleich, S; Frieling, H; Löscher, W
Contributor organization: Biosciences
Laboratory of Neurotherapeutics
Date: 2018-01-22
Language: eng
Number of pages: 13
Belongs to series: Translational Psychiatry
ISSN: 2158-3188
DOI: https://doi.org/10.1038/s41398-017-0077-3
URI: http://hdl.handle.net/10138/233655
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.
Subject: 3112 Neurosciences
3124 Neurology and psychiatry
CHRONIC MILD STRESS
EPIGENETIC REGULATION
TREATMENT RESISTANCE
UNIPOLAR DEPRESSION
NEUROTROPHIC FACTOR
INDUCED ANHEDONIA
MAJOR DEPRESSION
RAT MODEL
RESILIENCE
BDNF
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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