title: Elevated methylation and decreased serum concentrations of BDNF in patients in levomethadone compared to diamorphine maintenance treatment.
abstract: Brain-derived neurotrophic factor (BDNF) appears to play a crucial role in the reward response to drugs such as heroin. The primary objective of the present study was to examine epigenetic changes and serum levels of BDNF in patients undergoing different opiate-based maintenance treatments. We compared patients receiving treatment with either levomethadone (n = 55) or diamorphine (n = 28) with a healthy control group (n = 51). When comparing all subjects (patients and controls), BDNF serum levels showed a negative correlation with the BDNF IV promoter methylation rate (r = -0.177, p = 0.048). Furthermore, BDNF serum levels negatively correlated with Beck's Depression Inventory measurements (r = -0.177, p < 0.001). Patients receiving diamorphine maintenance treatment showed slightly decreased BDNF serum levels compared to healthy controls, whereas patients on levomethadone maintenance treatment with or without heroine co-use showed a pronounced decrease (analysis of covariance: control vs. levomethadone with and without heroine co-use: p < 0.0001, diamorphine vs. levomethadone with heroine co-use: p = 0.043, diamorphine vs. levomethadone without heroine co-use: p < 0.0001). According to these findings, methylation of the BDNF IV promoter showed the highest level in patients receiving levomethadone without heroine co-use (linear mixed model: control vs. levomethadone group without heroine co-use: p = 0.008, with heroin co-use: p = 0.050, diamorphine vs. levomethadone group with heroine co-use: p = 0.077 and without heroine co-use: p = 0.015.). For the first time, we show an epigenetic mechanism that may provide an explanation for mood destabilization in levomethadone maintenance treatment.
authors.affiliation: Department of Addictive Behavior and Addiction Medicine, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany. rilana.schuster@zi-mannheim.de.|Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany. rilana.schuster@zi-mannheim.de.
authors.forename: Rilana
authors.initials: R
authors.lastname: Schuster
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kleimann
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.
authors.forename: Marie-Kathrin
authors.initials: MK
authors.lastname: Rehme
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.
authors.forename: Leonie
authors.initials: L
authors.lastname: Taschner
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Glahn
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Groh
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.
authors.forename: Helge
authors.initials: H
authors.lastname: Frieling
authors.affiliation: Institute of Clinical Chemistry, Hanover Medical School, Hanover, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Lichtinghagen
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hillemacher
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bleich
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Heberlein
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D003863:Depression / Q000209:etiology; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D003932:Heroin / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008691:Methadone / Q000494:pharmacology / Q000627:therapeutic use*; D008745:Methylation / Q000187:drug effects; D008875:Middle Aged; D009293:Opioid-Related Disorders / Q000097:blood* / Q000188:drug therapy* / Q000523:psychology; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires; D064232:Visual Analog Scale
chemical_list: D000701:Analgesics, Opioid; D019208:Brain-Derived Neurotrophic Factor; D003932:Heroin; D008691:Methadone
keywords: BDNF; Brain-derived neurotrophic factor; DNA methylation; Epigenetic regulation; Opiate dependence; Opiate maintenance