TY - JOUR
KW - Adult
KW - Analgesics, Opioid/pharmacology/therapeutic use
KW - Brain-Derived Neurotrophic Factor/blood/genetics
KW - Case-Control Studies
KW - Depression/etiology
KW - Epigenesis, Genetic/drug effects
KW - Female
KW - Heroin/pharmacology/therapeutic use
KW - Humans
KW - Male
KW - Methadone/pharmacology/therapeutic use
KW - Methylation/drug effects
KW - Middle Aged
KW - Opioid-Related Disorders/blood/drug therapy/psychology
KW - Promoter Regions, Genetic/drug effects/genetics
KW - Prospective Studies
KW - Psychiatric Status Rating Scales
KW - Statistics, Nonparametric
KW - Surveys and Questionnaires
KW - Visual Analog Scale
KW - BDNF
KW - Brain-derived neurotrophic factor
KW - DNA methylation
KW - Epigenetic regulation
KW - opiate dependence
KW - Opiate maintenance
AU - R. Schuster
AU - A. Kleimann
AU - M. K. Rehme
AU - L. Taschner
AU - A. Glahn
AU - A. Groh
AU - H. Frieling
AU - R. Lichtinghagen
AU - T. Hillemacher
AU - S. Bleich
AU - A. Heberlein
A1 - 
AB - 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.
AD - 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.; Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.; Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.; Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.; Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.; Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.; Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.; Institute of Clinical Chemistry, Hanover Medical School, Hanover, Germany.; Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.; Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.; Department of Psychiatry, Social Psychiatry and Psychotherapy, Center for Addiction Research (CARe), Hanover Medical School, Hanover, Germany.
BT - European archives of psychiatry and clinical neuroscience
C5 - Opioids & Substance Use
CP - 1
CY - Germany
DO - 10.1007/s00406-016-0668-7
IS - 1
JF - European archives of psychiatry and clinical neuroscience
M1 - Journal Article
N2 - 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.
PP - Germany
PY - 2017
SN - 1433-8491; 0940-1334
SP - 33
EP - 40
EP - 
T1 - Elevated methylation and decreased serum concentrations of BDNF in patients in levomethadone compared to diamorphine maintenance treatment
T2 - European archives of psychiatry and clinical neuroscience
TI - Elevated methylation and decreased serum concentrations of BDNF in patients in levomethadone compared to diamorphine maintenance treatment
U1 - Opioids & Substance Use
U2 - 26801497
U3 - 10.1007/s00406-016-0668-7
VL - 267
VO - 1433-8491; 0940-1334
Y1 - 2017
Y2 - Feb
ER -