DNA methylation signatures of mood stabilizers and antipsychotics in bipolar disorder

被引：61
作者：
Houtepen, Lotte C. [1 ]
van Bergen, Annet H. [1 ]
Vinkers, Christiaan H. [1 ]
Boks, Marco P. M. [1 ]
机构：
[1] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, Utrecht, Netherlands
来源：
EPIGENOMICS | 2016年 / 8卷 / 02期
关键词：
antidepressant; antipsychotics; bipolar; cell type; DNA methylation; medication; mood stabilizer; HISTONE DEACETYLASE INHIBITORS; VALPROIC ACID; GENE-EXPRESSION; MICROGLIAL ACTIVATION; EPIGENETIC MECHANISMS; SCHIZOPHRENIA; QUETIAPINE; NEURONS; BRAIN; DEMETHYLATION;
D O I：
10.2217/epi.15.98
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
Aim: In view of the potential effects of psychiatric drugs on DNA methylation, we investigated whether medication use in bipolar disorder is associated with DNA methylation signatures. Experimental procedures: Blood-based DNA methylation patterns of six frequently used psychotropic drugs (lithium, quetiapine, olanzapine, lamotrigine, carbamazepine, and valproic acid) were examined in 172 bipolar disorder patients. After adjustment for cell type composition, we investigated gene networks, principal components, hypothesis-driven genes and epigenome-wide individual loci. Results: Valproic acid and quetiapine were significantly associated with altered methylation signatures after adjustment for drug-related changes on celltype composition. Conclusion: Psychiatric drugs influence DNA methylation patterns over and above cell type composition in bipolar disorder. Drug-related changes in DNA methylation are therefore not only an important confounder in psychiatric epigenetics but may also inform on the biological mechanisms underlying drug efficacy.
引用
收藏
页码：197 / 208
页数：12
相关论文
共 83 条
[31]   Persistent epigenetic differences associated with prenatal exposure to famine in humans [J].
Heijmans, Bastiaan T. ;
Tobi, Elmar W. ;
Stein, Aryeh D. ;
Putter, Hein ;
Blauw, Gerard J. ;
Susser, Ezra S. ;
Slagboom, P. Eline ;
Lumey, L. H. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (44) :17046-17049
[32]   Possible association between a haplotype of the GABA-A receptor alpha 1 subunit gene (GABRA1) and mood disorders [J].
Horiuchi, Y ;
Nakayama, J ;
Ishiguro, H ;
Ohtsuki, T ;
Detera-Wadleigh, SD ;
Toyota, T ;
Yamada, K ;
Nankai, M ;
Shibuya, H ;
Yoshikawa, T ;
Arinami, T .
BIOLOGICAL PSYCHIATRY, 2004, 55 (01) :40-45
[33]   DNA Methylation in Whole Blood: Uses and Challenges [J].
Houseman E.A. ;
Kim S. ;
Kelsey K.T. ;
Wiencke J.K. .
Current Environmental Health Reports, 2015, 2 (2) :145-154
[34]   DNA methylation arrays as surrogate measures of cell mixture distribution [J].
Houseman, Eugene Andres ;
Accomando, William P. ;
Koestler, Devin C. ;
Christensen, Brock C. ;
Marsit, Carmen J. ;
Nelson, Heather H. ;
Wiencke, John K. ;
Kelsey, Karl T. .
BMC BIOINFORMATICS, 2012, 13
[35]   Thrombotic thrombocytopenic purpura associated with quetiapine [J].
Huynh, M ;
Chee, K ;
Lau, DHM .
ANNALS OF PHARMACOTHERAPY, 2005, 39 (7-8) :1346-1348
[36]   Inter-individual variability contrasts with regional homogeneity in the human brain DNA methylome [J].
Illingworth, Robert S. ;
Gruenewald-Schneider, Ulrike ;
De Sousa, Dina ;
Webb, Shaun ;
Merusi, Cara ;
Kerr, Alastair R. W. ;
James, Keith D. ;
Smith, Colin ;
Walker, Robert ;
Andrews, Robert ;
Bird, Adrian P. .
NUCLEIC ACIDS RESEARCH, 2015, 43 (02) :732-744
[37]   The effect of the antipsychotic drug quetiapine and its metabolite norquetiapine on acute inflammation, memory and anhedonia [J].
Jaehne, Emily J. ;
Corrigan, Frances ;
Toben, Catherine ;
Jawahar, M. Catharine ;
Baune, Bernhard T. .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 2015, 135 :136-144
[38]   Adjusting batch effects in microarray expression data using empirical Bayes methods [J].
Johnson, W. Evan ;
Li, Cheng ;
Rabinovic, Ariel .
BIOSTATISTICS, 2007, 8 (01) :118-127
[39]   Clinically relevant concentrations of valproic acid modulate melatonin MT1 receptor, HDAC and MeCP2 mRNA expression in C6 glioma cells [J].
Kim, Bora ;
Castro, Lyda M. Rincon ;
Jawed, Sana ;
Niles, Lermard P. .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2008, 589 (1-3) :45-48
[40]   Epigenetic mechanisms in mammals [J].
Kim, J. K. ;
Samaranayake, M. ;
Pradhan, S. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2009, 66 (04) :596-612
123456789