Selective DNA Methylation of BDNF Promoter in Bipolar Disorder: Differences Among Patients with BDI and BDII

被引：133

作者：

D'Addario, Claudio ^{[2
]}

Dell'Osso, Bernardo ^{[1
]}

Palazzo, Maria Carlotta ^{[1
]}

Benatti, Beatrice ^{[1
]}

Lietti, Licia ^{[1
]}

Cattaneo, Elisabetta ^{[1
]}

Galimberti, Daniela ^{[3
]}

Fenoglio, Chiara ^{[3
]}

Cortini, Francesca ^{[3
]}

Scarpini, Elio ^{[3
]}

Arosio, Beatrice ^{[4
]}

Di Francesco, Andrea ^{[2
]}

Di Benedetto, Manuela ^{[5
]}

Romualdi, Patrizia ^{[5
]}

Candeletti, Sanzio ^{[5
]}

Mari, Daniela ^{[4
]}

Bergamaschini, Luigi ^{[6
]}

Bresolin, Nereo ^{[3
]}

Maccarrone, Mauro ^{[2
,7
]}

Altamura, A. Carlo ^{[1
]}

机构：

[1] Univ Milan, Fdn IRCCS Ca Granda, Osped Maggiore Policlin,Dept Clin Psychiat, Dept Mental Hlth,Dept Psychiat, I-20122 Milan, Italy

[2] Univ Teramo, Dept Biomed Sci, Teramo, Italy

[3] Univ Milan, Fdn IRCCS Ca Granda, Osped Maggiore Policlin,Dept Neurol Sci, Dept Neurol,Ctr Dino Ferrari, I-20122 Milan, Italy

[4] Univ Milan, Fdn IRCCS Ca Granda Osp Maggiore Policlin, Geriatr Unit, I-20122 Milan, Italy

[5] Univ Bologna, Dept Pharmacol, Bologna, Italy

[6] Univ Milan, ASP Pio Albergo Trivulzio, I-20122 Milan, Italy

[7] Santa Lucia Fdn, European Ctr Brain Res CERC, Rome, Italy

来源：

NEUROPSYCHOPHARMACOLOGY | 2012年 / 37卷 / 07期

关键词：

brain-derived neurotrophic factor (BDNF); peripheral blood mononuclear cells (PBMCs); DNA methylation; gene expression; bipolar disorder (BD); mood stabilizers and antidepressants; BINDING PROTEIN MECP2; NEUROTROPHIC FACTOR; GENE-EXPRESSION; ANTIDEPRESSANT MEDICATIONS; MESSENGER-RNA; RATING-SCALE; BRAIN; DEPRESSION; ASSOCIATION; NEUROPLASTICITY;

D O I：

10.1038/npp.2012.10

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

The etiology of bipolar disorder (BD) is still poorly understood, involving genetic and epigenetic mechanisms as well as environmental contributions. This study aimed to investigate the degree of DNA methylation at the promoter region of the brain-derived neurotrophic factor (BDNF) gene, as one of the candidate genes associated with major psychoses, in peripheral blood mononuclear cells isolated from 94 patients with BD (BD I = 49, BD II = 45) and 52 healthy controls. A significant BDNF gene expression downregulation was observed in BD II 0.53 +/- 0.11%; P<0.05), but not in BD I (1.13 +/- 0.19%) patients compared with controls (CONT: 1 +/- 0.2%). Consistently, an hypermethylation of the BDNF promoter region was specifically found in BD II patients (CONT: 24.0 +/- 2.1%; BDI: 20.4 +/- 1.7%; BDII: 33.3 +/- 3.5%, P<0.05). Of note, higher levels of DNA methylation were observed in BD subjects on pharmacological treatment with mood stabilizers plus antidepressants (34.6 +/- 4.2%, predominantly BD II) compared with those exclusively on mood-stabilizing agents (21.7 +/- 1.8%; P<0.01, predominantly BD I). Moreover, among the different pharmacological therapies, lithium (20.1 +/- 3.8%, P<0.05) and valproate (23.6 +/- 2.9%, P<0.05) were associated with a significant reduction of DNA methylation compared with other drugs (35.6 +/- 4.6%). Present findings suggest selective changes in DNA methylation of BDNF promoter in subjects with BD type II and highlight the importance of epigenetic factors in mediating the onset and/or susceptibility to BD, providing new insight into the mechanisms of gene expression. Moreover, they shed light on possible mechanisms of action of mood-stabilizing compounds vs antidepressants in the treatment of BD, pointing out that BDNF regulation might be a key target for their effects. Neuropsychopharmacology (2012) 37, 1647-1655; doi:10.1038/npp.2012.10; published online 22 February 2012

引用

页码：1647 / 1655

页数：9

共 72 条

[1]

Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder [J].