title: Epigenetic modulation of BDNF gene: differences in DNA methylation between unipolar and bipolar patients.
abstract: BACKGROUND
  The brain derived neurotrophic factor (BDNF) gene and its epigenetic regulation have been repeatedly implicated in the pathophysiology of mood disorders. Following previous investigation in the field, we further investigated differences in BDNF promoter gene methylation in patients with mood disorders, comparing unipolar and bipolar subjects, on the basis of illness phase, gender, age and psychotropic prescription.
  
  
  METHODS
  154 patients (43 MDD; 61 BD I; 50 BD II), on stable pharmacological treatment, and 44 age-matched, healthy controls were recruited. BDNF methylation levels from peripheral blood mononuclear cells (PBMCs) were compared by analysis of variance followed by Bonferroni׳s post-hoc test.
  
  
  RESULTS
  Similar, higher levels of BDNF gene promoter methylation were found in BD II and MDD patients, compared to BD I subjects (P<0.01). When stratified on the basis of mood status, methylation levels of depressed patients were significantly higher, compared to the levels of manic/mixed patients (P<0.01). While gender and age did not seem to influence methylation levels of BDNF gene promoter, patients on lithium and valproate showed overall lower levels.
  
  
  CONCLUSIONS
  Cross-sectional analysis using PBMCs with further investigation with larger samples, including drug-naïve patients, needed to replicate findings in neuronal cells.
  
  
  CONCLUSIONS
  Present data confirm our previous results of higher methylation levels in BD II (compared to BD I) and MDD patients (compared to controls). A closer relationship between BD II and MDD, compared to BD I patients as well an association of lower methylation levels with the presence of mania/mixed state, compared to the depressive phase, was observed.
authors.affiliation: Dipartimento di Fisiopatologia medico-chirurgica e dei trapianti, Università degli Studi di Milano, Dipartimento di Salute Mentale, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy. Electronic address: bernardo.dellosso@unimi.it.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Dell'Osso
authors.affiliation: Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Italy; Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden.
authors.forename: Claudio
authors.initials: C
authors.lastname: D'Addario
authors.affiliation: Dipartimento di Fisiopatologia medico-chirurgica e dei trapianti, Università degli Studi di Milano, Dipartimento di Salute Mentale, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Carlotta Palazzo
authors.affiliation: Dipartimento di Fisiopatologia medico-chirurgica e dei trapianti, Università degli Studi di Milano, Dipartimento di Salute Mentale, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Benatti
authors.affiliation: Dipartimento di Fisiopatologia medico-chirurgica e dei trapianti, Università degli Studi di Milano, Dipartimento di Salute Mentale, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Camuri
authors.affiliation: Department of Neurological Sciences, Università degli Studi di Milano, Fondazione IRRCS Cà Granda, Ospedale Maggiore Policlinico, Department of Neurology, Milano, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.affiliation: Department of Neurological Sciences, Università degli Studi di Milano, Fondazione IRRCS Cà Granda, Ospedale Maggiore Policlinico, Department of Neurology, Milano, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.affiliation: Department of Neurological Sciences, Università degli Studi di Milano, Fondazione IRRCS Cà Granda, Ospedale Maggiore Policlinico, Department of Neurology, Milano, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.affiliation: Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Francesco
authors.affiliation: Center of Integrated Research, Campus Bio-Medico University of Rome, Italy; European Center for Brain Research (CERC)/Santa Lucia Foundation, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
authors.affiliation: Dipartimento di Fisiopatologia medico-chirurgica e dei trapianti, Università degli Studi di Milano, Dipartimento di Salute Mentale, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: A Carlo
authors.initials: AC
authors.lastname: Altamura
mesh_terms: D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: Bipolar disorders; Brain derived neurotrophic factor (BDNF); Epigenetics; Major depressive disorder; Methylation