Research reportEpigenetic modulation of BDNF gene: Differences in DNA methylation between unipolar and bipolar patients
Section snippets
Objectives of the study and background
Major Depressive Disorder (MDD) and Bipolar Disorder (BD) are prevalent, recurring and highly disabling conditions, etiologically determined by gene–environment interactions (American Psychiatric Association, 1994, Boulle et al., 2012). Discriminating between bipolar and unipolar depression, as well as between bipolar I and II patients, remains a diagnostic challenge, with clinical consequences in terms of treatment selection and outcome.
Among genes potentially implicated in the pathophysiology
Materials and methods
One hundred and fifty-four subjects (43 MDD; 61 BD I; 50 BD II), on stable pharmacological treatment, along with 44 age-matched, healthy controls were recruited, after providing written informed consent to participate to a study, conducted with the appropriate ethical approval.
Diagnoses were obtained through the administration of semi-structured interviews based on DSM-IV criteria (i.e., SCID I and II: Dangond and Gullans, 1998, Davies et al., 2012, First et al., 1997). Controls were volunteers
Results
Results showed similar levels of BDNF DNA methylation in BD II and MDD subjects, with rates of DNA methylation, at BDNF gene promoter, respectively of 33.49±2.80% and 33.50±1.98%. Both MDD and BD II patients showed a significant increase in BDNF DNA methylation, compared to BD I (P<0.01; Bonferroni׳s post-hoc test; ANOVA: P=0.0014; F=6.849) (Fig. 1a).
When subjects were stratified according to mood status, 57 cases of depression, 42 of mania/mixed states and 47 of euthymia were observed. DNA
Discussion
Most important findings from the present study indicate higher levels of DNA methylation, at the BDNF gene promoter, in MDD and BD II compared to BD I patients, as well as higher methylation levels in depressed compared to manic/mixed patients. Taken as a whole, present data seem to confirm our previous results of higher methylation levels in subjects with BD II (compared to BD I) (D׳Addario et al., 2012) and MDD (compared to controls) (D׳Addario et al., 2013). In addition, further relevant
Role of funding source
This work was supported by grants from the Monzino Foundation, Programma Strategico RF 2007, conv. PS39 (Italian Ministry of Health), TERCAS 2009–2012 and Progetti di Ricerca di Interesse Nazionale (20077R93XF_004). ADF was supported by a “Fondazione TERCAS-Progetto Speciale Assegni di Ricerca 2011–2013” fellowship.
Conflict of interest
BDO has been in the Speaker Bureau of Astra Zeneca, Bristol Myers Squibb, Janssen-Cilag, Eli Lilly, Pfizer, Glaxo Smith Kline, Lundbeck, Cyberonics and Italfarmaco. ACA is a consultant for Roche, Merck, Astra Zeneca, Bristol Myers Squibb, Janssen-Cilag, and Lundbeck. The other authors report no biomedical financial interests or potential conflicts of interest.
Acknowledgment
We thank Dr. Spagnolin for his help with blood samples.
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