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Abstract

Associations between DNA methylation of Promoter Exon IX, Serum Protein and mRNA levels of Brain-derived Neurotrophic factor in Patients with Bipolar Mania

Author(s): Chin-Chuen Lin, Yi-Yung Hung, Tiao-Lai Huang

Abstract

Background: Brain-derived neurotrophic factor (BDNF) could be as a molecular candidate for the development of bipolar disorder. We tried to investigate the relationships among BDNF promoter exon IX gene methylation, BDNF protein, and mRNA levels between patients with bipolar mania and healthy controls in peripheral blood.

Methods: Thirty-nine patients with bipolar mania and 39 healthy controls were recruited in this study. Psychiatric diagnoses were made according to DSM-IV criteria. Clinical severity of mania was assessed by the Young Mania Rating Scale, and only those with a score greater than 26 were recruited. After four weeks of medical treatment, 34 patients agreed to a follow-up evaluation.

Results: The sequential methylation analysis was completed for the 39 patients with bipolar mania and 39 healthy controls at baseline. Using ANCOVA adjusted for age and gender, patients with bipolar mania had a higher degree of methylation at CpG site 217 (p < .001) and lower degree
of methylation at CpG site 391 (p = 0.013) than did the healthy controls. Serum BDNF protein level correlated significantly with the degree of methylation at CpG site 348 (p = .010). BDNF mRNA level correlated significantly with degree of methylation at CpG sites 134 (p = .004), 177 (p < .001) and 217 (p < .001). After four weeks of medical treatment, degrees of methylation of fourteen studied CpG sites did not change significantly in the 34 patients with bipolar mania, but YMRS score significantly correlated with the degree of methylation at CpG site 391 (r =-0.441, p = 0.009).

Conclusion: Our results indicated that the degree of BDNF promoter exon IX gene methylation in peripheral blood might be involved in the psychopathology of bipolar mania and its treatment response.


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