A Longitudinal Study of BDNF Promoter Methylation and Depression in Breast Cancer.
OBJECTIVE
Brain-derived neurotrophic factor (BDNF) is investigated in depression related to medical disorders and its secretion is influenced by epigenetic factors. We investigated the association between BDNF promoter methylation and depression following mastectomy for breast cancer.


METHODS
In total, 309 patients with breast cancer were evaluated 1 week after mastectomy, and 244 (79%) were followed up 1 year later. Depression was diagnosed (major or minor depressive disorder) according to DSM-IV criteria and depression severity was estimated by Montgomery-Asberg Depression Rating Scale (MADRS). We assessed BDNF promoter methylation using leukocyte DNA. The effects of BDNF methylation on depression diagnosis and severity were investigated using multivariate logistic and linear regression models, respectively. The two-way interaction between BDNF methylation and the val66met polymorphism on depression was also evaluated using multivariate logistic regression models.


RESULTS
Higher BDNF methylation was independently associated with depression diagnosis and with more severe symptoms at both 1 week and 1 year after mastectomy. No significant methylation-genotype interactions were found.


CONCLUSIONS
A role for BDNF in depression related to breast cancer was supported. Indeed, the association between depression and BDNF methylation may be useful for identifying patients who are at high risk for depression and for suggesting directions for promising drug research.
Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea.
Hee-Ju
HJ
Kang
Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea.
Jae-Min
JM
Kim
Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea.
Seon-Young
SY
Kim
Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea.
Sung-Wan
SW
Kim
Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea.
Il-Seon
IS
Shin
Brain Korea 21 Project, Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju, Republic of Korea.
Hye-Ran
HR
Kim
Breast and Endocrine Tumor Clinic, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
Min-Ho
MH
Park
Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
Myung-Geun
MG
Shin
Breast and Endocrine Tumor Clinic, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea.
Jung-Han
JH
Yoon
Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea.
Jin-Sang
JS
Yoon
BDNF; Breast cancer; DNA methylation; Depression; Epigenetics