Association of BDNF Promoter Methylation and Genotype with Suicidal Ideation in Elderly Koreans Jae-Min Kim, M.D., Ph.D., Hee-Ju Kang, M.D., M.Sc., Kyung-Yeol Bae, M.D., Ph.D., Sung-Wan Kim, M.D., Ph.D., Il-Seon Shin, M.D., Ph.D., Hye-Ran Kim, Ph.D., Myung-Geun Shin, M.D., Ph.D., Jin-Sang Yoon, M.D., Ph.D. Objectives: Brain-derived neurotrophic factor (BDNF) has been considered a risk factor for suicidal behavior in adult populations. BDNF secretion is influenced by epigenetic (DNA promoter methylation) and genetic (val66met polymorphism) profiles. We investigated the independent and interactive effects of BDNF methylation status and val66met polymorphisms on late-life suicidal ideation. Methods: In total, 732 Korean community residents aged 65þ years were evaluated; of 639 without suicidal ideation, 579 (90.6%) were followed up 2 years later. The prevalence and incidence of suicidal ideation were ascertained using the Geriatric Mental State Schedule. Socio- demographic and clinical covariates included age, sex, education, depressive symp- toms, cognitive function, and disability. The independent effects of BDNF methylation status on the prevalence and incidence of suicidal ideation were investigated using multivariate logistic regression models. The two-way interactions of BDNF methylation status and val66met polymorphism on suicidal ideation were assessed using the same models. Results: Higher BDNF methylation status was significantly associated with both prevalence and incidence of suicidal ideation, independent of potential cova- riates. No significant methylationegenotype interaction was found. Conclusions: The BDNF hypothesis and the epigenetic origin of the suicidal behavior were supported, even in old age. BDNF promoter methylation status may be useful as a biological marker for suicidality in late life. (Am J Geriatr Psychiatry 2014; -:-e-) Key Words: Suicidality, BDNF, DNA methylation, epigenetics, aged S uicide is a serious public health problem and a major cause of death worldwide. The spectrum of suicidal behavior ranges from suicidal ideation, through attempts, to completion. 1 Suicidal behavior is disproportionally high in older adults, and this is of increasing importance given demographic aging. 2 Received December 8, 2013; revised February 24, 2014; accepted February 27, 2014. From the Department of Psychiatry (JMK, HJK, KYB, SWK, ISS, JSY) and Department of Laboratory Medicine (MGS), Chonnam National University Medical School, Gwangju, Korea; Brain Korea 21 Project (HRK), Center for Biomedical Human Resources, Chonnam National University Medical School, Gwangju, Korea. Send corre- spondence and reprint requests to Jin-Sang Yoon, M.D., Ph.D., Department of Psychiatry, Chonnam National University Medical School, 160 Baekseoro, Dong-Ku, Gwangju 501-746, Republic of Korea. e-mail: jsyoon@chonnam.ac.kr Supplemental digital content is available for this article in the HTML and PDF versions of this article on the journal’s Web site (www. ajgponline.org). Ó 2014 American Association for Geriatric Psychiatry http://dx.doi.org/10.1016/j.jagp.2014.02.011 Am J Geriatr Psychiatry -:-, - 2014 1